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Two chronic gynecologic conditions notably affect a woman’s quality of life (QoL), including fertility – one is endometriosis, and the other is a fibroid uterus. For a benign tumor, fibroids have an impressive prevalence found in approximately 50%-60% of women during their reproductive years. By menopause, it is estimated that 70% of woman have a fibroid, yet the true incidence is unknown given that only 25% of women experience symptoms bothersome enough to warrant intervention. This month’s article reviews the burden of fibroids and the latest management options that may potentially avoid surgery.
Background
Fibroids are monoclonal tumors of uterine smooth muscle that originate from the myometrium. Risk factors include family history, being premenopausal, increasing time since last delivery, obesity, and hypertension (ACOG Practice Bulletin no. 228 Jun 2021: Obstet Gynecol. 2021 Jun 1;137[6]:e100-e15) but oral hormonal contraception, depot medroxyprogesterone acetate (MPA), and increased parity reduce the risk of fibroids. Compared with White women, Black women have a 2-3 times higher prevalence of fibroids, develop them at a younger age, and present with larger fibroids.
The FIGO leiomyoma classification is the agreed upon system for identifying fibroid location. Symptoms are all too familiar to gynecologists, with life-threatening hemorrhage with severe anemia being the most feared, particularly for FIGO types 1-5. Transvaginal ultrasound is the simplest imaging tool for evaluation.
Fibroids and fertility
Fibroids can impair fertility in several ways: alteration of local anatomy, including the detrimental effects of abnormal uterine bleeding; functional changes by increasing uterine contractions and impairing endometrium and myometrial blood supply; and changes to the local hormonal environment that could impair egg/sperm transport, or embryo implantation (Hum Reprod Update. 2017;22:665-86).
Prior to consideration of surgery, saline infusion sonogram can determine the degree of impact on the endometrium, which is most applicable to the infertility patient, but can also allow guidance toward the appropriate surgical approach.
Treatment options – medical
Management of fibroids is based on a woman’s age, desire for fertility, symptoms, and location of the fibroid(s). Expectant observation of a woman with fibroids may be a reasonable approach, provided the lack of symptoms impairing QoL and of anemia. Typically, there is no change in fibroid size during the short term, considered less than 1 year. Regarding fertility, studies are heterogeneous so there is no definitive conclusion that fibroids impair natural fertility (Reprod Biomed Online. 2021;43:100-10). Spontaneous regression, defined by a reduction in fibroid volume of greater than 20%, has been noted to occur in 7.0% of fibroids (Curr Obstet Gynecol Rep. 2018;7[3]:117-21).
When fertility is not desired, medical management of fibroids is the initial conservative approach. GnRH agonists have been utilized for temporary relief of menometrorrhagia because of fibroids and to reduce their volume, particularly preoperatively. However, extended treatment can induce bone mineral density loss. Add-back therapy (tibolone, raloxifene, estriol, and ipriflavone) is of value in reducing bone loss while MPA and tibolone may manage vasomotor symptoms. More recently, the use of a GnRH antagonist (elagolix) along with add-back therapy has been approved for up to 24 months by the Food and Drug Administration and has demonstrated a more than 50% amenorrhea rate at 12 months (Obstet Gynecol. 2020;135:1313-26).
Progesterone plays an important role in fibroid growth, but the mechanism is unclear. Although not FDA approved, selective progesterone receptor modulators (SPRM) act directly on fibroid size reduction at the level of the pituitary to induce amenorrhea through inhibition of ovulation. Also, more than one course of SPRMs can provide benefit for bleeding control and volume reduction. The SPRM ulipristal acetate for four courses of 3 months demonstrated 73.5% of patients experienced a fibroid volume reduction of greater than 25% and were amenorrheic (Fertil Steril. 2017;108:416-25). GnRH agonists or SPRMs may benefit women if the fibroid is larger than 3 cm or anemia exists, thereby precluding immediate surgery.
Other medication options include the levonorgestrel IUD, combined hormonal contraceptives, and tranexamic acid – all of which have limited data on effective results of treating abnormal uterine bleeding.
Treatment options – surgical
Fibroids are the most common reason for hysterectomy as they are the contributing indication in approximately one-third of surgeries. When future fertility is desired, current surgical options include hysteroscopic and laparoscopic (including robotic) myomectomy. Hysteroscopy is the standard approach for FIGO type 1 fibroids and can also manage some type 2 fibroids provided they are less than 3 cm and the latter is greater than 5 mm from the serosa. Type 2 fibroids may benefit from a “two-step” removal to allow the myometrium to contract and extrude the fibroid. In light of the risk of fluid overload with nonelectrolyte solutions that enable the use of monopolar cautery, many procedures are now performed with bipolar cautery or morcellators.
