Vaginal microbiota alterations under supraphysiological estradiol state during in vitro fertilization-embryo transfer (IVF-ET) and the association with reproductive outcomes
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Study information
incomplete
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Chen X., Chen F., Wu S., Lv P., Li P.
Journal
BMC microbiology
Year
2025
Keywords:
In vitro fertilization-embryo transfer (IVF-ET), Pregnancy outcomes, Supraphysiological estradiol (E2) level, Vaginal microbiome
BACKGROUND: The process of in vitro fertilization-embryo transfer (IVF-ET) induces a maternal supraphysiological estradiol environment during embryo implantation and early development. Estrogen is crucial in modulating the colonization of microbiota within the vaginal epithelium. However, the impact of supraphysiological estradiol levels on the vaginal microbiome and the relationship with pregnancy outcomes remains unclear. RESULTS: The study aimed to characterize the vaginal microbiota under supraphysiological hormonal conditions. A total of 67 patients undergoing fresh embryo transfer were divided into three groups based on their peak estradiol levels: high-estradiol (HE) group (E2 > 11,000 pmol/L), median-estradiol (ME) group (E2 5,000-11,000 pmol/L), and low-estradiol (LE) group (E2 < 5,000 pmol/L). Twenty-five patients undergoing frozen-thawed embryo transfer were categorized into natural cycle (NC) group and hormone replacement cycle (HRT) group according to endometrial preparation protocols. Using 16S rRNA sequencing, we found that the vaginal microbiome exhibited variations with changes in peak estradiol levels. The elevated estradiol levels during ovarian stimulation or exogenous estrogen supplementation, significantly reduced alpha diversity, altered beta diversity within the vaginal microbiome, and shifted the vaginal community state types (CSTs) in Chinese infertile women toward Lactobacillus-dominant profiles, resembling those observed in most Asian women previously. However, the reproductive outcomes were not improved by these variations. The Streptococcus_anginosus and Akkermansia abundance correlated with estradiol levels positively, whereas Escherichia-Shigella showed a negative correlation. The abundance of Streptococcus, Atopobium, and Bifidobacterium on the day of embryo transfer may serve as predictors for adverse pregnancy outcomes, as determined by calculating the area under the curve (AUC) values. CONCLUSIONS: Supraphysiological estradiol levels induced by IVF-ET significantly alter vaginal microbiota and shift the CSTs in Chinese infertile women toward patterns of most Asian women. The Lactobacillus dominance under supraphysiological estradiol conditions does not help improve assisted reproductive outcomes. The abundance of Streptococcus, Atopobium, and Bifidobacterium on the day of embryo transfer may serve as predictors for adverse pregnancy outcomes. Among them, Streptococcus correlates positively with peak estradiol levels and may act as a microbial mediator impairing reproductive success under hyperestrogenic conditions. However, further larger-scale researches are needed to identify and elucidate the potential mechanisms.
Experiment 1
incomplete
Subjects
- Location of subjects
- China
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Vagina Distal oviductal region,Distal portion of oviduct,Vaginae,Vagina,vagina
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Estradiol [H][C@]12CC[C@]3(C)C(O)CC[C@@]3([H])[C@]1([H])CCc1cc(O)ccc21,C18H24O2,estra-1,3,5(10)-triene-3,17-diol,InChI=1/C18H24O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3,5,10,14-17,19-20H,2,4,6-9H2,1H3/t14-,15-,16+,17?,18+/m1/s1,InChIKey=VOXZDWNPVJITMN-WKUFJEKOBY,oestradiol,Estradiol,estradiol
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Control group
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Estradiol/Cycle Group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients undergoing fresh embryo transfer divided into HE (> 11,000 pmol/L), ME (5,000–11,000 pmol/L), LE (< 5,000 pmol/L) based on trigger day E2 levels. Frozen-thawed transfer patients divided into NC or HRT protocols
- Group 1 sample size Number of subjects in the case (exposed) group
- 91
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Patients who had used antibiotics, vaginal probiotics, or immunomodulatory medication during the embryo transfer cycle were excluded.
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 1
Needs review
Source: Table
Description: Escherichia Shigella was identified as a biomarker for the HRT group in comparison of vaginal microbiota across different estradiol/cycle groups.
Abundance in Group 1: increased abundance in Estradiol/Cycle Group
| NCBI | Quality Control | Links |
|---|---|---|
| Escherichia ShigellaEscherichia Shigella |
Revision editor(s): Kimbrene Kakande
Signature 2
Needs review
Source: Table 2
Description: Prevotella was identified as a biomarker for the LE group in comparison of vaginal microbiota across different estradiol/cycle groups.
Abundance in Group 1: increased abundance in Estradiol/Cycle Group
| NCBI | Quality Control | Links |
|---|---|---|
| Prevotella |
Revision editor(s): Kimbrene Kakande
Signature 3
Needs review
Source: Table 2
Description: Akkermansia was identified as a biomarker for the HE group in comparison of vaginal microbiota across different estradiol/cycle groups.
Abundance in Group 1: increased abundance in Estradiol/Cycle Group
| NCBI | Quality Control | Links |
|---|---|---|
| Akkermansia |
Revision editor(s): Kimbrene Kakande
Signature 4
Needs review
Source: Table 2
Description: Lactobacillus_iners was identified as a biomarker for the HRT group in comparison of vaginal microbiota across different estradiol/cycle groups.
Abundance in Group 1: increased abundance in Estradiol/Cycle Group
| NCBI | Quality Control | Links |
|---|---|---|
| Lactobacillus_inersLactobacillus_iners |
Revision editor(s): Kimbrene Kakande
Experiment 2
incomplete
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Vaginal microbiome measurement vaginal flora measurement,vaginal microbiota measurement,Vaginal microbiome measurement,vaginal microbiome measurement
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Ongoing pregnancy(OP)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Adverse
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Not specified
- Group 0 sample size Number of subjects in the control (unexposed) group
- 70
- Group 1 sample size Number of subjects in the case (exposed) group
- 22
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Not specified
Lab analysis
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- Not specified
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