Overview
This single-center, prospective, two-stage clinical trial aims to evaluate the safety, preliminary efficacy, and reproductive outcomes of oral Fecal Microbiota Transplantation (FMT) freeze-dried capsules in overweight and obese patients with Polyendocrine Metabolic Ovarian Syndrome (PMOS) undergoing Frozen-Thawed Embryo Transfer (FET).The study is implemented in two sequential phases:
Phase Ⅰ (Pilot Exploration): A prospective, open-label, single-arm exploratory study in an initial evaluable cohort ($n=11$) to evaluate preliminary safety, dynamic gut microbiota colonization, endocrine/metabolic parameters, and pregnancy outcomes following FET.
Phase Ⅱ (Confirmatory RCT): A prospective, randomized controlled trial (RCT) designed to validate the clinical efficacy and underlying mechanisms of oral FMT capsules compared with control interventions, based on findings established in Phase Ⅰ.
Description
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 (BMI24.0kg/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: Two or 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.
Eligibility
Inclusion Criteria:
- 1\. Females aged 20 to 40 years old.
- 2\. Meeting the diagnostic criteria for Polyendocrine Metabolic Ovarian Syndrome (PMOS).
- 3\. Body Mass Index (BMI): \>24 kg/m²(covering overweight and obese patients according to Asian criteria, addressing the actual recruited cohort ranging from 24 kg/m² upwards).
- 4\. Scheduled to undergo Frozen-Thawed Embryo Transfer (FET) at the Reproductive Medicine Center.
- 5\. Voluntary participation with signed Informed Consent Form (ICF).
Exclusion Criteria:
- Age \< 20 or \> 40 years.
- Pregnancy or lactation.
- Other endocrine disorders (e.g., Cushing's syndrome, thyroid dysfunction); severe organ dysfunction or impaired intestinal mucosal barrier; use of antibiotics, probiotics, or prebiotics within 1 month.
- Use of ovulation-modifying or anti-androgen drugs within 3 months; severe psychiatric disorders.
- Concurrent participation in other clinical trials.