Laparoscopy (including robotic) has outcomes similar to those of laparotomy although the risk of uterine rupture with the former requires careful attention to thorough closure of the myometrial defect. Robotic myomectomy has outcomes similar to those of standard laparoscopy with less blood loss, but operating times may be prolonged (Best Pract Res Clin Obstet Gynaecol. 2018;46:113-9).
The rate of myomectomy is reported to be 9.2 per 10,000 woman-years in Black women and 1.3 per 10,000 woman years in White women (Fertil Steril 2017;108;416-25). The rate of recurrence after myomectomy can be as great as 60% when patients are followed up to 5 years. Intramural fibroids greater than 2.85 cm and not distorting the uterine cavity may decrease in vitro fertilization (IVF) success (Fertil Steril 2014;101:716-21).
Noninvasive treatment modalities
Uterine artery embolization (UAE) is the most popular minimally invasive alternative to surgical myomectomy. Risks include postembolization syndrome (pain, fever, nausea, leukocytosis, and occasionally malaise), infection, and damage to fertility. Rarely, loss of ovarian function can occur, particularly in women above age 45. Because of the disruption of uterine blood flow, UAE increases the risk of accelerating ovarian aging and infertility as well as atrophic endometrium. In addition, pregnancy complications are increased including miscarriage, preterm labor, and postpartum hemorrhage. There is debate regarding the need for cesarean section at time of delivery given the potential for weakening of the uterine wall following UAE.
High-intensity focused ultrasound (HIFU) is guided by ultrasound or MRI and involves a high-energy-density ultrasound wave passing through the skin. The wave is absorbed and transformed into heat, causing the tissue protein to coagulate, and to be absorbed by the body. The procedure is scarless, carries a minimal risk of infection, and offers less pain compared with traditional approaches. However, HIFU is time consuming, and skin burns and unintentional tissue injury are a risk. A meta-analysis demonstrated improved symptoms of fibroids at 6 and 12 months (J Min Invasive Gynecol. 2021 in press).
Ultrasound-guided microwave ablation (MWA) uses an ablative electrode that is directly inserted into the target tissue via transcutaneous or transcervical approach via ultrasound guidance using microwave to produce heat for tissue coagulation necrosis. The advantages of MWA compared with HIFU and RFA are a higher tissue temperature, larger ablation volume, shorter operating time, less pain and no adverse major events (J Min Invasive Gynecol. 2021, in press).
Conclusion
The current literature cannot conclude that fibroids reduce the likelihood of achieving pregnancy with or without fertility treatment, based on a specific size, number, or location (not including submucosal or cavity-distorting intramural fibroids). Definitive evidence on the efficacy of myomectomy to improve fertility remains limited. Hysteroscopic myomectomy presumably improves pregnancy rates, but there is uncertainty as to its role in reducing miscarriage. Novel nonsurgical modalities are available and are expected to continue being developed but clarity on fertility outcomes is needed.
Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts of interests. Please contact him at obnews@mdedge.com.
Two chronic gynecologic conditions notably affect a woman’s quality of life (QoL), including fertility – one is endometriosis, and the other is a fibroid uterus. For a benign tumor, fibroids have an impressive prevalence found in approximately 50%-60% of women during their reproductive years. By menopause, it is estimated that 70% of woman have a fibroid, yet the true incidence is unknown given that only 25% of women experience symptoms bothersome enough to warrant intervention. This month’s article reviews the burden of fibroids and the latest management options that may potentially avoid surgery.
Background
Fibroids are monoclonal tumors of uterine smooth muscle that originate from the myometrium. Risk factors include family history, being premenopausal, increasing time since last delivery, obesity, and hypertension (ACOG Practice Bulletin no. 228 Jun 2021: Obstet Gynecol. 2021 Jun 1;137[6]:e100-e15) but oral hormonal contraception, depot medroxyprogesterone acetate (MPA), and increased parity reduce the risk of fibroids. Compared with White women, Black women have a 2-3 times higher prevalence of fibroids, develop them at a younger age, and present with larger fibroids.
The FIGO leiomyoma classification is the agreed upon system for identifying fibroid location. Symptoms are all too familiar to gynecologists, with life-threatening hemorrhage with severe anemia being the most feared, particularly for FIGO types 1-5. Transvaginal ultrasound is the simplest imaging tool for evaluation.
Fibroids and fertility
Fibroids can impair fertility in several ways: alteration of local anatomy, including the detrimental effects of abnormal uterine bleeding; functional changes by increasing uterine contractions and impairing endometrium and myometrial blood supply; and changes to the local hormonal environment that could impair egg/sperm transport, or embryo implantation (Hum Reprod Update. 2017;22:665-86).
