Master Class

Surgery should be considered only in women who are hemodynamically stable and whose transvaginal ultrasound (TVUS) examination shows a tubal ectopic pregnancy or an adnexal mass suggestive of ectopic pregnancy. If TVUS does not show an abnormality, it is unlikely that an ectopic pregnancy will be visualized or palpated at surgery.

Moreover, when we need to treat surgically, we can and should use minimally invasive techniques whenever possible.

Alternatives to Surgery

Expectant management is the least desirable option because of the risk of tubal rupture. I take this approach only when I suspect ectopic pregnancy but TVUS fails to show the location of the gestational sac, and the serum levels of β-HCG are low and declining. Because of the possibility of tubal rupture, these patients must be carefully monitored until the serum β-HCG concentration falls below 15 IU/L; at this point, almost all ectopic pregnancies resolve spontaneously, without rupture.

Expectant management is never the best treatment when we have a diagnosis of ectopic pregnancy.

With an expectant management approach, we must monitor patients closely with serial β-HCG measurements every 2–3 days and also employ TVUS. The combination can provide us with information on whether we're dealing with an ectopic pregnancy or a miscarriage. A serum β-HCG concentration that is low and fails to double over 2–3 days suggests that we are dealing with either an ectopic pregnancy or failing intrauterine pregnancy.

Be aware that tubal rupture has been reported in women with low, declining, or even undetectable β-HCG levels. Rupture is mainly a result of blood distending the tube.

Some physicians will do a D&C when they're unsure about an ectopic pregnancy, but I would argue against this. First, it's surgery. Second, methotrexate (MTX) treatment has minimal side effects. Because a single intramuscular injection of methotrexate is safe, I would argue that it is the better alternative.

It can even be reasonably argued that MTX administration is a better approach to management than is expectant management. However, we have to make sure that the possibility of viable intrauterine pregnancy has been eliminated.

When MTX is administered to properly selected patients, it has a success rate up to 94%. Several randomized studies have even found that MTX treatment in selected patients with ectopic pregnancy was as effective as laparoscopic treatment.

MTX should be given to women who are hemodynamically stable and who are willing and able to comply with posttreatment monitoring; who have an initial serum β-HCG concentration lower than 5,000 IU/L; and who have no ultrasound evidence of fetal cardiac activity.

The main factor in determining who is a candidate for MTX is the level of β-HCG. A fairly recent metaanalysis of data for 1,327 women with ectopic pregnancy who were treated with MTX showed that success of the therapy was inversely associated with β-HCG levels, and that increasing levels were significantly correlated with treatment failure.

In general, if the β-HCG level is higher than 5,000 IU/L, the failure rate of therapy is significantly higher.

But other factors are important as well. Treatment failure is also associated with fetal cardiac activity. And you most certainly do not want to give MTX to a patient whom you won't see for 3 months.

Recent evidence suggests that tubal diameter or fetal size does not predict the success of medical treatment.

Laparoscopy: It's Clear

For those who do not meet the criteria for MTX administration—as well as for women who do not have timely access to a medical institution for management of tubal rupture and, of course, for women who have a ruptured ectopic pregnancy—surgery is necessary.

Three good prospective, randomized trials with a total of 231 women have compared laparotomy with laparoscopy, and have found that laparoscopic surgery is superior. Laparoscopic treatment of ectopic pregnancy resulted in less blood loss, lower analgesic requirements, shorter operative times, and briefer hospital stays. The studies also showed similar reproductive outcomes—subsequent uterine pregnancy and repeat ectopic pregnancy—after salpingostomy by either approach.

A Cochrane review published in 2000 also concluded that laparoscopic surgery is the best treatment. It reported a higher rate of persistent trophoblast with laparoscopic surgery, but concluded this was outweighed by the benefits of the more conservative laparoscopic approach. As I see it, the incidence of persistent trophoblast is related to the laparoscopic experience of the surgeon.

When a patient is unstable or in shock, I stabilize the patient first and then consult with the anesthesiologist to see if he or she is comfortable with my doing laparoscopy. In my experience, most will offer their support for a laparoscopic approach.

Most ectopic pregnancies—even interstitial pregnancy, heterotopic pregnancy, and ectopic pregnancy in the presence of hemoperitoneum—can be treated through a laparoscopic procedure. Your approach, or course, should depend upon your experience and the judgment of the anesthesiologist.

To Spare the Tube or Not

When it comes to choosing salpingostomy or salpingectomy, there are some uncertainties, and we face an absence of data from randomized studies. In some—but not all—of the nonrandomized studies that have been done, the intrauterine pregnancy rate has been higher after the tube-sparing surgery than after salpingectomy. However, the risk of recurrent ectopic pregnancy has been shown to be slightly higher after the more conservative treatment.

These differences most likely reflect tubal status and not the choice of surgical procedure. In other words, contralateral tubal abnormalities predispose patients to recurrent ectopic pregnancy regardless of the type of surgery. In one study of women who underwent laparoscopic salpingectomy, rates of intrauterine pregnancy and recurrent ectopic pregnancy were better among women who had normal contralateral tubal anatomy and no history of infertility (approximately 75% and 10%, respectively), compared with women who had abnormal tube anatomy or infertility (37% and 18%, respectively).

In the absence of data from a randomized study, though, salpingostomy should be the treatment of choice, particularly for women who want another pregnancy. I do not remove the tube in patients who wish to conceive again, provided the tube is relatively normal by gross inspection. If the patient has completed her family, I will remove the tube.

Some other ectopic pregnancies are often best treated by salpingectomy. These include cases of uncontrolled bleeding, a severely damaged tube, most cases of recurrent ectopic pregnancy within the same tube, and a tubal gestational sac larger than 3 cm in diameter. In these cases, the probability of normal tubal function in the future is low, and the likelihood of recurrent tubal problems is high.

Salpingostomy Technique

Laparoscopic salpingostomy is fairly straightforward. First, inject a dilute solution of vasopressin (0.2 IU/mL of physiologic saline) into the tubal wall at the area of maximal distention. This will minimize bleeding. Using a unipolar needle electrocautery (laser and scissors can also be used), make a 10− to 15-mm linear incision along the antimesenteric border overlying the ectopic site.

Do not use forceps and do not pull the products of conception out piece by piece, or you could cause more bleeding and mistakenly leave tissue behind. Instead, use a combination of hydrodissection with irrigating solution under high pressure and gentle blunt dissection with a suction irrigator. Remove the specimen from the abdominal cavity. A laparoscopic pouch can be useful for removing large pieces of gestational tissue.

Carefully irrigate the tube and make sure there is no bleeding. Control any bleeding points with pressure or with a light application of bipolar coagulation. If bleeding persists, ligate the vessels in the mesosalpinx with a 6–0 polyglactin suture. The suturing is technically demanding, but this is one condition in which suturing skill is extremely helpful, and all laparoscopists should acquire it.

Do not keep coagulating the inside of the tube to stop the bleeding. The thermal damage will affect the integrity of the tube, and that integrity is important for future pregnancies.

Leave the incision open to heal by secondary intention. A randomized study I led several years ago showed no difference in the rates of adhesion formation and subsequent fertility between patients who had suturing after laparotomy and those who did not. If there is no difference after laparotomy, then the outcomes associated with secondary intention and primary closure after laparoscopy will also be similar.

Some physicians have proposed giving women MTX right after surgery. Although I do not recommend administering MTX prophylactically, it might be worthwhile to administer one dose of MTX in those rare cases in which you suspect that you might have left behind some gestational tissue.

Salpingectomy Technique

There are several methods for laparoscopic salpingectomy. For one, you may ligate the part of the tube that contains the ectopic pregnancy, then resect and remove the tube.

Alternatively, use electrosurgery to coagulate the tube and mesosalpinx and then resect the specimen with scissors. The cornual portion of the tube should be desiccated close to the uterus. Elevate the tube when using the electrocautery, or you may inadvertently damage the ovarian vessels. You may perform either partial or segmental salpingectomy using a laparoscopic approach.

Regardless of the method of treatment, always check the patient's blood group. If she is Rh negative and the male partner's Rh factor is positive or unknown, the patient should be given RhoGAM.

Interstitial Pregnancy

Especially among patients who have had in vitro fertilization (IVF), you may encounter interstitial pregnancy. The conventional treatment is hysterectomy or cornual resection. But with earlier diagnosis using TVUS and β-HCG assays, it can be diagnosed early and treated medically or laparoscopically.

Start with medical treatment and resort to surgery if there is any deterioration in clinical status. There are several options for surgery, including laparoscopic cornual resection, cornuostomy, or salpingotomy. In most cases, you will want to use dilute intramyometrial vasopressin at the start of the surgery to minimize blood loss. And remember the value of suturing and the option of achieving hemostasis by ligating the ascending branches of the uterine vessels.

If you perform surgery, make sure you have expertise in suturing, because you will be working in a very vascular area. Be comfortable with the procedure you are doing. I prefer laparoscopic removal of the gestation, with removal of the interstitial portion of the tube if necessary.

The risk of uterine rupture in future pregnancies after medical treatment of an interstitial pregnancy is unknown, as is the future integrity of the uterus following laparoscopic surgical treatment. We may be able to prevent future uterine rupture with proper suturing of the uterine cornu after laparoscopic treatment. Nevertheless, discuss the possibility of rupture occurring during a subsequent pregnancy with patients undergoing any treatment for interstitial pregnancy.

Likewise, monitor women with a history of interstitial pregnancy very closely. I usually recommend cesarean delivery to avoid potential uterine rupture during labor.

With any pregnancy after IVF, make sure that an ectopic pregnancy is not accompanied by pregnancy in the uterus. If you see both, you should not even consider medical therapy.

Persistent Ectopic Pregnancy

Persistent ectopic pregnancy occurs more often after salpingostomy performed with laparoscopy than after salpingostomy through laparotomy (about 8% compared with 4%). The difference used to be much greater and probably reflects the surgeon's learning curve.

Some authors have recommended weekly serum β-HCG measurements after laparoscopic salpingostomy to exclude persistent ectopic pregnancy. We perform a single serum β-HCG measurement 1 week after surgery. If the level is more than 5% of the preoperative value, we will repeat the measurement 1 week later.

If the level does not decline after the second week, we administer a single dose of MTX (50 mg/m

A large ischemic ectopic pregnancy can be painful emotionally as well as physically.

Salpingostomy has been performed and the ectopic gestation extruded outside the fallopian tube.

One suture to approximate the tubal incision has been placed, a step that requires exacting skill. Photos courtesy Dr. Togas Tulandi

Treating Ectopic Pregnancy

As editor of Master Class columns on gynecologic surgery, I am especially pleased to have Togas Tulandi, M.D., contribute this article on the current treatment of ectopic pregnancy. Dr. Tulandi is a professor of ob.gyn. and the Milton Leong Chair in Reproductive Medicine (the first Canadian chair in reproductive medicine) at McGill University in Montreal.

As a clinical researcher, Dr. Tulandi has been quite prolific. He has published more than 200 articles, 250 abstracts, 40 book chapters, and eight books. Dr. Tulandi also is the current president of the Society of Reproductive Surgeons, an affiliated society of the American Society for Reproductive Medicine.

As the readership no doubt will observe, Dr. Tulandi has a rather conservative view of treatment of ectopic pregnancy with medical therapy (methotrexate). Moreover, he provides valid reasons why laparoscopy is considered the preferred surgical treatment for ectopic pregnancy.

Although Dr. Tulandi points out that data are lacking when deciding between salpingectomy vs. salpingostomy, he does provide reasonable recommendations to assist in deciding between the two procedures.

In addition, Dr. Tulandi shares valuable insight on interstitial pregnancy as well as persistent ectopic pregnancy.

Once again, I am very proud to have Dr. Tulandi's involvement with OB.GYN. NEWS and the Master Class.

Surgery should be considered only in women who are hemodynamically stable and whose transvaginal ultrasound (TVUS) examination shows a tubal ectopic pregnancy or an adnexal mass suggestive of ectopic pregnancy. If TVUS does not show an abnormality, it is unlikely that an ectopic pregnancy will be visualized or palpated at surgery.

Moreover, when we need to treat surgically, we can and should use minimally invasive techniques whenever possible.

Alternatives to Surgery

Expectant management is the least desirable option because of the risk of tubal rupture. I take this approach only when I suspect ectopic pregnancy but TVUS fails to show the location of the gestational sac, and the serum levels of β-HCG are low and declining. Because of the possibility of tubal rupture, these patients must be carefully monitored until the serum β-HCG concentration falls below 15 IU/L; at this point, almost all ectopic pregnancies resolve spontaneously, without rupture.

Expectant management is never the best treatment when we have a diagnosis of ectopic pregnancy.

With an expectant management approach, we must monitor patients closely with serial β-HCG measurements every 2–3 days and also employ TVUS. The combination can provide us with information on whether we're dealing with an ectopic pregnancy or a miscarriage. A serum β-HCG concentration that is low and fails to double over 2–3 days suggests that we are dealing with either an ectopic pregnancy or failing intrauterine pregnancy.

Be aware that tubal rupture has been reported in women with low, declining, or even undetectable β-HCG levels. Rupture is mainly a result of blood distending the tube.

Some physicians will do a D&C when they're unsure about an ectopic pregnancy, but I would argue against this. First, it's surgery. Second, methotrexate (MTX) treatment has minimal side effects. Because a single intramuscular injection of methotrexate is safe, I would argue that it is the better alternative.

It can even be reasonably argued that MTX administration is a better approach to management than is expectant management. However, we have to make sure that the possibility of viable intrauterine pregnancy has been eliminated.

When MTX is administered to properly selected patients, it has a success rate up to 94%. Several randomized studies have even found that MTX treatment in selected patients with ectopic pregnancy was as effective as laparoscopic treatment.

MTX should be given to women who are hemodynamically stable and who are willing and able to comply with posttreatment monitoring; who have an initial serum β-HCG concentration lower than 5,000 IU/L; and who have no ultrasound evidence of fetal cardiac activity.

The main factor in determining who is a candidate for MTX is the level of β-HCG. A fairly recent metaanalysis of data for 1,327 women with ectopic pregnancy who were treated with MTX showed that success of the therapy was inversely associated with β-HCG levels, and that increasing levels were significantly correlated with treatment failure.

In general, if the β-HCG level is higher than 5,000 IU/L, the failure rate of therapy is significantly higher.

But other factors are important as well. Treatment failure is also associated with fetal cardiac activity. And you most certainly do not want to give MTX to a patient whom you won't see for 3 months.

Recent evidence suggests that tubal diameter or fetal size does not predict the success of medical treatment.

Laparoscopy: It's Clear

For those who do not meet the criteria for MTX administration—as well as for women who do not have timely access to a medical institution for management of tubal rupture and, of course, for women who have a ruptured ectopic pregnancy—surgery is necessary.

Three good prospective, randomized trials with a total of 231 women have compared laparotomy with laparoscopy, and have found that laparoscopic surgery is superior. Laparoscopic treatment of ectopic pregnancy resulted in less blood loss, lower analgesic requirements, shorter operative times, and briefer hospital stays. The studies also showed similar reproductive outcomes—subsequent uterine pregnancy and repeat ectopic pregnancy—after salpingostomy by either approach.

A Cochrane review published in 2000 also concluded that laparoscopic surgery is the best treatment. It reported a higher rate of persistent trophoblast with laparoscopic surgery, but concluded this was outweighed by the benefits of the more conservative laparoscopic approach. As I see it, the incidence of persistent trophoblast is related to the laparoscopic experience of the surgeon.

When a patient is unstable or in shock, I stabilize the patient first and then consult with the anesthesiologist to see if he or she is comfortable with my doing laparoscopy. In my experience, most will offer their support for a laparoscopic approach.

Most ectopic pregnancies—even interstitial pregnancy, heterotopic pregnancy, and ectopic pregnancy in the presence of hemoperitoneum—can be treated through a laparoscopic procedure. Your approach, or course, should depend upon your experience and the judgment of the anesthesiologist.

To Spare the Tube or Not

When it comes to choosing salpingostomy or salpingectomy, there are some uncertainties, and we face an absence of data from randomized studies. In some—but not all—of the nonrandomized studies that have been done, the intrauterine pregnancy rate has been higher after the tube-sparing surgery than after salpingectomy. However, the risk of recurrent ectopic pregnancy has been shown to be slightly higher after the more conservative treatment.

These differences most likely reflect tubal status and not the choice of surgical procedure. In other words, contralateral tubal abnormalities predispose patients to recurrent ectopic pregnancy regardless of the type of surgery. In one study of women who underwent laparoscopic salpingectomy, rates of intrauterine pregnancy and recurrent ectopic pregnancy were better among women who had normal contralateral tubal anatomy and no history of infertility (approximately 75% and 10%, respectively), compared with women who had abnormal tube anatomy or infertility (37% and 18%, respectively).

In the absence of data from a randomized study, though, salpingostomy should be the treatment of choice, particularly for women who want another pregnancy. I do not remove the tube in patients who wish to conceive again, provided the tube is relatively normal by gross inspection. If the patient has completed her family, I will remove the tube.

Some other ectopic pregnancies are often best treated by salpingectomy. These include cases of uncontrolled bleeding, a severely damaged tube, most cases of recurrent ectopic pregnancy within the same tube, and a tubal gestational sac larger than 3 cm in diameter. In these cases, the probability of normal tubal function in the future is low, and the likelihood of recurrent tubal problems is high.

Salpingostomy Technique

Laparoscopic salpingostomy is fairly straightforward. First, inject a dilute solution of vasopressin (0.2 IU/mL of physiologic saline) into the tubal wall at the area of maximal distention. This will minimize bleeding. Using a unipolar needle electrocautery (laser and scissors can also be used), make a 10− to 15-mm linear incision along the antimesenteric border overlying the ectopic site.

Do not use forceps and do not pull the products of conception out piece by piece, or you could cause more bleeding and mistakenly leave tissue behind. Instead, use a combination of hydrodissection with irrigating solution under high pressure and gentle blunt dissection with a suction irrigator. Remove the specimen from the abdominal cavity. A laparoscopic pouch can be useful for removing large pieces of gestational tissue.

Carefully irrigate the tube and make sure there is no bleeding. Control any bleeding points with pressure or with a light application of bipolar coagulation. If bleeding persists, ligate the vessels in the mesosalpinx with a 6–0 polyglactin suture. The suturing is technically demanding, but this is one condition in which suturing skill is extremely helpful, and all laparoscopists should acquire it.

Do not keep coagulating the inside of the tube to stop the bleeding. The thermal damage will affect the integrity of the tube, and that integrity is important for future pregnancies.

Leave the incision open to heal by secondary intention. A randomized study I led several years ago showed no difference in the rates of adhesion formation and subsequent fertility between patients who had suturing after laparotomy and those who did not. If there is no difference after laparotomy, then the outcomes associated with secondary intention and primary closure after laparoscopy will also be similar.

Some physicians have proposed giving women MTX right after surgery. Although I do not recommend administering MTX prophylactically, it might be worthwhile to administer one dose of MTX in those rare cases in which you suspect that you might have left behind some gestational tissue.

Salpingectomy Technique

There are several methods for laparoscopic salpingectomy. For one, you may ligate the part of the tube that contains the ectopic pregnancy, then resect and remove the tube.

Alternatively, use electrosurgery to coagulate the tube and mesosalpinx and then resect the specimen with scissors. The cornual portion of the tube should be desiccated close to the uterus. Elevate the tube when using the electrocautery, or you may inadvertently damage the ovarian vessels. You may perform either partial or segmental salpingectomy using a laparoscopic approach.

Regardless of the method of treatment, always check the patient's blood group. If she is Rh negative and the male partner's Rh factor is positive or unknown, the patient should be given RhoGAM.

Interstitial Pregnancy

Especially among patients who have had in vitro fertilization (IVF), you may encounter interstitial pregnancy. The conventional treatment is hysterectomy or cornual resection. But with earlier diagnosis using TVUS and β-HCG assays, it can be diagnosed early and treated medically or laparoscopically.

Start with medical treatment and resort to surgery if there is any deterioration in clinical status. There are several options for surgery, including laparoscopic cornual resection, cornuostomy, or salpingotomy. In most cases, you will want to use dilute intramyometrial vasopressin at the start of the surgery to minimize blood loss. And remember the value of suturing and the option of achieving hemostasis by ligating the ascending branches of the uterine vessels.

If you perform surgery, make sure you have expertise in suturing, because you will be working in a very vascular area. Be comfortable with the procedure you are doing. I prefer laparoscopic removal of the gestation, with removal of the interstitial portion of the tube if necessary.

The risk of uterine rupture in future pregnancies after medical treatment of an interstitial pregnancy is unknown, as is the future integrity of the uterus following laparoscopic surgical treatment. We may be able to prevent future uterine rupture with proper suturing of the uterine cornu after laparoscopic treatment. Nevertheless, discuss the possibility of rupture occurring during a subsequent pregnancy with patients undergoing any treatment for interstitial pregnancy.

Likewise, monitor women with a history of interstitial pregnancy very closely. I usually recommend cesarean delivery to avoid potential uterine rupture during labor.

With any pregnancy after IVF, make sure that an ectopic pregnancy is not accompanied by pregnancy in the uterus. If you see both, you should not even consider medical therapy.

Persistent Ectopic Pregnancy

Persistent ectopic pregnancy occurs more often after salpingostomy performed with laparoscopy than after salpingostomy through laparotomy (about 8% compared with 4%). The difference used to be much greater and probably reflects the surgeon's learning curve.

Some authors have recommended weekly serum β-HCG measurements after laparoscopic salpingostomy to exclude persistent ectopic pregnancy. We perform a single serum β-HCG measurement 1 week after surgery. If the level is more than 5% of the preoperative value, we will repeat the measurement 1 week later.

If the level does not decline after the second week, we administer a single dose of MTX (50 mg/m

A large ischemic ectopic pregnancy can be painful emotionally as well as physically.

Salpingostomy has been performed and the ectopic gestation extruded outside the fallopian tube.

One suture to approximate the tubal incision has been placed, a step that requires exacting skill. Photos courtesy Dr. Togas Tulandi

Treating Ectopic Pregnancy

As editor of Master Class columns on gynecologic surgery, I am especially pleased to have Togas Tulandi, M.D., contribute this article on the current treatment of ectopic pregnancy. Dr. Tulandi is a professor of ob.gyn. and the Milton Leong Chair in Reproductive Medicine (the first Canadian chair in reproductive medicine) at McGill University in Montreal.

As a clinical researcher, Dr. Tulandi has been quite prolific. He has published more than 200 articles, 250 abstracts, 40 book chapters, and eight books. Dr. Tulandi also is the current president of the Society of Reproductive Surgeons, an affiliated society of the American Society for Reproductive Medicine.

As the readership no doubt will observe, Dr. Tulandi has a rather conservative view of treatment of ectopic pregnancy with medical therapy (methotrexate). Moreover, he provides valid reasons why laparoscopy is considered the preferred surgical treatment for ectopic pregnancy.

Although Dr. Tulandi points out that data are lacking when deciding between salpingectomy vs. salpingostomy, he does provide reasonable recommendations to assist in deciding between the two procedures.

In addition, Dr. Tulandi shares valuable insight on interstitial pregnancy as well as persistent ectopic pregnancy.

Once again, I am very proud to have Dr. Tulandi's involvement with OB.GYN. NEWS and the Master Class.

Surgery should be considered only in women who are hemodynamically stable and whose transvaginal ultrasound (TVUS) examination shows a tubal ectopic pregnancy or an adnexal mass suggestive of ectopic pregnancy. If TVUS does not show an abnormality, it is unlikely that an ectopic pregnancy will be visualized or palpated at surgery.

Moreover, when we need to treat surgically, we can and should use minimally invasive techniques whenever possible.

Alternatives to Surgery

Expectant management is the least desirable option because of the risk of tubal rupture. I take this approach only when I suspect ectopic pregnancy but TVUS fails to show the location of the gestational sac, and the serum levels of β-HCG are low and declining. Because of the possibility of tubal rupture, these patients must be carefully monitored until the serum β-HCG concentration falls below 15 IU/L; at this point, almost all ectopic pregnancies resolve spontaneously, without rupture.

Expectant management is never the best treatment when we have a diagnosis of ectopic pregnancy.

With an expectant management approach, we must monitor patients closely with serial β-HCG measurements every 2–3 days and also employ TVUS. The combination can provide us with information on whether we're dealing with an ectopic pregnancy or a miscarriage. A serum β-HCG concentration that is low and fails to double over 2–3 days suggests that we are dealing with either an ectopic pregnancy or failing intrauterine pregnancy.

Be aware that tubal rupture has been reported in women with low, declining, or even undetectable β-HCG levels. Rupture is mainly a result of blood distending the tube.

Some physicians will do a D&C when they're unsure about an ectopic pregnancy, but I would argue against this. First, it's surgery. Second, methotrexate (MTX) treatment has minimal side effects. Because a single intramuscular injection of methotrexate is safe, I would argue that it is the better alternative.

It can even be reasonably argued that MTX administration is a better approach to management than is expectant management. However, we have to make sure that the possibility of viable intrauterine pregnancy has been eliminated.

When MTX is administered to properly selected patients, it has a success rate up to 94%. Several randomized studies have even found that MTX treatment in selected patients with ectopic pregnancy was as effective as laparoscopic treatment.

MTX should be given to women who are hemodynamically stable and who are willing and able to comply with posttreatment monitoring; who have an initial serum β-HCG concentration lower than 5,000 IU/L; and who have no ultrasound evidence of fetal cardiac activity.

