This 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 planned multicenter, 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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
201
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.
Center for Reproductive Medicine,Shanghai Changzheng Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGClinical Pregnancy Rate
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.
Time frame: Assessed up to 8 weeks following the Frozen-Thawed Embryo Transfer (FET)(approximately within 6 months following the completion of the FMT intervention).
Biochemical Pregnancy Rate
The percentage of participants who achieve a biochemical pregnancy, confirmed by a serum beta-hCG level \> 10 mIU/mL.
Time frame: Assessed at 14 days following the Frozen-Thawed Embryo Transfer (FET)
Incidence of Adverse Events (AEs)
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.
Time frame: Assessed from the first dose of FMT through the 12-week post-treatment follow-up
Change in Body Mass Index (BMI)
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.
Time frame: Baseline and 4 weeks post-FMT.
Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
Evaluation of the mean change in insulin resistance assessed by the HOMA-IR index (calculated from fasting blood glucose and fasting insulin levels).
Time frame: Baseline, 4 weeks post-FMT, and 12 weeks post-FMT.
Change in Serum Total Testosterone (T) Level
Evaluation of the mean change in fasting serum total testosterone levels from baseline.
Time frame: Baseline, 4 weeks post-FMT, and 12 weeks post-FMT.
Change in Serum Luteinizing Hormone (LH) Level
Evaluation of the mean change in fasting serum luteinizing hormone levels from baseline.
Time frame: Baseline, 4 weeks post-FMT, and 12 weeks post-FMT.
Change in Serum Interleukin-6 (IL-6) Level
Evaluation of the mean change in systemic inflammatory marker Interleukin-6 (IL-6) from baseline.
Time frame: Baseline, 4 weeks post-FMT, and 12 weeks post-FMT.
Change in Gut Microbiota Alpha Diversity (Shannon Index)
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.
Time frame: Baseline and 4 weeks post-FMT.
Live Birth Rate (LBR)
The percentage of participants who deliver at least one live-born infant after 24 weeks of gestation.
Time frame: Assesssed up to 42 weeks following the Frozen-Thawed Embryo Transfer (FET)
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