Journal of Assisted Reproduction and Genetics

, Volume 29, Issue 2, pp 105–115 | Cite as

The dynamics of the vaginal microbiome during infertility therapy with in vitro fertilization-embryo transfer

  • Richard W. Hyman
  • Christopher N. Herndon
  • Hui Jiang
  • Curtis Palm
  • Marilyn Fukushima
  • Denise Bernstein
  • Kim Chi Vo
  • Zara Zelenko
  • Ronald W. Davis
  • Linda C. Giudice
ASSISTED REPRODUCTION TECHNOLOGIES

Abstract

Purpose

To determine the vaginal microbiome in women undergoing IVF-ET and investigate correlations with clinical outcomes.

Methods

Thirty patients had blood drawn for estradiol (E2) and progesterone (P4) at four time points during the IVF-ET cycle and at 4–6 weeks of gestation, if pregnant. Vaginal swabs were obtained in different hormonal milieu, and the vaginal microbiome determined by deep sequencing of the 16S ribosomal RNA gene.

Results

The vaginal microbiome underwent a transition during therapy in some but not all patients. Novel bacteria were found in 33% of women tested during the treatment cycle, but not at 6–8 weeks of gestation. Diversity of species varied across different hormonal milieu, and on the day of embryo transfer correlated with outcome (live birth/no live birth). The species diversity index distinguished women who had a live birth from those who did not.

Conclusions

This metagenomics approach has enabled discovery of novel, previously unidentified bacterial species in the human vagina in different hormonal milieu and supports a shift in the vaginal microbiome during IVF-ET therapy using standard protocols. Furthermore, the data suggest that the vaginal microbiome on the day of embryo transfer affects pregnancy outcome.

Keywords

Metagenomics Vagina Microbiome Infertility IVF Pregnancy 

Abbreviations

AP

Antagonist Protocol

B

At baseline

DH

Demi-Halt Protocol

E2

Estradiol

GE

After 6-to-8 weeks of gestation

GnRH

Gonadotropin-releasing hormone

hCG

Human chorionic gonadotropin

IRB

Institutional Review Board

IVF-ET

In vitro fertilization-embryo transfer

LF

At late follicular stage

LLP

Long Luteal Protocol

MFP

Microflare Protocol

P4

Progesterone

PCA

Principal Component Analysis

RDP

Ribosomal Database Project

rDNA

The 16S ribosomal RNA gene

SDI

Shannon Diversity Index

SGTC

Stanford Genome Technology Center

TR

At embryo transfer

UCSF

University of California San Francisco

VLDL

Very Low Dose leuprolide acetate Protocol

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Richard W. Hyman
    • 1
    • 2
  • Christopher N. Herndon
    • 3
  • Hui Jiang
    • 2
    • 4
    • 6
  • Curtis Palm
    • 1
    • 2
  • Marilyn Fukushima
    • 2
  • Denise Bernstein
    • 3
  • Kim Chi Vo
    • 3
  • Zara Zelenko
    • 3
  • Ronald W. Davis
    • 1
    • 2
    • 5
  • Linda C. Giudice
    • 3
  1. 1.Department of BiochemistryStanford UniversityStanfordUSA
  2. 2.Department of Stanford Genome Technology CenterStanford UniversityStanfordUSA
  3. 3.Department of Obstetrics, Gynecology and Reproductive SciencesUniversity of CaliforniaSan FranciscoUSA
  4. 4.Department of StatisticsStanford UniversityStanfordUSA
  5. 5.Department of GeneticsStanford UniversityStanfordUSA
  6. 6.Department of BiostatisticsUniversity of MichiganAnn ArborUSA

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