Vaginal microbiota alterations under supraphysiological estradiol state during in vitro fertilization-embryo transfer (IVF-ET) and the association with reproductive outcomes
Abstract 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, th...
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2025-08-01
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| Online Access: | https://doi.org/10.1186/s12866-025-04242-7 |
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| author | Xijing Chen Feng Chen Shufang Wu Pingping Lv Ping Li |
| author_facet | Xijing Chen Feng Chen Shufang Wu Pingping Lv Ping Li |
| author_sort | Xijing Chen |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-5e4d9bc676194d21b2df800d149ce013 |
| institution | Kabale University |
| issn | 1471-2180 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
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| series | BMC Microbiology |
| spelling | doaj-art-5e4d9bc676194d21b2df800d149ce0132025-08-20T04:01:53ZengBMCBMC Microbiology1471-21802025-08-0125111410.1186/s12866-025-04242-7Vaginal microbiota alterations under supraphysiological estradiol state during in vitro fertilization-embryo transfer (IVF-ET) and the association with reproductive outcomesXijing Chen0Feng Chen1Shufang Wu2Pingping Lv3Ping Li4Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of MedicineDepartment of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of MedicineDepartment of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of MedicineDepartment of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of MedicineZhejiang Key Laboratory of Food Microbiology and Nutritional Health, College of Food Science and Biotechnology, Zhejiang Gongshang University, Xiasha University TownAbstract 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.https://doi.org/10.1186/s12866-025-04242-7Vaginal microbiomeIn vitro fertilization-embryo transfer (IVF-ET)Supraphysiological estradiol (E2) levelPregnancy outcomes |
| spellingShingle | Xijing Chen Feng Chen Shufang Wu Pingping Lv Ping Li Vaginal microbiota alterations under supraphysiological estradiol state during in vitro fertilization-embryo transfer (IVF-ET) and the association with reproductive outcomes BMC Microbiology Vaginal microbiome In vitro fertilization-embryo transfer (IVF-ET) Supraphysiological estradiol (E2) level Pregnancy outcomes |
| title | Vaginal microbiota alterations under supraphysiological estradiol state during in vitro fertilization-embryo transfer (IVF-ET) and the association with reproductive outcomes |
| title_full | Vaginal microbiota alterations under supraphysiological estradiol state during in vitro fertilization-embryo transfer (IVF-ET) and the association with reproductive outcomes |
| title_fullStr | Vaginal microbiota alterations under supraphysiological estradiol state during in vitro fertilization-embryo transfer (IVF-ET) and the association with reproductive outcomes |
| title_full_unstemmed | Vaginal microbiota alterations under supraphysiological estradiol state during in vitro fertilization-embryo transfer (IVF-ET) and the association with reproductive outcomes |
| title_short | Vaginal microbiota alterations under supraphysiological estradiol state during in vitro fertilization-embryo transfer (IVF-ET) and the association with reproductive outcomes |
| title_sort | vaginal microbiota alterations under supraphysiological estradiol state during in vitro fertilization embryo transfer ivf et and the association with reproductive outcomes |
| topic | Vaginal microbiome In vitro fertilization-embryo transfer (IVF-ET) Supraphysiological estradiol (E2) level Pregnancy outcomes |
| url | https://doi.org/10.1186/s12866-025-04242-7 |
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