Fertility unaffected by myomectomy route

Sept. 30, 2022

A large, prospective, multicenter registry led by a Mayo Clinic investigator has found no appreciable differences in probability of pregnancy or live birth after the use of any myomectomy route: laparoscopic, hysteroscopic or abdominal. The investigators published their findings in a 2022 issue of Fertility and Sterility.

"This is a reassuring message for physicians and their patients," says Elizabeth A. Stewart, M.D., a reproductive endocrinologist at Mayo Clinic's Minnesota campus and senior study author. "The most important finding in this publication is that the probability of becoming pregnant and having a live birth is similar no matter the route of myomectomy chosen. Previous data showed worse pregnancy outcomes for abdominal myomectomy. That is not what we found in this large study."

Dr. Stewart says collecting detailed information prior to fibroid treatment was a key facet of the multisite Comparing Treatment Options for Uterine Fibroids (COMPARE-UF) study, of which the current study is a part. She says the investigators aimed to recruit women of multiple ethnicities with uterine fibroids — especially African American women, who experience a higher fibroid rate and more-severe symptoms.

COMPARE-UF is a national registry of eight primary clinical centers across the United States and includes 1,095 reproductive-age women. Study participants' mean age was mid-30s, and mean BMI was 28. Of these participants, 388 underwent abdominal myomectomy, 273 had hysteroscopic myomectomy and 434 had laparoscopic myomectomy. Over three years' follow-up, 202 women in the study reported pregnancy and 91 reported live births. Overall and also specifically among study participants intending conception, pregnancy or live birth rates did not differ significantly by myomectomy route.

The investigators conducted interval-based analyses, with adjusted odds ratios for pregnancy of 1.28 for hysteroscopic myomectomy and 1.19 for laparoscopic myomectomy compared with abdominal myomectomy. Adjusted odds ratios for study participants intending to become pregnant were 1.27 for hysteroscopic myomectomy and 1.26 for laparoscopic myomectomy compared with abdominal myomectomy.

"Women with fibroids — especially young women — shouldn't be concerned about the specific route of surgery when their desire is to get pregnant," says Dr. Stewart. "Patients can do whatever surgery they need to do to relieve symptoms and normalize their uteruses, and it doesn't appear to have a significant impact on pregnancy. For whatever myomectomy route the women chose or was available to them based on their uterus, they did well."

These findings are crucial, according to Dr. Stewart, due to the number of U.S. women affected. The No. 1 indication for hysterectomy in the U.S. is uterine fibroids, according to findings published by Farquhar and colleagues in a 2002 Obstetrics & Gynecology publication. Lifetime cumulative incidence of uterine fibroid diagnosis is approximately 30%. Estimated clinical incidence of uterine fibroids detectable by ultrasound by age 50 is greater than 70% according to a study published by Baird and colleagues in a 2003 article in American Journal of Obstetrics and Gynecology. Lifetime fibroid risk is 80%, according to Dr. Stewart. Fibroids almost exclusively affect women in their reproductive years, she notes, as oocyte numbers decrease significantly by the early 50s.

Gynecologists do not yet know uterine fibroids' cause. Further, though some say hysterectomy cures uterine fibroids, this isn't quite correct, says Dr. Stewart.

"While fibroids cannot recur when you remove the uterus, the long-term sequelae of hysterectomy, even with ovarian conservation, are substantial and that means that moving straight to hysterectomy when less invasive options are available is unwise," she says.

Unique study methodologies

A notable aspect of the study's methodology includes assessment of women's pregnancy intentions pre-surgically. Another key aspect involves the investigators' use of propensity scores to adjust for differences among groups undergoing each myomectomy route. For example, women undergoing hysteroscopic myomectomy tend to have smaller and more numerous fibroids compared with women undergoing other fibroid removal methods.

"Without the propensity scoring adjustment, this study's results would not be supported," says Dr. Stewart.

Women studied also varied in uterine volume, a factor surgeons consider to determine myomectomy route. Mean uterine volumes differed, which was notable in type of myomectomy performed: The mean was 812.8 cc for women undergoing abdominal myomectomy, 486.4 cc for women undergoing laparoscopic myomectomy and 265.6 cc for women undergoing hysteroscopic myomectomy.

