Mindy S. Christianson, MD

A recent study by Lee et al in the Journal of Obstetrics and Gynaecology Research evaluated the feasibility of robotic single-port myomectomy (RSPM) using the da Vinci SP surgical system. In this prospective observational study, 61 women with symptomatic fibroids underwent RSPM. In women with less than 7 resected uterine fibroids (maximal diameter < 10 cm) as well as those with at least 7 resected fibroids (maximal diameter of resected fibroids ≥10 cm), there was no conversion to single-port laparoscopic myomectomy, multiport laparoscopic myomectomy, or laparotomy. Reported complications were minor and included fever, transient ileus and blood transfusion in 15 patients. The authors proposed that robotic single-port myomectomy could solve many of the ergonomic problems associated with single-port laparoscopic myomectomy.

When performing myomectomy during C-section, is there a method that is advantageous? This question was evaluated by Karaca SY et al in European Journal of Obstetrics and Gynecology and Reproductive Biology who compared transendometrial myomectomy with conventional myomectomy. Overall, 41 patients underwent transendometrial myomectomy, and 52 patients underwent conventional myomectomy, with all patients having one single anterior intramural fibroid removed. The mean duration of surgery (50.5 minutes vs 63.6 minutes; P = .001) was lower in the transendometrial group versus the conventional myomectomy group. Additionally, patients who underwent transendometrial myomectomy (0.58 ± 0.61) had significantly lower adhesion scores in their subsequent pregnancy compared to patients who underwent conventional myomectomy (1,76 ± 1,1) (P = 0.001). Length of hospital stay, procedure-related hemoglobin difference, blood transfusion requirement, and postoperative fever were similar in both groups.

A recent study by Lee et al in the Journal of Obstetrics and Gynaecology Research evaluated the feasibility of robotic single-port myomectomy (RSPM) using the da Vinci SP surgical system. In this prospective observational study, 61 women with symptomatic fibroids underwent RSPM. In women with less than 7 resected uterine fibroids (maximal diameter < 10 cm) as well as those with at least 7 resected fibroids (maximal diameter of resected fibroids ≥10 cm), there was no conversion to single-port laparoscopic myomectomy, multiport laparoscopic myomectomy, or laparotomy. Reported complications were minor and included fever, transient ileus and blood transfusion in 15 patients. The authors proposed that robotic single-port myomectomy could solve many of the ergonomic problems associated with single-port laparoscopic myomectomy.

When performing myomectomy during C-section, is there a method that is advantageous? This question was evaluated by Karaca SY et al in European Journal of Obstetrics and Gynecology and Reproductive Biology who compared transendometrial myomectomy with conventional myomectomy. Overall, 41 patients underwent transendometrial myomectomy, and 52 patients underwent conventional myomectomy, with all patients having one single anterior intramural fibroid removed. The mean duration of surgery (50.5 minutes vs 63.6 minutes; P = .001) was lower in the transendometrial group versus the conventional myomectomy group. Additionally, patients who underwent transendometrial myomectomy (0.58 ± 0.61) had significantly lower adhesion scores in their subsequent pregnancy compared to patients who underwent conventional myomectomy (1,76 ± 1,1) (P = 0.001). Length of hospital stay, procedure-related hemoglobin difference, blood transfusion requirement, and postoperative fever were similar in both groups.

A recent study by Lee et al in the Journal of Obstetrics and Gynaecology Research evaluated the feasibility of robotic single-port myomectomy (RSPM) using the da Vinci SP surgical system. In this prospective observational study, 61 women with symptomatic fibroids underwent RSPM. In women with less than 7 resected uterine fibroids (maximal diameter < 10 cm) as well as those with at least 7 resected fibroids (maximal diameter of resected fibroids ≥10 cm), there was no conversion to single-port laparoscopic myomectomy, multiport laparoscopic myomectomy, or laparotomy. Reported complications were minor and included fever, transient ileus and blood transfusion in 15 patients. The authors proposed that robotic single-port myomectomy could solve many of the ergonomic problems associated with single-port laparoscopic myomectomy.

When performing myomectomy during C-section, is there a method that is advantageous? This question was evaluated by Karaca SY et al in European Journal of Obstetrics and Gynecology and Reproductive Biology who compared transendometrial myomectomy with conventional myomectomy. Overall, 41 patients underwent transendometrial myomectomy, and 52 patients underwent conventional myomectomy, with all patients having one single anterior intramural fibroid removed. The mean duration of surgery (50.5 minutes vs 63.6 minutes; P = .001) was lower in the transendometrial group versus the conventional myomectomy group. Additionally, patients who underwent transendometrial myomectomy (0.58 ± 0.61) had significantly lower adhesion scores in their subsequent pregnancy compared to patients who underwent conventional myomectomy (1,76 ± 1,1) (P = 0.001). Length of hospital stay, procedure-related hemoglobin difference, blood transfusion requirement, and postoperative fever were similar in both groups.

Mahalingam et al in the Journal of Maternal-Fetal & Neonatal Medicine reported the risk of preterm birth among women with uterine fibroids who underwent myomectomy versus those who did not prior to pregnancy. In this retrospective cohort study, the team evaluated 290 women with a viable intrauterine pregnancy and history of uterine fibroids and compared two groups: 70 with history of a prior myomectomy and 220 who did not undergo myomectomy and had at least 1 fibroid of size 5 cm or more detected at less than 21 weeks’ gestation. The team found that women who underwent prior myomectomy versus those who did not were more likely to deliver preterm < 37 weeks gestation (35% vs 21%; P = .02) and deliver a mean 1.4 weeks earlier (36.3±3.6 vs 37.7±3.7 weeks gestation; P = .02). Patients with history of myomectomy had a higher C-section rate (88% vs 53%, P < 0.001). However, when the authors controlled for late preterm pre-labor C-sections recommended by physicians in the myomectomy cohort (n=5), the difference in preterm birth was not significant between the groups.

