REVIEW article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Reproduction
The Role of the Reproductive Tract and Follicular Fluid Microbiota in IVF/ICSI Pregnancy Outcomes: A Systematic Review of Microbial Diversity and Probiotic Interventions
Guangyu Ma
Leixi Peng
Rui Cai
Bixi He
Jinbiao Han
Rui Gao
Lang Qin
Reproductive Centre, Department of Obstetrics and Gynaecology, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
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Abstract
Objective: To investigate associations between reproductive tract and follicular fluid microbiota composition, microbial diversity, and probiotic interventions with pregnancy outcomes after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Data sources: PubMed, Embase, Web of Science, and the Cochrane Library were searched from January 2000 to August 2025, with manual screening of references. Study eligibility criteria: Original human studies on women undergoing IVF/ICSI reporting reproductive tract or follicular fluid microbiota, pregnancy outcomes, or probiotic interventions. Included designs comprised randomized controlled trials and observational studies. Study appraisal and synthesis methods: Two reviewers independently screened, extracted, and assessed study quality using RoB 2.0, ROBINS-I, and JBI tools. Due to heterogeneity in study designs, sampling sites, and microbiota methods, we performed a qualitative synthesis. Results: Of 2546 records, 40 studies were finally included. Most studies reported that a Lactobacillus-dominant reproductive tract microbiota, particularly Lactobacillus crispatus, was associated with higher implantation, clinical pregnancy, and live birth rates, whereas non-Lactobacillus or pathogen-enriched profiles correlated with poorer outcomes. Microbial diversity alone was inconsistently predictive. Evidence for follicular fluid microbiota influencing pregnancy outcomes was limited. Longer-term or individualized probiotic regimens increased Lactobacillus abundance and were linked to improved outcomes, while short-term interventions showed minimal effect. Conclusion: Species-level and site-specific reproductive tract microbiota better predict assisted reproductive technology outcomes than diversity measures alone. Personalized or longer-duration probiotic strategies may be beneficial, but current evidence is limited and heterogeneous. Well-designed longitudinal, site-specific trials are needed to determine the efficacy of microbiota-targeted interventions in IVF/ICSI.
Summary
Keywords
Follicular Fluid, in vitro fertilization, Intracytoplasmic sperm injection, pregnancy outcomes, Probiotics, reproductive tract microbiota
Received
02 December 2025
Accepted
05 February 2026
Copyright
© 2026 Ma, Peng, Cai, He, Han, Gao and Qin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Rui Gao; Lang Qin
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