SYSTEMATIC REVIEW OF THE ASSOCIATION BETWEEN VAGINAL MICROBIOME COMPOSITION AND THE SUCCESS OF FROZEN EMBRYO TRANSFER

Authors

  • Fatima Noor Mercy Teaching Hospital, Riphah International University, Islamabad, Pakistan. Author
  • Mah Noor Khan Mercy Teaching Hospital, Riphah International University, Islamabad, Pakistan. Author
  • Mahin Aftab Lady Reading Hospital, Peshawar, Pakistan. Author
  • Farhat R Malik Peshawar Medical College, Riphah International University, Islamabad, Pakistan. Author
  • Aisha Ali Peshawar Medical College, Riphah International University, Islamabad, Pakistan. Author
  • Muniba Ali Khyber Medical University Peshawar, Pakistan. Author
  • Zarina Naz National University of Medical Sciences, Rawalpindi, Pakistan. Author

DOI:

https://doi.org/10.71000/q57vbs63

Keywords:

Vaginal Microbiome, Frozen Embryo Transfer, Infertility, Implantation, Lactobacillus, Systematic Review

Abstract

Background: Infertility remains a significant global health burden, with frozen embryo transfer (FET) constituting an increasingly prevalent and successful assisted reproductive technology. Despite advancements, implantation failure persists, prompting investigation into the endometrial microenvironment. The vaginal microbiome is a dynamic component of this environment, yet its specific association with FET outcomes remains inconsistently reported, necessitating a systematic synthesis of the evidence.

Objective: This systematic review aims to synthesize the available evidence linking specific vaginal microbiome compositions to implantation and clinical pregnancy rates in individuals undergoing frozen embryo transfer.

Methods: Following PRISMA guidelines, a comprehensive search of PubMed/MEDLINE, Scopus, Cochrane Library, and Web of Science was conducted for observational studies published between 2014-2024. Eligible studies reported on vaginal microbiome composition prior to or during an FET cycle and its association with reproductive outcomes. Two independent reviewers performed study selection, data extraction, and quality assessment using the Newcastle-Ottawa Scale.

Results: Eight observational studies (n=1,347 participants) were included. A key finding was methodological divergence: studies using molecular sequencing (16S rRNA) consistently associated a Lactobacillus-dominant microbiome, particularly with L. crispatus, with significantly higher clinical pregnancy rates. Conversely, studies utilizing Nugent scoring found no significant association between bacterial vaginosis-defined dysbiosis and FET outcomes.

Conclusion: The association between vaginal microbiome and FET success appears contingent on assessment methodology. An optimal microbiome, characterized by specific beneficial lactobacilli, may support implantation, whereas traditional diagnostic criteria lack sensitivity for this predictive role. Current evidence, while promising, is observational and heterogeneous. Future research requires standardized molecular methodologies and randomized controlled trials to explore causal relationships and therapeutic modulation.

Author Biographies

  • Fatima Noor, Mercy Teaching Hospital, Riphah International University, Islamabad, Pakistan.

    FCPS Trainee, (Completed Training) Gynecology and Obstetrics Unit, Mercy Teaching Hospital, Riphah International University, Islamabad, Pakistan.

  • Mah Noor Khan, Mercy Teaching Hospital, Riphah International University, Islamabad, Pakistan.

    FCPS Trainee, Gynecology and Obstetrics Unit, Mercy Teaching Hospital, Riphah International University, Islamabad, Pakistan.

  • Mahin Aftab, Lady Reading Hospital, Peshawar, Pakistan.

    FCPS Trainee, Gynecology and Obstetrics, Lady Reading Hospital, Peshawar, Pakistan.

  • Farhat R Malik, Peshawar Medical College, Riphah International University, Islamabad, Pakistan.

    Professor, Community Health Sciences, Peshawar Medical College, Riphah International University, Islamabad, Pakistan.

  • Aisha Ali, Peshawar Medical College, Riphah International University, Islamabad, Pakistan.

    Registrar, Gynecology and Obstetrics Unit, Mercy Teaching Hospital, affiliated with Peshawar Medical College, Riphah International University, Islamabad, Pakistan.

  • Muniba Ali, Khyber Medical University Peshawar, Pakistan.

    MBBS, FCPS Gynaecology and Obstetrics, MRCOG 1 UK,  MRCOG 2 UK, BCRM, Consultant Gynecologist and Obstetrician, Khyber Medical University Peshawar, Pakistan.

  • Zarina Naz, National University of Medical Sciences, Rawalpindi, Pakistan.

    MSN and MHPE Scholar, National University of Medical Sciences, Rawalpindi, Pakistan.

References

WHO. Infertility Prevalence Estimates, 1990–2021. Geneva: World Health Organization; 2023.

Wei D, Liu JY, Sun Y, Shi Y, Zhang B, Liu JQ, et al. Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial. Lancet. 2019;393(10178):1310-8.

Craciunas L, Gallos I, Chu J, Bourne T, Quenby S, Brosens JJ, et al. Conventional and modern markers of endometrial receptivity: a systematic review and meta-analysis. Hum Reprod Update. 2019;25(2):202-23.

Kroon SJ, Ravel J, Huston WM. Cervicovaginal microbiota, women's health, and reproductive outcomes. Fertil Steril. 2018;110(3):327-36.

Moreno I, Simon C. Deciphering the effect of reproductive tract microbiota on human reproduction. Reprod Med Biol. 2019;18(1):40-50.

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.

Ko HS, Lee Y, Lee SK, Kim S, Kang M, Yang KM. Vaginal microbiome composition and pregnancy outcomes in women undergoing frozen-thawed single blastocyst transfer. Sci Rep. 2023;13(1):4518.

Fu M, Zhang X, Liang Y, Lin S, Qian W, Fan J. Alterations in vaginal microbiota and associated metabolome in women with recurrent implantation failure. mBio. 2020;11(3):e03242-19.

Haahr T, Jensen JS, Thomsen L, Duus L, Rygaard K, Humaidan P. Abnormal vaginal microbiota may be associated with poor reproductive outcomes: a prospective study in IVF patients. Hum Reprod. 2016;31(4):795-803. (Included as a seminal study frequently cited within the 5-year window).

Park S, You YA, Yun H, Choi SJ, Hwang HS, Choi SK, et al. Cervicovaginal fluid cytokines as predictive markers of pregnancy outcome in frozen-thawed embryo transfer cycles. Am J Reprod Immunol. 2021;85(3):e13348.

Vergaro P, Tiscornia G, Barragán M, García D, Rodriguez A, Santaló J, et al. Vaginal microbiota profile at the time of embryo transfer does not affect live birth rate in IVF cycles: a prospective cohort study. Hum Reprod. 2022;37(5):1014-1025.

Benner M, Ferwerda G, Joosten I, van der Molen RG. How uterine microbiota might be responsible for a receptive, fertile endometrium. Hum Reprod Update. 2018;24(4):393-415. (Included for its comprehensive mechanistic framework relevant to interpretation).

Wee BA, Thomas M, Sweeney EL, Frentiu FD, Samios M, Ravel J, et al. A retrospective pilot study to determine whether the reproductive tract microbiota differs between women with a history of infertility and fertile women. Aust N Z J Obstet Gynaecol. 2018;58(3):341-348.

Kyono K, Hashimoto T, Nagai Y, Sakuraba Y. Analysis of endometrial and vaginal microbiota in patients with repeated implantation failure and recurrent pregnancy loss. J Assist Reprod Genet. 2018;35(2):355-362.

Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603-5.

Downloads

Published

2025-12-12