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



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


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.


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.


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.


Metagenomics Vagina Microbiome Infertility IVF Pregnancy 



Antagonist Protocol


At baseline


Demi-Halt Protocol




After 6-to-8 weeks of gestation


Gonadotropin-releasing hormone


Human chorionic gonadotropin


Institutional Review Board


In vitro fertilization-embryo transfer


At late follicular stage


Long Luteal Protocol


Microflare Protocol




Principal Component Analysis


Ribosomal Database Project


The 16S ribosomal RNA gene


Shannon Diversity Index


Stanford Genome Technology Center


At embryo transfer


University of California San Francisco


Very Low Dose leuprolide acetate Protocol



We thank Liza Jalalian and Shehua Shen for assistance with the measurement of the serum hormone concentrations, and Monika Trebo for posting the CEL files on the Stanford Genome Technology Center website.

This work was supported by National Human Genome Research Institute grant P01 HG000205 (RWD, LCG).

Competing interests statement

The authors declare no competing financial interests.

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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