The Impact of Myomectomy on IVF Outcomes: A Multicenter Randomized Controlled Trial

Обзор

Uterine fibroids are the most common benign tumors of the female reproductive system and are frequently encountered in women of reproductive age. Although many fibroids are asymptomatic, 5%-10% of women with infertility have coexisting fibroids, and in a small proportion fibroids may be the only identifiable cause of infertility. Fibroids may impair fertility by altering uterine anatomy, affecting uterine blood supply, inducing abnormal uterine contractions or endometrial peristalsis, and impairing endometrial receptivity. The impact of fibroids on fertility depends strongly on their type, size, number, and relationship to the uterine cavity. Submucosal fibroids clearly reduce clinical pregnancy, implantation, and live birth rates and increase miscarriage risk in patients undergoing assisted reproductive technology. In contrast, the effect of intramural fibroids, especially those that do not distort the uterine cavity, remains controversial. Some studies suggest no significant effect on IVF outcomes, whereas others report reduced clinical pregnancy and live birth rates. Evidence also suggests that fibroids located close to the endometrium or measuring ≥4 cm may be more clinically relevant for assisted reproduction. Current guidelines differ regarding whether infertile women with fibroids should undergo myomectomy before IVF. Chinese expert consensus recommends myomectomy for women preparing for pregnancy when fibroid diameter is ≥4 cm, whereas other international guidelines emphasize individualized management and note the lack of high-quality evidence. Existing studies are limited by small sample size, retrospective design, and inconsistent inclusion criteria. Therefore, whether myomectomy improves IVF outcomes in women with non-cavity-distorting intramural or subserosal fibroids remains uncertain. Imaging plays an important role in fibroid assessment. Transvaginal ultrasound is widely used because it is inexpensive and accessible, but it has limitations in accurately localizing fibroids and detecting small lesions. Pelvic MRI provides more accurate evaluation of fibroid location, size, and relationship to the myometrium and endometrium, and is particularly useful for study eligibility assessment. This multicenter randomized controlled trial is designed to evaluate whether myomectomy improves IVF outcomes in infertile women with FIGO type IV, V, or VI uterine fibroids measuring 4-6 cm. The study will compare IVF outcomes between women who undergo myomectomy before IVF and women who proceed directly to IVF without fibroid removal. The main objective is to determine whether surgical removal of these fibroids improves cumulative live birth after IVF.

Вмешательства

• Процедура Myomectomy
  Laparoscopic myomectomy is preferred. Abdominal myomectomy is also acceptable. In principle, layered closure with absorbable sutures should be used. If the full thickness of the myometrium is involved, closure should include at least two layers. Intraoperative tubal patency testing must be performed during surgery. If an endometrial polyp is present in a participant undergoing myomectomy, hysteroscopic endometrial polypectomy should be performed during the same operation.

Первичные конечные точки

• cumulative live birth rate within 1 year after IVF treatment. [Срок оценки: within 1 year after IVF treatment]

Вторичные конечные точки (5)

• Clinical pregnancy rate after IVF [Срок оценки: within 1 year of IVF]
• Biochemical pregnancy rate after IVF [Срок оценки: within 1 year of IVF]
• Ongoing pregnancy rate after IVF [Срок оценки: within 1 year of IVF]
• Miscarriage rate after IVF [Срок оценки: within 1 year of IVF]
• Pregnancy-related complications [Срок оценки: within 1 year of IVF]

Критерии участия

Критерии включения

• Female patients aged 20 years or older and younger than 40 years.
• Primary infertility or secondary infertility. Infertility factors may include male partner factors, ovulatory disorders, tubal factors, endometriosis, other non-uterine corpus disease factors, or unexplained infertility.
• Pelvic MRI indicating intramural fibroids: FIGO type 4-6; the largest fibroid has a maximum diameter of at least 4 cm and less than 6 cm; a total of no more than two fibroids measuring 4-6 cm; fibroids smaller than 4 cm may be disregarded.
• Meets indications for IVF and is willing to undergo IVF treatment.

