Female reproductive tract microbiota and recurrent pregnancy loss: a nested case-control study

Peuranpää, Pirkko; Holster, Tiina; Saqib, Schahzad; Kalliala, Ilkka; Tiitinen, Aila; Salonen, Anne; Hautamäki, Hanna

doi:10.1016/j.rbmo.2022.06.008

Cited by 25 publications

(20 citation statements)

References 59 publications

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“…The beneficial role of lactobacilli, especially L. crispatus, has been shown in several studies ( 38 – 40 ). L. crispatus possesses the enzymatic machinery to debranch and ferment the polymers derived from glycogen from the vaginal epithelium, producing lactic acid and hydrogen peroxide (H 2 O 2 ), lowering the pH of the vagina ( 41 , 42 ).…”

Section: Discussionmentioning

confidence: 91%

Longitudinal analysis of vaginal microbiota during IVF fresh embryo transfer and in early pregnancy

Väinämö,

Saqib,

Kalliala

et al. 2023

Microbiol Spectr

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Non- Lactobacillus -dominated vaginal microbiota has been associated with poor gynecologic health and complications during pregnancy. Lactobacilli and especially Lactobacillus crispatus associate with good reproductive health and dominate the microbiota during healthy pregnancy. We examined whether the composition of vaginal microbiota at the time of fresh embryo transfer (ET) has an impact on the success of in vitro fertilization (IVF) and whether vaginal microbiota changes from IVF-ET to early pregnancy within individuals. Vaginal swab samples were collected from subfertile women at the time of IVF-ET ( n = 76) and at the eighth gestational week ( n = 21) from those who achieved clinical pregnancy. The microbiota composition was analyzed using 16S rRNA gene amplicon sequencing. L. crispatus was more abundant among the 30 women who achieved clinical pregnancy (46.9% vs. 19.1%, q = 0.039) and the 26 women who had live birth (43.3% vs. 23.1%, q = 0.32) compared to those who did not. Lactobacilli, mainly L. crispatus (76.2%), dominated all early pregnancy samples. Microbiota remained the same, i.e., Lactobacillus -dominated type in 52% (11/21), shifted from one Lactobacillus- dominated type to another in 24% (5/21), or shifted from mixed community to Lactobacillus -dominated type in 24% (5/21) women, but never from Lactobacillus dominance to non-lactobacilli dominance. Our results emphasize the role of L. crispatus in the success of IVF-ET and in early pregnancy. During pregnancy, the microbiota shifted toward L. crispatus dominance even if it was undetectable before pregnancy, indicating that most women hold a reservoir of this beneficial Lactobacillus in their reproductive tract. IMPORTANCE Infertility is a global public health issue which leads many couples to seek fertility treatments, of which in vitro fertilization (IVF) is considered to be the most effective. Still, only about one-third of the women achieve live birth after the first IVF embryo transfer (IVF-ET). Factors affecting embryo implantation are poorly known, but the female reproductive tract microbiota may play a key role. Our study confirms the beneficial role of vaginal lactobacilli, especially Lactobacillus crispatus, in the probability of achieving clinical pregnancy and live birth following IVF-ET. Our findings regarding the intra-individual shift of vaginal microbiota between non-pregnancy and pregnancy states are novel and provide new information about the dynamics of microbiota in the early steps of human reproduction. These findings may help clinicians in their attempts to optimize the conditions for ET by microbiota screening or modulation and timing the ET when the microbiota is the most favorable.

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Section: Discussionmentioning

confidence: 91%

Longitudinal analysis of vaginal microbiota during IVF fresh embryo transfer and in early pregnancy

Väinämö,

Saqib,

Kalliala

et al. 2023

Microbiol Spectr

Self Cite

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“…Previous studies have reported that in women with repeated embryo arrest, the relative abundance of L. crispatus in the endometrium was significantly lower than that in healthy women, while the abundance of Gardnerella vaginalis in the vagina and endometrium was significantly higher than that in healthy women. Changes in the microecology of the reproductive tract are significantly associated with embryonic development and prognosis ( Stout et al, 2017 ; Peuranpaa et al, 2022 ). Therefore, the development and prognosis of the reproductive tract microbiome and embryos have attracted increasing attention.…”

Section: Discussionmentioning

confidence: 99%

Association between the vaginal and uterine microbiota and the risk of early embryonic arrest

Wang

Chen

et al. 2023

Front. Microbiol.