Prior to consideration of surgery, saline infusion sonogram can determine the degree of impact on the endometrium, which is most applicable to the infertility patient, but can also allow guidance toward the appropriate surgical approach.
Treatment options – medical
Management of fibroids is based on a woman’s age, desire for fertility, symptoms, and location of the fibroid(s). Expectant observation of a woman with fibroids may be a reasonable approach, provided the lack of symptoms impairing QoL and of anemia. Typically, there is no change in fibroid size during the short term, considered less than 1 year. Regarding fertility, studies are heterogeneous so there is no definitive conclusion that fibroids impair natural fertility (Reprod Biomed Online. 2021;43:100-10). Spontaneous regression, defined by a reduction in fibroid volume of greater than 20%, has been noted to occur in 7.0% of fibroids (Curr Obstet Gynecol Rep. 2018;7[3]:117-21).
When fertility is not desired, medical management of fibroids is the initial conservative approach. GnRH agonists have been utilized for temporary relief of menometrorrhagia because of fibroids and to reduce their volume, particularly preoperatively. However, extended treatment can induce bone mineral density loss. Add-back therapy (tibolone, raloxifene, estriol, and ipriflavone) is of value in reducing bone loss while MPA and tibolone may manage vasomotor symptoms. More recently, the use of a GnRH antagonist (elagolix) along with add-back therapy has been approved for up to 24 months by the Food and Drug Administration and has demonstrated a more than 50% amenorrhea rate at 12 months (Obstet Gynecol. 2020;135:1313-26).
Progesterone plays an important role in fibroid growth, but the mechanism is unclear. Although not FDA approved, selective progesterone receptor modulators (SPRM) act directly on fibroid size reduction at the level of the pituitary to induce amenorrhea through inhibition of ovulation. Also, more than one course of SPRMs can provide benefit for bleeding control and volume reduction. The SPRM ulipristal acetate for four courses of 3 months demonstrated 73.5% of patients experienced a fibroid volume reduction of greater than 25% and were amenorrheic (Fertil Steril. 2017;108:416-25). GnRH agonists or SPRMs may benefit women if the fibroid is larger than 3 cm or anemia exists, thereby precluding immediate surgery.
Other medication options include the levonorgestrel IUD, combined hormonal contraceptives, and tranexamic acid – all of which have limited data on effective results of treating abnormal uterine bleeding.
Treatment options – surgical
Fibroids are the most common reason for hysterectomy as they are the contributing indication in approximately one-third of surgeries. When future fertility is desired, current surgical options include hysteroscopic and laparoscopic (including robotic) myomectomy. Hysteroscopy is the standard approach for FIGO type 1 fibroids and can also manage some type 2 fibroids provided they are less than 3 cm and the latter is greater than 5 mm from the serosa. Type 2 fibroids may benefit from a “two-step” removal to allow the myometrium to contract and extrude the fibroid. In light of the risk of fluid overload with nonelectrolyte solutions that enable the use of monopolar cautery, many procedures are now performed with bipolar cautery or morcellators.
Laparoscopy (including robotic) has outcomes similar to those of laparotomy although the risk of uterine rupture with the former requires careful attention to thorough closure of the myometrial defect. Robotic myomectomy has outcomes similar to those of standard laparoscopy with less blood loss, but operating times may be prolonged (Best Pract Res Clin Obstet Gynaecol. 2018;46:113-9).
The rate of myomectomy is reported to be 9.2 per 10,000 woman-years in Black women and 1.3 per 10,000 woman years in White women (Fertil Steril 2017;108;416-25). The rate of recurrence after myomectomy can be as great as 60% when patients are followed up to 5 years. Intramural fibroids greater than 2.85 cm and not distorting the uterine cavity may decrease in vitro fertilization (IVF) success (Fertil Steril 2014;101:716-21).
Noninvasive treatment modalities
Uterine artery embolization (UAE) is the most popular minimally invasive alternative to surgical myomectomy. Risks include postembolization syndrome (pain, fever, nausea, leukocytosis, and occasionally malaise), infection, and damage to fertility. Rarely, loss of ovarian function can occur, particularly in women above age 45. Because of the disruption of uterine blood flow, UAE increases the risk of accelerating ovarian aging and infertility as well as atrophic endometrium. In addition, pregnancy complications are increased including miscarriage, preterm labor, and postpartum hemorrhage. There is debate regarding the need for cesarean section at time of delivery given the potential for weakening of the uterine wall following UAE.