Lee et al reported that MRI can potentially predict the benefit of GnRH-agonist treatment prior to for large fibroids. In this retrospective analysis published in Acta Radiologica, 30 patients with large uterine fibroids received GnRH agonist prior to uterine artery embolization (UAE) with MRI evaluation before and after treatment. Indications for GnRH-agonist treatment (monthly 3.75 mg leuprolide acetate injections) included intramural or subserosal fibroids > 10 cm in diameter or pedunculated submucosal fibroids > 8 cm, as well as contrast enhancement observed on T1-weighted (T1W) images. Mean maximum fibroid diameter was 11.1 + 1.9 cm and mean number of GnRH-agonist injections received was 2.8. Signal intensity (SI) of the predominant fibroid on T2-weighted (T2W) images was referenced to the SI of the rectus abdominus muscle (F/R). For predicting a volume reduction rate of the large fibroid of >50%, the optimal cut-off value of F/R was 2.58 (sensitivity 80%, specificity 80%). Likewise, large fibroids with a volume rate reduction of <30% had an optimal cut-off volume of 1.69 (sensitivity 100%, specificity 70%). From a clinical perspective, both surgeons and radiologists could use SI of the predominant fibroid on T2W to predict response to GnRH agonist pretreatment.

Mahalingam et al in the Journal of Maternal-Fetal & Neonatal Medicine reported the risk of preterm birth among women with uterine fibroids who underwent myomectomy versus those who did not prior to pregnancy. In this retrospective cohort study, the team evaluated 290 women with a viable intrauterine pregnancy and history of uterine fibroids and compared two groups: 70 with history of a prior myomectomy and 220 who did not undergo myomectomy and had at least 1 fibroid of size 5 cm or more detected at less than 21 weeks’ gestation. The team found that women who underwent prior myomectomy versus those who did not were more likely to deliver preterm < 37 weeks gestation (35% vs 21%; P = .02) and deliver a mean 1.4 weeks earlier (36.3±3.6 vs 37.7±3.7 weeks gestation; P = .02). Patients with history of myomectomy had a higher C-section rate (88% vs 53%, P < 0.001). However, when the authors controlled for late preterm pre-labor C-sections recommended by physicians in the myomectomy cohort (n=5), the difference in preterm birth was not significant between the groups.

Lee et al reported that MRI can potentially predict the benefit of GnRH-agonist treatment prior to for large fibroids. In this retrospective analysis published in Acta Radiologica, 30 patients with large uterine fibroids received GnRH agonist prior to uterine artery embolization (UAE) with MRI evaluation before and after treatment. Indications for GnRH-agonist treatment (monthly 3.75 mg leuprolide acetate injections) included intramural or subserosal fibroids > 10 cm in diameter or pedunculated submucosal fibroids > 8 cm, as well as contrast enhancement observed on T1-weighted (T1W) images. Mean maximum fibroid diameter was 11.1 + 1.9 cm and mean number of GnRH-agonist injections received was 2.8. Signal intensity (SI) of the predominant fibroid on T2-weighted (T2W) images was referenced to the SI of the rectus abdominus muscle (F/R). For predicting a volume reduction rate of the large fibroid of >50%, the optimal cut-off value of F/R was 2.58 (sensitivity 80%, specificity 80%). Likewise, large fibroids with a volume rate reduction of <30% had an optimal cut-off volume of 1.69 (sensitivity 100%, specificity 70%). From a clinical perspective, both surgeons and radiologists could use SI of the predominant fibroid on T2W to predict response to GnRH agonist pretreatment.

Mahalingam et al in the Journal of Maternal-Fetal & Neonatal Medicine reported the risk of preterm birth among women with uterine fibroids who underwent myomectomy versus those who did not prior to pregnancy. In this retrospective cohort study, the team evaluated 290 women with a viable intrauterine pregnancy and history of uterine fibroids and compared two groups: 70 with history of a prior myomectomy and 220 who did not undergo myomectomy and had at least 1 fibroid of size 5 cm or more detected at less than 21 weeks’ gestation. The team found that women who underwent prior myomectomy versus those who did not were more likely to deliver preterm < 37 weeks gestation (35% vs 21%; P = .02) and deliver a mean 1.4 weeks earlier (36.3±3.6 vs 37.7±3.7 weeks gestation; P = .02). Patients with history of myomectomy had a higher C-section rate (88% vs 53%, P < 0.001). However, when the authors controlled for late preterm pre-labor C-sections recommended by physicians in the myomectomy cohort (n=5), the difference in preterm birth was not significant between the groups.

Lee et al reported that MRI can potentially predict the benefit of GnRH-agonist treatment prior to for large fibroids. In this retrospective analysis published in Acta Radiologica, 30 patients with large uterine fibroids received GnRH agonist prior to uterine artery embolization (UAE) with MRI evaluation before and after treatment. Indications for GnRH-agonist treatment (monthly 3.75 mg leuprolide acetate injections) included intramural or subserosal fibroids > 10 cm in diameter or pedunculated submucosal fibroids > 8 cm, as well as contrast enhancement observed on T1-weighted (T1W) images. Mean maximum fibroid diameter was 11.1 + 1.9 cm and mean number of GnRH-agonist injections received was 2.8. Signal intensity (SI) of the predominant fibroid on T2-weighted (T2W) images was referenced to the SI of the rectus abdominus muscle (F/R). For predicting a volume reduction rate of the large fibroid of >50%, the optimal cut-off value of F/R was 2.58 (sensitivity 80%, specificity 80%). Likewise, large fibroids with a volume rate reduction of <30% had an optimal cut-off volume of 1.69 (sensitivity 100%, specificity 70%). From a clinical perspective, both surgeons and radiologists could use SI of the predominant fibroid on T2W to predict response to GnRH agonist pretreatment.