The main factor in determining who is a candidate for MTX is the level of β-HCG. A fairly recent metaanalysis of data for 1,327 women with ectopic pregnancy who were treated with MTX showed that success of the therapy was inversely associated with β-HCG levels, and that increasing levels were significantly correlated with treatment failure.

In general, if the β-HCG level is higher than 5,000 IU/L, the failure rate of therapy is significantly higher.

But other factors are important as well. Treatment failure is also associated with fetal cardiac activity. And you most certainly do not want to give MTX to a patient whom you won't see for 3 months.

Recent evidence suggests that tubal diameter or fetal size does not predict the success of medical treatment.

Laparoscopy: It's Clear

For those who do not meet the criteria for MTX administration—as well as for women who do not have timely access to a medical institution for management of tubal rupture and, of course, for women who have a ruptured ectopic pregnancy—surgery is necessary.

Three good prospective, randomized trials with a total of 231 women have compared laparotomy with laparoscopy, and have found that laparoscopic surgery is superior. Laparoscopic treatment of ectopic pregnancy resulted in less blood loss, lower analgesic requirements, shorter operative times, and briefer hospital stays. The studies also showed similar reproductive outcomes—subsequent uterine pregnancy and repeat ectopic pregnancy—after salpingostomy by either approach.

A Cochrane review published in 2000 also concluded that laparoscopic surgery is the best treatment. It reported a higher rate of persistent trophoblast with laparoscopic surgery, but concluded this was outweighed by the benefits of the more conservative laparoscopic approach. As I see it, the incidence of persistent trophoblast is related to the laparoscopic experience of the surgeon.

When a patient is unstable or in shock, I stabilize the patient first and then consult with the anesthesiologist to see if he or she is comfortable with my doing laparoscopy. In my experience, most will offer their support for a laparoscopic approach.

Most ectopic pregnancies—even interstitial pregnancy, heterotopic pregnancy, and ectopic pregnancy in the presence of hemoperitoneum—can be treated through a laparoscopic procedure. Your approach, or course, should depend upon your experience and the judgment of the anesthesiologist.

To Spare the Tube or Not

When it comes to choosing salpingostomy or salpingectomy, there are some uncertainties, and we face an absence of data from randomized studies. In some—but not all—of the nonrandomized studies that have been done, the intrauterine pregnancy rate has been higher after the tube-sparing surgery than after salpingectomy. However, the risk of recurrent ectopic pregnancy has been shown to be slightly higher after the more conservative treatment.

These differences most likely reflect tubal status and not the choice of surgical procedure. In other words, contralateral tubal abnormalities predispose patients to recurrent ectopic pregnancy regardless of the type of surgery. In one study of women who underwent laparoscopic salpingectomy, rates of intrauterine pregnancy and recurrent ectopic pregnancy were better among women who had normal contralateral tubal anatomy and no history of infertility (approximately 75% and 10%, respectively), compared with women who had abnormal tube anatomy or infertility (37% and 18%, respectively).

In the absence of data from a randomized study, though, salpingostomy should be the treatment of choice, particularly for women who want another pregnancy. I do not remove the tube in patients who wish to conceive again, provided the tube is relatively normal by gross inspection. If the patient has completed her family, I will remove the tube.

Some other ectopic pregnancies are often best treated by salpingectomy. These include cases of uncontrolled bleeding, a severely damaged tube, most cases of recurrent ectopic pregnancy within the same tube, and a tubal gestational sac larger than 3 cm in diameter. In these cases, the probability of normal tubal function in the future is low, and the likelihood of recurrent tubal problems is high.

Salpingostomy Technique

Laparoscopic salpingostomy is fairly straightforward. First, inject a dilute solution of vasopressin (0.2 IU/mL of physiologic saline) into the tubal wall at the area of maximal distention. This will minimize bleeding. Using a unipolar needle electrocautery (laser and scissors can also be used), make a 10− to 15-mm linear incision along the antimesenteric border overlying the ectopic site.

Do not use forceps and do not pull the products of conception out piece by piece, or you could cause more bleeding and mistakenly leave tissue behind. Instead, use a combination of hydrodissection with irrigating solution under high pressure and gentle blunt dissection with a suction irrigator. Remove the specimen from the abdominal cavity. A laparoscopic pouch can be useful for removing large pieces of gestational tissue.

Carefully irrigate the tube and make sure there is no bleeding. Control any bleeding points with pressure or with a light application of bipolar coagulation. If bleeding persists, ligate the vessels in the mesosalpinx with a 6–0 polyglactin suture. The suturing is technically demanding, but this is one condition in which suturing skill is extremely helpful, and all laparoscopists should acquire it.

Do not keep coagulating the inside of the tube to stop the bleeding. The thermal damage will affect the integrity of the tube, and that integrity is important for future pregnancies.

Leave the incision open to heal by secondary intention. A randomized study I led several years ago showed no difference in the rates of adhesion formation and subsequent fertility between patients who had suturing after laparotomy and those who did not. If there is no difference after laparotomy, then the outcomes associated with secondary intention and primary closure after laparoscopy will also be similar.

Some physicians have proposed giving women MTX right after surgery. Although I do not recommend administering MTX prophylactically, it might be worthwhile to administer one dose of MTX in those rare cases in which you suspect that you might have left behind some gestational tissue.

Salpingectomy Technique

There are several methods for laparoscopic salpingectomy. For one, you may ligate the part of the tube that contains the ectopic pregnancy, then resect and remove the tube.

Alternatively, use electrosurgery to coagulate the tube and mesosalpinx and then resect the specimen with scissors. The cornual portion of the tube should be desiccated close to the uterus. Elevate the tube when using the electrocautery, or you may inadvertently damage the ovarian vessels. You may perform either partial or segmental salpingectomy using a laparoscopic approach.

Regardless of the method of treatment, always check the patient's blood group. If she is Rh negative and the male partner's Rh factor is positive or unknown, the patient should be given RhoGAM.

Interstitial Pregnancy

Especially among patients who have had in vitro fertilization (IVF), you may encounter interstitial pregnancy. The conventional treatment is hysterectomy or cornual resection. But with earlier diagnosis using TVUS and β-HCG assays, it can be diagnosed early and treated medically or laparoscopically.

Start with medical treatment and resort to surgery if there is any deterioration in clinical status. There are several options for surgery, including laparoscopic cornual resection, cornuostomy, or salpingotomy. In most cases, you will want to use dilute intramyometrial vasopressin at the start of the surgery to minimize blood loss. And remember the value of suturing and the option of achieving hemostasis by ligating the ascending branches of the uterine vessels.

If you perform surgery, make sure you have expertise in suturing, because you will be working in a very vascular area. Be comfortable with the procedure you are doing. I prefer laparoscopic removal of the gestation, with removal of the interstitial portion of the tube if necessary.

The risk of uterine rupture in future pregnancies after medical treatment of an interstitial pregnancy is unknown, as is the future integrity of the uterus following laparoscopic surgical treatment. We may be able to prevent future uterine rupture with proper suturing of the uterine cornu after laparoscopic treatment. Nevertheless, discuss the possibility of rupture occurring during a subsequent pregnancy with patients undergoing any treatment for interstitial pregnancy.

Likewise, monitor women with a history of interstitial pregnancy very closely. I usually recommend cesarean delivery to avoid potential uterine rupture during labor.

With any pregnancy after IVF, make sure that an ectopic pregnancy is not accompanied by pregnancy in the uterus. If you see both, you should not even consider medical therapy.

Persistent Ectopic Pregnancy

Persistent ectopic pregnancy occurs more often after salpingostomy performed with laparoscopy than after salpingostomy through laparotomy (about 8% compared with 4%). The difference used to be much greater and probably reflects the surgeon's learning curve.

Some authors have recommended weekly serum β-HCG measurements after laparoscopic salpingostomy to exclude persistent ectopic pregnancy. We perform a single serum β-HCG measurement 1 week after surgery. If the level is more than 5% of the preoperative value, we will repeat the measurement 1 week later.

If the level does not decline after the second week, we administer a single dose of MTX (50 mg/m

A large ischemic ectopic pregnancy can be painful emotionally as well as physically.

Salpingostomy has been performed and the ectopic gestation extruded outside the fallopian tube.

One suture to approximate the tubal incision has been placed, a step that requires exacting skill. Photos courtesy Dr. Togas Tulandi

Treating Ectopic Pregnancy

As editor of Master Class columns on gynecologic surgery, I am especially pleased to have Togas Tulandi, M.D., contribute this article on the current treatment of ectopic pregnancy. Dr. Tulandi is a professor of ob.gyn. and the Milton Leong Chair in Reproductive Medicine (the first Canadian chair in reproductive medicine) at McGill University in Montreal.

As a clinical researcher, Dr. Tulandi has been quite prolific. He has published more than 200 articles, 250 abstracts, 40 book chapters, and eight books. Dr. Tulandi also is the current president of the Society of Reproductive Surgeons, an affiliated society of the American Society for Reproductive Medicine.

As the readership no doubt will observe, Dr. Tulandi has a rather conservative view of treatment of ectopic pregnancy with medical therapy (methotrexate). Moreover, he provides valid reasons why laparoscopy is considered the preferred surgical treatment for ectopic pregnancy.

Although Dr. Tulandi points out that data are lacking when deciding between salpingectomy vs. salpingostomy, he does provide reasonable recommendations to assist in deciding between the two procedures.

In addition, Dr. Tulandi shares valuable insight on interstitial pregnancy as well as persistent ectopic pregnancy.

Once again, I am very proud to have Dr. Tulandi's involvement with OB.GYN. NEWS and the Master Class.

BETHESDA, MD. — Drug resistance poses a problem in treating HIV patients, in part because of the virus's high mutation rate, Roy M. Gulick, M.D., said at an annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

Factors affecting HIV drug resistance include the virus itself, the antiretroviral drugs used, and the characteristics of the individual patient. Drug resistance is one of the main reasons why HIV treatments fail, said Dr. Gulick, director of the Cornell HIV Clinical Trials Unit at Weill Medical College of Cornell University, New York.

The goal of antiretroviral therapy (ART) is to suppress the viral load to as low a level as possible for as long as possible, he noted. Due to the high rate of mutation in the HIV virus, viral diversity is extensive. Failure to suppress viral load levels in the presence of antiretroviral drugs leads to the development of a resistant strain, Dr. Gulick explained.

Patient-related factors that can contribute to the development of resistance include the stage of disease, use of other medications, medication adherence, and side effects.

“We used to follow resistance clinically. If someone was taking their drugs, and their viral load went down, but then rose again, if we were sure that they were taking the medication, we assumed that they had developed resistance,” he said. Today, genotypic tests provide viral sequencing of a patient's viral strain, and phenotypic tests can grow the patient's virus in vitro and assess resistance in the presence of the available antiretroviral drugs.

Are resistance tests clinically valuable? Dr. Gulick cited three studies, including one published in the Lancet, in which several hundred patients who had failed drug therapies were randomized to either genotypic or phenotypic drug resistance testing or standard care (Lancet 1999;353:2195–9).

Overall, the patients who fared better in terms of viral load reduction on their new regimens were those who had the resistance tests. “Simply put, resistance tests help clinicians choose active drugs for the next regimen,” Dr. Gulick said. Guidelines from the Department of Health and Human Services recommend resistance tests in the clinical setting in cases of virologic failure, suboptimal virologic suppression, and acute HIV infection.

These tests could be considered in cases of HIV infection before starting ART, but they are generally not recommended for patients more than 4 weeks after ART drug use ends, or when viral load levels are less than 1,000 copies per million.

However, studies of the effectiveness of resistance testing are limited by several factors, including problems with the clinical cutoffs—when the drugs lose activity over time—and questions as to whether the studies had enrolled patients who had failed multiple treatments.

Other studies show conflicting results on the use of resistance tests, especially for highly resistant patients. “The best resistance tests can't help a patient if they have no drug options to go to,” Dr. Gulick said.

Asked whether he recommends genotypic or phenotypic testing for patients who are just starting antiretroviral therapy or who already have resistance, Dr. Gulick commented that although sufficient clinical evidence is lacking, most experts recommend a genotype test for patients who are treatment naive or have failed their first regimen, when it is relatively easy to figure out what the mutations mean. But in patients who have been through multiple regimens, phenotype is easier to interpret.

BETHESDA, MD. — Drug resistance poses a problem in treating HIV patients, in part because of the virus's high mutation rate, Roy M. Gulick, M.D., said at an annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

Factors affecting HIV drug resistance include the virus itself, the antiretroviral drugs used, and the characteristics of the individual patient. Drug resistance is one of the main reasons why HIV treatments fail, said Dr. Gulick, director of the Cornell HIV Clinical Trials Unit at Weill Medical College of Cornell University, New York.

The goal of antiretroviral therapy (ART) is to suppress the viral load to as low a level as possible for as long as possible, he noted. Due to the high rate of mutation in the HIV virus, viral diversity is extensive. Failure to suppress viral load levels in the presence of antiretroviral drugs leads to the development of a resistant strain, Dr. Gulick explained.

Patient-related factors that can contribute to the development of resistance include the stage of disease, use of other medications, medication adherence, and side effects.

“We used to follow resistance clinically. If someone was taking their drugs, and their viral load went down, but then rose again, if we were sure that they were taking the medication, we assumed that they had developed resistance,” he said. Today, genotypic tests provide viral sequencing of a patient's viral strain, and phenotypic tests can grow the patient's virus in vitro and assess resistance in the presence of the available antiretroviral drugs.

Are resistance tests clinically valuable? Dr. Gulick cited three studies, including one published in the Lancet, in which several hundred patients who had failed drug therapies were randomized to either genotypic or phenotypic drug resistance testing or standard care (Lancet 1999;353:2195–9).

Overall, the patients who fared better in terms of viral load reduction on their new regimens were those who had the resistance tests. “Simply put, resistance tests help clinicians choose active drugs for the next regimen,” Dr. Gulick said. Guidelines from the Department of Health and Human Services recommend resistance tests in the clinical setting in cases of virologic failure, suboptimal virologic suppression, and acute HIV infection.

These tests could be considered in cases of HIV infection before starting ART, but they are generally not recommended for patients more than 4 weeks after ART drug use ends, or when viral load levels are less than 1,000 copies per million.

However, studies of the effectiveness of resistance testing are limited by several factors, including problems with the clinical cutoffs—when the drugs lose activity over time—and questions as to whether the studies had enrolled patients who had failed multiple treatments.

Other studies show conflicting results on the use of resistance tests, especially for highly resistant patients. “The best resistance tests can't help a patient if they have no drug options to go to,” Dr. Gulick said.

Asked whether he recommends genotypic or phenotypic testing for patients who are just starting antiretroviral therapy or who already have resistance, Dr. Gulick commented that although sufficient clinical evidence is lacking, most experts recommend a genotype test for patients who are treatment naive or have failed their first regimen, when it is relatively easy to figure out what the mutations mean. But in patients who have been through multiple regimens, phenotype is easier to interpret.

BETHESDA, MD. — Drug resistance poses a problem in treating HIV patients, in part because of the virus's high mutation rate, Roy M. Gulick, M.D., said at an annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

Factors affecting HIV drug resistance include the virus itself, the antiretroviral drugs used, and the characteristics of the individual patient. Drug resistance is one of the main reasons why HIV treatments fail, said Dr. Gulick, director of the Cornell HIV Clinical Trials Unit at Weill Medical College of Cornell University, New York.

The goal of antiretroviral therapy (ART) is to suppress the viral load to as low a level as possible for as long as possible, he noted. Due to the high rate of mutation in the HIV virus, viral diversity is extensive. Failure to suppress viral load levels in the presence of antiretroviral drugs leads to the development of a resistant strain, Dr. Gulick explained.

Patient-related factors that can contribute to the development of resistance include the stage of disease, use of other medications, medication adherence, and side effects.

“We used to follow resistance clinically. If someone was taking their drugs, and their viral load went down, but then rose again, if we were sure that they were taking the medication, we assumed that they had developed resistance,” he said. Today, genotypic tests provide viral sequencing of a patient's viral strain, and phenotypic tests can grow the patient's virus in vitro and assess resistance in the presence of the available antiretroviral drugs.

Are resistance tests clinically valuable? Dr. Gulick cited three studies, including one published in the Lancet, in which several hundred patients who had failed drug therapies were randomized to either genotypic or phenotypic drug resistance testing or standard care (Lancet 1999;353:2195–9).

Overall, the patients who fared better in terms of viral load reduction on their new regimens were those who had the resistance tests. “Simply put, resistance tests help clinicians choose active drugs for the next regimen,” Dr. Gulick said. Guidelines from the Department of Health and Human Services recommend resistance tests in the clinical setting in cases of virologic failure, suboptimal virologic suppression, and acute HIV infection.

These tests could be considered in cases of HIV infection before starting ART, but they are generally not recommended for patients more than 4 weeks after ART drug use ends, or when viral load levels are less than 1,000 copies per million.

However, studies of the effectiveness of resistance testing are limited by several factors, including problems with the clinical cutoffs—when the drugs lose activity over time—and questions as to whether the studies had enrolled patients who had failed multiple treatments.

Other studies show conflicting results on the use of resistance tests, especially for highly resistant patients. “The best resistance tests can't help a patient if they have no drug options to go to,” Dr. Gulick said.

Asked whether he recommends genotypic or phenotypic testing for patients who are just starting antiretroviral therapy or who already have resistance, Dr. Gulick commented that although sufficient clinical evidence is lacking, most experts recommend a genotype test for patients who are treatment naive or have failed their first regimen, when it is relatively easy to figure out what the mutations mean. But in patients who have been through multiple regimens, phenotype is easier to interpret.

KEVIN FOLEY, RESEARCH/ANGIE RIES DESIGN

KEVIN FOLEY, RESEARCH/ANGIE RIES DESIGN

KEVIN FOLEY, RESEARCH/ANGIE RIES DESIGN

Yet we have reasons to be optimistic. When it comes to treating the disease, we're nowhere near where we were 20 years ago—or even 10 years ago. In communities with access to care, prognoses have improved significantly. As obstetricians, we now have the tools that allow us to provide effective care for HIV-infected pregnant women and to reduce perinatal transmission. Because of our increasing use of highly active antiretroviral therapy in addition to zidovudine chemoprophylaxis and the appropriate use of elective cesarean section, we now see only a few hundred HIV-infected newborns a year.

We could reduce perinatal transmission even further with two actions: embracing the Institute of Medicine's simple and practical “opt-out” approach to HIV testing, and using rapid screening tests more frequently. The use of a rapid screening test is an important evolving step, or shift, in the management of the HIV-infected pregnant woman. It is vital that these tests be used when necessary during labor.

Once a diagnosis is made, it is our job to guide the patient through the complex but promising process of treatment and monitoring, including, when necessary, the use of resistance testing. To do this, obstetricians can partner with HIV specialists and access up-to-date, practical treatment information online.

'Opt-Out' Testing, Rapid Tests

Many of the infants born HIV-positive today are infected because their mothers were not tested. Perhaps one in nine HIV-infected pregnant women gets minimal or no prenatal care. A significant number of others do not initiate care until the third trimester.

In 1999, the Institute of Medicine recommended an informed right-of-refusal approach to testing.

In this approach, the physician informs the patient that she is going to be tested for the virus that causes AIDS and that she has the right to refuse the test. She can “opt out” by signing a consent form.

That does not mean that there are fewer safeguards with HIV testing. We're still respecting patients' autonomy. In fact, we are more cautious with this test than with other screening procedures that we routinely perform. For example, we don't have individual, informed opt-out policies for breast exams that may detect cancer. HIV infection is treatable. With early diagnosis and therapy, women have decades to live and babies can be free of the disease.

Obstetricians need to put their imprimatur on the test. That's part of our role in caring for pregnant women. If we say, “You don't need this test, do you?” instead of saying “This is a test that's good for everybody,” we may as well not offer it. The goal simply put is to have HIV status determined as early as possible in all pregnancies.

The focus most recently among scientific and public health experts has been on rapid HIV tests. The Centers for Disease Control and Prevention has recommended that physicians liberalize the use of rapid screening in labor and delivery suites, emergency departments, and other settings.

These tests should be offered to any woman in labor whose serostatus is unknown. Although not as reliable as the standard approach used for prenatal testing, these tests are sensitive enough to identify HIV-infected women, and the results can be used as a basis for offering treatment while confirmatory tests are performed. Obstetricians should not wait for definitive follow-up tests to begin intrapartum and early neonatal prophylaxis. We can tell patients that if confirmatory tests turn out negative, treatment will be discontinued.

Therapy

If a pregnant woman tests positive, it is the obstetrician's job to monitor her immunologic and virologic status. Studies have shown a direct correlation between viral load and perinatal transmission, with transmission lower at any given viral load if antiretroviral therapy is used.

The viral load also can be used to counsel women about the potential utility of cesarean section: With plasma HIV-1 RNA levels higher than 1,000 copies/mL, cesarean section will reduce rates of transmission. Below that level, the additive benefit of cesarean section, beyond that which can be achieved with highly active retroviral therapy, is less certain.

A lot has changed since 1994, when the Pediatric AIDS Clinical Trials Group reported that zidovudine could reduce the risk for mother-to-child transmission 70%. Current interventions for all HIV-infected individuals focus on early initiation of HAART (highly active antiretroviral therapy)—the term used for the more aggressive and more potent combination antiretroviral regimens that can better suppress viral replication, preserve immune function, and minimize the development of resistance.

Although there are special and complex considerations to be made with regard to the choice of HAART agents in pregnancy, pregnancy per se is not a reason to defer what is now standard therapy.

In pregnancy, zidovudine should still be used whenever possible as a component of HAART regimens. Although it is similar in many ways to other nucleoside reverse transcriptase inhibitors, it has the advantage of demonstrated efficacy in preventing perinatal transmission.

If you don't see a substantial number of HIV-infected women, or if you don't keep up with the ever-expanding body of literature on antiretroviral drugs and patient management, I would advise comanaging your patient with an HIV specialist.

The obstetrician's key role is to ask the consultant what he or she would recommend if the patient were not pregnant, and then to take the lead in evaluating the drugs' benefits, toxicities, and risks. Obstetricians—with their dual roles of optimizing the health of the mother and preventing transmission of the virus to the child, in that order of priority—should be the ones to modify the regimen if necessary.

We often use category C drugs during pregnancy if we know that a drug is much more effective than a category B drug. However, specialists in other disciplines might recommend category B drugs, not because they are better but because of those specialists' unfamiliarity with the care of pregnant women and their fear of using category C drugs. We should be the ones to make that call, and should work with the HIV specialist in balancing efficacy and fetal safety.

The HIV specialists, on the other hand, are going to know all the ins and outs about drug combinations, about acceptable rates of viral load decrease, and about dosing schedules and other logistical details.

In general, the use of two nucleoside reverse transcriptase inhibitors along with a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor is recommended. It also is often useful to choose a regimen that spares one class of antiretroviral agents in case resistance develops. There are choices within each of the three drug categories, but there also are certain medications that should not be used in combination because of overlapping toxicities or diminished efficacy.

There are also certain potential perinatal risks. Nevirapine, for instance, can cause fulminant liver disease in women who have CD4 counts greater than 250 cells/mm

Treatment with efavirenz, for example, should be avoided during the first trimester because the drug has been associated with severe central nervous system anomalies. Overall, it's important to recognize and tell patients that we do not have long-term outcome data on the use during pregnancy of any of the available antiretroviral drugs.

The number of HAART regimens continues to increase, and there may be new reports of problems, so in addition to consulting with HIV specialists, obstetricians should also make use of the Public Health Service's Web site (

www.aidsinfo.nih.gov/guidelines

Prevention of Resistance

Once therapy is underway, viral loads should be checked every month until the viral load is undetectable. At that point, monitoring should be done every 2–3 months. If the viral load is not dropping or does not become undetectable within 6 months, a decision about new therapy will have to be made.

Before therapy is stopped, however, your patient must undergo resistance testing—a practice that has become a standard component of HIV care, mainly for identifying therapies that should not be used in the new regimen.

If you stop therapy first and draw blood just a week later, the wild-type virus (the nonmutant strain) may have overgrown a minority mutant strain, and the resistant virus may not be detected. You must draw blood before discontinuing therapy.

Also remember that second regimens do not work as well as first regimens, so it is important to do everything possible to prevent nonadherence. Patients who are only intermittently adherent—who have intermediate drug levels—are more likely to develop resistance.

Be sure to explain at the start that it is critical for the patient to be committed to therapy and to take drugs in a timely fashion. And if a patient develops nausea and vomiting, have her stop her drug regimen until the symptoms subside.

Mode of Delivery

As a rule, women who have scheduled a cesarean delivery before the onset of labor and before rupture of membranes have a lower rate of perinatal HIV-1 transmission. However, for a patient whose viral load is very low, there really is no evidence that scheduled cesarean delivery can lower the risk of transmission.

In addition, there is some preliminary evidence to support the notion that even some patients whose viral load is not that low—plasma HIV-1 RNA levels higher than 1,000 copies/mL—may not benefit from cesarean delivery if they are being given HAART. Those data remain to be confirmed.

Considering all that is known and unknown, I would advise a cesarean section for women whose viral load is greater than 1,000 copies/mL. When a patient's viral load is low, however, I would tell her that there is no proven benefit to delivering surgically.

