Fecal Microbiota Transplantation for Obese Women With Polyendocrine Metabolic Ovarian Syndrome

Background:Polyendocrine Metabolic Ovarian Syndrome (PMOS), formerly recognized as Polycystic Ovary Syndrome (PCOS), is a systemic disorder characterized by hyperandrogenism, insulin resistance, chronic low-grade inflammation, and gut microbiota dysbiosis. These abnormalities frequently impair endometrial receptivity, oocyte quality, and clinical pregnancy outcomes in assisted reproductive technology (ART) cycles. Fecal Microbiota Transplantation (FMT) offers a targeted approach to restore gut microecology and alleviate metabolic-endocrine dysfunction.

Study Design:This study adopts a prospective, two-stage sequential implementation framework.

Phase 1 (Single-Arm Exploratory Pilot Stage):

Objective: To establish preliminary safety, tolerability, gut microbiota remodeling, and reproductive feasibility of oral FMT in PMOS patients undergoing FET.

Cohort: An initial exploratory cohort of 11 evaluable overweight or obese patients with PMOS (BMI≥24.0kg/m2) scheduled for Frozen-Thawed Embryo Transfer (FET).

Design: Prospective, open-label, single-arm pilot study without a concurrent control group.

Phase 2 (Randomized Controlled Trial Stage):

Objective: To rigorously confirm therapeutic efficacy, metabolic amelioration, and pregnancy rate enhancement in a larger sample size based on Phase 1 safety and biomarker findings.

Design: Prospective, randomized controlled trial comparing oral FMT capsule intervention with standard care/placebo control.

Intervention Protocol:Participants in the FMT intervention receive oral FMT freeze-dried powder capsules derived from strictly screened, traceable healthy donors provided by a standardized Microbiota Biobank.

Dosage: 5 capsules twice daily, taken orally on an empty stomach for 6 consecutive days per course.

Schedule: Three identical courses separated by a 4-week interval. Background Care: Standardized lifestyle and dietary guidance are maintained throughout both phases.

Study Endpoints:

Primary Endpoints:Reproductive and pregnancy outcomes following FET (biochemical pregnancy rate, clinical pregnancy rate, embryo implantation rate).Safety and tolerability (incidence, severity, and causality of Adverse Events).

Secondary Endpoints:

Endocrine profiles (LH, FSH, Total Testosterone, Free Testosterone, PRL, Progesterone, Estradiol).

Metabolic and glycemic parameters (BMI, fasting blood glucose, HbA1c, fasting insulin, HOMA-IR, lipid profiles).

Systemic inflammatory and gut barrier markers (CRP, TNF-α, IL-6, IL-22, LPS). Gut microbiota structure and diversity via metagenomic sequencing and bile acid metabolomics.

Participants in this experimental arm are overweight and obese patients with Polyendocrine Metabolic Ovarian Syndrome (PMOS) scheduled for Frozen-Thawed Embryo Transfer (FET). They will receive standardized oral fecal microbiota transplantation (FMT) capsules without antibiotic pretreatment. Standardized lifestyle and dietary guidance will be provided throughout the study.

Biological: oral Fecal Microbiota Transplantation

Participants in this comparing arm are overweight and obese patients with Polyendocrine Metabolic Ovarian Syndrome (PMOS) scheduled for Frozen-Thawed Embryo Transfer (FET). They will receive visually and olfactory-matched placebo capsules without antibiotic pretreatment. Standardized lifestyle and dietary guidance will be provided throughout the study.

Other: Placebo

Participants will receive standardized oral FMT freeze-dried powder capsules without antibiotic pretreatment. The capsules are derived from strictly screened, traceable healthy donors from a standardized Microbiota Biobank.

Dosage and Regimen: Oral administration of 5 capsules twice daily on an empty stomach for 6 consecutive days, which constitutes one course. The complete regimen consists of 3 identical courses administered at Week 0, Week 4, and Week 8.

Background: Standardized lifestyle and dietary guidance will be provided throughout the study.

Participants will receive visually and olfactory-matched placebo capsules without antibiotic pretreatment.

Dosage and Regimen:Oral administration of 5 capsules twice daily on an empty stomach for 6 consecutive days per course. The complete regimen consists of 3 identical courses administered at Week 0, Week 4, and Week 8, exactly mirroring the experimental arm.

Background: Standardized lifestyle and dietary guidance will be provided throughout the study.

Plazo: Assessed up to 8 weeks following the Frozen-Thawed Embryo Transfer (FET)(approximately within 6 months following the completion of the FMT intervention).

The percentage of participants who achieve a confirmed clinical pregnancy, defined as the presence of at least one intrauterine gestational sac with a viable fetal heartbeat confirmed by transvaginal ultrasound.

Plazo: Assessed at 14 days following the Frozen-Thawed Embryo Transfer (FET)

The percentage of participants who achieve a biochemical pregnancy, confirmed by a serum beta-hCG level \> 10 mIU/mL.

Plazo: Assessed from the first dose of FMT through the 12-week post-treatment follow-up

The number of participants experiencing any treatment-related adverse events or serious adverse events, graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0),including diarrhea,bloating,abdominal pain,constipation,etc.

Plazo: Baseline and 4 weeks post-FMT.

Evaluation of the mean change in Body Mass Index (calculated as weight in kilograms divided by height in meters squared) from baseline to post-treatment.

Plazo: Baseline, 4 weeks post-FMT, and 12 weeks post-FMT.

Evaluation of the mean change in insulin resistance assessed by the HOMA-IR index (calculated from fasting blood glucose and fasting insulin levels).

Plazo: Baseline, 4 weeks post-FMT, and 12 weeks post-FMT.

Evaluation of the mean change in fasting serum total testosterone levels from baseline.

Plazo: Baseline, 4 weeks post-FMT, and 12 weeks post-FMT.

Evaluation of the mean change in fasting serum luteinizing hormone levels from baseline.

Plazo: Baseline, 4 weeks post-FMT, and 12 weeks post-FMT.

Evaluation of the mean change in systemic inflammatory marker Interleukin-6 (IL-6) from baseline.

Plazo: Baseline and 4 weeks post-FMT.

Evaluation of the change in gut microbial alpha diversity from baseline, primarily assessed using the Shannon Diversity Index derived from metagenomic or 16S rRNA sequencing of fecal samples.

Plazo: Assesssed up to 42 weeks following the Frozen-Thawed Embryo Transfer (FET)

The percentage of participants who deliver at least one live-born infant after 24 weeks of gestation.

Fecal Microbiota Transplantation for the Treatment of Polyendocrine Metabolic Ovarian Syndrome in Obese Women:A Phase Ⅰ/ⅡSingle-Arm Pilot Study and Planned Randomized Controlled Trial