Infertility, In Vitro Fertilization (IVF), Uterine Myomas, Leiomyomas, or Fibromas
Conditions
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.
Interventions
PROCEDUREMyomectomy
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.
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
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.
Intervention model description
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.
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| cumulative live birth rate within 1 year after IVF treatment. | within 1 year after IVF treatment | number of participants with live birth / total number of participants who initiated treatment x 100%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical pregnancy rate after IVF | within 1 year of IVF | Visualization of an intrauterine gestational sac by transvaginal ultrasound after embryo transfer, with or without yolk sac, fetal heartbeat, or fetal pole. Calculation: number of clinical pregnancy cycles/number of embryo transfer cycles x 100%. |
| Biochemical pregnancy rate after IVF | within 1 year of IVF | a pregnancy state in which blood hCG is positive after embryo transfer but subsequently decreases, and no gestational sac is visualized by ultrasound. Calculation: number of biochemical pregnancy cycles / total number of cycles x 100%. |
| Ongoing pregnancy rate after IVF | within 1 year of IVF | Ongoing pregnancy is defined as an IVF pregnancy that progresses to 20 weeks of gestation or beyond. Calculation: number of pregnancy cycles with fetal heartbeat beyond 20 weeks / number of embryo transfer cycles x 100%. |
| Miscarriage rate after IVF | within 1 year of IVF | Miscarriage rate is defined as the proportion of pregnancy losses after clinical pregnancy. Calculation: number of miscarriages after clinical pregnancy / total number of clinical pregnancies x 100%. |
| Pregnancy-related complications | within 1 year of IVF | These include ectopic pregnancy, preterm birth, premature rupture of membranes, fetal distress, uterine rupture, fibroid degeneration during pregnancy, gestational diabetes mellitus, hypertensive disorders of pregnancy, and other relevant complications. |
Contacts
CONTACTHanbi Wang, Dr.
CONTACTLan Zhu, Dr.
Outcome results
None listed