Managing HIV in Pregnancy

When the HIV-AIDS epidemic spread across the Western hemisphere and into the United States, we all were petrified. We've made great strides with research and investigation. Today, we have a greater understanding of the biology of the disease, ways to prevent its transmission, and methods of control. Medication development has moved rapidly.

However, in concert with this good news, patients have become less anxious and, to some extent, have let their guards down. The scare factor seems to have decreased among women and their partners. As a consequence, the rapid decline in incidence that we had hoped for has not materialized.

The number of reported HIV cases in the United States now exceeds 1 million, and the Centers for Disease Control and Prevention estimates that about 25% of those living with HIV are unaware that they have the infection. Increasingly, women are at risk; the CDC reports that from 1999 to 2003, the estimate of AIDS cases increased by 15% among females and 1% among males.

Physicians will therefore continue to be confronted with women who are HIV infected. Like other women, these patients want to have children and provide for their families, so a thorough discussion of the management of HIV in pregnancy is most appropriate at this time. It is particularly important for obstetricians in urban areas, where the presentation of HIV-infected women can be higher. But it is also certainly important in suburban areas, which will see their share of pregnancies in HIV-infected women. Nobody is immune and no community is spared.

I am very pleased to have Howard L. Minkoff, M.D., as my Master Class guest professor this month. He is currently a distinguished professor of ob.gyn. at the State University of New York, and is chair of the department of ob.gyn. at Maimonides Medical Center, both in Brooklyn. Dr. Minkoff has done extensive research and has published widely on the topic of HIV in pregnancy.

Yet we have reasons to be optimistic. When it comes to treating the disease, we're nowhere near where we were 20 years ago—or even 10 years ago. In communities with access to care, prognoses have improved significantly. As obstetricians, we now have the tools that allow us to provide effective care for HIV-infected pregnant women and to reduce perinatal transmission. Because of our increasing use of highly active antiretroviral therapy in addition to zidovudine chemoprophylaxis and the appropriate use of elective cesarean section, we now see only a few hundred HIV-infected newborns a year.

We could reduce perinatal transmission even further with two actions: embracing the Institute of Medicine's simple and practical “opt-out” approach to HIV testing, and using rapid screening tests more frequently. The use of a rapid screening test is an important evolving step, or shift, in the management of the HIV-infected pregnant woman. It is vital that these tests be used when necessary during labor.

Once a diagnosis is made, it is our job to guide the patient through the complex but promising process of treatment and monitoring, including, when necessary, the use of resistance testing. To do this, obstetricians can partner with HIV specialists and access up-to-date, practical treatment information online.

'Opt-Out' Testing, Rapid Tests

Many of the infants born HIV-positive today are infected because their mothers were not tested. Perhaps one in nine HIV-infected pregnant women gets minimal or no prenatal care. A significant number of others do not initiate care until the third trimester.

In 1999, the Institute of Medicine recommended an informed right-of-refusal approach to testing.

In this approach, the physician informs the patient that she is going to be tested for the virus that causes AIDS and that she has the right to refuse the test. She can “opt out” by signing a consent form.

That does not mean that there are fewer safeguards with HIV testing. We're still respecting patients' autonomy. In fact, we are more cautious with this test than with other screening procedures that we routinely perform. For example, we don't have individual, informed opt-out policies for breast exams that may detect cancer. HIV infection is treatable. With early diagnosis and therapy, women have decades to live and babies can be free of the disease.

Obstetricians need to put their imprimatur on the test. That's part of our role in caring for pregnant women. If we say, “You don't need this test, do you?” instead of saying “This is a test that's good for everybody,” we may as well not offer it. The goal simply put is to have HIV status determined as early as possible in all pregnancies.

The focus most recently among scientific and public health experts has been on rapid HIV tests. The Centers for Disease Control and Prevention has recommended that physicians liberalize the use of rapid screening in labor and delivery suites, emergency departments, and other settings.

These tests should be offered to any woman in labor whose serostatus is unknown. Although not as reliable as the standard approach used for prenatal testing, these tests are sensitive enough to identify HIV-infected women, and the results can be used as a basis for offering treatment while confirmatory tests are performed. Obstetricians should not wait for definitive follow-up tests to begin intrapartum and early neonatal prophylaxis. We can tell patients that if confirmatory tests turn out negative, treatment will be discontinued.

Therapy

If a pregnant woman tests positive, it is the obstetrician's job to monitor her immunologic and virologic status. Studies have shown a direct correlation between viral load and perinatal transmission, with transmission lower at any given viral load if antiretroviral therapy is used.

The viral load also can be used to counsel women about the potential utility of cesarean section: With plasma HIV-1 RNA levels higher than 1,000 copies/mL, cesarean section will reduce rates of transmission. Below that level, the additive benefit of cesarean section, beyond that which can be achieved with highly active retroviral therapy, is less certain.

A lot has changed since 1994, when the Pediatric AIDS Clinical Trials Group reported that zidovudine could reduce the risk for mother-to-child transmission 70%. Current interventions for all HIV-infected individuals focus on early initiation of HAART (highly active antiretroviral therapy)—the term used for the more aggressive and more potent combination antiretroviral regimens that can better suppress viral replication, preserve immune function, and minimize the development of resistance.

Although there are special and complex considerations to be made with regard to the choice of HAART agents in pregnancy, pregnancy per se is not a reason to defer what is now standard therapy.

In pregnancy, zidovudine should still be used whenever possible as a component of HAART regimens. Although it is similar in many ways to other nucleoside reverse transcriptase inhibitors, it has the advantage of demonstrated efficacy in preventing perinatal transmission.

If you don't see a substantial number of HIV-infected women, or if you don't keep up with the ever-expanding body of literature on antiretroviral drugs and patient management, I would advise comanaging your patient with an HIV specialist.

The obstetrician's key role is to ask the consultant what he or she would recommend if the patient were not pregnant, and then to take the lead in evaluating the drugs' benefits, toxicities, and risks. Obstetricians—with their dual roles of optimizing the health of the mother and preventing transmission of the virus to the child, in that order of priority—should be the ones to modify the regimen if necessary.

We often use category C drugs during pregnancy if we know that a drug is much more effective than a category B drug. However, specialists in other disciplines might recommend category B drugs, not because they are better but because of those specialists' unfamiliarity with the care of pregnant women and their fear of using category C drugs. We should be the ones to make that call, and should work with the HIV specialist in balancing efficacy and fetal safety.

The HIV specialists, on the other hand, are going to know all the ins and outs about drug combinations, about acceptable rates of viral load decrease, and about dosing schedules and other logistical details.

In general, the use of two nucleoside reverse transcriptase inhibitors along with a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor is recommended. It also is often useful to choose a regimen that spares one class of antiretroviral agents in case resistance develops. There are choices within each of the three drug categories, but there also are certain medications that should not be used in combination because of overlapping toxicities or diminished efficacy.

There are also certain potential perinatal risks. Nevirapine, for instance, can cause fulminant liver disease in women who have CD4 counts greater than 250 cells/mm

Treatment with efavirenz, for example, should be avoided during the first trimester because the drug has been associated with severe central nervous system anomalies. Overall, it's important to recognize and tell patients that we do not have long-term outcome data on the use during pregnancy of any of the available antiretroviral drugs.

The number of HAART regimens continues to increase, and there may be new reports of problems, so in addition to consulting with HIV specialists, obstetricians should also make use of the Public Health Service's Web site (

www.aidsinfo.nih.gov/guidelines

Prevention of Resistance

Once therapy is underway, viral loads should be checked every month until the viral load is undetectable. At that point, monitoring should be done every 2–3 months. If the viral load is not dropping or does not become undetectable within 6 months, a decision about new therapy will have to be made.

Before therapy is stopped, however, your patient must undergo resistance testing—a practice that has become a standard component of HIV care, mainly for identifying therapies that should not be used in the new regimen.

If you stop therapy first and draw blood just a week later, the wild-type virus (the nonmutant strain) may have overgrown a minority mutant strain, and the resistant virus may not be detected. You must draw blood before discontinuing therapy.

Also remember that second regimens do not work as well as first regimens, so it is important to do everything possible to prevent nonadherence. Patients who are only intermittently adherent—who have intermediate drug levels—are more likely to develop resistance.

Be sure to explain at the start that it is critical for the patient to be committed to therapy and to take drugs in a timely fashion. And if a patient develops nausea and vomiting, have her stop her drug regimen until the symptoms subside.

Mode of Delivery

As a rule, women who have scheduled a cesarean delivery before the onset of labor and before rupture of membranes have a lower rate of perinatal HIV-1 transmission. However, for a patient whose viral load is very low, there really is no evidence that scheduled cesarean delivery can lower the risk of transmission.

In addition, there is some preliminary evidence to support the notion that even some patients whose viral load is not that low—plasma HIV-1 RNA levels higher than 1,000 copies/mL—may not benefit from cesarean delivery if they are being given HAART. Those data remain to be confirmed.

Considering all that is known and unknown, I would advise a cesarean section for women whose viral load is greater than 1,000 copies/mL. When a patient's viral load is low, however, I would tell her that there is no proven benefit to delivering surgically.

Managing HIV in Pregnancy

When the HIV-AIDS epidemic spread across the Western hemisphere and into the United States, we all were petrified. We've made great strides with research and investigation. Today, we have a greater understanding of the biology of the disease, ways to prevent its transmission, and methods of control. Medication development has moved rapidly.

However, in concert with this good news, patients have become less anxious and, to some extent, have let their guards down. The scare factor seems to have decreased among women and their partners. As a consequence, the rapid decline in incidence that we had hoped for has not materialized.

The number of reported HIV cases in the United States now exceeds 1 million, and the Centers for Disease Control and Prevention estimates that about 25% of those living with HIV are unaware that they have the infection. Increasingly, women are at risk; the CDC reports that from 1999 to 2003, the estimate of AIDS cases increased by 15% among females and 1% among males.

Physicians will therefore continue to be confronted with women who are HIV infected. Like other women, these patients want to have children and provide for their families, so a thorough discussion of the management of HIV in pregnancy is most appropriate at this time. It is particularly important for obstetricians in urban areas, where the presentation of HIV-infected women can be higher. But it is also certainly important in suburban areas, which will see their share of pregnancies in HIV-infected women. Nobody is immune and no community is spared.

I am very pleased to have Howard L. Minkoff, M.D., as my Master Class guest professor this month. He is currently a distinguished professor of ob.gyn. at the State University of New York, and is chair of the department of ob.gyn. at Maimonides Medical Center, both in Brooklyn. Dr. Minkoff has done extensive research and has published widely on the topic of HIV in pregnancy.

Yet we have reasons to be optimistic. When it comes to treating the disease, we're nowhere near where we were 20 years ago—or even 10 years ago. In communities with access to care, prognoses have improved significantly. As obstetricians, we now have the tools that allow us to provide effective care for HIV-infected pregnant women and to reduce perinatal transmission. Because of our increasing use of highly active antiretroviral therapy in addition to zidovudine chemoprophylaxis and the appropriate use of elective cesarean section, we now see only a few hundred HIV-infected newborns a year.

We could reduce perinatal transmission even further with two actions: embracing the Institute of Medicine's simple and practical “opt-out” approach to HIV testing, and using rapid screening tests more frequently. The use of a rapid screening test is an important evolving step, or shift, in the management of the HIV-infected pregnant woman. It is vital that these tests be used when necessary during labor.

Once a diagnosis is made, it is our job to guide the patient through the complex but promising process of treatment and monitoring, including, when necessary, the use of resistance testing. To do this, obstetricians can partner with HIV specialists and access up-to-date, practical treatment information online.

'Opt-Out' Testing, Rapid Tests

Many of the infants born HIV-positive today are infected because their mothers were not tested. Perhaps one in nine HIV-infected pregnant women gets minimal or no prenatal care. A significant number of others do not initiate care until the third trimester.

In 1999, the Institute of Medicine recommended an informed right-of-refusal approach to testing.

In this approach, the physician informs the patient that she is going to be tested for the virus that causes AIDS and that she has the right to refuse the test. She can “opt out” by signing a consent form.

That does not mean that there are fewer safeguards with HIV testing. We're still respecting patients' autonomy. In fact, we are more cautious with this test than with other screening procedures that we routinely perform. For example, we don't have individual, informed opt-out policies for breast exams that may detect cancer. HIV infection is treatable. With early diagnosis and therapy, women have decades to live and babies can be free of the disease.

Obstetricians need to put their imprimatur on the test. That's part of our role in caring for pregnant women. If we say, “You don't need this test, do you?” instead of saying “This is a test that's good for everybody,” we may as well not offer it. The goal simply put is to have HIV status determined as early as possible in all pregnancies.

The focus most recently among scientific and public health experts has been on rapid HIV tests. The Centers for Disease Control and Prevention has recommended that physicians liberalize the use of rapid screening in labor and delivery suites, emergency departments, and other settings.

These tests should be offered to any woman in labor whose serostatus is unknown. Although not as reliable as the standard approach used for prenatal testing, these tests are sensitive enough to identify HIV-infected women, and the results can be used as a basis for offering treatment while confirmatory tests are performed. Obstetricians should not wait for definitive follow-up tests to begin intrapartum and early neonatal prophylaxis. We can tell patients that if confirmatory tests turn out negative, treatment will be discontinued.

Therapy

If a pregnant woman tests positive, it is the obstetrician's job to monitor her immunologic and virologic status. Studies have shown a direct correlation between viral load and perinatal transmission, with transmission lower at any given viral load if antiretroviral therapy is used.

The viral load also can be used to counsel women about the potential utility of cesarean section: With plasma HIV-1 RNA levels higher than 1,000 copies/mL, cesarean section will reduce rates of transmission. Below that level, the additive benefit of cesarean section, beyond that which can be achieved with highly active retroviral therapy, is less certain.

A lot has changed since 1994, when the Pediatric AIDS Clinical Trials Group reported that zidovudine could reduce the risk for mother-to-child transmission 70%. Current interventions for all HIV-infected individuals focus on early initiation of HAART (highly active antiretroviral therapy)—the term used for the more aggressive and more potent combination antiretroviral regimens that can better suppress viral replication, preserve immune function, and minimize the development of resistance.

Although there are special and complex considerations to be made with regard to the choice of HAART agents in pregnancy, pregnancy per se is not a reason to defer what is now standard therapy.

In pregnancy, zidovudine should still be used whenever possible as a component of HAART regimens. Although it is similar in many ways to other nucleoside reverse transcriptase inhibitors, it has the advantage of demonstrated efficacy in preventing perinatal transmission.

If you don't see a substantial number of HIV-infected women, or if you don't keep up with the ever-expanding body of literature on antiretroviral drugs and patient management, I would advise comanaging your patient with an HIV specialist.

The obstetrician's key role is to ask the consultant what he or she would recommend if the patient were not pregnant, and then to take the lead in evaluating the drugs' benefits, toxicities, and risks. Obstetricians—with their dual roles of optimizing the health of the mother and preventing transmission of the virus to the child, in that order of priority—should be the ones to modify the regimen if necessary.

We often use category C drugs during pregnancy if we know that a drug is much more effective than a category B drug. However, specialists in other disciplines might recommend category B drugs, not because they are better but because of those specialists' unfamiliarity with the care of pregnant women and their fear of using category C drugs. We should be the ones to make that call, and should work with the HIV specialist in balancing efficacy and fetal safety.

The HIV specialists, on the other hand, are going to know all the ins and outs about drug combinations, about acceptable rates of viral load decrease, and about dosing schedules and other logistical details.

In general, the use of two nucleoside reverse transcriptase inhibitors along with a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor is recommended. It also is often useful to choose a regimen that spares one class of antiretroviral agents in case resistance develops. There are choices within each of the three drug categories, but there also are certain medications that should not be used in combination because of overlapping toxicities or diminished efficacy.

There are also certain potential perinatal risks. Nevirapine, for instance, can cause fulminant liver disease in women who have CD4 counts greater than 250 cells/mm

Treatment with efavirenz, for example, should be avoided during the first trimester because the drug has been associated with severe central nervous system anomalies. Overall, it's important to recognize and tell patients that we do not have long-term outcome data on the use during pregnancy of any of the available antiretroviral drugs.

The number of HAART regimens continues to increase, and there may be new reports of problems, so in addition to consulting with HIV specialists, obstetricians should also make use of the Public Health Service's Web site (

www.aidsinfo.nih.gov/guidelines

Prevention of Resistance

Once therapy is underway, viral loads should be checked every month until the viral load is undetectable. At that point, monitoring should be done every 2–3 months. If the viral load is not dropping or does not become undetectable within 6 months, a decision about new therapy will have to be made.

Before therapy is stopped, however, your patient must undergo resistance testing—a practice that has become a standard component of HIV care, mainly for identifying therapies that should not be used in the new regimen.

If you stop therapy first and draw blood just a week later, the wild-type virus (the nonmutant strain) may have overgrown a minority mutant strain, and the resistant virus may not be detected. You must draw blood before discontinuing therapy.

Also remember that second regimens do not work as well as first regimens, so it is important to do everything possible to prevent nonadherence. Patients who are only intermittently adherent—who have intermediate drug levels—are more likely to develop resistance.

Be sure to explain at the start that it is critical for the patient to be committed to therapy and to take drugs in a timely fashion. And if a patient develops nausea and vomiting, have her stop her drug regimen until the symptoms subside.

Mode of Delivery

As a rule, women who have scheduled a cesarean delivery before the onset of labor and before rupture of membranes have a lower rate of perinatal HIV-1 transmission. However, for a patient whose viral load is very low, there really is no evidence that scheduled cesarean delivery can lower the risk of transmission.

In addition, there is some preliminary evidence to support the notion that even some patients whose viral load is not that low—plasma HIV-1 RNA levels higher than 1,000 copies/mL—may not benefit from cesarean delivery if they are being given HAART. Those data remain to be confirmed.

Considering all that is known and unknown, I would advise a cesarean section for women whose viral load is greater than 1,000 copies/mL. When a patient's viral load is low, however, I would tell her that there is no proven benefit to delivering surgically.

Managing HIV in Pregnancy

When the HIV-AIDS epidemic spread across the Western hemisphere and into the United States, we all were petrified. We've made great strides with research and investigation. Today, we have a greater understanding of the biology of the disease, ways to prevent its transmission, and methods of control. Medication development has moved rapidly.

However, in concert with this good news, patients have become less anxious and, to some extent, have let their guards down. The scare factor seems to have decreased among women and their partners. As a consequence, the rapid decline in incidence that we had hoped for has not materialized.

The number of reported HIV cases in the United States now exceeds 1 million, and the Centers for Disease Control and Prevention estimates that about 25% of those living with HIV are unaware that they have the infection. Increasingly, women are at risk; the CDC reports that from 1999 to 2003, the estimate of AIDS cases increased by 15% among females and 1% among males.

Physicians will therefore continue to be confronted with women who are HIV infected. Like other women, these patients want to have children and provide for their families, so a thorough discussion of the management of HIV in pregnancy is most appropriate at this time. It is particularly important for obstetricians in urban areas, where the presentation of HIV-infected women can be higher. But it is also certainly important in suburban areas, which will see their share of pregnancies in HIV-infected women. Nobody is immune and no community is spared.

I am very pleased to have Howard L. Minkoff, M.D., as my Master Class guest professor this month. He is currently a distinguished professor of ob.gyn. at the State University of New York, and is chair of the department of ob.gyn. at Maimonides Medical Center, both in Brooklyn. Dr. Minkoff has done extensive research and has published widely on the topic of HIV in pregnancy.

Despite many advances in minimally invasive tubal ligation surgery, it remains a more complicated procedure than vasectomy to achieve sterilization, the most common contraceptive option in the United States today.

The introduction of a transcervical method of sterilization through the use of the Essure procedure is changing that. We can now offer patients a quick, exceedingly safe, incisionless tubal occlusion procedure that has been found 99.8% effective at 3 years, and, in one report, 99.74% effective at 5 years of follow-up.

I am incorporating Essure into my practice, and have found it so useful that I have chosen to share it in this month's Master Class.

In general terms, Essure is a microinsert placed into the fallopian tube via a hysteroscopically guided catheter.

The microinsert consists of a flexible stainless-steel inner coil, a dynamic outer coil made of nickel titanium alloy (nitinol), and an innermost layer of polyethylene terephthalate (PET) fibers. These fibers gradually elicit a benign localized tissue ingrowth that occludes the tubal lumen.

A follow-up hysterosalpingogram (HSG) 3 months post procedure confirms proper device placement and tubal occlusion.

The concept that led to the development of Essure tubal occlusion evolved from neurosurgery, in which coils have been used to block vessels. However, specialized coils had to be designed that would expand to the diameter and length of the fallopian tube.

The tissue response that is seen following placement of the microinsert is comparable to what has long been seen with heart valves and vascular grafts. Thus, even though this precise indication is new, the technology has been around for quite some time, and has been found to be safe and effective.

When I talk with a potential candidate for Essure tubal occlusion, our discussion is much the same as it would be for tubal ligation: The patient must desire permanent, nonreversible contraception.

She must be at least 3 months post pregnancy, and must not have tubal disease or scarring inside the uterus that would preclude visualization of the tubal ostia.

The patient cannot have a severe nickel allergy, because nitinol makes up the outer coil of the microinsert. Moreover, women who have a history of a severe allergic response to iodine are poor candidates because iodine is used during the follow-up HSG.

Finally, women who are on immunosuppressive therapy may take longer than 3 months to have an occlusive response. As long as such patients understand this potential limitation, immunosuppressive therapy is not a contraindication. In fact, my first Essure patient was on immunosuppressive therapy secondary to breast cancer.

Presurgical steps can be taken to improve visualization of the ostia. I sometimes prescribe oral, transdermal, or injectable contraception for 3 months before the procedure to thin the endometrium. Visualization also is enhanced by scheduling the procedure within the first 2 weeks of a patient's menstrual cycle.

General anesthesia is not required for the procedure. I instruct patients to take an NSAID 1 hour before surgery. I perform the procedure with intravenous sedation (30 mg IV ketorolac) in an outpatient surgical suite. However, many physicians are simply using a paracervical block and performing the Essure procedure in their offices.

If visualization is inadequate because of debris, endometrial fluff, or clots, simply flush the uterus, aspirate, and gently remove the obstructive material with graspers. Confirm visibility of both ostia before placing either microinsert. Start with the tube that appears to be the most difficult.

Use 2–3 liters of warmed saline to enhance uterine dilatation and tubal cannulation; the warmth will minimize tubal spasm as well as increase patient comfort. Avoid uterine overdistention by using gravity feed rather than pump-delivered saline for input and output.

Inadequate uterine distention resulting from a patulous cervix may be overcome by gently twisting the tenaculum 45 degrees, either by using an additional tenaculum to seal the cervix, or by placing the tenaculum at the 1 o'clock and 5 o'clock positions or the 7 o'clock and 11 o'clock positions (or both).

Feed the introducer through the cervix and uterus into the fallopian tube.

To minimize “splash back” of fluid when inserting the Essure catheter into the introducer, leave the stylet within the introducer until the last minute, just before you are ready to deliver the catheter into it. When you remove the stylet, squeeze the end of the introducer and then insert the Essure catheter. Do not use the stopcock to block the fluid until the introducer is withdrawn; otherwise, the introducer might be severed while in the hysteroscope.

Depending on the size of the hysteroscope, the introducer may be a tight fit. To minimize the risk of damage to the tip of the Essure catheter, do not force the introducer when resistance is felt. In such a case, simply withdraw the introducer/stylet unit approximately 1 mm. This may mean the introducer/stylet extends more than halfway outside the sealing cap of the working channel, but this is not a problem. Just insert the catheter through the introducer as usual once the stylet is removed.

Approach the ostia as closely as possible, waiting until the ostium occupies most of the hysteroscope's screen.

The Essure catheter includes visual cues to guide you, including a flat black positioning marker.

Before you deploy the microinsert by depressing the button on the handle, check the position of the catheter by looking for the marker just outside the tubal ostia. You should also see the distal tip of the orange release catheter in the same visual field.

Reducing tubal spasm will greatly improve the ease of placement. Wait a few seconds for a spasm to pass, then approach the tube very closely and gently rotate the device inside the tube.

Once the procedure is complete, patients should remain in the office for about 45 minutes before returning home. Some can return to work and daily activities immediately; virtually all will be back to their normal routines within 24 hours.

Almost always, ibuprofen is the strongest medication required for postprocedural pain.

The procedure is exceedingly safe. There is a small risk (less than 1%) of tubal perforation at the time of the procedure; however, no interventional therapy is required.

Likewise, the risks of infection, bleeding, and uterine perforation are extremely low.

Schedule patients for a return visit in 3 months for an HSG, during which you will inspect the tubes for evidence of tissue ingrowth. In the meantime, stress the importance of using an alternative form of contraception, as sterilization cannot be guaranteed until tubal occlusion can be confirmed.

When performing the postprocedure HSG, use minimal volume and pressure. Doing so serves two purposes: avoiding unnecessary patient discomfort, and minimizing the chance of a false-positive result because of high-pressure instillation.

If you refer patients to a radiologist for HSGs, emphasize the importance of these key points. When capturing images, the clinician should ensure proper occlusion by magnifying the cornual region of each implanted tube.

With proper technique, competency in this procedure can be achieved quickly. I have found patient satisfaction to be very high.

The ease and efficacy of the procedure, lack of necessity for general anesthetic, and rapid patient recovery all combine to make Essure tubal occlusion a valuable technique for gynecologists to master.

Confirm visibility of both ostia before placing either microinsert.

The Essure microinsert is inserted into the tubal ostia at the level of the black marker.

