Alterations in Vaginal Microbiota and Associated Metabolome in Women with Recurrent Implantation Failure

ABSTRACT Recurrent implantation failure (RIF) refers to repeated failure to become pregnant after transferring embryos with normal morphology. However, the pathogenesis of RIF remains unrevealed, especially for those without any pathological features. In this study, we characterized the vaginal micr...

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Autores principales:	Min Fu, Xiaowei Zhang, Yiheng Liang, Shouren Lin, Weiping Qian, Shangrong Fan
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	recurrent implantation failure RIF vaginal microbiota metabolome in vitro fertilization IVF Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/8976f6105f7b4da0b56d65efa89b5f95
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spelling	oai:doaj.org-article:8976f6105f7b4da0b56d65efa89b5f952021-11-15T15:56:47ZAlterations in Vaginal Microbiota and Associated Metabolome in Women with Recurrent Implantation Failure10.1128/mBio.03242-192150-7511https://doaj.org/article/8976f6105f7b4da0b56d65efa89b5f952020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.03242-19https://doaj.org/toc/2150-7511ABSTRACT Recurrent implantation failure (RIF) refers to repeated failure to become pregnant after transferring embryos with normal morphology. However, the pathogenesis of RIF remains unrevealed, especially for those without any pathological features. In this study, we characterized the vaginal microbiota and metabolomes of patients with unexplained RIF, while patients who achieved clinical pregnancy in the first frozen embryo transfer (FET) cycle were used as controls. Based on 16S rRNA gene sequencing of the vaginal microbiota, the vaginal Lactobacillus showed a significant positive correlation with the pregnancy rate, and the RIF group presented higher microbial α-diversity than the control group (P value = 0.016). The metabolomic profile identified 2,507 metabolites, of which 37 were significantly different between the two groups (P value < 0.05, variable importance for the projection [VIP] > 1). Among them, 2′,3-cyclic UMP and inositol phosphate were the top two metabolites that were higher in the RIF group, while glycerophospholipids and benzopyran were important metabolites that were lower in the RIF group. A lack of lysobisphosphatidic acid and prostaglandin metabolized from glycerophospholipids will lead to deferred implantation and embryo crowding. Benzopyran, as a selective estrogen receptor modulator, may affect the outcome of pregnancy. All of the changes in metabolite profiles may result in or from the differential microbiota compositions in RIF patients. In conclusion, significant differences were presented in the vaginal microbiota and metabolomes between patients with unexplained RIF and women who became pregnant in the first FET cycle. For the first time, this study elaborates the possible pathogenesis of RIF by investigating the vaginal microbiota and metabolites in RIF patients. IMPORTANCE In vitro fertilization-embryo transfer (IVF-ET) is now widely applied for treating infertility, and unexplained recurrent implantation failure (RIF) has become a substantial challenge. We hypothesize that vaginal microbial dysbiosis is associated with RIF, as it is linked to many female reproductive diseases. In this study, we characterized the vaginal microbiota and metabolomes of patients with unexplained RIF, while patients who achieved clinical pregnancy in the first IVF cycle were set as controls. In general, significant differences were discovered in the vaginal microbiota and metabolomes between the two groups. This study is the first detailed elaboration of the vaginal microbiota and metabolites associated with RIF. We believe that our findings will inspire researchers to consider the dynamics of microbiomes related to the microenvironment as a critical feature for future studies of nosogenesis not only for RIF but also for other reproductive diseases.Min FuXiaowei ZhangYiheng LiangShouren LinWeiping QianShangrong FanAmerican Society for Microbiologyarticlerecurrent implantation failureRIFvaginal microbiotametabolomein vitro fertilizationIVFMicrobiologyQR1-502ENmBio, Vol 11, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	recurrent implantation failure RIF vaginal microbiota metabolome in vitro fertilization IVF Microbiology QR1-502
spellingShingle	recurrent implantation failure RIF vaginal microbiota metabolome in vitro fertilization IVF Microbiology QR1-502 Min Fu Xiaowei Zhang Yiheng Liang Shouren Lin Weiping Qian Shangrong Fan Alterations in Vaginal Microbiota and Associated Metabolome in Women with Recurrent Implantation Failure
