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Therapeutic intervention based on gene sequencing analysis of microbial 16S ribosomal RNA of the intrauterine microbiome improves pregnancy outcomes in IVF patients: a prospective cohort study

  • Assisted Reproduction Technologies
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Abstract

Purpose

A Lactobacillus-dominated microbiota in the endometrium was reported to be associated with favorable reproductive outcomes. We investigated in this study whether 16S ribosomal RNA (rRNA) gene sequencing analysis of the uterine microbiome improves pregnancy outcomes.

Methods

This prospective cohort study recruited a total of 195 women with recurrent implantation failure (RIF) between March 2019 and April 2021 in our fertility center. Analysis of the endometrial microbiota by 16S rRNA gene sequencing was suggested for all patients who had three or more failed embryo transfers (ETs). One hundred and thirty-one patients underwent microbial 16S rRNA gene sequencing (study group) before additional transfers, while 64 patients proceeded to ET without that analysis (control group). The primary outcome was to compare the cumulative clinical pregnancy rate of two additional ETs.

Main results

An endometrial microbiota considered abnormal was detected in 30 patients (22.9%). All but one of these 30 patients received antibiotics according to the bacterial genus detected in their sample, followed by treatment with probiotics. As a result, the cumulative clinical pregnancy rate (study group: 64.5% vs. control group: 33.3%, p = 0.005) and the ongoing pregnancy rate (study group: 48.9% vs. control group: 32.8%, p = 0.028) were significantly increased in the study group compared to the control group.

Conclusion

Personalized treatment recommendations based on the microbial 16S rRNA gene sequencing of the uterine microbiota can improve IVF outcomes of patients with RIF.

Trial registration

The University Hospital Medical Information Network (UMIN) Clinical Trial Registry: UMIN000036050 (date of registration: March 1, 2019).

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Data availability

The results of EMMA and datasets analyzed in this study are available from the corresponding author upon reasonable request. Here is the link to the data depository: https://center6.umin.ac.jp/cgi-bin/icdr_e/ctr_view.cgi?recptno=R000041006.

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Acknowledgements

We thank Ms. Viviane Casaroli MSc, for her excellent help with English proofreading. We also wish to thank Ms. Yuko Takeda for data collection, and Ms. Nami Hirayama and Ms. Masae Shibasaki for the statistical analysis (both are clinical staff in the Kamiya Ladies Clinic). Finally, we would like to extend our gratitude to Professor Daiki Iwami Ph.D., from Jichi Medical University, for proofreading the manuscript.

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Authors and Affiliations

  1. Department of Reproductive Health, Iryo Ho** Shadan Kamiya Ladies Clinic, Nittsu Bldg 2nd floor 2-1, Nishi 2-Chome, Kita 3-Jo, Chuo-Ku, Sapporo, Hokkaido, 060-0003, Japan

    Nanako Iwami, Miho Kawamata, Naoko Ozawa, Takahiro Yamamoto, Eri Watanabe, Masahito Mizuuchi, Osamu Moriwaka & Hirobumi Kamiya

  2. Department of Reproductive Health, Iryo Ho** Shadan Mizuuchi Women’s Clinic, 2-5 Toyooka 4Jo 3Chome, Asahikawa, Hokkaido, 078-8234, Japan

    Masahito Mizuuchi

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  1. Nanako Iwami
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Contributions

NI: protocol development, data analysis, data collection, and manuscript writing. MK, NO, TY, EW, MM, and OM: data collection. HK: data collection, protocol development, and supervision.

Corresponding author

Correspondence to Nanako Iwami.

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Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the Kamiya Ladies Clinic and with the 1964 Helsinki Declaration and its later amendments or similar ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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The authors declare no competing interests.

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Iwami, N., Kawamata, M., Ozawa, N. et al. Therapeutic intervention based on gene sequencing analysis of microbial 16S ribosomal RNA of the intrauterine microbiome improves pregnancy outcomes in IVF patients: a prospective cohort study. J Assist Reprod Genet 40, 125–135 (2023). https://doi.org/10.1007/s10815-022-02688-6

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