The delivery catheter is retracted. The notch at the opening of the tubal ostia shows correct placement.

The delivery wire is retracted from the microinsert.

The microinsert is now firmly embedded in the fallopian tube. Photos courtesy Dr. Charles E. Miller

Despite many advances in minimally invasive tubal ligation surgery, it remains a more complicated procedure than vasectomy to achieve sterilization, the most common contraceptive option in the United States today.

The introduction of a transcervical method of sterilization through the use of the Essure procedure is changing that. We can now offer patients a quick, exceedingly safe, incisionless tubal occlusion procedure that has been found 99.8% effective at 3 years, and, in one report, 99.74% effective at 5 years of follow-up.

I am incorporating Essure into my practice, and have found it so useful that I have chosen to share it in this month's Master Class.

In general terms, Essure is a microinsert placed into the fallopian tube via a hysteroscopically guided catheter.

The microinsert consists of a flexible stainless-steel inner coil, a dynamic outer coil made of nickel titanium alloy (nitinol), and an innermost layer of polyethylene terephthalate (PET) fibers. These fibers gradually elicit a benign localized tissue ingrowth that occludes the tubal lumen.

A follow-up hysterosalpingogram (HSG) 3 months post procedure confirms proper device placement and tubal occlusion.

The concept that led to the development of Essure tubal occlusion evolved from neurosurgery, in which coils have been used to block vessels. However, specialized coils had to be designed that would expand to the diameter and length of the fallopian tube.

The tissue response that is seen following placement of the microinsert is comparable to what has long been seen with heart valves and vascular grafts. Thus, even though this precise indication is new, the technology has been around for quite some time, and has been found to be safe and effective.

When I talk with a potential candidate for Essure tubal occlusion, our discussion is much the same as it would be for tubal ligation: The patient must desire permanent, nonreversible contraception.

She must be at least 3 months post pregnancy, and must not have tubal disease or scarring inside the uterus that would preclude visualization of the tubal ostia.

The patient cannot have a severe nickel allergy, because nitinol makes up the outer coil of the microinsert. Moreover, women who have a history of a severe allergic response to iodine are poor candidates because iodine is used during the follow-up HSG.

Finally, women who are on immunosuppressive therapy may take longer than 3 months to have an occlusive response. As long as such patients understand this potential limitation, immunosuppressive therapy is not a contraindication. In fact, my first Essure patient was on immunosuppressive therapy secondary to breast cancer.

Presurgical steps can be taken to improve visualization of the ostia. I sometimes prescribe oral, transdermal, or injectable contraception for 3 months before the procedure to thin the endometrium. Visualization also is enhanced by scheduling the procedure within the first 2 weeks of a patient's menstrual cycle.

General anesthesia is not required for the procedure. I instruct patients to take an NSAID 1 hour before surgery. I perform the procedure with intravenous sedation (30 mg IV ketorolac) in an outpatient surgical suite. However, many physicians are simply using a paracervical block and performing the Essure procedure in their offices.

If visualization is inadequate because of debris, endometrial fluff, or clots, simply flush the uterus, aspirate, and gently remove the obstructive material with graspers. Confirm visibility of both ostia before placing either microinsert. Start with the tube that appears to be the most difficult.

Use 2–3 liters of warmed saline to enhance uterine dilatation and tubal cannulation; the warmth will minimize tubal spasm as well as increase patient comfort. Avoid uterine overdistention by using gravity feed rather than pump-delivered saline for input and output.

Inadequate uterine distention resulting from a patulous cervix may be overcome by gently twisting the tenaculum 45 degrees, either by using an additional tenaculum to seal the cervix, or by placing the tenaculum at the 1 o'clock and 5 o'clock positions or the 7 o'clock and 11 o'clock positions (or both).

Feed the introducer through the cervix and uterus into the fallopian tube.

To minimize “splash back” of fluid when inserting the Essure catheter into the introducer, leave the stylet within the introducer until the last minute, just before you are ready to deliver the catheter into it. When you remove the stylet, squeeze the end of the introducer and then insert the Essure catheter. Do not use the stopcock to block the fluid until the introducer is withdrawn; otherwise, the introducer might be severed while in the hysteroscope.

Depending on the size of the hysteroscope, the introducer may be a tight fit. To minimize the risk of damage to the tip of the Essure catheter, do not force the introducer when resistance is felt. In such a case, simply withdraw the introducer/stylet unit approximately 1 mm. This may mean the introducer/stylet extends more than halfway outside the sealing cap of the working channel, but this is not a problem. Just insert the catheter through the introducer as usual once the stylet is removed.

Approach the ostia as closely as possible, waiting until the ostium occupies most of the hysteroscope's screen.

The Essure catheter includes visual cues to guide you, including a flat black positioning marker.

Before you deploy the microinsert by depressing the button on the handle, check the position of the catheter by looking for the marker just outside the tubal ostia. You should also see the distal tip of the orange release catheter in the same visual field.

Reducing tubal spasm will greatly improve the ease of placement. Wait a few seconds for a spasm to pass, then approach the tube very closely and gently rotate the device inside the tube.

Once the procedure is complete, patients should remain in the office for about 45 minutes before returning home. Some can return to work and daily activities immediately; virtually all will be back to their normal routines within 24 hours.

Almost always, ibuprofen is the strongest medication required for postprocedural pain.

The procedure is exceedingly safe. There is a small risk (less than 1%) of tubal perforation at the time of the procedure; however, no interventional therapy is required.

Likewise, the risks of infection, bleeding, and uterine perforation are extremely low.

Schedule patients for a return visit in 3 months for an HSG, during which you will inspect the tubes for evidence of tissue ingrowth. In the meantime, stress the importance of using an alternative form of contraception, as sterilization cannot be guaranteed until tubal occlusion can be confirmed.

When performing the postprocedure HSG, use minimal volume and pressure. Doing so serves two purposes: avoiding unnecessary patient discomfort, and minimizing the chance of a false-positive result because of high-pressure instillation.

If you refer patients to a radiologist for HSGs, emphasize the importance of these key points. When capturing images, the clinician should ensure proper occlusion by magnifying the cornual region of each implanted tube.

With proper technique, competency in this procedure can be achieved quickly. I have found patient satisfaction to be very high.

The ease and efficacy of the procedure, lack of necessity for general anesthetic, and rapid patient recovery all combine to make Essure tubal occlusion a valuable technique for gynecologists to master.

Confirm visibility of both ostia before placing either microinsert.

The Essure microinsert is inserted into the tubal ostia at the level of the black marker.

The delivery catheter is retracted. The notch at the opening of the tubal ostia shows correct placement.

The delivery wire is retracted from the microinsert.

The microinsert is now firmly embedded in the fallopian tube. Photos courtesy Dr. Charles E. Miller

Despite many advances in minimally invasive tubal ligation surgery, it remains a more complicated procedure than vasectomy to achieve sterilization, the most common contraceptive option in the United States today.

The introduction of a transcervical method of sterilization through the use of the Essure procedure is changing that. We can now offer patients a quick, exceedingly safe, incisionless tubal occlusion procedure that has been found 99.8% effective at 3 years, and, in one report, 99.74% effective at 5 years of follow-up.

I am incorporating Essure into my practice, and have found it so useful that I have chosen to share it in this month's Master Class.

In general terms, Essure is a microinsert placed into the fallopian tube via a hysteroscopically guided catheter.

The microinsert consists of a flexible stainless-steel inner coil, a dynamic outer coil made of nickel titanium alloy (nitinol), and an innermost layer of polyethylene terephthalate (PET) fibers. These fibers gradually elicit a benign localized tissue ingrowth that occludes the tubal lumen.

A follow-up hysterosalpingogram (HSG) 3 months post procedure confirms proper device placement and tubal occlusion.

The concept that led to the development of Essure tubal occlusion evolved from neurosurgery, in which coils have been used to block vessels. However, specialized coils had to be designed that would expand to the diameter and length of the fallopian tube.

The tissue response that is seen following placement of the microinsert is comparable to what has long been seen with heart valves and vascular grafts. Thus, even though this precise indication is new, the technology has been around for quite some time, and has been found to be safe and effective.

When I talk with a potential candidate for Essure tubal occlusion, our discussion is much the same as it would be for tubal ligation: The patient must desire permanent, nonreversible contraception.

She must be at least 3 months post pregnancy, and must not have tubal disease or scarring inside the uterus that would preclude visualization of the tubal ostia.

The patient cannot have a severe nickel allergy, because nitinol makes up the outer coil of the microinsert. Moreover, women who have a history of a severe allergic response to iodine are poor candidates because iodine is used during the follow-up HSG.

Finally, women who are on immunosuppressive therapy may take longer than 3 months to have an occlusive response. As long as such patients understand this potential limitation, immunosuppressive therapy is not a contraindication. In fact, my first Essure patient was on immunosuppressive therapy secondary to breast cancer.

Presurgical steps can be taken to improve visualization of the ostia. I sometimes prescribe oral, transdermal, or injectable contraception for 3 months before the procedure to thin the endometrium. Visualization also is enhanced by scheduling the procedure within the first 2 weeks of a patient's menstrual cycle.

General anesthesia is not required for the procedure. I instruct patients to take an NSAID 1 hour before surgery. I perform the procedure with intravenous sedation (30 mg IV ketorolac) in an outpatient surgical suite. However, many physicians are simply using a paracervical block and performing the Essure procedure in their offices.

If visualization is inadequate because of debris, endometrial fluff, or clots, simply flush the uterus, aspirate, and gently remove the obstructive material with graspers. Confirm visibility of both ostia before placing either microinsert. Start with the tube that appears to be the most difficult.

Use 2–3 liters of warmed saline to enhance uterine dilatation and tubal cannulation; the warmth will minimize tubal spasm as well as increase patient comfort. Avoid uterine overdistention by using gravity feed rather than pump-delivered saline for input and output.

Inadequate uterine distention resulting from a patulous cervix may be overcome by gently twisting the tenaculum 45 degrees, either by using an additional tenaculum to seal the cervix, or by placing the tenaculum at the 1 o'clock and 5 o'clock positions or the 7 o'clock and 11 o'clock positions (or both).

Feed the introducer through the cervix and uterus into the fallopian tube.

To minimize “splash back” of fluid when inserting the Essure catheter into the introducer, leave the stylet within the introducer until the last minute, just before you are ready to deliver the catheter into it. When you remove the stylet, squeeze the end of the introducer and then insert the Essure catheter. Do not use the stopcock to block the fluid until the introducer is withdrawn; otherwise, the introducer might be severed while in the hysteroscope.

Depending on the size of the hysteroscope, the introducer may be a tight fit. To minimize the risk of damage to the tip of the Essure catheter, do not force the introducer when resistance is felt. In such a case, simply withdraw the introducer/stylet unit approximately 1 mm. This may mean the introducer/stylet extends more than halfway outside the sealing cap of the working channel, but this is not a problem. Just insert the catheter through the introducer as usual once the stylet is removed.

Approach the ostia as closely as possible, waiting until the ostium occupies most of the hysteroscope's screen.

The Essure catheter includes visual cues to guide you, including a flat black positioning marker.

Before you deploy the microinsert by depressing the button on the handle, check the position of the catheter by looking for the marker just outside the tubal ostia. You should also see the distal tip of the orange release catheter in the same visual field.

Reducing tubal spasm will greatly improve the ease of placement. Wait a few seconds for a spasm to pass, then approach the tube very closely and gently rotate the device inside the tube.

Once the procedure is complete, patients should remain in the office for about 45 minutes before returning home. Some can return to work and daily activities immediately; virtually all will be back to their normal routines within 24 hours.

Almost always, ibuprofen is the strongest medication required for postprocedural pain.

The procedure is exceedingly safe. There is a small risk (less than 1%) of tubal perforation at the time of the procedure; however, no interventional therapy is required.

Likewise, the risks of infection, bleeding, and uterine perforation are extremely low.

Schedule patients for a return visit in 3 months for an HSG, during which you will inspect the tubes for evidence of tissue ingrowth. In the meantime, stress the importance of using an alternative form of contraception, as sterilization cannot be guaranteed until tubal occlusion can be confirmed.

When performing the postprocedure HSG, use minimal volume and pressure. Doing so serves two purposes: avoiding unnecessary patient discomfort, and minimizing the chance of a false-positive result because of high-pressure instillation.

If you refer patients to a radiologist for HSGs, emphasize the importance of these key points. When capturing images, the clinician should ensure proper occlusion by magnifying the cornual region of each implanted tube.

With proper technique, competency in this procedure can be achieved quickly. I have found patient satisfaction to be very high.

The ease and efficacy of the procedure, lack of necessity for general anesthetic, and rapid patient recovery all combine to make Essure tubal occlusion a valuable technique for gynecologists to master.

Confirm visibility of both ostia before placing either microinsert.

The Essure microinsert is inserted into the tubal ostia at the level of the black marker.

The delivery catheter is retracted. The notch at the opening of the tubal ostia shows correct placement.

The delivery wire is retracted from the microinsert.

The microinsert is now firmly embedded in the fallopian tube. Photos courtesy Dr. Charles E. Miller

The hesitance of obstetricians to recommend exercise to pregnant women is rooted in old-fashioned notions of pregnancy as a time of confinement. In the absence of reassuring data regarding the effects of exercise on the mother and fetus, most obstetricians adhered to the principle of doing no harm—advising women to eat for two and not to move.

With ample evidence to show that regular, moderate exercise in women with healthy pregnancies results in no adverse maternal or fetal effects, it could be argued that, in the spirit of “primum non nocere,” obstetricians should make exercise recommendations a top priority.

Indeed, because it is recognized that habits adopted during pregnancy can result in persistent lifestyle improvements, the promotion of exercise during pregnancy is an important public health issue that could significantly reduce the lifetime risks of obesity, chronic hypertension, and diabetes—not only for our patients, but for their families as well.

Recently, exercise has been recognized as an effective alternative to insulin therapy for treating gestational diabetes and as a means of preventing this disorder, which is frequently the first manifestation of what can become a lifelong condition.

Healthy Pregnancy? Few Restrictions

Despite the profound anatomical and physiologic changes of pregnancy, women with healthy pregnancies and no contraindications can exercise just as their nonpregnant counterparts do, combining both aerobic and resistive elements in their workouts. (See box on opposite page.)

A clinical evaluation of each patient is recommended before prescribing exercise, and physicians must consider the type and intensity of exercise—as well as the duration and frequency of exercise sessions—for each patient, based on her level of fitness and familiarity with various activities.

Contact sports and exercises with a high risk of falling or abdominal trauma should be avoided. Scuba diving should be avoided throughout pregnancy because this activity puts the fetus at increased risk for decompression sickness secondary to the inability of the fetal pulmonary circulation to filter bubbles.

Exercise Intensity

Moderate exercise is defined as a level of intensity that still allows normal conversation—equivalent, for example, to brisk walking at 3–4 miles per hour. For women who have been sedentary and are taking up exercise for the first time, a gradual progression to this intensity for up to 30 minutes per day is recommended. Those who are already fit when they become pregnant should be advised that pregnancy is not a time for greatly improving physical fitness and that, in general, overall activity and fitness levels tend to decline during pregnancy.

Pregnant women should exercise caution in increasing the intensity of their workouts, especially when they are extending exercise sessions beyond 45 minutes, because body core temperatures can rise above safe limits after that time. Strenuous exercise has not been proved to increase overall benefit and could actually be harmful, so this level of exercise intensity should be avoided.

Fetal Effects

Maternal cardiovascular, respiratory, and thermoregulatory adaptation occurs as a result of pregnancy and is further challenged by the addition of exercise. There is decreased availability of maternal oxygen during exercise because of increased maternal oxygen requirements at rest and the increased difficulty in breathing caused by the pressure of the enlarged uterus on the diaphragm. In addition, pregnancy raises basal metabolic rate and heat production, which are then further raised by exercise.

The hesitance of many obstetricians to prescribe exercise for pregnant women centers on the hypothetical fetal risks of impaired transplacental blood flow of oxygen, carbon dioxide, and nutrients during maternal exercise, as well as the potentially teratogenic effects of raising fetal temperature.

Most studies show a minimal to moderate increase in fetal heart rate during maternal exercise, and there is also evidence of fetal heart rate decelerations and bradycardia; however, no lasting fetal effects have been reported.

Data on the effects of increased maternal core temperatures are limited. Hyperthermia during embryogenesis (the first 45–60 days following the last menstrual period) has been shown to cause major congenital malformations (JAMA 1992;268:882–5).

The temperature threshold for human teratogenesis is 39.2° C (103° F). Moderate exercise performed in conditions allowing adequate heat dissipation has been shown to raise core temperatures no higher than 1.5° C during 30 minutes of exercise in nonpregnant women—and this temperature plateaus during as much as 1 hour of exercise.

Loss of fluid through sweat may compromise heat dissipation, so maintenance of euhydration—and thus blood volume—is essential to controlling core temperature.

Extra Nutritional Requirements

Although the published data on a link between low birth weight and maternal exercise are conflicting, it appears that adequate energy intake can offset any exercise-induced decreases in birth weight.

By the second trimester of pregnancy, an extra 1.3 MJ (300 kcal) per day are required to meet general metabolic needs in pregnancy, and this energy requirement is increased with exercise. Pregnant women use carbohydrates at a greater rate than do nonpregnant women—both at rest and during exercise—and there is preferential use of this form of energy during non-weight-bearing exercise, making adequate carbohydrate intake of particular importance.

Elite Athletes

Although routine prenatal care is sufficient for monitoring women in average exercise programs, closer obstetric observation is required for women who are elite athletes.

Most elite athletes choose to continue training during pregnancy, but they must be told that they probably will not achieve the same level of performance as they did before pregnancy, and the physiologic changes they experience—such as weight gain and joint or ligament laxity—will also make them more prone to injury. Women engaging in endurance sports can be prone to anemia that results from increased blood volume during pregnancy. High intensity, prolonged, and frequent exercise can put women at greater risk of thermoregulatory complications as well, and will usually result in less maternal and fetal weight gain than occurs in less active women.

Gestational Diabetes

The American Diabetes Association has endorsed exercise as a helpful adjunctive therapy for gestational diabetes mellitus (GDM) when glycemic control cannot be achieved through diet alone. Approximately 39% of patients with GDM require insulin therapy, but in my experience, exercise is a safe and effective alternative for most of these women.

The key to achieving euglycemia through exercise is ensuring the adequate duration and intensity of the activity. Exercise improves the impaired insulin sensitivity of women with GDM, which in turn increases glucose uptake by muscles and splanchnic organs, but this effect is achieved only through the activation of large muscles, such as the quadriceps, at adequate intensity, which explains why some studies in the literature fail to show normalization of glucose levels after exercise. At least half an hour of brisk walking per day is sufficient to upregulate insulin sensitivity in patients with GDM, obviating the need for insulin therapy.

Additionally, epidemiologic data suggest that exercise may act as primary prevention for GDM in morbidly obese women, but not in women of normal weight.

Weight Control

Although exercise should never be used for weight control during pregnancy, excessive weight gain should be avoided.

The current Institute of Medicine (IOM) guidelines on weight gain—which recommend a gain of 25–35 pounds for normal-weight women with a singleton pregnancy—are too high and are based on historical concerns about the effects of famine on fetal growth retardation.

The effect of gestational weight gain on pregnancy outcomes in obese women is not well studied. It is my opinion that the IOM guidelines are outdated, and that weight gain recommendations should be individualized. Compared with IOM recommendations for adequate gestational weight gain in obese women (at least 15 pounds), it is well recognized that a gain of less than 15 pounds in this population significantly reduces the risks of preeclampsia, C-section, and large-for-gestational-age infants.

The risk for small-for-gestational-age infants varies significantly, particularly among morbidly obese women in whom no weight gain—or even weight loss—may not have any adverse effect on birth weight.

Postpartum Exercise

Because failure to lose weight gained in pregnancy is a significant contributor to the obesity epidemic, the promotion of good exercise habits during pregnancy can also sow the seeds for postpartum exercise and weight loss.

One study showed that the amount of postpartum weight retention increases with each subsequent pregnancy (Acta. Obstet. Gynecol. Scand. 1979;58:45–7). Another study found that women who gained excessive weight during pregnancy and failed to lose it within 6 months post partum were 8.3 kg heavier 10 years later (Obstet. Gynecol. 2002;100:245–52).

Our study found that a weekly structured exercise program plus diet in postpartum overweight women were much more effective in achieving weight loss after 12 weeks compared with a single 1-hour education session about diet and exercise (J. Women's Health [Larchmt] 2003;12:991–8).

Therefore, women whose exercise habits have become firmly entrenched during pregnancy stand a much better chance of maintaining them post partum—and perhaps even into their next pregnancy.

Maintenance of euhydration is essential to controlling core temperature while exercising in pregnancy. Lynda Banzi

Exercise in Pregnancy

The extraordinary increase in obesity in the United States is giving rise not only to direct complications, such as hypertension and cardiovascular disease, but also to indirect problems such as diabetes. Hence, we have one problem leading into many others, ultimately resulting in a significant increase in morbidity and mortality.

Unfortunately, exercise—which can counter obesity—is not increasing at a concomitant rate. As a result, an emphasis on healthy lifestyles, with exercise as a central theme, has become the focus of national and international efforts undertaken by such groups as the World Health Organization, many of our medical societies, and even certain governmental agencies.

Just as exercise outside of pregnancy has clear benefits, exercise during pregnancy is also very important. For example, we know that a woman with gestational diabetes can certainly improve glucose control with exercise. However, there are clearly guidelines that must be followed when engaging in exercise during pregnancy.

In this month's Master Class, my guest professor is Raul Artal, M.D., who is an internationally recognized expert in the area of exercise physiology and exercise in pregnancy. He will lead us through specific recommendations concerning exercise during pregnancy, with references to gestational diabetes, weight control, and postpartum exercise.

Dr. Artal is professor and chair of the department of ob.gyn. at St. Louis University. He received his medical degree in Israel and his residency and fellowship training in the United States. He served as a faculty member at University of Southern California in Los Angeles and as chairman of ob.gyn. at the State University of New York, Syracuse, before attaining his current position. Dr. Artal is the lead author of the American College of Obstetricians and Gynecologists' Committee Opinion #267, “Exercise During Pregnancy and the Postpartum Period.”

Contraindications To Exercise In Pregnancy

Absolute Contraindications

Hemodynamically significant heart disease

Restrictive lung disease

Incompetent cervix/cerclage

Multiple gestation at risk for premature labor

Persistent second- or third-trimester bleeding

Placenta previa that occurs after 26 weeks' gestation

Premature labor during the current pregnancy

Ruptured membranes

Preeclampsia/pregnancy-induced hypertension

Relative Contraindications

Severe anemia

Unevaluated maternal cardiac arrhythmia

Chronic bronchitis

Poorly controlled type 1 diabetes

Extreme morbid obesity

Extreme underweight

History of extremely sedentary lifestyle

Intrauterine growth restriction in current pregnancy

Poorly controlled hypertension

Orthopedic limitations

Poorly controlled seizure disorder

Poorly controlled hyperthyroidism

Heavy smoker

Source: Obstet. Gynecol. 2002;99:171–3

The hesitance of obstetricians to recommend exercise to pregnant women is rooted in old-fashioned notions of pregnancy as a time of confinement. In the absence of reassuring data regarding the effects of exercise on the mother and fetus, most obstetricians adhered to the principle of doing no harm—advising women to eat for two and not to move.

With ample evidence to show that regular, moderate exercise in women with healthy pregnancies results in no adverse maternal or fetal effects, it could be argued that, in the spirit of “primum non nocere,” obstetricians should make exercise recommendations a top priority.

Indeed, because it is recognized that habits adopted during pregnancy can result in persistent lifestyle improvements, the promotion of exercise during pregnancy is an important public health issue that could significantly reduce the lifetime risks of obesity, chronic hypertension, and diabetes—not only for our patients, but for their families as well.

Recently, exercise has been recognized as an effective alternative to insulin therapy for treating gestational diabetes and as a means of preventing this disorder, which is frequently the first manifestation of what can become a lifelong condition.

Healthy Pregnancy? Few Restrictions

Despite the profound anatomical and physiologic changes of pregnancy, women with healthy pregnancies and no contraindications can exercise just as their nonpregnant counterparts do, combining both aerobic and resistive elements in their workouts. (See box on opposite page.)

A clinical evaluation of each patient is recommended before prescribing exercise, and physicians must consider the type and intensity of exercise—as well as the duration and frequency of exercise sessions—for each patient, based on her level of fitness and familiarity with various activities.

Contact sports and exercises with a high risk of falling or abdominal trauma should be avoided. Scuba diving should be avoided throughout pregnancy because this activity puts the fetus at increased risk for decompression sickness secondary to the inability of the fetal pulmonary circulation to filter bubbles.

Exercise Intensity

Moderate exercise is defined as a level of intensity that still allows normal conversation—equivalent, for example, to brisk walking at 3–4 miles per hour. For women who have been sedentary and are taking up exercise for the first time, a gradual progression to this intensity for up to 30 minutes per day is recommended. Those who are already fit when they become pregnant should be advised that pregnancy is not a time for greatly improving physical fitness and that, in general, overall activity and fitness levels tend to decline during pregnancy.

Pregnant women should exercise caution in increasing the intensity of their workouts, especially when they are extending exercise sessions beyond 45 minutes, because body core temperatures can rise above safe limits after that time. Strenuous exercise has not been proved to increase overall benefit and could actually be harmful, so this level of exercise intensity should be avoided.

