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

  • ASSISTED REPRODUCTION TECHNOLOGIES
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

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.

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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

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Acknowledgements

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.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Stanford University, Stanford, CA, USA

    Richard W. Hyman, Curtis Palm & Ronald W. Davis

  2. Department of Stanford Genome Technology Center, Stanford University, Stanford, CA, USA

    Richard W. Hyman, Hui Jiang, Curtis Palm, Marilyn Fukushima & Ronald W. Davis

  3. Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, 505 Parnassus Avenue, Room M1496, San Francisco, CA, USA, 94143-0132

    Christopher N. Herndon, Denise Bernstein, Kim Chi Vo, Zara Zelenko & Linda C. Giudice

  4. Department of Statistics, Stanford University, Stanford, CA, USA

    Hui Jiang

  5. Department of Genetics, Stanford University, Stanford, CA, USA

    Ronald W. Davis

  6. Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA

    Hui Jiang

Authors
  1. Richard W. Hyman
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  2. Christopher N. Herndon
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  3. Hui Jiang
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  4. Curtis Palm
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  5. Marilyn Fukushima
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  6. Denise Bernstein
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  7. Kim Chi Vo
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  8. Zara Zelenko
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  9. Ronald W. Davis
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  10. Linda C. Giudice
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Corresponding author

Correspondence to Linda C. Giudice.

Additional information

Author contributions

RWH and LCG designed the experiments and wrote this manuscript. CNH developed the clinical database of IVF-ET patients and coordinated running the hormone assays. HJ performed several of the statistical analyses. CP applied UniFrac to the data and undertook the QIIME analyses. MF carried out the sequencing reactions, processed and assembled the sequence reads, and compared the consensus sequences to the data in the RDP. MF and RWH hand edited the contigs. KCV and DB identified appropriate patients, screened and enrolled patients, facilitated UCSF IRB compliance and sample collection, and transfer to the SGTC. ZZ measured the hormone concentrations. RWD provided the intellectual, physical, and financial milieu for the experiments at the SGTC.

Capsule

Metagenomics was used to determine the vaginal microbiome in IVF-ET cycles. Diversity of species varied in 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.

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Hyman, R.W., Herndon, C.N., Jiang, H. et al. The dynamics of the vaginal microbiome during infertility therapy with in vitro fertilization-embryo transfer. J Assist Reprod Genet 29, 105–115 (2012). https://doi.org/10.1007/s10815-011-9694-6

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  • DOI: https://doi.org/10.1007/s10815-011-9694-6

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