The Dynamics of the Vaginal Microbiome During Infertility Therapy with In Vitro Fertilization-Embryo Transfer


Clinical treatment protocols for infertility with in vitro fertilization-embryo transfer (IVF-ET) provide a unique opportunity to assess the human vaginal microbiome in defined hormonal milieu. Herein, we have investigated the association of circulating ovarian-derived estradiol (E2) and progesterone (P4) concentrations to the vaginal microbiome.

Methods and Findings

Thirty IVF-ET patients were enrolled in this study, after informed consent. Blood was drawn at four time points during the IVF-ET procedure. In addition, if a pregnancy resulted, blood was drawn at 4-to-6 weeks of gestation. The serum concentrations of E2 and P4 were measured. Vaginal swabs were obtained in different hormonal milieu. Two independent genome-based technologies (and the second assayed in two different ways) were employed to identify the vaginal microbes. The vaginal microbiome underwent a transition with a decrease in E2 (and/or a decrease in P4). Novel bacteria were found in the vagina of 33% of the women undergoing IVF-ET.


Our approach has enabled the discovery of novel, previously unidentified bacterial species in the human vagina in different hormonal milieu. While the relationship of hormone concentration and vaginal microbes was found to be complex, the data support a shift in the microbiome of the human vagina during IVF-ET therapy using standard protocols. The data also set the foundation for further studies examining correlations between IVF-ET outcome and the vaginal microbiome within a larger study population.
The CEL files for this project are available for download at


Richard W. Hyman
(rhyman at stanford dot edu)

Project Team

Richard W. Hyman 1,3
Christopher N. Herndon 4
Marilyn Fukushima 3
Denise Bernstein 4
Kim Chi Vo 4
Robert P. St.Onge 3
Molly Miranda 3
Ana Maria Aparicio 3
Hyunsung Kim 5
Nader Pourmand 5
Zara Zelenko 4
Hui Jiang 3,6
Ronald W. Davis 1,2,3
Linda C. Giudice 4


Stanford University
Department of Biochemistry1
Department of Genetics2
Stanford Genome Technology Center3
Department of Statistics6

Uinversity of California, Santa Cruz
Biomelecular Engineering Department, Jack Baskin School of Engineering5

University of California, San Francisco
Department of Obstetrics and Gynecology4