Fetal Effects

Maternal cardiovascular, respiratory, and thermoregulatory adaptation occurs as a result of pregnancy and is further challenged by the addition of exercise. There is decreased availability of maternal oxygen during exercise because of increased maternal oxygen requirements at rest and the increased difficulty in breathing caused by the pressure of the enlarged uterus on the diaphragm. In addition, pregnancy raises basal metabolic rate and heat production, which are then further raised by exercise.

The hesitance of many obstetricians to prescribe exercise for pregnant women centers on the hypothetical fetal risks of impaired transplacental blood flow of oxygen, carbon dioxide, and nutrients during maternal exercise, as well as the potentially teratogenic effects of raising fetal temperature.

Most studies show a minimal to moderate increase in fetal heart rate during maternal exercise, and there is also evidence of fetal heart rate decelerations and bradycardia; however, no lasting fetal effects have been reported.

Data on the effects of increased maternal core temperatures are limited. Hyperthermia during embryogenesis (the first 45–60 days following the last menstrual period) has been shown to cause major congenital malformations (JAMA 1992;268:882–5).

The temperature threshold for human teratogenesis is 39.2° C (103° F). Moderate exercise performed in conditions allowing adequate heat dissipation has been shown to raise core temperatures no higher than 1.5° C during 30 minutes of exercise in nonpregnant women—and this temperature plateaus during as much as 1 hour of exercise.

Loss of fluid through sweat may compromise heat dissipation, so maintenance of euhydration—and thus blood volume—is essential to controlling core temperature.

Extra Nutritional Requirements

Although the published data on a link between low birth weight and maternal exercise are conflicting, it appears that adequate energy intake can offset any exercise-induced decreases in birth weight.

By the second trimester of pregnancy, an extra 1.3 MJ (300 kcal) per day are required to meet general metabolic needs in pregnancy, and this energy requirement is increased with exercise. Pregnant women use carbohydrates at a greater rate than do nonpregnant women—both at rest and during exercise—and there is preferential use of this form of energy during non-weight-bearing exercise, making adequate carbohydrate intake of particular importance.

Elite Athletes

Although routine prenatal care is sufficient for monitoring women in average exercise programs, closer obstetric observation is required for women who are elite athletes.

Most elite athletes choose to continue training during pregnancy, but they must be told that they probably will not achieve the same level of performance as they did before pregnancy, and the physiologic changes they experience—such as weight gain and joint or ligament laxity—will also make them more prone to injury. Women engaging in endurance sports can be prone to anemia that results from increased blood volume during pregnancy. High intensity, prolonged, and frequent exercise can put women at greater risk of thermoregulatory complications as well, and will usually result in less maternal and fetal weight gain than occurs in less active women.

Gestational Diabetes

The American Diabetes Association has endorsed exercise as a helpful adjunctive therapy for gestational diabetes mellitus (GDM) when glycemic control cannot be achieved through diet alone. Approximately 39% of patients with GDM require insulin therapy, but in my experience, exercise is a safe and effective alternative for most of these women.

The key to achieving euglycemia through exercise is ensuring the adequate duration and intensity of the activity. Exercise improves the impaired insulin sensitivity of women with GDM, which in turn increases glucose uptake by muscles and splanchnic organs, but this effect is achieved only through the activation of large muscles, such as the quadriceps, at adequate intensity, which explains why some studies in the literature fail to show normalization of glucose levels after exercise. At least half an hour of brisk walking per day is sufficient to upregulate insulin sensitivity in patients with GDM, obviating the need for insulin therapy.

Additionally, epidemiologic data suggest that exercise may act as primary prevention for GDM in morbidly obese women, but not in women of normal weight.

Weight Control

Although exercise should never be used for weight control during pregnancy, excessive weight gain should be avoided.

The current Institute of Medicine (IOM) guidelines on weight gain—which recommend a gain of 25–35 pounds for normal-weight women with a singleton pregnancy—are too high and are based on historical concerns about the effects of famine on fetal growth retardation.

The effect of gestational weight gain on pregnancy outcomes in obese women is not well studied. It is my opinion that the IOM guidelines are outdated, and that weight gain recommendations should be individualized. Compared with IOM recommendations for adequate gestational weight gain in obese women (at least 15 pounds), it is well recognized that a gain of less than 15 pounds in this population significantly reduces the risks of preeclampsia, C-section, and large-for-gestational-age infants.

The risk for small-for-gestational-age infants varies significantly, particularly among morbidly obese women in whom no weight gain—or even weight loss—may not have any adverse effect on birth weight.

Postpartum Exercise

Because failure to lose weight gained in pregnancy is a significant contributor to the obesity epidemic, the promotion of good exercise habits during pregnancy can also sow the seeds for postpartum exercise and weight loss.

One study showed that the amount of postpartum weight retention increases with each subsequent pregnancy (Acta. Obstet. Gynecol. Scand. 1979;58:45–7). Another study found that women who gained excessive weight during pregnancy and failed to lose it within 6 months post partum were 8.3 kg heavier 10 years later (Obstet. Gynecol. 2002;100:245–52).

Our study found that a weekly structured exercise program plus diet in postpartum overweight women were much more effective in achieving weight loss after 12 weeks compared with a single 1-hour education session about diet and exercise (J. Women's Health [Larchmt] 2003;12:991–8).

Therefore, women whose exercise habits have become firmly entrenched during pregnancy stand a much better chance of maintaining them post partum—and perhaps even into their next pregnancy.

Maintenance of euhydration is essential to controlling core temperature while exercising in pregnancy. Lynda Banzi

Exercise in Pregnancy

The extraordinary increase in obesity in the United States is giving rise not only to direct complications, such as hypertension and cardiovascular disease, but also to indirect problems such as diabetes. Hence, we have one problem leading into many others, ultimately resulting in a significant increase in morbidity and mortality.

Unfortunately, exercise—which can counter obesity—is not increasing at a concomitant rate. As a result, an emphasis on healthy lifestyles, with exercise as a central theme, has become the focus of national and international efforts undertaken by such groups as the World Health Organization, many of our medical societies, and even certain governmental agencies.

Just as exercise outside of pregnancy has clear benefits, exercise during pregnancy is also very important. For example, we know that a woman with gestational diabetes can certainly improve glucose control with exercise. However, there are clearly guidelines that must be followed when engaging in exercise during pregnancy.

In this month's Master Class, my guest professor is Raul Artal, M.D., who is an internationally recognized expert in the area of exercise physiology and exercise in pregnancy. He will lead us through specific recommendations concerning exercise during pregnancy, with references to gestational diabetes, weight control, and postpartum exercise.

Dr. Artal is professor and chair of the department of ob.gyn. at St. Louis University. He received his medical degree in Israel and his residency and fellowship training in the United States. He served as a faculty member at University of Southern California in Los Angeles and as chairman of ob.gyn. at the State University of New York, Syracuse, before attaining his current position. Dr. Artal is the lead author of the American College of Obstetricians and Gynecologists' Committee Opinion #267, “Exercise During Pregnancy and the Postpartum Period.”

Contraindications To Exercise In Pregnancy

Absolute Contraindications

Hemodynamically significant heart disease

Restrictive lung disease

Incompetent cervix/cerclage

Multiple gestation at risk for premature labor

Persistent second- or third-trimester bleeding

Placenta previa that occurs after 26 weeks' gestation

Premature labor during the current pregnancy

Ruptured membranes

Preeclampsia/pregnancy-induced hypertension

Relative Contraindications

Severe anemia

Unevaluated maternal cardiac arrhythmia

Chronic bronchitis

Poorly controlled type 1 diabetes

Extreme morbid obesity

Extreme underweight

History of extremely sedentary lifestyle

Intrauterine growth restriction in current pregnancy

Poorly controlled hypertension

Orthopedic limitations

Poorly controlled seizure disorder

Poorly controlled hyperthyroidism

Heavy smoker

Source: Obstet. Gynecol. 2002;99:171–3

The hesitance of obstetricians to recommend exercise to pregnant women is rooted in old-fashioned notions of pregnancy as a time of confinement. In the absence of reassuring data regarding the effects of exercise on the mother and fetus, most obstetricians adhered to the principle of doing no harm—advising women to eat for two and not to move.

With ample evidence to show that regular, moderate exercise in women with healthy pregnancies results in no adverse maternal or fetal effects, it could be argued that, in the spirit of “primum non nocere,” obstetricians should make exercise recommendations a top priority.

Indeed, because it is recognized that habits adopted during pregnancy can result in persistent lifestyle improvements, the promotion of exercise during pregnancy is an important public health issue that could significantly reduce the lifetime risks of obesity, chronic hypertension, and diabetes—not only for our patients, but for their families as well.

Recently, exercise has been recognized as an effective alternative to insulin therapy for treating gestational diabetes and as a means of preventing this disorder, which is frequently the first manifestation of what can become a lifelong condition.

Healthy Pregnancy? Few Restrictions

Despite the profound anatomical and physiologic changes of pregnancy, women with healthy pregnancies and no contraindications can exercise just as their nonpregnant counterparts do, combining both aerobic and resistive elements in their workouts. (See box on opposite page.)

A clinical evaluation of each patient is recommended before prescribing exercise, and physicians must consider the type and intensity of exercise—as well as the duration and frequency of exercise sessions—for each patient, based on her level of fitness and familiarity with various activities.

Contact sports and exercises with a high risk of falling or abdominal trauma should be avoided. Scuba diving should be avoided throughout pregnancy because this activity puts the fetus at increased risk for decompression sickness secondary to the inability of the fetal pulmonary circulation to filter bubbles.

Exercise Intensity

Moderate exercise is defined as a level of intensity that still allows normal conversation—equivalent, for example, to brisk walking at 3–4 miles per hour. For women who have been sedentary and are taking up exercise for the first time, a gradual progression to this intensity for up to 30 minutes per day is recommended. Those who are already fit when they become pregnant should be advised that pregnancy is not a time for greatly improving physical fitness and that, in general, overall activity and fitness levels tend to decline during pregnancy.

Pregnant women should exercise caution in increasing the intensity of their workouts, especially when they are extending exercise sessions beyond 45 minutes, because body core temperatures can rise above safe limits after that time. Strenuous exercise has not been proved to increase overall benefit and could actually be harmful, so this level of exercise intensity should be avoided.

Fetal Effects

Maternal cardiovascular, respiratory, and thermoregulatory adaptation occurs as a result of pregnancy and is further challenged by the addition of exercise. There is decreased availability of maternal oxygen during exercise because of increased maternal oxygen requirements at rest and the increased difficulty in breathing caused by the pressure of the enlarged uterus on the diaphragm. In addition, pregnancy raises basal metabolic rate and heat production, which are then further raised by exercise.

The hesitance of many obstetricians to prescribe exercise for pregnant women centers on the hypothetical fetal risks of impaired transplacental blood flow of oxygen, carbon dioxide, and nutrients during maternal exercise, as well as the potentially teratogenic effects of raising fetal temperature.

Most studies show a minimal to moderate increase in fetal heart rate during maternal exercise, and there is also evidence of fetal heart rate decelerations and bradycardia; however, no lasting fetal effects have been reported.

Data on the effects of increased maternal core temperatures are limited. Hyperthermia during embryogenesis (the first 45–60 days following the last menstrual period) has been shown to cause major congenital malformations (JAMA 1992;268:882–5).

The temperature threshold for human teratogenesis is 39.2° C (103° F). Moderate exercise performed in conditions allowing adequate heat dissipation has been shown to raise core temperatures no higher than 1.5° C during 30 minutes of exercise in nonpregnant women—and this temperature plateaus during as much as 1 hour of exercise.

Loss of fluid through sweat may compromise heat dissipation, so maintenance of euhydration—and thus blood volume—is essential to controlling core temperature.

Extra Nutritional Requirements

Although the published data on a link between low birth weight and maternal exercise are conflicting, it appears that adequate energy intake can offset any exercise-induced decreases in birth weight.

By the second trimester of pregnancy, an extra 1.3 MJ (300 kcal) per day are required to meet general metabolic needs in pregnancy, and this energy requirement is increased with exercise. Pregnant women use carbohydrates at a greater rate than do nonpregnant women—both at rest and during exercise—and there is preferential use of this form of energy during non-weight-bearing exercise, making adequate carbohydrate intake of particular importance.

Elite Athletes

Although routine prenatal care is sufficient for monitoring women in average exercise programs, closer obstetric observation is required for women who are elite athletes.

Most elite athletes choose to continue training during pregnancy, but they must be told that they probably will not achieve the same level of performance as they did before pregnancy, and the physiologic changes they experience—such as weight gain and joint or ligament laxity—will also make them more prone to injury. Women engaging in endurance sports can be prone to anemia that results from increased blood volume during pregnancy. High intensity, prolonged, and frequent exercise can put women at greater risk of thermoregulatory complications as well, and will usually result in less maternal and fetal weight gain than occurs in less active women.

Gestational Diabetes

The American Diabetes Association has endorsed exercise as a helpful adjunctive therapy for gestational diabetes mellitus (GDM) when glycemic control cannot be achieved through diet alone. Approximately 39% of patients with GDM require insulin therapy, but in my experience, exercise is a safe and effective alternative for most of these women.

The key to achieving euglycemia through exercise is ensuring the adequate duration and intensity of the activity. Exercise improves the impaired insulin sensitivity of women with GDM, which in turn increases glucose uptake by muscles and splanchnic organs, but this effect is achieved only through the activation of large muscles, such as the quadriceps, at adequate intensity, which explains why some studies in the literature fail to show normalization of glucose levels after exercise. At least half an hour of brisk walking per day is sufficient to upregulate insulin sensitivity in patients with GDM, obviating the need for insulin therapy.

Additionally, epidemiologic data suggest that exercise may act as primary prevention for GDM in morbidly obese women, but not in women of normal weight.

Weight Control

Although exercise should never be used for weight control during pregnancy, excessive weight gain should be avoided.

The current Institute of Medicine (IOM) guidelines on weight gain—which recommend a gain of 25–35 pounds for normal-weight women with a singleton pregnancy—are too high and are based on historical concerns about the effects of famine on fetal growth retardation.

The effect of gestational weight gain on pregnancy outcomes in obese women is not well studied. It is my opinion that the IOM guidelines are outdated, and that weight gain recommendations should be individualized. Compared with IOM recommendations for adequate gestational weight gain in obese women (at least 15 pounds), it is well recognized that a gain of less than 15 pounds in this population significantly reduces the risks of preeclampsia, C-section, and large-for-gestational-age infants.

The risk for small-for-gestational-age infants varies significantly, particularly among morbidly obese women in whom no weight gain—or even weight loss—may not have any adverse effect on birth weight.

Postpartum Exercise

Because failure to lose weight gained in pregnancy is a significant contributor to the obesity epidemic, the promotion of good exercise habits during pregnancy can also sow the seeds for postpartum exercise and weight loss.

One study showed that the amount of postpartum weight retention increases with each subsequent pregnancy (Acta. Obstet. Gynecol. Scand. 1979;58:45–7). Another study found that women who gained excessive weight during pregnancy and failed to lose it within 6 months post partum were 8.3 kg heavier 10 years later (Obstet. Gynecol. 2002;100:245–52).

Our study found that a weekly structured exercise program plus diet in postpartum overweight women were much more effective in achieving weight loss after 12 weeks compared with a single 1-hour education session about diet and exercise (J. Women's Health [Larchmt] 2003;12:991–8).

Therefore, women whose exercise habits have become firmly entrenched during pregnancy stand a much better chance of maintaining them post partum—and perhaps even into their next pregnancy.

Maintenance of euhydration is essential to controlling core temperature while exercising in pregnancy. Lynda Banzi

Exercise in Pregnancy

The extraordinary increase in obesity in the United States is giving rise not only to direct complications, such as hypertension and cardiovascular disease, but also to indirect problems such as diabetes. Hence, we have one problem leading into many others, ultimately resulting in a significant increase in morbidity and mortality.

Unfortunately, exercise—which can counter obesity—is not increasing at a concomitant rate. As a result, an emphasis on healthy lifestyles, with exercise as a central theme, has become the focus of national and international efforts undertaken by such groups as the World Health Organization, many of our medical societies, and even certain governmental agencies.

Just as exercise outside of pregnancy has clear benefits, exercise during pregnancy is also very important. For example, we know that a woman with gestational diabetes can certainly improve glucose control with exercise. However, there are clearly guidelines that must be followed when engaging in exercise during pregnancy.

In this month's Master Class, my guest professor is Raul Artal, M.D., who is an internationally recognized expert in the area of exercise physiology and exercise in pregnancy. He will lead us through specific recommendations concerning exercise during pregnancy, with references to gestational diabetes, weight control, and postpartum exercise.

Dr. Artal is professor and chair of the department of ob.gyn. at St. Louis University. He received his medical degree in Israel and his residency and fellowship training in the United States. He served as a faculty member at University of Southern California in Los Angeles and as chairman of ob.gyn. at the State University of New York, Syracuse, before attaining his current position. Dr. Artal is the lead author of the American College of Obstetricians and Gynecologists' Committee Opinion #267, “Exercise During Pregnancy and the Postpartum Period.”

Contraindications To Exercise In Pregnancy

Absolute Contraindications

Hemodynamically significant heart disease

Restrictive lung disease

Incompetent cervix/cerclage

Multiple gestation at risk for premature labor

Persistent second- or third-trimester bleeding

Placenta previa that occurs after 26 weeks' gestation

Premature labor during the current pregnancy

Ruptured membranes

Preeclampsia/pregnancy-induced hypertension

Relative Contraindications

Severe anemia

Unevaluated maternal cardiac arrhythmia

Chronic bronchitis

Poorly controlled type 1 diabetes

Extreme morbid obesity

Extreme underweight

History of extremely sedentary lifestyle

Intrauterine growth restriction in current pregnancy

Poorly controlled hypertension

Orthopedic limitations

Poorly controlled seizure disorder

Poorly controlled hyperthyroidism

Heavy smoker

Source: Obstet. Gynecol. 2002;99:171–3

NEW ORLEANS — Apligraf has been used successfully to line a new vagina in a patient with Mayer-Rokitansky-Küster-Hauser syndrome.

The human skin equivalent derived from human infant foreskin has been used widely for wound repair, but this is the first reported successful use for this purpose, Albert Altchek, M.D., reported at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology.

The 19-year-old patient with congenital absence of the uterus and vagina refused the split-thickness skin graft typically used for treating the condition and instead underwent the Apligraf procedure. Perineal biopsy and dissection were used to create a vaginal space, and 20 Apligraf patches—sewn together and wrapped around a soft, inflatable vaginal stent—were applied to the space, said Dr. Altchek of Mount Sinai School of Medicine, New York.

After the patient remained on bed rest for 1 week, the stent was removed and a second Apligraf application was placed. A week later, the Apligraf lining was found to be degenerating as a result of graft rejection; however, a small patch of vaginal mucosal cells that had been present proliferated to cover the entire neovagina. Soft vaginal stents were used to prevent strictures.

The result was a soft, pliable, moist, normal-looking vaginal mucosal wall, which has maintained patency for 61/2 years without a stent, Dr. Altchek said.

Apligraf was previously thought to stimulate only skin growth, but based on this case, it appears that it “actually preferentially stimulates another tissue—mucosa,” he said.

In the case of the 19-year-old patient, she had an excellent result. At 6-month follow-up she had normal cytology, and at 4 years she reported frequent sexual activity with orgasm. At last contact she was being referred for a surrogate gestational carrier.

This new method for correcting the defects associated with Mayer-Rokitansky-Küster-Hauser syndrome is investigational but shows great promise, he said, noting that it has several advantages over the split-thickness skin graft approach. Aside from scarring at the donor site, the split-thickness graft approach—unlike the Apligraf approach—results in atypical appearance and function; it also tends to cause malodor because the vagina is created using skin.

NEW ORLEANS — Apligraf has been used successfully to line a new vagina in a patient with Mayer-Rokitansky-Küster-Hauser syndrome.

The human skin equivalent derived from human infant foreskin has been used widely for wound repair, but this is the first reported successful use for this purpose, Albert Altchek, M.D., reported at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology.

The 19-year-old patient with congenital absence of the uterus and vagina refused the split-thickness skin graft typically used for treating the condition and instead underwent the Apligraf procedure. Perineal biopsy and dissection were used to create a vaginal space, and 20 Apligraf patches—sewn together and wrapped around a soft, inflatable vaginal stent—were applied to the space, said Dr. Altchek of Mount Sinai School of Medicine, New York.

After the patient remained on bed rest for 1 week, the stent was removed and a second Apligraf application was placed. A week later, the Apligraf lining was found to be degenerating as a result of graft rejection; however, a small patch of vaginal mucosal cells that had been present proliferated to cover the entire neovagina. Soft vaginal stents were used to prevent strictures.

The result was a soft, pliable, moist, normal-looking vaginal mucosal wall, which has maintained patency for 61/2 years without a stent, Dr. Altchek said.

Apligraf was previously thought to stimulate only skin growth, but based on this case, it appears that it “actually preferentially stimulates another tissue—mucosa,” he said.

In the case of the 19-year-old patient, she had an excellent result. At 6-month follow-up she had normal cytology, and at 4 years she reported frequent sexual activity with orgasm. At last contact she was being referred for a surrogate gestational carrier.

This new method for correcting the defects associated with Mayer-Rokitansky-Küster-Hauser syndrome is investigational but shows great promise, he said, noting that it has several advantages over the split-thickness skin graft approach. Aside from scarring at the donor site, the split-thickness graft approach—unlike the Apligraf approach—results in atypical appearance and function; it also tends to cause malodor because the vagina is created using skin.

NEW ORLEANS — Apligraf has been used successfully to line a new vagina in a patient with Mayer-Rokitansky-Küster-Hauser syndrome.

The human skin equivalent derived from human infant foreskin has been used widely for wound repair, but this is the first reported successful use for this purpose, Albert Altchek, M.D., reported at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology.

The 19-year-old patient with congenital absence of the uterus and vagina refused the split-thickness skin graft typically used for treating the condition and instead underwent the Apligraf procedure. Perineal biopsy and dissection were used to create a vaginal space, and 20 Apligraf patches—sewn together and wrapped around a soft, inflatable vaginal stent—were applied to the space, said Dr. Altchek of Mount Sinai School of Medicine, New York.

After the patient remained on bed rest for 1 week, the stent was removed and a second Apligraf application was placed. A week later, the Apligraf lining was found to be degenerating as a result of graft rejection; however, a small patch of vaginal mucosal cells that had been present proliferated to cover the entire neovagina. Soft vaginal stents were used to prevent strictures.

The result was a soft, pliable, moist, normal-looking vaginal mucosal wall, which has maintained patency for 61/2 years without a stent, Dr. Altchek said.

Apligraf was previously thought to stimulate only skin growth, but based on this case, it appears that it “actually preferentially stimulates another tissue—mucosa,” he said.

In the case of the 19-year-old patient, she had an excellent result. At 6-month follow-up she had normal cytology, and at 4 years she reported frequent sexual activity with orgasm. At last contact she was being referred for a surrogate gestational carrier.

This new method for correcting the defects associated with Mayer-Rokitansky-Küster-Hauser syndrome is investigational but shows great promise, he said, noting that it has several advantages over the split-thickness skin graft approach. Aside from scarring at the donor site, the split-thickness graft approach—unlike the Apligraf approach—results in atypical appearance and function; it also tends to cause malodor because the vagina is created using skin.

There was a time when almost all women with symptomatic leiomyomas were amenable to hysterectomy or myomectomy when medical therapy failed to relieve their pelvic pressure and pain, menorrhagia, and, in many cases, anemia.

Today, that has changed.

An increasing number of women don't want myomectomies or hysterectomies, regardless of whether they are performed abdominally or laparoscopically or—in the case of hysterectomies—vaginally. They go to the Internet and easily click on the names of 1,000 radiologists who promise a nonsurgical alternative that will “melt away” their fibroids.

Uterine artery embolization (UAE) involves making an incision in the groin and then threading a catheter through the femoral artery to the uterine artery to deliver thousands of polyvinyl particles into the uterus, as well as into the arteries, veins, and peripheral vessels that supply it. The intention is to cause transient uterine ischemia.

Originally used as a presurgical procedure to reduce blood loss during myomectomy or hysterectomy, UAE was also found to be effective in treating life-threatening bleeding that resulted from myomas. Success in controlling bleeding and improving symptoms led to its use as an alternative to primary surgery for leiomyomas in the late 1990s.

A recent surge in popularity was sparked by Food and Drug Administration approval of Embosphere microparticles for UAE and an aggressive marketing campaign by radiologists performing the procedure.

An Alternative to UAE

Laparoscopic uterine artery occlusion (UAO) offers a minimally invasive surgical option that also causes transient uterine ischemia and subsequent relief of leiomyoma symptoms, utilizing the same principles as UAE but permitting the gynecologic surgeon to inspect the uterine cavity, address other gynecologic issues, and rule out uterine cancer. Understanding either procedure requires a basic understanding of the principle behind bilateral UAO.

The uterine arteries provide most of the uterine blood supply. When this blood flow is blocked—either by polyvinyl microparticles, as in UAE, or by vascular clips during laparoscopic UAO—blood will then clot within the myometrium.

The myometrium becomes hypoxic and its metabolism undergoes a shift from oxidative pathways to anaerobic glycolysis.

Within hours to days, clots are lysed within the myometrium, and collateral arteries begin to reperfuse the uterus.