A second study also evaluated the growth uterine fibroids during a different time during a woman’s lifespan - pregnancy. While it’s commonly thought that fibroids grow during pregnancy, a prospective cross-sectional study in the International Journal of Gynecology & Obstetrics (Tian et al) evaluated 394 women with uterine fibroids and found that growth depended on gestational age. In this group, ultrasound examinations were conducted to measure the size of uterine fibroids during weeks 6–7, 11–14, 22–24 and 28–34 of pregnancy and before delivery. The study team found that uterine fibroid size commonly increased before 22–24 weeks of pregnancy with the fastest growth occurring before 11–14 weeks gestation. Later in pregnancy, from 22–24 weeks to the date of delivery, uterine fibroid size remained unchanged.

Lin et al published a large-scale nationwide cohort study in PLoS One that evaluated whether women with uterine fibroids were at increased risk of developing endometriosis. Overall, 31,239 women with uterine fibroids were matched to 124, 956 control participants and followed for 14 years. Compared to controls, patients with uterine fibroids were at a higher risk of developing endometriosis (adjusted hazard ratio [aHR] 6.44, P < 0.05). Other conditions associated with a higher risk of endometriosis included history of tubo-ovarian infection (aHR 2.86, P = 0.01), endometritis (aHR 1.14, P < 0.001), infertility (aHR 1.26, P < 0.001) and allergic diseases (aHR, 1.11, P < .001). Similarly, having both uterine fibroids and infertility significantly increased the risk of endometriosis (aHR 6.95; P < 0.001).

A second study also evaluated the growth uterine fibroids during a different time during a woman’s lifespan - pregnancy. While it’s commonly thought that fibroids grow during pregnancy, a prospective cross-sectional study in the International Journal of Gynecology & Obstetrics (Tian et al) evaluated 394 women with uterine fibroids and found that growth depended on gestational age. In this group, ultrasound examinations were conducted to measure the size of uterine fibroids during weeks 6–7, 11–14, 22–24 and 28–34 of pregnancy and before delivery. The study team found that uterine fibroid size commonly increased before 22–24 weeks of pregnancy with the fastest growth occurring before 11–14 weeks gestation. Later in pregnancy, from 22–24 weeks to the date of delivery, uterine fibroid size remained unchanged.

Lin et al published a large-scale nationwide cohort study in PLoS One that evaluated whether women with uterine fibroids were at increased risk of developing endometriosis. Overall, 31,239 women with uterine fibroids were matched to 124, 956 control participants and followed for 14 years. Compared to controls, patients with uterine fibroids were at a higher risk of developing endometriosis (adjusted hazard ratio [aHR] 6.44, P < 0.05). Other conditions associated with a higher risk of endometriosis included history of tubo-ovarian infection (aHR 2.86, P = 0.01), endometritis (aHR 1.14, P < 0.001), infertility (aHR 1.26, P < 0.001) and allergic diseases (aHR, 1.11, P < .001). Similarly, having both uterine fibroids and infertility significantly increased the risk of endometriosis (aHR 6.95; P < 0.001).

A second study also evaluated the growth uterine fibroids during a different time during a woman’s lifespan - pregnancy. While it’s commonly thought that fibroids grow during pregnancy, a prospective cross-sectional study in the International Journal of Gynecology & Obstetrics (Tian et al) evaluated 394 women with uterine fibroids and found that growth depended on gestational age. In this group, ultrasound examinations were conducted to measure the size of uterine fibroids during weeks 6–7, 11–14, 22–24 and 28–34 of pregnancy and before delivery. The study team found that uterine fibroid size commonly increased before 22–24 weeks of pregnancy with the fastest growth occurring before 11–14 weeks gestation. Later in pregnancy, from 22–24 weeks to the date of delivery, uterine fibroid size remained unchanged.

Lin et al published a large-scale nationwide cohort study in PLoS One that evaluated whether women with uterine fibroids were at increased risk of developing endometriosis. Overall, 31,239 women with uterine fibroids were matched to 124, 956 control participants and followed for 14 years. Compared to controls, patients with uterine fibroids were at a higher risk of developing endometriosis (adjusted hazard ratio [aHR] 6.44, P < 0.05). Other conditions associated with a higher risk of endometriosis included history of tubo-ovarian infection (aHR 2.86, P = 0.01), endometritis (aHR 1.14, P < 0.001), infertility (aHR 1.26, P < 0.001) and allergic diseases (aHR, 1.11, P < .001). Similarly, having both uterine fibroids and infertility significantly increased the risk of endometriosis (aHR 6.95; P < 0.001).

Q1: How do/can fibroids influence fertility?

When considering how uterine fibroids influence fertility, it's important to understand that uterine fibroids are very common. Uterine fibroids are the most common pelvic tumor in women, and they're non-cancerous tumors that are developed from the muscle cells of the uterus. The lifetime risk, before the age of 50, of a woman having fibroids varies by race and ethnicity, but in general, about 80% of Black women and 70% of Caucasian women will have at least one uterine fibroid diagnosed before the age of 50.

It's also important to understand when considering fertility that the prevalence of uterine fibroids increases as someone gets older. So uterine fibroids are much less common in younger women in their 20s as they are in women in their upper 30s and 40s. That's important to understand when looking at fertility because we also know that with age, fertility decreases. Thus, uterine fibroids also can impact fertility. There's also this age-related factor, which makes it difficult to really look at fibroids as far as being a causative agent for infertility.

We do know that approximately 10% of women with infertility will be diagnosed with uterine fibroids during their evaluation, and there's multiple ways that uterine fibroids impact fertility. In general, it's going to depend on the location of the uterine fibroids, the size and the bulk or the number of uterine fibroids that a woman has.  But when we look at the ways that uterine fibroids can impact fertility, what they can do is they distort the uterine cavity. This is the most common for submucosal fibroids or fibroids that have a component that's present inside the uterine cavity. Fibroids that are submucosal or intramural fibroids  are in the muscle of the uterus and have an intracavitary component. They're well-known to distort the uterine cavity and that can impact implantation of an embryo. There's also thought that it can impact an ongoing pregnancy.