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The aim of this study was to explore the microecological distribution and differences in the uterus and vaginal microbiome in women with early embryonic arrest and those with normal pregnancy by high-throughput sequencing. We systematically sampled the vaginal and uterine microbiomes of 56 pregnant women, namely, 38 patients with early embryonic arrest and 18 pregnant women with normal pregnancy-induced abortion. We obtained colonization data by 16S rRNA gene amplicon sequencing. In the vagina, Lactobacillus, Bacteroidetes and Helicobacter exhibited significant differences between the groups. We further found that Lactobacillus iners, Lactobacillus crispatus, Lactobacillus gasseri and Lactobacillus jensenii were the most dominant Lactobacillus species and that L. iners was significantly different between the groups. Receiver operating characteristic (ROC) curve analysis confirmed that Ensifer had the highest predictive value for early embryonic arrest. In the uterine cavity, we determined that Proteobacteria, Bacteroidetes, Firmicutes and Actinobacteria were the dominant bacteria at the phylum level and that Bacteroides, Pseudarthrobacter, Lactobacillus and Ralstonia were the dominant genera. Further classification of Lactobacillus revealed that L. iners, L. crispatus, L. gasseri, and L. jensenii were the main species. There was a significant difference in L. jensenii between the normal pregnancy group and early embryonic arrest group. Random forest analysis revealed 18 different genera in the uterus, and ROC curve analysis indicated that Candidatus Symbiobacter, Odoribacter, Blautia, Nocardioides and Ileibacterium had a certain predictive value.

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“…Negative reagent controls were used by Peuranpää et al (2022) who conducted a nested case-controlled study of the vaginal and endometrial microbiota of 47 women with a history of two or more early pregnancy losses and 39 healthy controls. Overall, strong inter-individual correlation between the vaginal and endometrial microbiota compositions was observed ( R = 0.85, P < 0.001).…”

Section: The Association Between the Endometrial Microbiota And Misca...mentioning

confidence: 99%

The endometrial microbiota and early pregnancy loss

Odendaal,

Black,

Bennett

et al. 2024

Human Reproduction

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The human endometrium is a dynamic entity that plays a pivotal role in mediating the complex interplay between the mother and developing embryo. Endometrial disruption can lead to pregnancy loss, impacting both maternal physical and psychological health. Recent research suggests that the endometrial microbiota may play a role in this, although the exact mechanisms are still being explored, aided by recent technological advancements and our growing understanding of host immune responses. Suboptimal or dysbiotic vaginal microbiota, characterized by increased microbial diversity and reduced Lactobacillus dominance, has been associated with various adverse reproductive events, including miscarriage. However, the mechanisms linking the lower reproductive tract microbiota with pregnancy loss remain unclear. Recent observational studies implicate a potential microbial continuum between the vaginal and endometrial niche in patients with pregnancy loss; however, transcervical sampling of the low biomass endometrium is highly prone to cross-contamination, which is often not controlled for. In this review, we explore emerging evidence supporting the theory that a dysbiotic endometrial microbiota may modulate key inflammatory pathways required for successful embryo implantation and pregnancy development. We also highlight that a greater understanding of the endometrial microbiota, its relationship with the local endometrial microenvironment, and potential interventions remain a focus for future research.

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Female reproductive tract microbiota and recurrent pregnancy loss: a nested case-control study

Cited by 25 publications

References 59 publications

Longitudinal analysis of vaginal microbiota during IVF fresh embryo transfer and in early pregnancy

Longitudinal analysis of vaginal microbiota during IVF fresh embryo transfer and in early pregnancy

Association between the vaginal and uterine microbiota and the risk of early embryonic arrest

The endometrial microbiota and early pregnancy loss

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