Myomas, in contrast, cannot lyse clotted blood and reperfuse. They eventually become infarcted and die.

In a proof-of-hypothesis study conducted by my colleagues and me several years ago, we found that the percentage and rate of decline and the return to baseline of pH (a proxy for hypoxia and lactic acidosis) after bilateral UAO were quite variable.

The myometrium has a complex, redundant blood supply that varies from patient to patient (J. Am. Assoc. Gynecol. Laparosc. 2003;10:553–66).

In the vast majority of women, these secondary, tertiary, and quaternary vascular pathways are insufficient to maintain aerobic metabolism.

In 1%–2% of women, however, one uterine artery is hypoplastic, and a large communicating artery connects the ovarian artery to the uterus. Without occlusion of this artery in these patients, the blood supply to the uterus would be maintained despite bilateral UAO.

In our study reviewing eight cases, the uterine pH change from baseline ranged from 0.4 to 1.7 units over a time period that ranged from 5 minutes to 210 minutes after bilateral UAO.

The time for pH to return to baseline ranged from 20 minutes to 660 minutes (J. Am. Assoc. Gynecol. Laparosc. 2002; 9:191–8).

Other investigators have shown via MRI that clots form more quickly in myomas (as indicated by uptake of contrast media) than in the myometrium, and myoma tissue remains unperfused at 1 year, even as myometrium demonstrates normal perfusion at 1, 2, 3, 4, and 6 months, and 1 year.

In our first study of laparoscopic UAO for symptomatic leiomyomas, we enrolled eight women whom we had counseled extensively about various alternatives, including gonadotropin-releasing hormones, hysterectomy, myomectomy, and embolization.

Operative Technique

The operative procedure is quite straightforward.

Patients are placed in dorsolithotomy position under general anesthesia. A Foley catheter is placed into the bladder. An examination is performed, followed by hysteroscopy, and—if warranted by findings—endometrial biopsies are performed. A uterine cannula is inserted for uterine manipulation.

Depending on uterine size, a 10-mm port is inserted using open technique in the umbilicus or the left upper abdominal quadrant.

For safety reasons, accessing the peritoneum above the psoas muscle prevents direct trauma to retroperitoneal vessels. Entering retroperitoneum lateral to the posterior broad ligament avoids uterine expansion.

Pneumoperitoneum is established under videolaparoscopic guidance. Two additional ports—one is a 5-mm port; the other is a 5-mm or 12-mm port—are then inserted under visualization bilaterally above the inferior epigastric vessels.

Use uterine countertraction on the ipsilateral side while identifying the round ligament. Incise the posterior broad ligament laterally next to the round ligament over the psoas muscle, using endoscopic scissors.

This will free periadnexal adhesions and release uterine lateral displacement from myomas; it also avoids injury to the femoral vessels.

Grasp the cut edges of peritoneum and pull them laterally. Dissect to below the round ligament and lateral to the uterus.

Identify the lateral umbilical ligaments—vestigial obliterated umbilical arteries that reflect from the anterior peritoneum and become retroperitoneal in this avascular area. Trace the fibrous white element cephalad.

When this ligament is pulled laterally, it is easy to visualize the origin of the uterine artery by following the fibrous, bloodless, obliterant hypogastric artery to the internal iliac artery. This artery is straight for the first 2–3 cm, where it can be seen pulsating; it then becomes tortuous and surrounded by veins as it crosses medially above the ureter. It is an extensible artery that tolerates significant maneuvers.

Apply two successive preloaded 5-mm or 10-mm vascular clips at an area that is devoid of venous plexus, further from the ureter and more lateral to the uterus than during laparoscopic hysterectomy.

We do not dissect the round ligaments, vesicouterine space, or ureters.

Blanching of the uterus can be observed once both arteries are occluded.

Manageable Complications

In our study, there were no perioperative complications, and estimated blood loss was less than 25 dL in all cases. The average operating time was 35 minutes, which we have now reduced to 20 minutes in our current experience of more than 100 cases.

Postoperative pain was managed by nonsteroidal anti-inflammatory drugs in all but one case, a patient who requested parenteral narcotic analgesia in the recovery room. In our more recent experience, the majority of patients require only ibuprofen, with an occasional use of Vicodin or Tylenol #3. The study patients were discharged after 12–20 hours, a period primarily for monitoring purposes related to the protocol; today, our patients go home the same day as their surgery.

Among eight patients in the study, seven reported complete resolution of fibroid-related pain at 3 months. One patient's pain declined from moderate to mild. These results have remained consistent in our larger series.

The five patients who previously reported menorrhagia reported eumenorrhea; no patients became amenorrheic. We have seen two patients in our larger series become menopausal, but both were older than 50 years at the time of surgery. None of the patients we have followed with FSH levels has lost ovarian function.

The average decrease in uterine volume at 3 months was 39.4%.

One of our patients has become pregnant and is currently doing well at 20 weeks' gestation.

Complications have been few. Among our original study patients, one passed round tissue vaginally 3 months postoperatively, but her white blood count was normal and she showed no signs of infection.

Simple endometrial adenomatous hyperplasia was diagnosed on the day of another patient's procedure; repeat office curettage showed benign endometrium 3 months later.

We bill for this procedure using code #37617 (ligation of major artery of the abdomen), after having obtained precertification with insurance companies. We have had no trouble being reimbursed for the procedure.

This procedure carries a very low risk of anesthesia complications, and abdominal entry injuries are possible.

Any procedure involving UAO has potential complications related to uterine ischemia.

Prolapse, vaginal expulsion of necrotic tissue, and pelvic infection are possible. Selecting patients who have adequate perfusion around myomas may decrease the risk of postocclusion infection.

Patient selection is also important with regard to myoma size. Laparoscopic visualization becomes difficult in patients beyond a 20-week gestation uterine size, and we therefore refer these patients for embolization if they will not consider myomectomy or hysterectomy.

A Comparison of the Two Procedures

As opposed to radiologic embolization, which is a blind procedure, laparoscopic UAO offers an opportunity to diagnose endometrial cancer and sarcomas via fine-needle aspiration and myometrial biopsy.

Additionally, it can be offered as a global treatment for gynecologic complaints other than leiomyomas.

The majority of patients who are candidates for these procedures also have adhesions and/or endometriosis that may be a cocontributor to their pelvic pain.

In conclusion, we have found that the risks of laparoscopic UAO are minimal, and the benefits to carefully selected patients are considerable.

By contrast, radiologic UAE is a simple procedure that has been proven efficacious for reducing symptoms. It is not, however, without risks.

Misembolization has been reported to the collateral uterine-ovarian vessel and the legs. Unintended embolization can lead to ovarian failure in 1%–4% of cases.

Pain is a considerable feature of the procedure, both from hypoxia and cramping, as the uterus attempts to expel the polyvinyl pellets. Many patients remain in the hospital for 23 hours on a morphine pump.

Up to 15% of patients experience postembolization syndrome, characterized by fever, anorexia, and nausea/vomiting.

Most importantly, radiologic UAE can be performed in patients with undiagnosed cancer that can evade diagnosis for many months.

There are several reports of embolization in a patient with undiagnosed uterine sarcoma.

Endometrial biopsy and MRI can assist in the presurgical diagnosis of sarcoma; however, the laparoscopic approach is clearly more thorough in ruling out cancer.

The only real obstacle to widespread use of laparoscopic UAO is the dearth of advanced laparoscopic surgery training among U.S. gynecologic surgeons. This is a retroperitoneal vascular procedure, requiring skillful knowledge of the vascular anatomy.

Future Vaginal Approach?

Because there appears to be a need for a gynecologic alternative to the increasingly popular radiologic UAE, I have recently been working with colleagues and a private company—Vascular Control Systems of San Juan Capistrano, Calif.—to develop a technique to temporarily occlude the uterine arteries with a Doppler-guided, uterine artery clamp using a vaginal approach.

This procedure is still experimental, and we have thus far achieved fibroid shrinkage of approximately 30%. A clinical trial is under way to advance and improve this technique.

In this view of the left retroperitoneum, two 5-mm endoscopic clips occlude the proximal portion of the left uterine artery.

This uterus is blanched as a result of hypoperfusion and ischemia after laparoscopic bilateral uterine artery occlusion. Photos courtesy Dr. Moises Lichtinger

Gynecologists Strike Back With Laparoscopic Uterine Artery Occlusion

One only needs to check the Internet to see how aggressively our colleagues in radiology are marketing uterine artery embolization/uterine fibroid embolization.

Although the radiologic approach certainly has merit, the risk of inadvertent embolization to other organs is recognized. Laparoscopic uterine artery occlusion not only removes this concern but also returns to the practicing gynecologist the treatment of leiomyomas.

Moises Lichtinger, M.D., is a well-known advocate of laparoscopic uterine artery occlusion for the symptomatic uterine fibroid. Not only has he worked to develop a safe and reproducible technique for the laparoscopic approach, but he is researching a transvaginal approach to uterine artery occlusion as well, in cooperation with Vascular Control Systems of San Juan Capistrano, Calif.

Dr. Lichtinger currently chairs the department of obstetrics and gynecology at Holy Cross Hospital in Fort Lauderdale, Fla.

He received his undergraduate and M.D. degrees in Mexico and completed his internship and residency at Jackson Memorial Hospital in Miami. He remained at Jackson Memorial to complete a gynecologic oncology fellowship as well.

There was a time when almost all women with symptomatic leiomyomas were amenable to hysterectomy or myomectomy when medical therapy failed to relieve their pelvic pressure and pain, menorrhagia, and, in many cases, anemia.

Today, that has changed.

An increasing number of women don't want myomectomies or hysterectomies, regardless of whether they are performed abdominally or laparoscopically or—in the case of hysterectomies—vaginally. They go to the Internet and easily click on the names of 1,000 radiologists who promise a nonsurgical alternative that will “melt away” their fibroids.

Uterine artery embolization (UAE) involves making an incision in the groin and then threading a catheter through the femoral artery to the uterine artery to deliver thousands of polyvinyl particles into the uterus, as well as into the arteries, veins, and peripheral vessels that supply it. The intention is to cause transient uterine ischemia.

Originally used as a presurgical procedure to reduce blood loss during myomectomy or hysterectomy, UAE was also found to be effective in treating life-threatening bleeding that resulted from myomas. Success in controlling bleeding and improving symptoms led to its use as an alternative to primary surgery for leiomyomas in the late 1990s.

A recent surge in popularity was sparked by Food and Drug Administration approval of Embosphere microparticles for UAE and an aggressive marketing campaign by radiologists performing the procedure.

An Alternative to UAE

Laparoscopic uterine artery occlusion (UAO) offers a minimally invasive surgical option that also causes transient uterine ischemia and subsequent relief of leiomyoma symptoms, utilizing the same principles as UAE but permitting the gynecologic surgeon to inspect the uterine cavity, address other gynecologic issues, and rule out uterine cancer. Understanding either procedure requires a basic understanding of the principle behind bilateral UAO.

The uterine arteries provide most of the uterine blood supply. When this blood flow is blocked—either by polyvinyl microparticles, as in UAE, or by vascular clips during laparoscopic UAO—blood will then clot within the myometrium.

The myometrium becomes hypoxic and its metabolism undergoes a shift from oxidative pathways to anaerobic glycolysis.

Within hours to days, clots are lysed within the myometrium, and collateral arteries begin to reperfuse the uterus.

Myomas, in contrast, cannot lyse clotted blood and reperfuse. They eventually become infarcted and die.

In a proof-of-hypothesis study conducted by my colleagues and me several years ago, we found that the percentage and rate of decline and the return to baseline of pH (a proxy for hypoxia and lactic acidosis) after bilateral UAO were quite variable.

The myometrium has a complex, redundant blood supply that varies from patient to patient (J. Am. Assoc. Gynecol. Laparosc. 2003;10:553–66).

In the vast majority of women, these secondary, tertiary, and quaternary vascular pathways are insufficient to maintain aerobic metabolism.

In 1%–2% of women, however, one uterine artery is hypoplastic, and a large communicating artery connects the ovarian artery to the uterus. Without occlusion of this artery in these patients, the blood supply to the uterus would be maintained despite bilateral UAO.

In our study reviewing eight cases, the uterine pH change from baseline ranged from 0.4 to 1.7 units over a time period that ranged from 5 minutes to 210 minutes after bilateral UAO.

The time for pH to return to baseline ranged from 20 minutes to 660 minutes (J. Am. Assoc. Gynecol. Laparosc. 2002; 9:191–8).

Other investigators have shown via MRI that clots form more quickly in myomas (as indicated by uptake of contrast media) than in the myometrium, and myoma tissue remains unperfused at 1 year, even as myometrium demonstrates normal perfusion at 1, 2, 3, 4, and 6 months, and 1 year.

In our first study of laparoscopic UAO for symptomatic leiomyomas, we enrolled eight women whom we had counseled extensively about various alternatives, including gonadotropin-releasing hormones, hysterectomy, myomectomy, and embolization.

Operative Technique

The operative procedure is quite straightforward.

Patients are placed in dorsolithotomy position under general anesthesia. A Foley catheter is placed into the bladder. An examination is performed, followed by hysteroscopy, and—if warranted by findings—endometrial biopsies are performed. A uterine cannula is inserted for uterine manipulation.

Depending on uterine size, a 10-mm port is inserted using open technique in the umbilicus or the left upper abdominal quadrant.

For safety reasons, accessing the peritoneum above the psoas muscle prevents direct trauma to retroperitoneal vessels. Entering retroperitoneum lateral to the posterior broad ligament avoids uterine expansion.

Pneumoperitoneum is established under videolaparoscopic guidance. Two additional ports—one is a 5-mm port; the other is a 5-mm or 12-mm port—are then inserted under visualization bilaterally above the inferior epigastric vessels.

Use uterine countertraction on the ipsilateral side while identifying the round ligament. Incise the posterior broad ligament laterally next to the round ligament over the psoas muscle, using endoscopic scissors.

This will free periadnexal adhesions and release uterine lateral displacement from myomas; it also avoids injury to the femoral vessels.

Grasp the cut edges of peritoneum and pull them laterally. Dissect to below the round ligament and lateral to the uterus.

Identify the lateral umbilical ligaments—vestigial obliterated umbilical arteries that reflect from the anterior peritoneum and become retroperitoneal in this avascular area. Trace the fibrous white element cephalad.

When this ligament is pulled laterally, it is easy to visualize the origin of the uterine artery by following the fibrous, bloodless, obliterant hypogastric artery to the internal iliac artery. This artery is straight for the first 2–3 cm, where it can be seen pulsating; it then becomes tortuous and surrounded by veins as it crosses medially above the ureter. It is an extensible artery that tolerates significant maneuvers.

Apply two successive preloaded 5-mm or 10-mm vascular clips at an area that is devoid of venous plexus, further from the ureter and more lateral to the uterus than during laparoscopic hysterectomy.

We do not dissect the round ligaments, vesicouterine space, or ureters.

Blanching of the uterus can be observed once both arteries are occluded.

Manageable Complications

In our study, there were no perioperative complications, and estimated blood loss was less than 25 dL in all cases. The average operating time was 35 minutes, which we have now reduced to 20 minutes in our current experience of more than 100 cases.

Postoperative pain was managed by nonsteroidal anti-inflammatory drugs in all but one case, a patient who requested parenteral narcotic analgesia in the recovery room. In our more recent experience, the majority of patients require only ibuprofen, with an occasional use of Vicodin or Tylenol #3. The study patients were discharged after 12–20 hours, a period primarily for monitoring purposes related to the protocol; today, our patients go home the same day as their surgery.

Among eight patients in the study, seven reported complete resolution of fibroid-related pain at 3 months. One patient's pain declined from moderate to mild. These results have remained consistent in our larger series.

The five patients who previously reported menorrhagia reported eumenorrhea; no patients became amenorrheic. We have seen two patients in our larger series become menopausal, but both were older than 50 years at the time of surgery. None of the patients we have followed with FSH levels has lost ovarian function.

The average decrease in uterine volume at 3 months was 39.4%.

One of our patients has become pregnant and is currently doing well at 20 weeks' gestation.

Complications have been few. Among our original study patients, one passed round tissue vaginally 3 months postoperatively, but her white blood count was normal and she showed no signs of infection.

Simple endometrial adenomatous hyperplasia was diagnosed on the day of another patient's procedure; repeat office curettage showed benign endometrium 3 months later.

We bill for this procedure using code #37617 (ligation of major artery of the abdomen), after having obtained precertification with insurance companies. We have had no trouble being reimbursed for the procedure.

This procedure carries a very low risk of anesthesia complications, and abdominal entry injuries are possible.

Any procedure involving UAO has potential complications related to uterine ischemia.

Prolapse, vaginal expulsion of necrotic tissue, and pelvic infection are possible. Selecting patients who have adequate perfusion around myomas may decrease the risk of postocclusion infection.

Patient selection is also important with regard to myoma size. Laparoscopic visualization becomes difficult in patients beyond a 20-week gestation uterine size, and we therefore refer these patients for embolization if they will not consider myomectomy or hysterectomy.

A Comparison of the Two Procedures

As opposed to radiologic embolization, which is a blind procedure, laparoscopic UAO offers an opportunity to diagnose endometrial cancer and sarcomas via fine-needle aspiration and myometrial biopsy.

Additionally, it can be offered as a global treatment for gynecologic complaints other than leiomyomas.

The majority of patients who are candidates for these procedures also have adhesions and/or endometriosis that may be a cocontributor to their pelvic pain.

In conclusion, we have found that the risks of laparoscopic UAO are minimal, and the benefits to carefully selected patients are considerable.

By contrast, radiologic UAE is a simple procedure that has been proven efficacious for reducing symptoms. It is not, however, without risks.

Misembolization has been reported to the collateral uterine-ovarian vessel and the legs. Unintended embolization can lead to ovarian failure in 1%–4% of cases.

Pain is a considerable feature of the procedure, both from hypoxia and cramping, as the uterus attempts to expel the polyvinyl pellets. Many patients remain in the hospital for 23 hours on a morphine pump.

Up to 15% of patients experience postembolization syndrome, characterized by fever, anorexia, and nausea/vomiting.

Most importantly, radiologic UAE can be performed in patients with undiagnosed cancer that can evade diagnosis for many months.

There are several reports of embolization in a patient with undiagnosed uterine sarcoma.

Endometrial biopsy and MRI can assist in the presurgical diagnosis of sarcoma; however, the laparoscopic approach is clearly more thorough in ruling out cancer.

The only real obstacle to widespread use of laparoscopic UAO is the dearth of advanced laparoscopic surgery training among U.S. gynecologic surgeons. This is a retroperitoneal vascular procedure, requiring skillful knowledge of the vascular anatomy.

Future Vaginal Approach?

Because there appears to be a need for a gynecologic alternative to the increasingly popular radiologic UAE, I have recently been working with colleagues and a private company—Vascular Control Systems of San Juan Capistrano, Calif.—to develop a technique to temporarily occlude the uterine arteries with a Doppler-guided, uterine artery clamp using a vaginal approach.

This procedure is still experimental, and we have thus far achieved fibroid shrinkage of approximately 30%. A clinical trial is under way to advance and improve this technique.

In this view of the left retroperitoneum, two 5-mm endoscopic clips occlude the proximal portion of the left uterine artery.

This uterus is blanched as a result of hypoperfusion and ischemia after laparoscopic bilateral uterine artery occlusion. Photos courtesy Dr. Moises Lichtinger

Gynecologists Strike Back With Laparoscopic Uterine Artery Occlusion

One only needs to check the Internet to see how aggressively our colleagues in radiology are marketing uterine artery embolization/uterine fibroid embolization.

Although the radiologic approach certainly has merit, the risk of inadvertent embolization to other organs is recognized. Laparoscopic uterine artery occlusion not only removes this concern but also returns to the practicing gynecologist the treatment of leiomyomas.

Moises Lichtinger, M.D., is a well-known advocate of laparoscopic uterine artery occlusion for the symptomatic uterine fibroid. Not only has he worked to develop a safe and reproducible technique for the laparoscopic approach, but he is researching a transvaginal approach to uterine artery occlusion as well, in cooperation with Vascular Control Systems of San Juan Capistrano, Calif.

Dr. Lichtinger currently chairs the department of obstetrics and gynecology at Holy Cross Hospital in Fort Lauderdale, Fla.

He received his undergraduate and M.D. degrees in Mexico and completed his internship and residency at Jackson Memorial Hospital in Miami. He remained at Jackson Memorial to complete a gynecologic oncology fellowship as well.

There was a time when almost all women with symptomatic leiomyomas were amenable to hysterectomy or myomectomy when medical therapy failed to relieve their pelvic pressure and pain, menorrhagia, and, in many cases, anemia.

Today, that has changed.

An increasing number of women don't want myomectomies or hysterectomies, regardless of whether they are performed abdominally or laparoscopically or—in the case of hysterectomies—vaginally. They go to the Internet and easily click on the names of 1,000 radiologists who promise a nonsurgical alternative that will “melt away” their fibroids.

Uterine artery embolization (UAE) involves making an incision in the groin and then threading a catheter through the femoral artery to the uterine artery to deliver thousands of polyvinyl particles into the uterus, as well as into the arteries, veins, and peripheral vessels that supply it. The intention is to cause transient uterine ischemia.

Originally used as a presurgical procedure to reduce blood loss during myomectomy or hysterectomy, UAE was also found to be effective in treating life-threatening bleeding that resulted from myomas. Success in controlling bleeding and improving symptoms led to its use as an alternative to primary surgery for leiomyomas in the late 1990s.

A recent surge in popularity was sparked by Food and Drug Administration approval of Embosphere microparticles for UAE and an aggressive marketing campaign by radiologists performing the procedure.

An Alternative to UAE

Laparoscopic uterine artery occlusion (UAO) offers a minimally invasive surgical option that also causes transient uterine ischemia and subsequent relief of leiomyoma symptoms, utilizing the same principles as UAE but permitting the gynecologic surgeon to inspect the uterine cavity, address other gynecologic issues, and rule out uterine cancer. Understanding either procedure requires a basic understanding of the principle behind bilateral UAO.

The uterine arteries provide most of the uterine blood supply. When this blood flow is blocked—either by polyvinyl microparticles, as in UAE, or by vascular clips during laparoscopic UAO—blood will then clot within the myometrium.

The myometrium becomes hypoxic and its metabolism undergoes a shift from oxidative pathways to anaerobic glycolysis.

Within hours to days, clots are lysed within the myometrium, and collateral arteries begin to reperfuse the uterus.

Myomas, in contrast, cannot lyse clotted blood and reperfuse. They eventually become infarcted and die.

In a proof-of-hypothesis study conducted by my colleagues and me several years ago, we found that the percentage and rate of decline and the return to baseline of pH (a proxy for hypoxia and lactic acidosis) after bilateral UAO were quite variable.

The myometrium has a complex, redundant blood supply that varies from patient to patient (J. Am. Assoc. Gynecol. Laparosc. 2003;10:553–66).

In the vast majority of women, these secondary, tertiary, and quaternary vascular pathways are insufficient to maintain aerobic metabolism.

In 1%–2% of women, however, one uterine artery is hypoplastic, and a large communicating artery connects the ovarian artery to the uterus. Without occlusion of this artery in these patients, the blood supply to the uterus would be maintained despite bilateral UAO.

In our study reviewing eight cases, the uterine pH change from baseline ranged from 0.4 to 1.7 units over a time period that ranged from 5 minutes to 210 minutes after bilateral UAO.

The time for pH to return to baseline ranged from 20 minutes to 660 minutes (J. Am. Assoc. Gynecol. Laparosc. 2002; 9:191–8).

Other investigators have shown via MRI that clots form more quickly in myomas (as indicated by uptake of contrast media) than in the myometrium, and myoma tissue remains unperfused at 1 year, even as myometrium demonstrates normal perfusion at 1, 2, 3, 4, and 6 months, and 1 year.

In our first study of laparoscopic UAO for symptomatic leiomyomas, we enrolled eight women whom we had counseled extensively about various alternatives, including gonadotropin-releasing hormones, hysterectomy, myomectomy, and embolization.

Operative Technique

The operative procedure is quite straightforward.

Patients are placed in dorsolithotomy position under general anesthesia. A Foley catheter is placed into the bladder. An examination is performed, followed by hysteroscopy, and—if warranted by findings—endometrial biopsies are performed. A uterine cannula is inserted for uterine manipulation.

Depending on uterine size, a 10-mm port is inserted using open technique in the umbilicus or the left upper abdominal quadrant.

For safety reasons, accessing the peritoneum above the psoas muscle prevents direct trauma to retroperitoneal vessels. Entering retroperitoneum lateral to the posterior broad ligament avoids uterine expansion.

Pneumoperitoneum is established under videolaparoscopic guidance. Two additional ports—one is a 5-mm port; the other is a 5-mm or 12-mm port—are then inserted under visualization bilaterally above the inferior epigastric vessels.

Use uterine countertraction on the ipsilateral side while identifying the round ligament. Incise the posterior broad ligament laterally next to the round ligament over the psoas muscle, using endoscopic scissors.

This will free periadnexal adhesions and release uterine lateral displacement from myomas; it also avoids injury to the femoral vessels.

Grasp the cut edges of peritoneum and pull them laterally. Dissect to below the round ligament and lateral to the uterus.

Identify the lateral umbilical ligaments—vestigial obliterated umbilical arteries that reflect from the anterior peritoneum and become retroperitoneal in this avascular area. Trace the fibrous white element cephalad.