There's speculation that uterine fibroids can impact the blood flow to a pregnancy as well and they may impact fertility. Depending on the size of the uterine fibroid, they may block the fallopian tubes. And so, if you have a uterine fibroid that's in the corner of the uterus, that could cause a tubal factor type of infertility where there's occlusion of the fallopian tube. But in general, the most concern we have for uterine fibroids is how those fibroids impact the uterine lining and implantation of an embryo, and it's thought that those are most likely due to submucosal fibroids, or some intramural fibroids that may be particularly large, or that have a component that's inside the cavity.

Q2. Several studies have attempted to clarify the influence of fibroids on fertility, however, there have been various, sometimes contradictory findings and a lack of well-designed trials. Why is this?

One of the challenges in counseling patients regarding uterine fibroids is that there's really a lack of  high-quality studies assessing uterine fibroids and fertility. And we all know that the gold standard research study is a randomized control trial, as they provide the highest level of evidence, but those are very difficult to conduct especially for women with uterine fibroids, as many women will decline randomization.

It's difficult to design a study where there's one treatment that can be beneficial versus no treatment. That's one challenge. Because of that, the study designs that we've had to date have mostly been retrospective, and there's been some observational studies. But even those studies, unfortunately, are complicated by the fact that fibroids themselves are very heterogeneous. It's a very heterogeneous condition. There's a lot of difference between the size of the uterine fibroids, the location and the bulk of the fibroid, and then there's also going to be the issue with age. If you have a woman who's older with uterine fibroids, obviously her age is also going to impact her fertility. We know that women with uterine fibroids tend to be older and that also impacts fertility. So that's going to have an impact on any research as well.

What we do know from some of the research to date is that it's well-known that submucosal fibroids impair fertility, that's well established. We do know that subserosal fibroids or the fibroids on the surface of the uterus do not impact uterine fibroids. The question that really hasn't been answered because there hasn't been adequate research and there's just not enough data of high quality is, whether intramural fibroids or fibroids inside the uterine muscle, whether they impact fertility.

Many women who have intramural uterine fibroids are asymptomatic. They don't have symptoms at all. So, the question is whether a woman should undergo an invasive procedure to remove that fibroid and if it’s going to help or not? That's one of the questions that we just don't have enough adequate research on because there are some limitations in the literature.

Q3. What are the current treatments, both surgical and nonsurgical, for patients with fibroids who may want to become pregnant?

I think if there's a patient, a woman with uterine fibroids who's interested in fertility, she may be a patient who is diagnosed with symptomatic fibroids, who wants to preserve her fertility, or she may be a patient who's an infertility patient who during her fertility evaluation discovers she has fibroids. It is important to determine whether treatment is appropriate for that patient, and as we just discussed, there's not a lot of answers in the literature for some patients. I think the most important thing to do first before deciding on a treatment is  to determine the best type of treatment. At Johns Hopkins, for many of our patients with uterine fibroids, they'll undergo a pelvic MRI because the pelvic MRI can provide the most detailed information regarding the size and exact location of the uterine fibroids.

We then have a multidisciplinary conference every two weeks where we review the MRIs with a group of minimally invasive surgeons, interventional radiologists, and fertility specialist where we can really decide the best treatment for the individual patient. In deciding on a patient, it's important to make the right decision and have the most information. So as far as treatments that are available, for women who are wanting to preserve their fertility or planning to get pregnant very soon, the most common options are going to be surgical.

The least invasive surgical treatment would be a hysteroscopic myomectomy where we would do a hysteroscopy and remove the uterine fibroids by either shaving the pieces of the submucosal fibroid or we can remove it with a hysteroscopic morcellator. There are various techniques. But for the submucosal fibroids that are inside the uterine cavity, hysteroscopic myomectomy is very minimally invasive. It's an outpatient procedure. It's very safe and it's something that we will typically offer to patients who have submucosal fibroids.

For patients who have symptomatic uterine fibroids and may have bulk symptoms, or have numerous uterine fibroids, we typically would recommend either a laparoscopic robotic-assisted myomectomy, sometimes just a laparoscopic myomectomy, or for women who have the most severe, a very large fibroid uterus, let's say greater than 20 centimeters, they may actually need to undergo an exploratory laparotomy or abdominal myomectomy. For patients who have symptomatic subserosal fibroids and large intramural fibroids that need to be removed, it really depends on the size, location, and bulk of the uterine fibroids. And that's where the pelvic MRI becomes very useful.

I would say that for the majority of my patients that have a large amount of fibroids, are still able to undergo a robotic-assisted laparoscopic hysterectomy which oftentimes can be an outpatient procedure just because we've had this improvement in technology with robotic and laparoscopic surgery. But surgery can be very beneficial as far as removing the bulk of the uterine fibroids. And so that is typically our treatments that we would recommend for those who want future fertility or who are imminently trying to get pregnant.

There are medical treatments as well or non-surgical treatments such as GnRH analogs that can shrink the size of the uterine fibroids. Unfortunately, the uterine fibroids are still there and typically will still impact fertility. So that's not something that we do often for those that are actively trying to get pregnant. The same for uterine artery embolization or uterine fibroids embolization. We will not recommend that for patients who want to have future fertility because the fibroids will still be in that location and they're typically in a location that's impairing fertility.

Q4. How long do patients have to wait after a fibroid treatment to try to get pregnant?

The length of time that a patient needs to wait after having fibroids removed for surgical treatment typically depends on the type of surgery the patient undergoes as well as the size of the fibroids and the extent of the surgery. For a patient who's undergoing a hysteroscopic myomectomy, they typically only must wait a month or two. Once they're assessed that there's no residual fibroid that's left, then they can try to conceive.