"You can't control what you've got — if a patient arrives with a 900 cc uterine volume and the physician recommends abdominal surgery, now the patient can be sure her pregnancy outcome can be as good as with other myomectomy routes," says Dr. Stewart.

She notes that regardless of uterine fibroids or other factors, age makes becoming pregnant more difficult.

Study points to note

The investigators knew myomectomy had potential to normalize the uterus or cause scar tissue buildup and that hysteroscopic surgery tends to produce less scar tissue do than other routes.

A study limitation, says Dr. Stewart, is that investigators did not collect detailed information on how women reporting pregnancy became pregnant, such as conception on their own or with in vitro fertilization.

Dr. Stewart notes that regardless of how women and their partners attempt to conceive, fibroid removal is important due to symptoms such as pain and excessive bleeding, as well as because evidence has indicated that fibroids themselves can interfere with conception.

She also underlines that multiple factors beyond myomectomy route impact fertility. Having fibroids isn't the full story: Factors such as issues with ovulation or partner sperm also can impact fertility. Dr. Stewart suggests that women who have concerns about fibroids' impact on their pregnancy goals should not have fibroid treatment until they have completed a full fertility workup.

Notably, hysteroscopic and laparoscopic hysterectomy routes can be more difficult for the surgeon, says Dr. Stewart, indicating that learning curves for these methods can be more complex. Yet she indicates that in 2022, surgeons have more training in these methods.

The institutions participating in the COMPARE-UF study are all large, high-complexity fibroid care centers, which Dr. Stewart indicates presents a potential study bias.

"We don't know if the results translate to surgeons who only do one or two myomectomies a year," she says.

Dr. Stewart also points out that high-volume care for medical conditions such as fibroid removal is usually better than that at lower-volume centers due to higher levels of practice and expertise.

About myomectomy

The primary myomectomy objective is treatment of symptomatic fibroids, says Dr. Stewart. Fibroid specialists consider this surgery conservative, as it is uterine-sparing. She indicates that due to long-term side effects, the field is moving away from considering hysterectomy the gold standard fibroid treatment option for women who do not want to conceive post-surgically.

Dr. Stewart says that while fibroid prevention would be desirable, no prophylactic medication or surgery exists currently for this purpose.

Until two years ago, Dr. Stewart says fibroid specialists had only birth control pills and medicated IUDs as fibroid medication options to surgery. Specialists did not consider these therapies broadly effective, as they did not address pressure and uterine fibroid size, she says.

Two new fibroid treatment medications approved by the FDA in the last two years include elagolix with add-back therapy in 2020 and relugolix combination therapy in 2021, both of which address intense menstrual bleeding and other fibroid symptoms. Findings supporting both oral medications appeared in the New England Journal of Medicine in 2020 and 2021.

Now, other therapies such as magnetic resonance-guided ultrasound and uterine fibroid embolization are available, but the number of patients receiving these therapies in the COMPARE-UF study was too small for analysis, says Dr. Stewart.

She says those who undergo myomectomy have a high fibroid recurrence risk. Accordingly, she counsels women undergoing myomectomy who intend to conceive afterward to time their surgeries so they can attempt conception shortly thereafter for lowest fibroid recurrence risk.

Dr. Stewart says that similar to their insights on hysterectomy, gynecologists need long-term data — looking beyond five years — to counsel, say, a 22-year-old in need of symptomatic fibroid treatment.

For more information

Wise, LA, et al. Route of myomectomy and fertility: a prospective cohort study. Fertility and Sterility. 2022; 117 (5): 1083.

Farquhar CM, et al. Hysterectomy rates in the United States 1990-1997. Obstetrics & Gynecology. 2002;99:229.

Baird DD, et al. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. American Journal of Obstetrics and Gynecology. 2003;188:100.

FDA approves new option to treat heavy menstrual bleeding associated with fibroids in women.

Schlaff WD, et al. Elagolix for heavy menstrual bleeding in women with uterine fibroids. The New England Journal of Medicine. 2020; 382:328.

Ayman A-H, et al. Treatment of uterine fibroid symptoms with relugolix combination therapy. The New England Journal of Medicine. 2021;384:630.

Refer a patient to Mayo Clinic.