When this ligament is pulled laterally, it is easy to visualize the origin of the uterine artery by following the fibrous, bloodless, obliterant hypogastric artery to the internal iliac artery. This artery is straight for the first 2–3 cm, where it can be seen pulsating; it then becomes tortuous and surrounded by veins as it crosses medially above the ureter. It is an extensible artery that tolerates significant maneuvers.

Apply two successive preloaded 5-mm or 10-mm vascular clips at an area that is devoid of venous plexus, further from the ureter and more lateral to the uterus than during laparoscopic hysterectomy.

We do not dissect the round ligaments, vesicouterine space, or ureters.

Blanching of the uterus can be observed once both arteries are occluded.

Manageable Complications

In our study, there were no perioperative complications, and estimated blood loss was less than 25 dL in all cases. The average operating time was 35 minutes, which we have now reduced to 20 minutes in our current experience of more than 100 cases.

Postoperative pain was managed by nonsteroidal anti-inflammatory drugs in all but one case, a patient who requested parenteral narcotic analgesia in the recovery room. In our more recent experience, the majority of patients require only ibuprofen, with an occasional use of Vicodin or Tylenol #3. The study patients were discharged after 12–20 hours, a period primarily for monitoring purposes related to the protocol; today, our patients go home the same day as their surgery.

Among eight patients in the study, seven reported complete resolution of fibroid-related pain at 3 months. One patient's pain declined from moderate to mild. These results have remained consistent in our larger series.

The five patients who previously reported menorrhagia reported eumenorrhea; no patients became amenorrheic. We have seen two patients in our larger series become menopausal, but both were older than 50 years at the time of surgery. None of the patients we have followed with FSH levels has lost ovarian function.

The average decrease in uterine volume at 3 months was 39.4%.

One of our patients has become pregnant and is currently doing well at 20 weeks' gestation.

Complications have been few. Among our original study patients, one passed round tissue vaginally 3 months postoperatively, but her white blood count was normal and she showed no signs of infection.

Simple endometrial adenomatous hyperplasia was diagnosed on the day of another patient's procedure; repeat office curettage showed benign endometrium 3 months later.

We bill for this procedure using code #37617 (ligation of major artery of the abdomen), after having obtained precertification with insurance companies. We have had no trouble being reimbursed for the procedure.

This procedure carries a very low risk of anesthesia complications, and abdominal entry injuries are possible.

Any procedure involving UAO has potential complications related to uterine ischemia.

Prolapse, vaginal expulsion of necrotic tissue, and pelvic infection are possible. Selecting patients who have adequate perfusion around myomas may decrease the risk of postocclusion infection.

Patient selection is also important with regard to myoma size. Laparoscopic visualization becomes difficult in patients beyond a 20-week gestation uterine size, and we therefore refer these patients for embolization if they will not consider myomectomy or hysterectomy.

A Comparison of the Two Procedures

As opposed to radiologic embolization, which is a blind procedure, laparoscopic UAO offers an opportunity to diagnose endometrial cancer and sarcomas via fine-needle aspiration and myometrial biopsy.

Additionally, it can be offered as a global treatment for gynecologic complaints other than leiomyomas.

The majority of patients who are candidates for these procedures also have adhesions and/or endometriosis that may be a cocontributor to their pelvic pain.

In conclusion, we have found that the risks of laparoscopic UAO are minimal, and the benefits to carefully selected patients are considerable.

By contrast, radiologic UAE is a simple procedure that has been proven efficacious for reducing symptoms. It is not, however, without risks.

Misembolization has been reported to the collateral uterine-ovarian vessel and the legs. Unintended embolization can lead to ovarian failure in 1%–4% of cases.

Pain is a considerable feature of the procedure, both from hypoxia and cramping, as the uterus attempts to expel the polyvinyl pellets. Many patients remain in the hospital for 23 hours on a morphine pump.

Up to 15% of patients experience postembolization syndrome, characterized by fever, anorexia, and nausea/vomiting.

Most importantly, radiologic UAE can be performed in patients with undiagnosed cancer that can evade diagnosis for many months.

There are several reports of embolization in a patient with undiagnosed uterine sarcoma.

Endometrial biopsy and MRI can assist in the presurgical diagnosis of sarcoma; however, the laparoscopic approach is clearly more thorough in ruling out cancer.

The only real obstacle to widespread use of laparoscopic UAO is the dearth of advanced laparoscopic surgery training among U.S. gynecologic surgeons. This is a retroperitoneal vascular procedure, requiring skillful knowledge of the vascular anatomy.

Future Vaginal Approach?

Because there appears to be a need for a gynecologic alternative to the increasingly popular radiologic UAE, I have recently been working with colleagues and a private company—Vascular Control Systems of San Juan Capistrano, Calif.—to develop a technique to temporarily occlude the uterine arteries with a Doppler-guided, uterine artery clamp using a vaginal approach.

This procedure is still experimental, and we have thus far achieved fibroid shrinkage of approximately 30%. A clinical trial is under way to advance and improve this technique.

In this view of the left retroperitoneum, two 5-mm endoscopic clips occlude the proximal portion of the left uterine artery.

This uterus is blanched as a result of hypoperfusion and ischemia after laparoscopic bilateral uterine artery occlusion. Photos courtesy Dr. Moises Lichtinger

Gynecologists Strike Back With Laparoscopic Uterine Artery Occlusion

One only needs to check the Internet to see how aggressively our colleagues in radiology are marketing uterine artery embolization/uterine fibroid embolization.

Although the radiologic approach certainly has merit, the risk of inadvertent embolization to other organs is recognized. Laparoscopic uterine artery occlusion not only removes this concern but also returns to the practicing gynecologist the treatment of leiomyomas.

Moises Lichtinger, M.D., is a well-known advocate of laparoscopic uterine artery occlusion for the symptomatic uterine fibroid. Not only has he worked to develop a safe and reproducible technique for the laparoscopic approach, but he is researching a transvaginal approach to uterine artery occlusion as well, in cooperation with Vascular Control Systems of San Juan Capistrano, Calif.

Dr. Lichtinger currently chairs the department of obstetrics and gynecology at Holy Cross Hospital in Fort Lauderdale, Fla.

He received his undergraduate and M.D. degrees in Mexico and completed his internship and residency at Jackson Memorial Hospital in Miami. He remained at Jackson Memorial to complete a gynecologic oncology fellowship as well.

KEVIN FOLEY, RESEARCH

KEVIN FOLEY, RESEARCH

KEVIN FOLEY, RESEARCH

Stroke is a rare but potentially devastating occurrence during pregnancy and the postpartum period. Maternal mortality is reported to be as high as 26%, and survivors may face long-term neurologic sequelae. Associated fetal mortality and morbidity also remain high. Although stroke is not preventable, early intervention can be key to saving lives and preserving brain function in some patients.

Therefore, even if the likelihood is that an obstetrician will never encounter a patient who suffers a stroke, it is critical that we all make the diagnosis promptly, obtain neurologic and other consultations appropriately, and direct state-of-the-art treatment of cerebrovascular disorders in this special population.

It is important to recognize that stroke occurs in young women of childbearing age at a rate of 10.7 per 100,000. Some have postulated that the risk is elevated during pregnancy for a number of reasons, including hypercoagulability, venous stasis, and blood pressure fluctuations. Indeed, some estimate that the risk of stroke is 13-fold higher in pregnant than in nonpregnant women, although the rarity of the condition makes the true prevalence a matter of debate.

Postpartum Risk Is Higher

The risk of stroke in the postpartum period is almost certainly higher still. Postpartum strokes generally occur from 5 days to 2 weeks after delivery—a vulnerable time when a headache from cerebral vasoconstriction syndrome may be mistaken for postepidural puncture syndrome.

The issue of stroke during pregnancy and the postpartum period is of increasing relevance to obstetricians. The incidence of stroke rises with age, and women are becoming pregnant at older ages than ever before; obstetric patients aged 45–50 years have become increasingly common. Obesity is also a risk factor for stroke, and pregnant women mirror American society at large, in which obesity has become epidemic. Longstanding hypertension and diabetes mellitus, both associated with obesity, further increase the risk of stroke.

Stroke can happen at any time. The clinical presentation is similar to that seen in nonpregnant patients; however, these symptoms can mimic those seen in preeclampsia and eclampsia, and the possibility of stroke may be overlooked.

Another potential delay in diagnosis and treatment may arise in patients who, like many nonpregnant patients, hesitate to seek immediate medical care when experiencing symptoms of stroke. Headache, for example, is common in pregnancy. Some women do not take it seriously unless it is very severe.

It is prudent to counsel all patients—and especially those with relevant risk factors—to seek care for any symptom that may be associated with stroke: headache; visual changes; epigastric pain; seizures; nausea and vomiting; or neurologic defects (focal or global). Severe hypertension and widened pulse pressures are symptomatic of stroke as well.

Cerebrovascular events may be associated with drug ingestion, infection, neoplasms, or trauma, as well as with metabolic factors. Researchers have been unable to determine the etiology of stroke in 23%–32% of cases.

Many medical conditions increase the risk of stroke, including cardioembolic diseases such as rheumatic heart disease or atrial septal defects; atherosclerosis (which may account for 15%–25% of cerebral infarctions in pregnancy); and disorders such as sickle cell disease, thrombophilias, central venous thrombosis, arteriovenous malformations and aneurysms, and cerebral vasoconstrictive syndrome.

Risk factors believed to be associated with pregnancy and the postpartum period include cesarean delivery and pregnancy-related hypertension. The link to hypertensive disorders of pregnancy seems to be an association in numerous studies, yet it is important to recognize that hypertension may be the result of a stroke rather than its cause. Seizures and central neurologic insult can undermine cerebral autoregulation and cause blood pressure to rise. Eclampsia and stroke produce similar clinical laboratory and neuroimaging findings.

Review of Stroke Cases

In a review of our 20-year institutional experience with postpartum stroke, we identified 20 cases among 130,000 deliveries at the E.H. Crump Women's Hospital of the University of Tennessee in Memphis (Am. J. Obstet. Gynecol. 2000;183:83–8).

In all cases, patients were discharged and later readmitted with findings consistent with a diagnosis of stroke. The mean age of these patients was 26 years; the mean gestational age at delivery was 27.3 weeks; and the mean birthweight was 2,617 grams, representing a group of patients with earlier deliveries and lower birthweights who were somewhat older than our obstetric population in general.

Of these 20 patients, 6 had a history of chronic hypertension. Preeclampsia was present in four pregnancies, and eight patients (40%) underwent a cesarean delivery, a rate approximately threefold higher than that in our overall obstetric population.

C-sections were performed for various reasons: three for nonreassuring fetal status, three for failure to progress, one for malpresentation, and one as an elective repeat C-section. Importantly, no intrapartum or postpartum complications presaged stroke in any patient. A review of antepartum, intrapartum, and in-hospital postpartum blood pressure values found normal measurements or well-controlled blood pressure in all women except one, whose blood pressure was elevated on postpartum day 3.

We found no correlation among trial of labor, mode of delivery, and the type of stroke suffered or outcome. We found no association with anesthesia type and stroke.

Presenting symptoms included headache in 16 patients, neurologic signs (motor weakness, blindness, aphasia, or coma) in 12, seizures in 11, and visual changes in 10.

Two deaths occurred, one associated with a cocaine-related hemorrhage and the other with a ruptured anatomical malformation.

A review of the medical records suggested that no case could have been prevented by the recognition of risk factors or alternative medical care.

In the diagnosis of stroke, the history and physical examination are critically important, although imaging is often needed to further clarify the diagnosis and distinguish stroke type and features.

The two basic causes of stroke are ischemia and postpartum hemorrhage.

Ischemia (infarction) may be caused by vascular thrombosis, embolism, vasospasm, or marked reduction in systemic perfusion pressure (hypotensive ischemic injury).

Postpartum Hemorrhage

Postpartum hemorrhage is divided into intracerebral or subarachnoid hemorrhage. Intracerebral hemorrhage refers to bleeding directly into brain tissue from small intracerebral vessels, caused by severe hypertension and/or coagulopathy or vascular malformations. In subarachnoid hemorrhage, blood seeps onto the brain's surface and merges with ambient cerebrospinal fluid, often as a result of a ruptured aneurysm or arteriovenous malformation.

Strokes of arterial origin most often occur during the second or third trimester, or within the first few weeks post partum. Symptoms include acute decompensation of cortical function, aphasia, hemiplegia, and/or hemianopsia.

Strokes of venous origin, on the other hand, are most likely to occur from 3 days to 4 weeks after delivery. Common symptoms include a severe, progressive headache; papilledema; weakness; convulsions; and/or aphasia.

Our review of 20 postpartum cases involved cerebritis (12 women), venous infarction (7 women), arterial infarction (6), intracerebral hemorrhage (5), and atrophy (1).

Among the 18 patients who survived, 12 suffered no residual defects, whereas others suffered hemiparesis, aphasia, or weakness. Although not statistically significant, there appeared to be a trend toward more adverse outcomes in women who suffered intracerebral hemorrhage vs. cerebral infarction.

Neuroimaging studies should be performed in any patient with symptoms that may be consistent with stroke. CT is widely available and may be very useful in confirming the diagnosis; however, a negative CT should not rule out further testing in the face of suspicious symptoms and/or physical examination findings. In our series, the initial CT was negative in 3 of 20 patients, with subsequent MRI or MRI angiography required to accurately diagnose stroke and elucidate its features.

Four-vessel traditional angiography, echocardiography, and lumbar puncture are other diagnostic modalities.

Of course, appropriate consultation is an integral part of stroke management, and may include a maternal-fetal medicine specialist as well as neurologists, neurosurgeons, radiologists, anesthesiologists, and later, rehabilitation specialists, social workers, and physical and occupational therapists.

Treatment hinges on protecting salvageable brain tissue; stabilizing the patient and preventing further complications such as aspiration; controlling blood pressure and other physiologic factors; and initiating physical rehabilitation.

As evidenced in our series, young patients have a great capacity for recovery in many cases.

My overall recommendation for stroke management is to admit the patient to labor and delivery, perform a thorough maternal and fetal evaluation, and use a multidisciplinary approach to care throughout.

Order antihypertensive medication if the systolic blood pressure is 160 mm Hg or greater, the diastolic blood pressure is 110 mm Hg or greater, or if the mean arterial pressure is 125 mm Hg or greater. Antiseizure, antiemetic, and anticoagulation medications should be administered as needed.

Neither medications nor surgery should be withheld because of pregnancy.

Deliver the patient in cases of maternal instability or nonreassuring fetal status; labor or rupture of membranes; or gestational age greater than 34 weeks.

When Intervention Is Necessary

At a gestational age of less than 24 weeks, intervention should be guided by the woman's diagnosis and condition.

Between 24 and 32 weeks' gestation, administer steroids for fetal lung maturity and conduct daily reassessments of the maternal and fetal condition with a planned delivery at 34 weeks, or term delivery if circumstances warrant.

Between 33 and 34 weeks, steroids should be administered and the baby delivered.

The nature of the stroke will determine the best course of medical and surgical management for the cerebrovascular event.

When anticoagulation is needed, keep in mind that warfarin crosses the placenta and has been linked to teratogenicity in the first trimester and bleeding complications in the third trimester. Heparin has been associated with thrombocytopenia, osteoporosis, and bleeding disorders, although it does not cross the placenta. After vaginal delivery, I recommend withholding anticoagulation for 6 hours. I recommend withholding anticoagulation for 12 hours following C-section.

When infection is implicated in stroke, antibiotics should be administered along with anticoagulation.

Low-dose aspirin may be sufficient to treat patients with a single episode of transient ischemic attack.

Hypertensive encephalopathy requires intensive management during labor and for 48 hours post partum. Response to antihypertensive therapy confirms the diagnosis. Volume contraction may be present, evidenced by a sharp drop in diastolic blood pressure and a rise in heart rate on standing from the supine position. Normal saline infusion for 24–48 hours may be considered to achieve volume expansion, decrease the activity of the renin-angiotensin-aldosterone axis, and maintain better blood pressure control. Careful attention should be paid to volume status, blood pressure urinary output, electrocardiographic readings, and mental status. Antepartum patients should have continuous fetal monitoring.

Eclampsia is treated with supportive care, including oxygenation; minimization of aspiration and future injuries; and lowering of blood pressure. Magnesium sulfate is used for the prevention of eclamptic seizures, although seizures may persist in 10% of patients. The medication should be maintained throughout labor and for 24 hours post partum.

Disturbances in the fetal heart rate are commonly seen after an eclamptic seizure, although resolution usually occurs within 5–10 minutes. Proceed to cesarean delivery only for obstetric indications, as vaginal delivery is preferred following a seizure.

Labor can be induced with oxytocin or prostaglandins.

Carefully monitor the patient's overall fluid status. These patients may have profound hemoconcentration, which necessitates close hemodynamic monitoring when epidural anesthesia is used and after severe blood loss. Acute blood loss can be a serious complication in hypovolemic patients. Limit fluids to prevent pulmonary edema secondary to capillary leakage.

Thrombolytic therapy with intraarterial recombinant tissue plasminogen activator has been used to treat ischemic stroke in pregnancy. This treatment must be administered within a window of 6 hours or less to be effective.

Course of Treatment

Patients who receive a diagnosis of arteriovenous malformation or aneurysm before hemorrhage should be referred for surgical embolization or clipping, as it is believed that patients with AVM may be at increased risk of bleeding during pregnancy. Patients with AVMs are also prone to bleed during delivery.

Once an intracerebral hemorrhage has occurred, the extent of the bleeding will determine the course of treatment. If the brain stem is compromised, surgical decompression is necessary. Surgery may also be necessary if the bleed is subarachnoid in origin; however, surgery itself may damage overlying normal brain tissue, and surgical morbidity is high.

If the bleeding and the patient are stable, surgery can be avoided. Blood pressure should be well controlled and seizures prevented. Steroids have not proven beneficial.

In summary, I would encourage obstetricians to become well versed in the symptoms of stroke and to have a low threshold for clinical suspicion of such symptoms, which may mimic common complaints of pregnancy.

A rapid diagnosis and close consultation with an interdisciplinary team of colleagues may maximizing outcome in patients suffering one of the most feared and serious complications of pregnancy.

This CT shows the brain of a pregnant woman who had a hemorrhagic stroke.

This MRI shows the brain of a pregnant woman who had an ischemic stroke. Photos courtesy Dr. Baha Sibai

How to Weigh Stroke History, Pregnancy

With enhanced diagnosis and management of stroke, more patients are recovering well. These patients will increasingly seek advice about the risks of subsequent pregnancy.

We recently conducted a review of 35 pregnancies in 23 women with a history of stroke, including 9 pregnancies in 4 women whose previous stroke had occurred during pregnancy or the postpartum period (Am. J. Obstet. Gynecol. 2004;190:1331–4).

Their risk factors for the prior stroke included thrombophilias, sickle cell disease, cardiac malformations, hypertension, oral contraceptive use, cerebral arteriovenous malformations, head trauma, meningitis, endocarditis, and idiopathic etiologies.

Anticoagulation was prescribed in two pregnancies in patients who had a reported history of pregnancy/postpartum stroke. Our findings were reassuring.

There were no recurrent thrombotic episodes during pregnancy or the postpartum period, although one patient required admission to the ICU for uncontrolled hypertension.

This result aligns with findings from another study (Neurology 2000;55:269–74), which found a 1% recurrence rate. The chance of recurrence in patients with thrombophilia is likely higher, perhaps 20%.

It makes sense to prescribe anticoagulation for women at risk of thromboembolic stroke, either low-dose aspirin plus prophylactic doses of unfractionated heparin, or low-molecular-weight heparin.

All women with a history of stroke deserve close monitoring during pregnancy, delivery, and the postpartum period.

Recognizing Stroke Is a Life or Death Issue

In high-risk obstetrics, we are faced with a variety of critical presentations: threatened early pregnancy loss, pregnant patients with preexisting medical conditions, and the development of acute medical complications during pregnancy.

Fortunately, the most serious complications of pregnancy—seizures, myocardial infarctions, and cerebrovascular events—are rare.

Despite their infrequency, we must become sufficiently familiar with the presenting symptoms of these life-threatening complications of pregnancy to be able to employ our clinical skills at a moment's notice.

Recent advances in stroke management make quick action vital. Medications or surgery not only may save the lives of the woman and fetus, but may preserve brain function in the woman as well.

Very often, but not always, clues to the possibility of a stroke may lie in the woman's medical history of hypertension, preeclampsia, seizures, or a bleeding disorder.

We need to be alert to these risk factors for stroke, and make sure that we include stroke in the differential diagnosis even when the patient's symptoms may be masquerading as less serious complications of pregnancy.

This month, my guest Master Class professor is Baha Sibai, M.D., a world expert on hypertensive disorders and complications in pregnancy who has authored or coauthored more than 350 peer-reviewed publications on the topics of preeclampsia and eclampsia.

Dr. Sibai is professor and director of the department of obstetrics and gynecology at the University of Cincinnati. He formerly directed the division of maternal/fetal medicine at the University of Tennessee, Memphis.

DR. REECE, who specializes in maternal-fetal medicine, is the vice chancellor and dean of the college of medicine at the University of Arkansas in Little Rock.

E. ALBERT REECE, M.D., PH.D., M.B.A.

Stroke is a rare but potentially devastating occurrence during pregnancy and the postpartum period. Maternal mortality is reported to be as high as 26%, and survivors may face long-term neurologic sequelae. Associated fetal mortality and morbidity also remain high. Although stroke is not preventable, early intervention can be key to saving lives and preserving brain function in some patients.

Therefore, even if the likelihood is that an obstetrician will never encounter a patient who suffers a stroke, it is critical that we all make the diagnosis promptly, obtain neurologic and other consultations appropriately, and direct state-of-the-art treatment of cerebrovascular disorders in this special population.

It is important to recognize that stroke occurs in young women of childbearing age at a rate of 10.7 per 100,000. Some have postulated that the risk is elevated during pregnancy for a number of reasons, including hypercoagulability, venous stasis, and blood pressure fluctuations. Indeed, some estimate that the risk of stroke is 13-fold higher in pregnant than in nonpregnant women, although the rarity of the condition makes the true prevalence a matter of debate.

Postpartum Risk Is Higher

The risk of stroke in the postpartum period is almost certainly higher still. Postpartum strokes generally occur from 5 days to 2 weeks after delivery—a vulnerable time when a headache from cerebral vasoconstriction syndrome may be mistaken for postepidural puncture syndrome.

The issue of stroke during pregnancy and the postpartum period is of increasing relevance to obstetricians. The incidence of stroke rises with age, and women are becoming pregnant at older ages than ever before; obstetric patients aged 45–50 years have become increasingly common. Obesity is also a risk factor for stroke, and pregnant women mirror American society at large, in which obesity has become epidemic. Longstanding hypertension and diabetes mellitus, both associated with obesity, further increase the risk of stroke.

Stroke can happen at any time. The clinical presentation is similar to that seen in nonpregnant patients; however, these symptoms can mimic those seen in preeclampsia and eclampsia, and the possibility of stroke may be overlooked.

Another potential delay in diagnosis and treatment may arise in patients who, like many nonpregnant patients, hesitate to seek immediate medical care when experiencing symptoms of stroke. Headache, for example, is common in pregnancy. Some women do not take it seriously unless it is very severe.

It is prudent to counsel all patients—and especially those with relevant risk factors—to seek care for any symptom that may be associated with stroke: headache; visual changes; epigastric pain; seizures; nausea and vomiting; or neurologic defects (focal or global). Severe hypertension and widened pulse pressures are symptomatic of stroke as well.

Cerebrovascular events may be associated with drug ingestion, infection, neoplasms, or trauma, as well as with metabolic factors. Researchers have been unable to determine the etiology of stroke in 23%–32% of cases.

Many medical conditions increase the risk of stroke, including cardioembolic diseases such as rheumatic heart disease or atrial septal defects; atherosclerosis (which may account for 15%–25% of cerebral infarctions in pregnancy); and disorders such as sickle cell disease, thrombophilias, central venous thrombosis, arteriovenous malformations and aneurysms, and cerebral vasoconstrictive syndrome.

Risk factors believed to be associated with pregnancy and the postpartum period include cesarean delivery and pregnancy-related hypertension. The link to hypertensive disorders of pregnancy seems to be an association in numerous studies, yet it is important to recognize that hypertension may be the result of a stroke rather than its cause. Seizures and central neurologic insult can undermine cerebral autoregulation and cause blood pressure to rise. Eclampsia and stroke produce similar clinical laboratory and neuroimaging findings.

Review of Stroke Cases

In a review of our 20-year institutional experience with postpartum stroke, we identified 20 cases among 130,000 deliveries at the E.H. Crump Women's Hospital of the University of Tennessee in Memphis (Am. J. Obstet. Gynecol. 2000;183:83–8).

In all cases, patients were discharged and later readmitted with findings consistent with a diagnosis of stroke. The mean age of these patients was 26 years; the mean gestational age at delivery was 27.3 weeks; and the mean birthweight was 2,617 grams, representing a group of patients with earlier deliveries and lower birthweights who were somewhat older than our obstetric population in general.

Of these 20 patients, 6 had a history of chronic hypertension. Preeclampsia was present in four pregnancies, and eight patients (40%) underwent a cesarean delivery, a rate approximately threefold higher than that in our overall obstetric population.