For patients who need to undergo abdominal myomectomy or laparoscopic myomectomy, those are much more extensive procedures. Typically, surgeons will recommend a patient wait three to six months to try to conceive. It's also important for the surgeon to discuss with the patient the extent of the myomectomy and whether that patient, when she does become pregnant, will require a c-section because typically if the uterine cavity is entered or if there are multiple incisions on the uterus during the myomectomy surgery, surgeons will recommend a c-section for that patient when she does become pregnant to decrease the risk of uterine rupture. And typically, that will be documented in the operative note, but the surgeon will also counsel the patient regarding this.

Q1: How do/can fibroids influence fertility?

When considering how uterine fibroids influence fertility, it's important to understand that uterine fibroids are very common. Uterine fibroids are the most common pelvic tumor in women, and they're non-cancerous tumors that are developed from the muscle cells of the uterus. The lifetime risk, before the age of 50, of a woman having fibroids varies by race and ethnicity, but in general, about 80% of Black women and 70% of Caucasian women will have at least one uterine fibroid diagnosed before the age of 50.

It's also important to understand when considering fertility that the prevalence of uterine fibroids increases as someone gets older. So uterine fibroids are much less common in younger women in their 20s as they are in women in their upper 30s and 40s. That's important to understand when looking at fertility because we also know that with age, fertility decreases. Thus, uterine fibroids also can impact fertility. There's also this age-related factor, which makes it difficult to really look at fibroids as far as being a causative agent for infertility.

We do know that approximately 10% of women with infertility will be diagnosed with uterine fibroids during their evaluation, and there's multiple ways that uterine fibroids impact fertility. In general, it's going to depend on the location of the uterine fibroids, the size and the bulk or the number of uterine fibroids that a woman has.  But when we look at the ways that uterine fibroids can impact fertility, what they can do is they distort the uterine cavity. This is the most common for submucosal fibroids or fibroids that have a component that's present inside the uterine cavity. Fibroids that are submucosal or intramural fibroids  are in the muscle of the uterus and have an intracavitary component. They're well-known to distort the uterine cavity and that can impact implantation of an embryo. There's also thought that it can impact an ongoing pregnancy.

There's speculation that uterine fibroids can impact the blood flow to a pregnancy as well and they may impact fertility. Depending on the size of the uterine fibroid, they may block the fallopian tubes. And so, if you have a uterine fibroid that's in the corner of the uterus, that could cause a tubal factor type of infertility where there's occlusion of the fallopian tube. But in general, the most concern we have for uterine fibroids is how those fibroids impact the uterine lining and implantation of an embryo, and it's thought that those are most likely due to submucosal fibroids, or some intramural fibroids that may be particularly large, or that have a component that's inside the cavity.

Q2. Several studies have attempted to clarify the influence of fibroids on fertility, however, there have been various, sometimes contradictory findings and a lack of well-designed trials. Why is this?

One of the challenges in counseling patients regarding uterine fibroids is that there's really a lack of  high-quality studies assessing uterine fibroids and fertility. And we all know that the gold standard research study is a randomized control trial, as they provide the highest level of evidence, but those are very difficult to conduct especially for women with uterine fibroids, as many women will decline randomization.

It's difficult to design a study where there's one treatment that can be beneficial versus no treatment. That's one challenge. Because of that, the study designs that we've had to date have mostly been retrospective, and there's been some observational studies. But even those studies, unfortunately, are complicated by the fact that fibroids themselves are very heterogeneous. It's a very heterogeneous condition. There's a lot of difference between the size of the uterine fibroids, the location and the bulk of the fibroid, and then there's also going to be the issue with age. If you have a woman who's older with uterine fibroids, obviously her age is also going to impact her fertility. We know that women with uterine fibroids tend to be older and that also impacts fertility. So that's going to have an impact on any research as well.

What we do know from some of the research to date is that it's well-known that submucosal fibroids impair fertility, that's well established. We do know that subserosal fibroids or the fibroids on the surface of the uterus do not impact uterine fibroids. The question that really hasn't been answered because there hasn't been adequate research and there's just not enough data of high quality is, whether intramural fibroids or fibroids inside the uterine muscle, whether they impact fertility.

Many women who have intramural uterine fibroids are asymptomatic. They don't have symptoms at all. So, the question is whether a woman should undergo an invasive procedure to remove that fibroid and if it’s going to help or not? That's one of the questions that we just don't have enough adequate research on because there are some limitations in the literature.

Q3. What are the current treatments, both surgical and nonsurgical, for patients with fibroids who may want to become pregnant?

I think if there's a patient, a woman with uterine fibroids who's interested in fertility, she may be a patient who is diagnosed with symptomatic fibroids, who wants to preserve her fertility, or she may be a patient who's an infertility patient who during her fertility evaluation discovers she has fibroids. It is important to determine whether treatment is appropriate for that patient, and as we just discussed, there's not a lot of answers in the literature for some patients. I think the most important thing to do first before deciding on a treatment is  to determine the best type of treatment. At Johns Hopkins, for many of our patients with uterine fibroids, they'll undergo a pelvic MRI because the pelvic MRI can provide the most detailed information regarding the size and exact location of the uterine fibroids.

We then have a multidisciplinary conference every two weeks where we review the MRIs with a group of minimally invasive surgeons, interventional radiologists, and fertility specialist where we can really decide the best treatment for the individual patient. In deciding on a patient, it's important to make the right decision and have the most information. So as far as treatments that are available, for women who are wanting to preserve their fertility or planning to get pregnant very soon, the most common options are going to be surgical.

The least invasive surgical treatment would be a hysteroscopic myomectomy where we would do a hysteroscopy and remove the uterine fibroids by either shaving the pieces of the submucosal fibroid or we can remove it with a hysteroscopic morcellator. There are various techniques. But for the submucosal fibroids that are inside the uterine cavity, hysteroscopic myomectomy is very minimally invasive. It's an outpatient procedure. It's very safe and it's something that we will typically offer to patients who have submucosal fibroids.