High-intensity focused ultrasound (HIFU) is guided by ultrasound or MRI and involves a high-energy-density ultrasound wave passing through the skin. The wave is absorbed and transformed into heat, causing the tissue protein to coagulate, and to be absorbed by the body. The procedure is scarless, carries a minimal risk of infection, and offers less pain compared with traditional approaches. However, HIFU is time consuming, and skin burns and unintentional tissue injury are a risk. A meta-analysis demonstrated improved symptoms of fibroids at 6 and 12 months (J Min Invasive Gynecol. 2021 in press).
Ultrasound-guided microwave ablation (MWA) uses an ablative electrode that is directly inserted into the target tissue via transcutaneous or transcervical approach via ultrasound guidance using microwave to produce heat for tissue coagulation necrosis. The advantages of MWA compared with HIFU and RFA are a higher tissue temperature, larger ablation volume, shorter operating time, less pain and no adverse major events (J Min Invasive Gynecol. 2021, in press).
Conclusion
The current literature cannot conclude that fibroids reduce the likelihood of achieving pregnancy with or without fertility treatment, based on a specific size, number, or location (not including submucosal or cavity-distorting intramural fibroids). Definitive evidence on the efficacy of myomectomy to improve fertility remains limited. Hysteroscopic myomectomy presumably improves pregnancy rates, but there is uncertainty as to its role in reducing miscarriage. Novel nonsurgical modalities are available and are expected to continue being developed but clarity on fertility outcomes is needed.
Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts of interests. Please contact him at obnews@mdedge.com.
Two chronic gynecologic conditions notably affect a woman’s quality of life (QoL), including fertility – one is endometriosis, and the other is a fibroid uterus. For a benign tumor, fibroids have an impressive prevalence found in approximately 50%-60% of women during their reproductive years. By menopause, it is estimated that 70% of woman have a fibroid, yet the true incidence is unknown given that only 25% of women experience symptoms bothersome enough to warrant intervention. This month’s article reviews the burden of fibroids and the latest management options that may potentially avoid surgery.
Background
Fibroids are monoclonal tumors of uterine smooth muscle that originate from the myometrium. Risk factors include family history, being premenopausal, increasing time since last delivery, obesity, and hypertension (ACOG Practice Bulletin no. 228 Jun 2021: Obstet Gynecol. 2021 Jun 1;137[6]:e100-e15) but oral hormonal contraception, depot medroxyprogesterone acetate (MPA), and increased parity reduce the risk of fibroids. Compared with White women, Black women have a 2-3 times higher prevalence of fibroids, develop them at a younger age, and present with larger fibroids.
The FIGO leiomyoma classification is the agreed upon system for identifying fibroid location. Symptoms are all too familiar to gynecologists, with life-threatening hemorrhage with severe anemia being the most feared, particularly for FIGO types 1-5. Transvaginal ultrasound is the simplest imaging tool for evaluation.
Fibroids and fertility
Fibroids can impair fertility in several ways: alteration of local anatomy, including the detrimental effects of abnormal uterine bleeding; functional changes by increasing uterine contractions and impairing endometrium and myometrial blood supply; and changes to the local hormonal environment that could impair egg/sperm transport, or embryo implantation (Hum Reprod Update. 2017;22:665-86).
Prior to consideration of surgery, saline infusion sonogram can determine the degree of impact on the endometrium, which is most applicable to the infertility patient, but can also allow guidance toward the appropriate surgical approach.
Treatment options – medical
Management of fibroids is based on a woman’s age, desire for fertility, symptoms, and location of the fibroid(s). Expectant observation of a woman with fibroids may be a reasonable approach, provided the lack of symptoms impairing QoL and of anemia. Typically, there is no change in fibroid size during the short term, considered less than 1 year. Regarding fertility, studies are heterogeneous so there is no definitive conclusion that fibroids impair natural fertility (Reprod Biomed Online. 2021;43:100-10). Spontaneous regression, defined by a reduction in fibroid volume of greater than 20%, has been noted to occur in 7.0% of fibroids (Curr Obstet Gynecol Rep. 2018;7[3]:117-21).
When fertility is not desired, medical management of fibroids is the initial conservative approach. GnRH agonists have been utilized for temporary relief of menometrorrhagia because of fibroids and to reduce their volume, particularly preoperatively. However, extended treatment can induce bone mineral density loss. Add-back therapy (tibolone, raloxifene, estriol, and ipriflavone) is of value in reducing bone loss while MPA and tibolone may manage vasomotor symptoms. More recently, the use of a GnRH antagonist (elagolix) along with add-back therapy has been approved for up to 24 months by the Food and Drug Administration and has demonstrated a more than 50% amenorrhea rate at 12 months (Obstet Gynecol. 2020;135:1313-26).