C-sections were performed for various reasons: three for nonreassuring fetal status, three for failure to progress, one for malpresentation, and one as an elective repeat C-section. Importantly, no intrapartum or postpartum complications presaged stroke in any patient. A review of antepartum, intrapartum, and in-hospital postpartum blood pressure values found normal measurements or well-controlled blood pressure in all women except one, whose blood pressure was elevated on postpartum day 3.

We found no correlation among trial of labor, mode of delivery, and the type of stroke suffered or outcome. We found no association with anesthesia type and stroke.

Presenting symptoms included headache in 16 patients, neurologic signs (motor weakness, blindness, aphasia, or coma) in 12, seizures in 11, and visual changes in 10.

Two deaths occurred, one associated with a cocaine-related hemorrhage and the other with a ruptured anatomical malformation.

A review of the medical records suggested that no case could have been prevented by the recognition of risk factors or alternative medical care.

In the diagnosis of stroke, the history and physical examination are critically important, although imaging is often needed to further clarify the diagnosis and distinguish stroke type and features.

The two basic causes of stroke are ischemia and postpartum hemorrhage.

Ischemia (infarction) may be caused by vascular thrombosis, embolism, vasospasm, or marked reduction in systemic perfusion pressure (hypotensive ischemic injury).

Postpartum Hemorrhage

Postpartum hemorrhage is divided into intracerebral or subarachnoid hemorrhage. Intracerebral hemorrhage refers to bleeding directly into brain tissue from small intracerebral vessels, caused by severe hypertension and/or coagulopathy or vascular malformations. In subarachnoid hemorrhage, blood seeps onto the brain's surface and merges with ambient cerebrospinal fluid, often as a result of a ruptured aneurysm or arteriovenous malformation.

Strokes of arterial origin most often occur during the second or third trimester, or within the first few weeks post partum. Symptoms include acute decompensation of cortical function, aphasia, hemiplegia, and/or hemianopsia.

Strokes of venous origin, on the other hand, are most likely to occur from 3 days to 4 weeks after delivery. Common symptoms include a severe, progressive headache; papilledema; weakness; convulsions; and/or aphasia.

Our review of 20 postpartum cases involved cerebritis (12 women), venous infarction (7 women), arterial infarction (6), intracerebral hemorrhage (5), and atrophy (1).

Among the 18 patients who survived, 12 suffered no residual defects, whereas others suffered hemiparesis, aphasia, or weakness. Although not statistically significant, there appeared to be a trend toward more adverse outcomes in women who suffered intracerebral hemorrhage vs. cerebral infarction.

Neuroimaging studies should be performed in any patient with symptoms that may be consistent with stroke. CT is widely available and may be very useful in confirming the diagnosis; however, a negative CT should not rule out further testing in the face of suspicious symptoms and/or physical examination findings. In our series, the initial CT was negative in 3 of 20 patients, with subsequent MRI or MRI angiography required to accurately diagnose stroke and elucidate its features.

Four-vessel traditional angiography, echocardiography, and lumbar puncture are other diagnostic modalities.

Of course, appropriate consultation is an integral part of stroke management, and may include a maternal-fetal medicine specialist as well as neurologists, neurosurgeons, radiologists, anesthesiologists, and later, rehabilitation specialists, social workers, and physical and occupational therapists.

Treatment hinges on protecting salvageable brain tissue; stabilizing the patient and preventing further complications such as aspiration; controlling blood pressure and other physiologic factors; and initiating physical rehabilitation.

As evidenced in our series, young patients have a great capacity for recovery in many cases.

My overall recommendation for stroke management is to admit the patient to labor and delivery, perform a thorough maternal and fetal evaluation, and use a multidisciplinary approach to care throughout.

Order antihypertensive medication if the systolic blood pressure is 160 mm Hg or greater, the diastolic blood pressure is 110 mm Hg or greater, or if the mean arterial pressure is 125 mm Hg or greater. Antiseizure, antiemetic, and anticoagulation medications should be administered as needed.

Neither medications nor surgery should be withheld because of pregnancy.

Deliver the patient in cases of maternal instability or nonreassuring fetal status; labor or rupture of membranes; or gestational age greater than 34 weeks.

When Intervention Is Necessary

At a gestational age of less than 24 weeks, intervention should be guided by the woman's diagnosis and condition.

Between 24 and 32 weeks' gestation, administer steroids for fetal lung maturity and conduct daily reassessments of the maternal and fetal condition with a planned delivery at 34 weeks, or term delivery if circumstances warrant.

Between 33 and 34 weeks, steroids should be administered and the baby delivered.

The nature of the stroke will determine the best course of medical and surgical management for the cerebrovascular event.

When anticoagulation is needed, keep in mind that warfarin crosses the placenta and has been linked to teratogenicity in the first trimester and bleeding complications in the third trimester. Heparin has been associated with thrombocytopenia, osteoporosis, and bleeding disorders, although it does not cross the placenta. After vaginal delivery, I recommend withholding anticoagulation for 6 hours. I recommend withholding anticoagulation for 12 hours following C-section.

When infection is implicated in stroke, antibiotics should be administered along with anticoagulation.

Low-dose aspirin may be sufficient to treat patients with a single episode of transient ischemic attack.

Hypertensive encephalopathy requires intensive management during labor and for 48 hours post partum. Response to antihypertensive therapy confirms the diagnosis. Volume contraction may be present, evidenced by a sharp drop in diastolic blood pressure and a rise in heart rate on standing from the supine position. Normal saline infusion for 24–48 hours may be considered to achieve volume expansion, decrease the activity of the renin-angiotensin-aldosterone axis, and maintain better blood pressure control. Careful attention should be paid to volume status, blood pressure urinary output, electrocardiographic readings, and mental status. Antepartum patients should have continuous fetal monitoring.

Eclampsia is treated with supportive care, including oxygenation; minimization of aspiration and future injuries; and lowering of blood pressure. Magnesium sulfate is used for the prevention of eclamptic seizures, although seizures may persist in 10% of patients. The medication should be maintained throughout labor and for 24 hours post partum.

Disturbances in the fetal heart rate are commonly seen after an eclamptic seizure, although resolution usually occurs within 5–10 minutes. Proceed to cesarean delivery only for obstetric indications, as vaginal delivery is preferred following a seizure.

Labor can be induced with oxytocin or prostaglandins.

Carefully monitor the patient's overall fluid status. These patients may have profound hemoconcentration, which necessitates close hemodynamic monitoring when epidural anesthesia is used and after severe blood loss. Acute blood loss can be a serious complication in hypovolemic patients. Limit fluids to prevent pulmonary edema secondary to capillary leakage.

Thrombolytic therapy with intraarterial recombinant tissue plasminogen activator has been used to treat ischemic stroke in pregnancy. This treatment must be administered within a window of 6 hours or less to be effective.

Course of Treatment

Patients who receive a diagnosis of arteriovenous malformation or aneurysm before hemorrhage should be referred for surgical embolization or clipping, as it is believed that patients with AVM may be at increased risk of bleeding during pregnancy. Patients with AVMs are also prone to bleed during delivery.

Once an intracerebral hemorrhage has occurred, the extent of the bleeding will determine the course of treatment. If the brain stem is compromised, surgical decompression is necessary. Surgery may also be necessary if the bleed is subarachnoid in origin; however, surgery itself may damage overlying normal brain tissue, and surgical morbidity is high.

If the bleeding and the patient are stable, surgery can be avoided. Blood pressure should be well controlled and seizures prevented. Steroids have not proven beneficial.

In summary, I would encourage obstetricians to become well versed in the symptoms of stroke and to have a low threshold for clinical suspicion of such symptoms, which may mimic common complaints of pregnancy.

A rapid diagnosis and close consultation with an interdisciplinary team of colleagues may maximizing outcome in patients suffering one of the most feared and serious complications of pregnancy.

This CT shows the brain of a pregnant woman who had a hemorrhagic stroke.

This MRI shows the brain of a pregnant woman who had an ischemic stroke. Photos courtesy Dr. Baha Sibai

How to Weigh Stroke History, Pregnancy

With enhanced diagnosis and management of stroke, more patients are recovering well. These patients will increasingly seek advice about the risks of subsequent pregnancy.

We recently conducted a review of 35 pregnancies in 23 women with a history of stroke, including 9 pregnancies in 4 women whose previous stroke had occurred during pregnancy or the postpartum period (Am. J. Obstet. Gynecol. 2004;190:1331–4).

Their risk factors for the prior stroke included thrombophilias, sickle cell disease, cardiac malformations, hypertension, oral contraceptive use, cerebral arteriovenous malformations, head trauma, meningitis, endocarditis, and idiopathic etiologies.

Anticoagulation was prescribed in two pregnancies in patients who had a reported history of pregnancy/postpartum stroke. Our findings were reassuring.

There were no recurrent thrombotic episodes during pregnancy or the postpartum period, although one patient required admission to the ICU for uncontrolled hypertension.

This result aligns with findings from another study (Neurology 2000;55:269–74), which found a 1% recurrence rate. The chance of recurrence in patients with thrombophilia is likely higher, perhaps 20%.

It makes sense to prescribe anticoagulation for women at risk of thromboembolic stroke, either low-dose aspirin plus prophylactic doses of unfractionated heparin, or low-molecular-weight heparin.

All women with a history of stroke deserve close monitoring during pregnancy, delivery, and the postpartum period.

Recognizing Stroke Is a Life or Death Issue

In high-risk obstetrics, we are faced with a variety of critical presentations: threatened early pregnancy loss, pregnant patients with preexisting medical conditions, and the development of acute medical complications during pregnancy.

Fortunately, the most serious complications of pregnancy—seizures, myocardial infarctions, and cerebrovascular events—are rare.

Despite their infrequency, we must become sufficiently familiar with the presenting symptoms of these life-threatening complications of pregnancy to be able to employ our clinical skills at a moment's notice.

Recent advances in stroke management make quick action vital. Medications or surgery not only may save the lives of the woman and fetus, but may preserve brain function in the woman as well.

Very often, but not always, clues to the possibility of a stroke may lie in the woman's medical history of hypertension, preeclampsia, seizures, or a bleeding disorder.

We need to be alert to these risk factors for stroke, and make sure that we include stroke in the differential diagnosis even when the patient's symptoms may be masquerading as less serious complications of pregnancy.

This month, my guest Master Class professor is Baha Sibai, M.D., a world expert on hypertensive disorders and complications in pregnancy who has authored or coauthored more than 350 peer-reviewed publications on the topics of preeclampsia and eclampsia.

Dr. Sibai is professor and director of the department of obstetrics and gynecology at the University of Cincinnati. He formerly directed the division of maternal/fetal medicine at the University of Tennessee, Memphis.

DR. REECE, who specializes in maternal-fetal medicine, is the vice chancellor and dean of the college of medicine at the University of Arkansas in Little Rock.

E. ALBERT REECE, M.D., PH.D., M.B.A.

Stroke is a rare but potentially devastating occurrence during pregnancy and the postpartum period. Maternal mortality is reported to be as high as 26%, and survivors may face long-term neurologic sequelae. Associated fetal mortality and morbidity also remain high. Although stroke is not preventable, early intervention can be key to saving lives and preserving brain function in some patients.

Therefore, even if the likelihood is that an obstetrician will never encounter a patient who suffers a stroke, it is critical that we all make the diagnosis promptly, obtain neurologic and other consultations appropriately, and direct state-of-the-art treatment of cerebrovascular disorders in this special population.

It is important to recognize that stroke occurs in young women of childbearing age at a rate of 10.7 per 100,000. Some have postulated that the risk is elevated during pregnancy for a number of reasons, including hypercoagulability, venous stasis, and blood pressure fluctuations. Indeed, some estimate that the risk of stroke is 13-fold higher in pregnant than in nonpregnant women, although the rarity of the condition makes the true prevalence a matter of debate.

Postpartum Risk Is Higher

The risk of stroke in the postpartum period is almost certainly higher still. Postpartum strokes generally occur from 5 days to 2 weeks after delivery—a vulnerable time when a headache from cerebral vasoconstriction syndrome may be mistaken for postepidural puncture syndrome.

The issue of stroke during pregnancy and the postpartum period is of increasing relevance to obstetricians. The incidence of stroke rises with age, and women are becoming pregnant at older ages than ever before; obstetric patients aged 45–50 years have become increasingly common. Obesity is also a risk factor for stroke, and pregnant women mirror American society at large, in which obesity has become epidemic. Longstanding hypertension and diabetes mellitus, both associated with obesity, further increase the risk of stroke.

Stroke can happen at any time. The clinical presentation is similar to that seen in nonpregnant patients; however, these symptoms can mimic those seen in preeclampsia and eclampsia, and the possibility of stroke may be overlooked.

Another potential delay in diagnosis and treatment may arise in patients who, like many nonpregnant patients, hesitate to seek immediate medical care when experiencing symptoms of stroke. Headache, for example, is common in pregnancy. Some women do not take it seriously unless it is very severe.

It is prudent to counsel all patients—and especially those with relevant risk factors—to seek care for any symptom that may be associated with stroke: headache; visual changes; epigastric pain; seizures; nausea and vomiting; or neurologic defects (focal or global). Severe hypertension and widened pulse pressures are symptomatic of stroke as well.

Cerebrovascular events may be associated with drug ingestion, infection, neoplasms, or trauma, as well as with metabolic factors. Researchers have been unable to determine the etiology of stroke in 23%–32% of cases.

Many medical conditions increase the risk of stroke, including cardioembolic diseases such as rheumatic heart disease or atrial septal defects; atherosclerosis (which may account for 15%–25% of cerebral infarctions in pregnancy); and disorders such as sickle cell disease, thrombophilias, central venous thrombosis, arteriovenous malformations and aneurysms, and cerebral vasoconstrictive syndrome.

Risk factors believed to be associated with pregnancy and the postpartum period include cesarean delivery and pregnancy-related hypertension. The link to hypertensive disorders of pregnancy seems to be an association in numerous studies, yet it is important to recognize that hypertension may be the result of a stroke rather than its cause. Seizures and central neurologic insult can undermine cerebral autoregulation and cause blood pressure to rise. Eclampsia and stroke produce similar clinical laboratory and neuroimaging findings.

Review of Stroke Cases

In a review of our 20-year institutional experience with postpartum stroke, we identified 20 cases among 130,000 deliveries at the E.H. Crump Women's Hospital of the University of Tennessee in Memphis (Am. J. Obstet. Gynecol. 2000;183:83–8).

In all cases, patients were discharged and later readmitted with findings consistent with a diagnosis of stroke. The mean age of these patients was 26 years; the mean gestational age at delivery was 27.3 weeks; and the mean birthweight was 2,617 grams, representing a group of patients with earlier deliveries and lower birthweights who were somewhat older than our obstetric population in general.

Of these 20 patients, 6 had a history of chronic hypertension. Preeclampsia was present in four pregnancies, and eight patients (40%) underwent a cesarean delivery, a rate approximately threefold higher than that in our overall obstetric population.

C-sections were performed for various reasons: three for nonreassuring fetal status, three for failure to progress, one for malpresentation, and one as an elective repeat C-section. Importantly, no intrapartum or postpartum complications presaged stroke in any patient. A review of antepartum, intrapartum, and in-hospital postpartum blood pressure values found normal measurements or well-controlled blood pressure in all women except one, whose blood pressure was elevated on postpartum day 3.

We found no correlation among trial of labor, mode of delivery, and the type of stroke suffered or outcome. We found no association with anesthesia type and stroke.

Presenting symptoms included headache in 16 patients, neurologic signs (motor weakness, blindness, aphasia, or coma) in 12, seizures in 11, and visual changes in 10.

Two deaths occurred, one associated with a cocaine-related hemorrhage and the other with a ruptured anatomical malformation.

A review of the medical records suggested that no case could have been prevented by the recognition of risk factors or alternative medical care.

In the diagnosis of stroke, the history and physical examination are critically important, although imaging is often needed to further clarify the diagnosis and distinguish stroke type and features.

The two basic causes of stroke are ischemia and postpartum hemorrhage.

Ischemia (infarction) may be caused by vascular thrombosis, embolism, vasospasm, or marked reduction in systemic perfusion pressure (hypotensive ischemic injury).

Postpartum Hemorrhage

Postpartum hemorrhage is divided into intracerebral or subarachnoid hemorrhage. Intracerebral hemorrhage refers to bleeding directly into brain tissue from small intracerebral vessels, caused by severe hypertension and/or coagulopathy or vascular malformations. In subarachnoid hemorrhage, blood seeps onto the brain's surface and merges with ambient cerebrospinal fluid, often as a result of a ruptured aneurysm or arteriovenous malformation.

Strokes of arterial origin most often occur during the second or third trimester, or within the first few weeks post partum. Symptoms include acute decompensation of cortical function, aphasia, hemiplegia, and/or hemianopsia.

Strokes of venous origin, on the other hand, are most likely to occur from 3 days to 4 weeks after delivery. Common symptoms include a severe, progressive headache; papilledema; weakness; convulsions; and/or aphasia.

Our review of 20 postpartum cases involved cerebritis (12 women), venous infarction (7 women), arterial infarction (6), intracerebral hemorrhage (5), and atrophy (1).

Among the 18 patients who survived, 12 suffered no residual defects, whereas others suffered hemiparesis, aphasia, or weakness. Although not statistically significant, there appeared to be a trend toward more adverse outcomes in women who suffered intracerebral hemorrhage vs. cerebral infarction.

Neuroimaging studies should be performed in any patient with symptoms that may be consistent with stroke. CT is widely available and may be very useful in confirming the diagnosis; however, a negative CT should not rule out further testing in the face of suspicious symptoms and/or physical examination findings. In our series, the initial CT was negative in 3 of 20 patients, with subsequent MRI or MRI angiography required to accurately diagnose stroke and elucidate its features.

Four-vessel traditional angiography, echocardiography, and lumbar puncture are other diagnostic modalities.

Of course, appropriate consultation is an integral part of stroke management, and may include a maternal-fetal medicine specialist as well as neurologists, neurosurgeons, radiologists, anesthesiologists, and later, rehabilitation specialists, social workers, and physical and occupational therapists.

Treatment hinges on protecting salvageable brain tissue; stabilizing the patient and preventing further complications such as aspiration; controlling blood pressure and other physiologic factors; and initiating physical rehabilitation.

As evidenced in our series, young patients have a great capacity for recovery in many cases.

My overall recommendation for stroke management is to admit the patient to labor and delivery, perform a thorough maternal and fetal evaluation, and use a multidisciplinary approach to care throughout.

Order antihypertensive medication if the systolic blood pressure is 160 mm Hg or greater, the diastolic blood pressure is 110 mm Hg or greater, or if the mean arterial pressure is 125 mm Hg or greater. Antiseizure, antiemetic, and anticoagulation medications should be administered as needed.

Neither medications nor surgery should be withheld because of pregnancy.

Deliver the patient in cases of maternal instability or nonreassuring fetal status; labor or rupture of membranes; or gestational age greater than 34 weeks.

When Intervention Is Necessary

At a gestational age of less than 24 weeks, intervention should be guided by the woman's diagnosis and condition.

Between 24 and 32 weeks' gestation, administer steroids for fetal lung maturity and conduct daily reassessments of the maternal and fetal condition with a planned delivery at 34 weeks, or term delivery if circumstances warrant.

Between 33 and 34 weeks, steroids should be administered and the baby delivered.

The nature of the stroke will determine the best course of medical and surgical management for the cerebrovascular event.

When anticoagulation is needed, keep in mind that warfarin crosses the placenta and has been linked to teratogenicity in the first trimester and bleeding complications in the third trimester. Heparin has been associated with thrombocytopenia, osteoporosis, and bleeding disorders, although it does not cross the placenta. After vaginal delivery, I recommend withholding anticoagulation for 6 hours. I recommend withholding anticoagulation for 12 hours following C-section.

When infection is implicated in stroke, antibiotics should be administered along with anticoagulation.

Low-dose aspirin may be sufficient to treat patients with a single episode of transient ischemic attack.

Hypertensive encephalopathy requires intensive management during labor and for 48 hours post partum. Response to antihypertensive therapy confirms the diagnosis. Volume contraction may be present, evidenced by a sharp drop in diastolic blood pressure and a rise in heart rate on standing from the supine position. Normal saline infusion for 24–48 hours may be considered to achieve volume expansion, decrease the activity of the renin-angiotensin-aldosterone axis, and maintain better blood pressure control. Careful attention should be paid to volume status, blood pressure urinary output, electrocardiographic readings, and mental status. Antepartum patients should have continuous fetal monitoring.

Eclampsia is treated with supportive care, including oxygenation; minimization of aspiration and future injuries; and lowering of blood pressure. Magnesium sulfate is used for the prevention of eclamptic seizures, although seizures may persist in 10% of patients. The medication should be maintained throughout labor and for 24 hours post partum.

Disturbances in the fetal heart rate are commonly seen after an eclamptic seizure, although resolution usually occurs within 5–10 minutes. Proceed to cesarean delivery only for obstetric indications, as vaginal delivery is preferred following a seizure.

Labor can be induced with oxytocin or prostaglandins.

Carefully monitor the patient's overall fluid status. These patients may have profound hemoconcentration, which necessitates close hemodynamic monitoring when epidural anesthesia is used and after severe blood loss. Acute blood loss can be a serious complication in hypovolemic patients. Limit fluids to prevent pulmonary edema secondary to capillary leakage.

Thrombolytic therapy with intraarterial recombinant tissue plasminogen activator has been used to treat ischemic stroke in pregnancy. This treatment must be administered within a window of 6 hours or less to be effective.

Course of Treatment

Patients who receive a diagnosis of arteriovenous malformation or aneurysm before hemorrhage should be referred for surgical embolization or clipping, as it is believed that patients with AVM may be at increased risk of bleeding during pregnancy. Patients with AVMs are also prone to bleed during delivery.

Once an intracerebral hemorrhage has occurred, the extent of the bleeding will determine the course of treatment. If the brain stem is compromised, surgical decompression is necessary. Surgery may also be necessary if the bleed is subarachnoid in origin; however, surgery itself may damage overlying normal brain tissue, and surgical morbidity is high.

If the bleeding and the patient are stable, surgery can be avoided. Blood pressure should be well controlled and seizures prevented. Steroids have not proven beneficial.

In summary, I would encourage obstetricians to become well versed in the symptoms of stroke and to have a low threshold for clinical suspicion of such symptoms, which may mimic common complaints of pregnancy.

A rapid diagnosis and close consultation with an interdisciplinary team of colleagues may maximizing outcome in patients suffering one of the most feared and serious complications of pregnancy.

This CT shows the brain of a pregnant woman who had a hemorrhagic stroke.

This MRI shows the brain of a pregnant woman who had an ischemic stroke. Photos courtesy Dr. Baha Sibai

How to Weigh Stroke History, Pregnancy

With enhanced diagnosis and management of stroke, more patients are recovering well. These patients will increasingly seek advice about the risks of subsequent pregnancy.

We recently conducted a review of 35 pregnancies in 23 women with a history of stroke, including 9 pregnancies in 4 women whose previous stroke had occurred during pregnancy or the postpartum period (Am. J. Obstet. Gynecol. 2004;190:1331–4).

Their risk factors for the prior stroke included thrombophilias, sickle cell disease, cardiac malformations, hypertension, oral contraceptive use, cerebral arteriovenous malformations, head trauma, meningitis, endocarditis, and idiopathic etiologies.

Anticoagulation was prescribed in two pregnancies in patients who had a reported history of pregnancy/postpartum stroke. Our findings were reassuring.

There were no recurrent thrombotic episodes during pregnancy or the postpartum period, although one patient required admission to the ICU for uncontrolled hypertension.

This result aligns with findings from another study (Neurology 2000;55:269–74), which found a 1% recurrence rate. The chance of recurrence in patients with thrombophilia is likely higher, perhaps 20%.

It makes sense to prescribe anticoagulation for women at risk of thromboembolic stroke, either low-dose aspirin plus prophylactic doses of unfractionated heparin, or low-molecular-weight heparin.

All women with a history of stroke deserve close monitoring during pregnancy, delivery, and the postpartum period.

Recognizing Stroke Is a Life or Death Issue

In high-risk obstetrics, we are faced with a variety of critical presentations: threatened early pregnancy loss, pregnant patients with preexisting medical conditions, and the development of acute medical complications during pregnancy.

Fortunately, the most serious complications of pregnancy—seizures, myocardial infarctions, and cerebrovascular events—are rare.

Despite their infrequency, we must become sufficiently familiar with the presenting symptoms of these life-threatening complications of pregnancy to be able to employ our clinical skills at a moment's notice.

Recent advances in stroke management make quick action vital. Medications or surgery not only may save the lives of the woman and fetus, but may preserve brain function in the woman as well.

Very often, but not always, clues to the possibility of a stroke may lie in the woman's medical history of hypertension, preeclampsia, seizures, or a bleeding disorder.

We need to be alert to these risk factors for stroke, and make sure that we include stroke in the differential diagnosis even when the patient's symptoms may be masquerading as less serious complications of pregnancy.

This month, my guest Master Class professor is Baha Sibai, M.D., a world expert on hypertensive disorders and complications in pregnancy who has authored or coauthored more than 350 peer-reviewed publications on the topics of preeclampsia and eclampsia.

Dr. Sibai is professor and director of the department of obstetrics and gynecology at the University of Cincinnati. He formerly directed the division of maternal/fetal medicine at the University of Tennessee, Memphis.

DR. REECE, who specializes in maternal-fetal medicine, is the vice chancellor and dean of the college of medicine at the University of Arkansas in Little Rock.

E. ALBERT REECE, M.D., PH.D., M.B.A.