The dynamics of the vaginal microbiome during infertility therapy with in vitro fertilization-embryo transfer
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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.
KeywordsMetagenomics Vagina Microbiome Infertility IVF Pregnancy
After 6-to-8 weeks of gestation
Human chorionic gonadotropin
Institutional Review Board
In vitro fertilization-embryo transfer
At late follicular stage
Long Luteal 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.
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