For patients who have symptomatic uterine fibroids and may have bulk symptoms, or have numerous uterine fibroids, we typically would recommend either a laparoscopic robotic-assisted myomectomy, sometimes just a laparoscopic myomectomy, or for women who have the most severe, a very large fibroid uterus, let's say greater than 20 centimeters, they may actually need to undergo an exploratory laparotomy or abdominal myomectomy. For patients who have symptomatic subserosal fibroids and large intramural fibroids that need to be removed, it really depends on the size, location, and bulk of the uterine fibroids. And that's where the pelvic MRI becomes very useful.

I would say that for the majority of my patients that have a large amount of fibroids, are still able to undergo a robotic-assisted laparoscopic hysterectomy which oftentimes can be an outpatient procedure just because we've had this improvement in technology with robotic and laparoscopic surgery. But surgery can be very beneficial as far as removing the bulk of the uterine fibroids. And so that is typically our treatments that we would recommend for those who want future fertility or who are imminently trying to get pregnant.

There are medical treatments as well or non-surgical treatments such as GnRH analogs that can shrink the size of the uterine fibroids. Unfortunately, the uterine fibroids are still there and typically will still impact fertility. So that's not something that we do often for those that are actively trying to get pregnant. The same for uterine artery embolization or uterine fibroids embolization. We will not recommend that for patients who want to have future fertility because the fibroids will still be in that location and they're typically in a location that's impairing fertility.

Q4. How long do patients have to wait after a fibroid treatment to try to get pregnant?

The length of time that a patient needs to wait after having fibroids removed for surgical treatment typically depends on the type of surgery the patient undergoes as well as the size of the fibroids and the extent of the surgery. For a patient who's undergoing a hysteroscopic myomectomy, they typically only must wait a month or two. Once they're assessed that there's no residual fibroid that's left, then they can try to conceive.

For patients who need to undergo abdominal myomectomy or laparoscopic myomectomy, those are much more extensive procedures. Typically, surgeons will recommend a patient wait three to six months to try to conceive. It's also important for the surgeon to discuss with the patient the extent of the myomectomy and whether that patient, when she does become pregnant, will require a c-section because typically if the uterine cavity is entered or if there are multiple incisions on the uterus during the myomectomy surgery, surgeons will recommend a c-section for that patient when she does become pregnant to decrease the risk of uterine rupture. And typically, that will be documented in the operative note, but the surgeon will also counsel the patient regarding this.

Q1: How do/can fibroids influence fertility?

When considering how uterine fibroids influence fertility, it's important to understand that uterine fibroids are very common. Uterine fibroids are the most common pelvic tumor in women, and they're non-cancerous tumors that are developed from the muscle cells of the uterus. The lifetime risk, before the age of 50, of a woman having fibroids varies by race and ethnicity, but in general, about 80% of Black women and 70% of Caucasian women will have at least one uterine fibroid diagnosed before the age of 50.

It's also important to understand when considering fertility that the prevalence of uterine fibroids increases as someone gets older. So uterine fibroids are much less common in younger women in their 20s as they are in women in their upper 30s and 40s. That's important to understand when looking at fertility because we also know that with age, fertility decreases. Thus, uterine fibroids also can impact fertility. There's also this age-related factor, which makes it difficult to really look at fibroids as far as being a causative agent for infertility.

We do know that approximately 10% of women with infertility will be diagnosed with uterine fibroids during their evaluation, and there's multiple ways that uterine fibroids impact fertility. In general, it's going to depend on the location of the uterine fibroids, the size and the bulk or the number of uterine fibroids that a woman has.  But when we look at the ways that uterine fibroids can impact fertility, what they can do is they distort the uterine cavity. This is the most common for submucosal fibroids or fibroids that have a component that's present inside the uterine cavity. Fibroids that are submucosal or intramural fibroids  are in the muscle of the uterus and have an intracavitary component. They're well-known to distort the uterine cavity and that can impact implantation of an embryo. There's also thought that it can impact an ongoing pregnancy.

There's speculation that uterine fibroids can impact the blood flow to a pregnancy as well and they may impact fertility. Depending on the size of the uterine fibroid, they may block the fallopian tubes. And so, if you have a uterine fibroid that's in the corner of the uterus, that could cause a tubal factor type of infertility where there's occlusion of the fallopian tube. But in general, the most concern we have for uterine fibroids is how those fibroids impact the uterine lining and implantation of an embryo, and it's thought that those are most likely due to submucosal fibroids, or some intramural fibroids that may be particularly large, or that have a component that's inside the cavity.

Q2. Several studies have attempted to clarify the influence of fibroids on fertility, however, there have been various, sometimes contradictory findings and a lack of well-designed trials. Why is this?

One of the challenges in counseling patients regarding uterine fibroids is that there's really a lack of  high-quality studies assessing uterine fibroids and fertility. And we all know that the gold standard research study is a randomized control trial, as they provide the highest level of evidence, but those are very difficult to conduct especially for women with uterine fibroids, as many women will decline randomization.

It's difficult to design a study where there's one treatment that can be beneficial versus no treatment. That's one challenge. Because of that, the study designs that we've had to date have mostly been retrospective, and there's been some observational studies. But even those studies, unfortunately, are complicated by the fact that fibroids themselves are very heterogeneous. It's a very heterogeneous condition. There's a lot of difference between the size of the uterine fibroids, the location and the bulk of the fibroid, and then there's also going to be the issue with age. If you have a woman who's older with uterine fibroids, obviously her age is also going to impact her fertility. We know that women with uterine fibroids tend to be older and that also impacts fertility. So that's going to have an impact on any research as well.

What we do know from some of the research to date is that it's well-known that submucosal fibroids impair fertility, that's well established. We do know that subserosal fibroids or the fibroids on the surface of the uterus do not impact uterine fibroids. The question that really hasn't been answered because there hasn't been adequate research and there's just not enough data of high quality is, whether intramural fibroids or fibroids inside the uterine muscle, whether they impact fertility.