Критерии исключения

• Infertility factors related to diseases of the uterine corpus, including but not limited to adenomyosis, intrauterine adhesions, endometritis, submucosal fibroids, and multiple endometrial polyps. A single endometrial polyp 1 cm or smaller does not require exclusion.
• Coexisting malignant or borderline tumors of the reproductive system, or other malignant tumors that are untreated or still under treatment.
• Active pelvic inflammatory disease.
• Previous cytotoxic therapy or pelvic/abdominal radiotherapy or chemotherapy.
• Previous surgery of the uterine corpus, including but not limited to myomectomy, uterine wedge resection, uterine artery embolization, tumor coagulation of the uterine corpus such as high-intensity focused ultrasound or electrocoagulation, and hysteroscopic myomectomy. Prior hysteroscopy, diagnostic curettage, or hysteroscopic polypectomy does not require exclusion.
• Expected inability to complete follow-up.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Levens ED, Stegmann BJ, Feinberg EC, Larsen FW. Ultrasonographic characteristics of the endometrium among patients with fibroids undergoing ART. Fertil Steril. 2008 Apr;89(4):1005-7. doi: 10.1016/j.fertnstert.2007.03.096. Epub 2007 Jul 26. PMID 17662279
• Yoshino O, Hayashi T, Osuga Y, Orisaka M, Asada H, Okuda S, Hori M, Furuya M, Onuki H, Sadoshima Y, Hiroi H, Fujiwara T, Kotsuji F, Yoshimura Y, Nishii O, Taketani Y. Decreased pregnancy rate is linked to abnormal uterine peristalsis caused by intramural fibroids. Hum Reprod. 2010 Oct;25(10):2475-9. doi: 10.1093/humrep/deq222. Epub 2010 Aug 18. PMID 20719814
• Ng EH, Yeung WS, Ho PC. Endometrial and subendometrial vascularity are significantly lower in patients with endometrial volume 2.5 ml or less. Reprod Biomed Online. 2009 Feb;18(2):262-8. doi: 10.1016/s1472-6483(10)60264-7. PMID 19192348
• Wang Y, Zhu Y, Sun Y, Di W, Qiu M, Kuang Y, Shen H. Ideal embryo transfer position and endometrial thickness in IVF embryo transfer treatment. Int J Gynaecol Obstet. 2018 Dec;143(3):282-288. doi: 10.1002/ijgo.12681. Epub 2018 Oct 8. PMID 30238667
• Gallos ID, Khairy M, Chu J, Rajkhowa M, Tobias A, Campbell A, Dowell K, Fishel S, Coomarasamy A. Optimal endometrial thickness to maximize live births and minimize pregnancy losses: Analysis of 25,767 fresh embryo transfers. Reprod Biomed Online. 2018 Nov;37(5):542-548. doi: 10.1016/j.rbmo.2018.08.025. Epub 2018 Oct 6. PMID 30366837
• Capmas P, Voulgaropoulos A, Legendre G, Pourcelot AG, Fernandez H. Hysteroscopic resection of type 3 myoma: a new challenge? Eur J Obstet Gynecol Reprod Biol. 2016 Oct;205:165-9. doi: 10.1016/j.ejogrb.2016.06.026. Epub 2016 Aug 31. PMID 27607740
• Casini ML, Rossi F, Agostini R, Unfer V. Effects of the position of fibroids on fertility. Gynecol Endocrinol. 2006 Feb;22(2):106-9. doi: 10.1080/09513590600604673. PMID 16603437
• Practice Committee of the American Society for Reproductive Medicine. Electronic address: ASRM@asrm.org; Practice Committee of the American Society for Reproductive Medicine. Removal of myomas in asymptomatic patients to improve fertility and/or reduce miscarriage rate: a guideline. Fertil Steril. 2017 Sep;108(3):416-425. doi: 10.1016/j.fertnstert.2017.06.034. PMID 28865538

Идентификаторы

NCT: NCT07578623 · K4218

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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