Progesterone plays an important role in fibroid growth, but the mechanism is unclear. Although not FDA approved, selective progesterone receptor modulators (SPRM) act directly on fibroid size reduction at the level of the pituitary to induce amenorrhea through inhibition of ovulation. Also, more than one course of SPRMs can provide benefit for bleeding control and volume reduction. The SPRM ulipristal acetate for four courses of 3 months demonstrated 73.5% of patients experienced a fibroid volume reduction of greater than 25% and were amenorrheic (Fertil Steril. 2017;108:416-25). GnRH agonists or SPRMs may benefit women if the fibroid is larger than 3 cm or anemia exists, thereby precluding immediate surgery.
Other medication options include the levonorgestrel IUD, combined hormonal contraceptives, and tranexamic acid – all of which have limited data on effective results of treating abnormal uterine bleeding.
Treatment options – surgical
Fibroids are the most common reason for hysterectomy as they are the contributing indication in approximately one-third of surgeries. When future fertility is desired, current surgical options include hysteroscopic and laparoscopic (including robotic) myomectomy. Hysteroscopy is the standard approach for FIGO type 1 fibroids and can also manage some type 2 fibroids provided they are less than 3 cm and the latter is greater than 5 mm from the serosa. Type 2 fibroids may benefit from a “two-step” removal to allow the myometrium to contract and extrude the fibroid. In light of the risk of fluid overload with nonelectrolyte solutions that enable the use of monopolar cautery, many procedures are now performed with bipolar cautery or morcellators.
Laparoscopy (including robotic) has outcomes similar to those of laparotomy although the risk of uterine rupture with the former requires careful attention to thorough closure of the myometrial defect. Robotic myomectomy has outcomes similar to those of standard laparoscopy with less blood loss, but operating times may be prolonged (Best Pract Res Clin Obstet Gynaecol. 2018;46:113-9).
The rate of myomectomy is reported to be 9.2 per 10,000 woman-years in Black women and 1.3 per 10,000 woman years in White women (Fertil Steril 2017;108;416-25). The rate of recurrence after myomectomy can be as great as 60% when patients are followed up to 5 years. Intramural fibroids greater than 2.85 cm and not distorting the uterine cavity may decrease in vitro fertilization (IVF) success (Fertil Steril 2014;101:716-21).
Noninvasive treatment modalities
Uterine artery embolization (UAE) is the most popular minimally invasive alternative to surgical myomectomy. Risks include postembolization syndrome (pain, fever, nausea, leukocytosis, and occasionally malaise), infection, and damage to fertility. Rarely, loss of ovarian function can occur, particularly in women above age 45. Because of the disruption of uterine blood flow, UAE increases the risk of accelerating ovarian aging and infertility as well as atrophic endometrium. In addition, pregnancy complications are increased including miscarriage, preterm labor, and postpartum hemorrhage. There is debate regarding the need for cesarean section at time of delivery given the potential for weakening of the uterine wall following UAE.
High-intensity focused ultrasound (HIFU) is guided by ultrasound or MRI and involves a high-energy-density ultrasound wave passing through the skin. The wave is absorbed and transformed into heat, causing the tissue protein to coagulate, and to be absorbed by the body. The procedure is scarless, carries a minimal risk of infection, and offers less pain compared with traditional approaches. However, HIFU is time consuming, and skin burns and unintentional tissue injury are a risk. A meta-analysis demonstrated improved symptoms of fibroids at 6 and 12 months (J Min Invasive Gynecol. 2021 in press).
Ultrasound-guided microwave ablation (MWA) uses an ablative electrode that is directly inserted into the target tissue via transcutaneous or transcervical approach via ultrasound guidance using microwave to produce heat for tissue coagulation necrosis. The advantages of MWA compared with HIFU and RFA are a higher tissue temperature, larger ablation volume, shorter operating time, less pain and no adverse major events (J Min Invasive Gynecol. 2021, in press).
Conclusion
The current literature cannot conclude that fibroids reduce the likelihood of achieving pregnancy with or without fertility treatment, based on a specific size, number, or location (not including submucosal or cavity-distorting intramural fibroids). Definitive evidence on the efficacy of myomectomy to improve fertility remains limited. Hysteroscopic myomectomy presumably improves pregnancy rates, but there is uncertainty as to its role in reducing miscarriage. Novel nonsurgical modalities are available and are expected to continue being developed but clarity on fertility outcomes is needed.
Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts of interests. Please contact him at obnews@mdedge.com.