Many women who have intramural uterine fibroids are asymptomatic. They don't have symptoms at all. So, the question is whether a woman should undergo an invasive procedure to remove that fibroid and if it’s going to help or not? That's one of the questions that we just don't have enough adequate research on because there are some limitations in the literature.

Q3. What are the current treatments, both surgical and nonsurgical, for patients with fibroids who may want to become pregnant?

I think if there's a patient, a woman with uterine fibroids who's interested in fertility, she may be a patient who is diagnosed with symptomatic fibroids, who wants to preserve her fertility, or she may be a patient who's an infertility patient who during her fertility evaluation discovers she has fibroids. It is important to determine whether treatment is appropriate for that patient, and as we just discussed, there's not a lot of answers in the literature for some patients. I think the most important thing to do first before deciding on a treatment is  to determine the best type of treatment. At Johns Hopkins, for many of our patients with uterine fibroids, they'll undergo a pelvic MRI because the pelvic MRI can provide the most detailed information regarding the size and exact location of the uterine fibroids.

We then have a multidisciplinary conference every two weeks where we review the MRIs with a group of minimally invasive surgeons, interventional radiologists, and fertility specialist where we can really decide the best treatment for the individual patient. In deciding on a patient, it's important to make the right decision and have the most information. So as far as treatments that are available, for women who are wanting to preserve their fertility or planning to get pregnant very soon, the most common options are going to be surgical.

The least invasive surgical treatment would be a hysteroscopic myomectomy where we would do a hysteroscopy and remove the uterine fibroids by either shaving the pieces of the submucosal fibroid or we can remove it with a hysteroscopic morcellator. There are various techniques. But for the submucosal fibroids that are inside the uterine cavity, hysteroscopic myomectomy is very minimally invasive. It's an outpatient procedure. It's very safe and it's something that we will typically offer to patients who have submucosal fibroids.

For patients who have symptomatic uterine fibroids and may have bulk symptoms, or have numerous uterine fibroids, we typically would recommend either a laparoscopic robotic-assisted myomectomy, sometimes just a laparoscopic myomectomy, or for women who have the most severe, a very large fibroid uterus, let's say greater than 20 centimeters, they may actually need to undergo an exploratory laparotomy or abdominal myomectomy. For patients who have symptomatic subserosal fibroids and large intramural fibroids that need to be removed, it really depends on the size, location, and bulk of the uterine fibroids. And that's where the pelvic MRI becomes very useful.

I would say that for the majority of my patients that have a large amount of fibroids, are still able to undergo a robotic-assisted laparoscopic hysterectomy which oftentimes can be an outpatient procedure just because we've had this improvement in technology with robotic and laparoscopic surgery. But surgery can be very beneficial as far as removing the bulk of the uterine fibroids. And so that is typically our treatments that we would recommend for those who want future fertility or who are imminently trying to get pregnant.

There are medical treatments as well or non-surgical treatments such as GnRH analogs that can shrink the size of the uterine fibroids. Unfortunately, the uterine fibroids are still there and typically will still impact fertility. So that's not something that we do often for those that are actively trying to get pregnant. The same for uterine artery embolization or uterine fibroids embolization. We will not recommend that for patients who want to have future fertility because the fibroids will still be in that location and they're typically in a location that's impairing fertility.

Q4. How long do patients have to wait after a fibroid treatment to try to get pregnant?

The length of time that a patient needs to wait after having fibroids removed for surgical treatment typically depends on the type of surgery the patient undergoes as well as the size of the fibroids and the extent of the surgery. For a patient who's undergoing a hysteroscopic myomectomy, they typically only must wait a month or two. Once they're assessed that there's no residual fibroid that's left, then they can try to conceive.

For patients who need to undergo abdominal myomectomy or laparoscopic myomectomy, those are much more extensive procedures. Typically, surgeons will recommend a patient wait three to six months to try to conceive. It's also important for the surgeon to discuss with the patient the extent of the myomectomy and whether that patient, when she does become pregnant, will require a c-section because typically if the uterine cavity is entered or if there are multiple incisions on the uterus during the myomectomy surgery, surgeons will recommend a c-section for that patient when she does become pregnant to decrease the risk of uterine rupture. And typically, that will be documented in the operative note, but the surgeon will also counsel the patient regarding this.

Chiuve et al published a large cohort study in the Journal of Epidemiology and Community Health that evaluated the association between uterine fibroids and diagnosed depression, anxiety and self-directed violence. Women aged 18-50 years with diagnosed uterine fibroids (n=313,754) were identified in the Optum Clinformatics commercial insurance claims database and matched 1:2 on age and calendar time to women without (n=627,539). After adjusting for confounders, women with uterine fibroids had a higher rate of depression, anxiety and self-directed violence then women not diagnosed with fibroids. Among women with pain symptoms and heavy menstrual bleeding, the hazard ratio comparing women with fibroids to women without was 1.21 for depression, 1.18 for anxiety and 1.68 for self-directed violence. Among women with fibroids, those who underwent hysterectomy had higher rates of depression, anxiety and self-directed violence.

A third study by Wesselink et al in Human Reproduction examined ambient air pollution exposure and the risk of developing uterine fibroids. This was a prospective cohort study of 21,998 premenopausal Black women in 56 US metropolitan areas from 1997 to 2011. During the follow up, 28.4% of participants (n=6238) reported uterine fibroid diagnosis by ultrasound or surgery. Increased ozone concentrations were associated with an increased risk of being diagnosed with uterine fibroids, with a stronger association among women less than 35 years of age and parous women. Other pollutants, specifically particulate matter <2.5 microns and nitrogen dioxide, were not associated with an increased risk of uterine fibroids.

