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

NCT07578623 | Not Yet Recruiting DMC

• 1 other identifier: K4218
• Study Type: interventional
• Target: 792
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Infertility; In Vitro Fertilization (IVF); Uterine Myomas, Leiomyomas, or Fibromas

Outcome Measures

Primary Outcomes (1)

• cumulative live birth rate within 1 year after IVF treatment.

  number of participants with live birth / total number of participants who initiated treatment x 100%.

  within 1 year after IVF treatment

Secondary Outcomes (5)

• Clinical pregnancy rate after IVF

  within 1 year of IVF

• Biochemical pregnancy rate after IVF

  within 1 year of IVF

• Ongoing pregnancy rate after IVF

  within 1 year of IVF

• Miscarriage rate after IVF

  within 1 year of IVF

• Pregnancy-related complications

  within 1 year of IVF

Study Arms (2)

Intervention arm

EXPERIMENTAL

This arm receives myomectomy before IVF.

Procedure: Myomectomy

Control arm

NO INTERVENTION

This arm receives IVF directly without surgical intervention for uterine myomas.

Interventions

Myomectomy PROCEDURE

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.

Intervention arm

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Expected inability to complete follow-up.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Related Publications (19)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Perez-Lopez FR, Ornat L, Ceausu I, Depypere H, Erel CT, Lambrinoudaki I, Schenck-Gustafsson K, Simoncini T, Tremollieres F, Rees M; EMAS. EMAS position statement: management of uterine fibroids. Maturitas. 2014 Sep;79(1):106-16. doi: 10.1016/j.maturitas.2014.06.002. Epub 2014 Jun 9.

  PMID: 24975954 BACKGROUND

• Marret H, Fritel X, Ouldamer L, Bendifallah S, Brun JL, De Jesus I, Derrien J, Giraudet G, Kahn V, Koskas M, Legendre G, Lucot JP, Niro J, Panel P, Pelage JP, Fernandez H; CNGOF (French College of Gynecology and Obstetrics). Therapeutic management of uterine fibroid tumors: updated French guidelines. Eur J Obstet Gynecol Reprod Biol. 2012 Dec;165(2):156-64. doi: 10.1016/j.ejogrb.2012.07.030. Epub 2012 Aug 29.

  PMID: 22939241 BACKGROUND

• Dolmans MM, Isaacson K, Zhang W, Gordts S, Munro MG, Stewart EA, Bourdon M, Santulli P, Donnez J. Intramural myomas more than 3-4 centimeters should be surgically removed before in vitro fertilization. Fertil Steril. 2021 Oct;116(4):945-958. doi: 10.1016/j.fertnstert.2021.08.016. No abstract available.

  PMID: 34579828 BACKGROUND

• Yan L, Ding L, Li C, Wang Y, Tang R, Chen ZJ. Effect of fibroids not distorting the endometrial cavity on the outcome of in vitro fertilization treatment: a retrospective cohort study. Fertil Steril. 2014 Mar;101(3):716-21. doi: 10.1016/j.fertnstert.2013.11.023. Epub 2014 Jan 11.

  PMID: 24424367 BACKGROUND

• Christopoulos G, Vlismas A, Salim R, Islam R, Trew G, Lavery S. Fibroids that do not distort the uterine cavity and IVF success rates: an observational study using extensive matching criteria. BJOG. 2017 Mar;124(4):615-621. doi: 10.1111/1471-0528.14362. Epub 2016 Dec 5.

  PMID: 27921379 BACKGROUND

• Khalaf Y, Ross C, El-Toukhy T, Hart R, Seed P, Braude P. The effect of small intramural uterine fibroids on the cumulative outcome of assisted conception. Hum Reprod. 2006 Oct;21(10):2640-4. doi: 10.1093/humrep/del218. Epub 2006 Jun 21.

  PMID: 16790615 BACKGROUND

• Sunkara SK, Khairy M, El-Toukhy T, Khalaf Y, Coomarasamy A. The effect of intramural fibroids without uterine cavity involvement on the outcome of IVF treatment: a systematic review and meta-analysis. Hum Reprod. 2010 Feb;25(2):418-29. doi: 10.1093/humrep/dep396. Epub 2009 Nov 12.

  PMID: 19910322 BACKGROUND

• Somigliana E, De Benedictis S, Vercellini P, Nicolosi AE, Benaglia L, Scarduelli C, Ragni G, Fedele L. Fibroids not encroaching the endometrial cavity and IVF success rate: a prospective study. Hum Reprod. 2011 Apr;26(4):834-9. doi: 10.1093/humrep/der015. Epub 2011 Feb 11.

  PMID: 21317415 BACKGROUND

• Carranza-Mamane B, Havelock J, Hemmings R; REPRODUCTIVE ENDOCRINOLOGY AND INFERTILITY COMMITTEE; SPECIAL CONTRIBUTOR. The management of uterine fibroids in women with otherwise unexplained infertility. J Obstet Gynaecol Can. 2015 Mar;37(3):277-285. doi: 10.1016/S1701-2163(15)30318-2.

  PMID: 26001875 BACKGROUND

• Pritts EA, Parker WH, Olive DL. Fibroids and infertility: an updated systematic review of the evidence. Fertil Steril. 2009 Apr;91(4):1215-23. doi: 10.1016/j.fertnstert.2008.01.051. Epub 2008 Mar 12.

  PMID: 18339376 BACKGROUND

• Ryan GL, Syrop CH, Van Voorhis BJ. Role, epidemiology, and natural history of benign uterine mass lesions. Clin Obstet Gynecol. 2005 Jun;48(2):312-24. doi: 10.1097/01.grf.0000159538.27221.8c. No abstract available.

  PMID: 15805789 BACKGROUND

MeSH Terms

Conditions

Infertility; Leiomyoma; Fibroma

Interventions

Uterine Myomectomy

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

Gynecologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Central Study Contacts

Hanbi Wang, Dr.

CONTACT

(+86)(010)69158620; zhw2005@aliyun.com

Lan Zhu, Dr.

CONTACT

zhu_julie@vip.sina.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Data analysts will be blinded to the surgical intervention assignment. Because the intervention is surgical in nature, blinding of the intervention providers and participants is not feasible.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a nationwide multicenter randomized controlled trial with a 1:1 allocation ratio between the intervention arm and the control arm. Each participating center will enroll participants competitively. Participants in the intervention arm will be instructed to undergo IVF after myomectomy, whereas participants in the control arm will proceed directly to IVF. A computer-generated randomization sequence will be used. Block randomization with randomly varying block sizes will be applied, with block sizes ranging from 4 to 8. Randomization will be stratified by study center. Allocation concealment will be implemented through a web-based randomization system.

Study Record Dates

• First Submitted: May 5, 2026
• First Posted: May 11, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: May 11, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share