description	ABSTRACT Recurrent implantation failure (RIF) refers to repeated failure to become pregnant after transferring embryos with normal morphology. However, the pathogenesis of RIF remains unrevealed, especially for those without any pathological features. In this study, we characterized the vaginal microbiota and metabolomes of patients with unexplained RIF, while patients who achieved clinical pregnancy in the first frozen embryo transfer (FET) cycle were used as controls. Based on 16S rRNA gene sequencing of the vaginal microbiota, the vaginal Lactobacillus showed a significant positive correlation with the pregnancy rate, and the RIF group presented higher microbial α-diversity than the control group (P value = 0.016). The metabolomic profile identified 2,507 metabolites, of which 37 were significantly different between the two groups (P value < 0.05, variable importance for the projection [VIP] > 1). Among them, 2′,3-cyclic UMP and inositol phosphate were the top two metabolites that were higher in the RIF group, while glycerophospholipids and benzopyran were important metabolites that were lower in the RIF group. A lack of lysobisphosphatidic acid and prostaglandin metabolized from glycerophospholipids will lead to deferred implantation and embryo crowding. Benzopyran, as a selective estrogen receptor modulator, may affect the outcome of pregnancy. All of the changes in metabolite profiles may result in or from the differential microbiota compositions in RIF patients. In conclusion, significant differences were presented in the vaginal microbiota and metabolomes between patients with unexplained RIF and women who became pregnant in the first FET cycle. For the first time, this study elaborates the possible pathogenesis of RIF by investigating the vaginal microbiota and metabolites in RIF patients. IMPORTANCE In vitro fertilization-embryo transfer (IVF-ET) is now widely applied for treating infertility, and unexplained recurrent implantation failure (RIF) has become a substantial challenge. We hypothesize that vaginal microbial dysbiosis is associated with RIF, as it is linked to many female reproductive diseases. In this study, we characterized the vaginal microbiota and metabolomes of patients with unexplained RIF, while patients who achieved clinical pregnancy in the first IVF cycle were set as controls. In general, significant differences were discovered in the vaginal microbiota and metabolomes between the two groups. This study is the first detailed elaboration of the vaginal microbiota and metabolites associated with RIF. We believe that our findings will inspire researchers to consider the dynamics of microbiomes related to the microenvironment as a critical feature for future studies of nosogenesis not only for RIF but also for other reproductive diseases.
format	article
author	Min Fu Xiaowei Zhang Yiheng Liang Shouren Lin Weiping Qian Shangrong Fan
author_facet	Min Fu Xiaowei Zhang Yiheng Liang Shouren Lin Weiping Qian Shangrong Fan
author_sort	Min Fu
title	Alterations in Vaginal Microbiota and Associated Metabolome in Women with Recurrent Implantation Failure
title_short	Alterations in Vaginal Microbiota and Associated Metabolome in Women with Recurrent Implantation Failure
title_full	Alterations in Vaginal Microbiota and Associated Metabolome in Women with Recurrent Implantation Failure
title_fullStr	Alterations in Vaginal Microbiota and Associated Metabolome in Women with Recurrent Implantation Failure
title_full_unstemmed	Alterations in Vaginal Microbiota and Associated Metabolome in Women with Recurrent Implantation Failure
title_sort	alterations in vaginal microbiota and associated metabolome in women with recurrent implantation failure
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/8976f6105f7b4da0b56d65efa89b5f95
work_keys_str_mv	AT minfu alterationsinvaginalmicrobiotaandassociatedmetabolomeinwomenwithrecurrentimplantationfailure AT xiaoweizhang alterationsinvaginalmicrobiotaandassociatedmetabolomeinwomenwithrecurrentimplantationfailure AT yihengliang alterationsinvaginalmicrobiotaandassociatedmetabolomeinwomenwithrecurrentimplantationfailure AT shourenlin alterationsinvaginalmicrobiotaandassociatedmetabolomeinwomenwithrecurrentimplantationfailure AT weipingqian alterationsinvaginalmicrobiotaandassociatedmetabolomeinwomenwithrecurrentimplantationfailure AT shangrongfan alterationsinvaginalmicrobiotaandassociatedmetabolomeinwomenwithrecurrentimplantationfailure
_version_	1718427102801297408

Alterations in Vaginal Microbiota and Associated Metabolome in Women with Recurrent Implantation Failure

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