Chiuve et al published a large cohort study in the Journal of Epidemiology and Community Health that evaluated the association between uterine fibroids and diagnosed depression, anxiety and self-directed violence. Women aged 18-50 years with diagnosed uterine fibroids (n=313,754) were identified in the Optum Clinformatics commercial insurance claims database and matched 1:2 on age and calendar time to women without (n=627,539). After adjusting for confounders, women with uterine fibroids had a higher rate of depression, anxiety and self-directed violence then women not diagnosed with fibroids. Among women with pain symptoms and heavy menstrual bleeding, the hazard ratio comparing women with fibroids to women without was 1.21 for depression, 1.18 for anxiety and 1.68 for self-directed violence. Among women with fibroids, those who underwent hysterectomy had higher rates of depression, anxiety and self-directed violence.

A third study by Wesselink et al in Human Reproduction examined ambient air pollution exposure and the risk of developing uterine fibroids. This was a prospective cohort study of 21,998 premenopausal Black women in 56 US metropolitan areas from 1997 to 2011. During the follow up, 28.4% of participants (n=6238) reported uterine fibroid diagnosis by ultrasound or surgery. Increased ozone concentrations were associated with an increased risk of being diagnosed with uterine fibroids, with a stronger association among women less than 35 years of age and parous women. Other pollutants, specifically particulate matter <2.5 microns and nitrogen dioxide, were not associated with an increased risk of uterine fibroids.

Chiuve et al published a large cohort study in the Journal of Epidemiology and Community Health that evaluated the association between uterine fibroids and diagnosed depression, anxiety and self-directed violence. Women aged 18-50 years with diagnosed uterine fibroids (n=313,754) were identified in the Optum Clinformatics commercial insurance claims database and matched 1:2 on age and calendar time to women without (n=627,539). After adjusting for confounders, women with uterine fibroids had a higher rate of depression, anxiety and self-directed violence then women not diagnosed with fibroids. Among women with pain symptoms and heavy menstrual bleeding, the hazard ratio comparing women with fibroids to women without was 1.21 for depression, 1.18 for anxiety and 1.68 for self-directed violence. Among women with fibroids, those who underwent hysterectomy had higher rates of depression, anxiety and self-directed violence.

A third study by Wesselink et al in Human Reproduction examined ambient air pollution exposure and the risk of developing uterine fibroids. This was a prospective cohort study of 21,998 premenopausal Black women in 56 US metropolitan areas from 1997 to 2011. During the follow up, 28.4% of participants (n=6238) reported uterine fibroid diagnosis by ultrasound or surgery. Increased ozone concentrations were associated with an increased risk of being diagnosed with uterine fibroids, with a stronger association among women less than 35 years of age and parous women. Other pollutants, specifically particulate matter <2.5 microns and nitrogen dioxide, were not associated with an increased risk of uterine fibroids.

Rana et al published a cost-effectiveness analysis in the British Journal of Obstetrics and Gynecology that evaluated the cost-effectiveness of uterine artery embolization (UAE) and myomectomy for women with symptomatic uterine fibroids wishing to avoid hysterectomy. The analysis was conducted along the FEMME randomized control trial, that examined the quality of life of menstruating women with symptomatic fibroids experience after treatment with UAE or myomectomy. Over a 2-year time period, UAE was associated with higher mean costs and lower quality-adjusted life years compared with myomectomy. Similar results were observed over the 4-year time period. The authors concluded that myomectomy is a cost-effective option for the treatment of uterine fibroids.

A third study by Moor et al evaluated the impact of herpes simplex type 2 (HSV-2) infection on incidence and growth of ultrasound-diagnosed uterine fibroids in a large group of African American women. As reproductive tract infections have long been suspected as risk factors for fibroid development, this is a key study. In this prospective study analyzing data from the Study of Environment, Lifestyle and a large cohort of 25-35 year-old African American women with uterine fibroids were monitored by ultrasound over a 5-year period. A key finding was that fibroid HSV-2 positive status was not associated with fibroid incidence.

Rana et al published a cost-effectiveness analysis in the British Journal of Obstetrics and Gynecology that evaluated the cost-effectiveness of uterine artery embolization (UAE) and myomectomy for women with symptomatic uterine fibroids wishing to avoid hysterectomy. The analysis was conducted along the FEMME randomized control trial, that examined the quality of life of menstruating women with symptomatic fibroids experience after treatment with UAE or myomectomy. Over a 2-year time period, UAE was associated with higher mean costs and lower quality-adjusted life years compared with myomectomy. Similar results were observed over the 4-year time period. The authors concluded that myomectomy is a cost-effective option for the treatment of uterine fibroids.

A third study by Moor et al evaluated the impact of herpes simplex type 2 (HSV-2) infection on incidence and growth of ultrasound-diagnosed uterine fibroids in a large group of African American women. As reproductive tract infections have long been suspected as risk factors for fibroid development, this is a key study. In this prospective study analyzing data from the Study of Environment, Lifestyle and a large cohort of 25-35 year-old African American women with uterine fibroids were monitored by ultrasound over a 5-year period. A key finding was that fibroid HSV-2 positive status was not associated with fibroid incidence.

Rana et al published a cost-effectiveness analysis in the British Journal of Obstetrics and Gynecology that evaluated the cost-effectiveness of uterine artery embolization (UAE) and myomectomy for women with symptomatic uterine fibroids wishing to avoid hysterectomy. The analysis was conducted along the FEMME randomized control trial, that examined the quality of life of menstruating women with symptomatic fibroids experience after treatment with UAE or myomectomy. Over a 2-year time period, UAE was associated with higher mean costs and lower quality-adjusted life years compared with myomectomy. Similar results were observed over the 4-year time period. The authors concluded that myomectomy is a cost-effective option for the treatment of uterine fibroids.

A third study by Moor et al evaluated the impact of herpes simplex type 2 (HSV-2) infection on incidence and growth of ultrasound-diagnosed uterine fibroids in a large group of African American women. As reproductive tract infections have long been suspected as risk factors for fibroid development, this is a key study. In this prospective study analyzing data from the Study of Environment, Lifestyle and a large cohort of 25-35 year-old African American women with uterine fibroids were monitored by ultrasound over a 5-year period. A key finding was that fibroid HSV-2 positive status was not associated with fibroid incidence.