Uterine microbiota plasticity during the menstrual cycle: Differences between healthy controls and patients with recurrent miscarriage or implantation failure

Vomstein, Kilian; Reider, Simon; Böttcher, Bettina; Watschinger, Christina; Kyvelidou, Christiana; Tilg, Herbert; Moschen, Alexander R.; Tóth, Bettina

doi:10.1016/j.jri.2022.103634

Cited by 24 publications

(19 citation statements)

References 36 publications

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“…Nonetheless, we believe that the potential involvement of genital infections by selected microbial agents deserves consideration in future studies on RPL. This concept is supported by recent evidence showing that differences exist in the uterine microbiota of women with RPL and RIF compared with healthy women [34]. ANA were detected in nearly 30% of our study population (Table 5).…”

Section: Discussionsupporting

confidence: 88%

Diagnostic factors for recurrent pregnancy loss: an expanded workup

Ticconi

Nicastri

D’Ippolito

et al. 2023

Arch Gynecol Obstet

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Purpose There is limited information on the risk factors for recurrent pregnancy loss (RPL). Methods In this study, a patient-based approach was used to investigate the possible involvement and relative relevance of a large number of diagnostic factors in 843 women with RPL who underwent an extensive diagnostic workup including 44 diagnostic factors divided into 7 major categories. Results The rates of abnormalities found were: (1) genital infections: 11.74%; (2) uterine anatomic defects: 23.72%; (3) endocrine disorders: 29.42%; (4) thrombophilias: 62%; (5) autoimmune abnormalities: 39.2%; (6) parental karyotype abnormalities 2.25%; (7) clinical factors: 87.78%. Six hundred and fifty-nine out of eight hundred and forty-three women (78.17%) had more than one abnormality. The mean number of pregnancy losses increased by increasing the number of the abnormalities found (r = 0.86949, P < 0.02). The factors associated with the highest mean number of pregnancy losses were cervical isthmic incompetence, anti-beta-2-glycoprotein-1 antibodies, unicornuate uterus, anti-prothrombin A antibodies, protein C deficiency, and lupus anticoagulant. The majority of the considered abnormalities had similar, non-significant prevalence between women with 2 versus ≥ 3 pregnancy losses with the exception of age ≥ 35 years and MTHFR A1298C heterozygote mutation. No difference was found between women with primary and secondary RPL stratified according to the number of abnormalities detected (Chi-square: 8.55, P = 0.07). In these women, the only factors found to be present with statistically different rates were age ≥ 35 years, cigarette smoking, and genital infection by Ureaplasma. Conclusion A patient-based diagnostic approach in women with RPL could be clinically useful and could represent a basis for future research.

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Section: Discussionsupporting

confidence: 88%

Diagnostic factors for recurrent pregnancy loss: an expanded workup

Ticconi

Nicastri

D’Ippolito

et al. 2023

Arch Gynecol Obstet

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“…In the recent study by Vomstein et al. [ 97 ], the endometrial microbiome was obtained by uterine flushing through a sterile catheter in non‐pregnant patients with a history of recurrent pregnancy loss (n = 20) and healthy controls, who had never been pregnant (n = 10). The absence of the vaginal contamination was proved by comparing the vaginal and endometrial samples.…”

Section: Resultsmentioning

confidence: 99%

Female reproductive tract microbiome and early miscarriages

Лебедева

Popov

Syromyatnikov

et al. 2023

APMIS

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Miscarriage is one of the main causes of reproductive loss, which can lead to a number of physical and psychological complications and other long‐term consequences. However, the role of vaginal and uterine microbiome in such complications is poorly understood. To review the published data on the function of the female reproductive tract microbiome in the pathogenesis of early miscarriages. The articles published over the past 20 years and deposited in PubMed, Google Academy, Scopus, Elibrary, ResearchGate, and EBSCO databases were analyzed. The review presents new data on the impact of the vaginal and uterine microbiome on the local immunity, including defense against sexually transmitted infections, and its association with other factors of miscarriages. The studies on the microbiome of non‐pregnant women with recurrent miscarriages in the anamnesis, patients undergoing IVF, and pregnant women with miscarriages, as well as new directions in the microbiome research are discussed. The majority of studies have demonstrated that the dominant species of the vaginal and uterine microbiome in patients with early miscarriages are non‐Lactobacillus bacteria. As many of these bacteria have not previously been detected by cultural studies and their role in obstetric complications is not well defined, further research on the female reproductive tract microbiome, including the microbiome of the cervix uteri, is needed to develop new approaches for the prognosis and prevention of miscarriages.

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“…The phase of the menstrual cycle may also have a slight influence on the endometrial microbiota; a difference between the follicular and luteal phases has been reported 38 ; a significant decrease in diversity and evenness, occurring around ovulation and continuing into the secretory phase, has also been reported 39 . Moreover, the endometrial microbiota may be altered by exogenous hormones, such as the hormones used in ovarian stimulation, progesterone supplementation, 14 or various types of ovulation induction and luteal support 40,41 …”

Section: Discussionmentioning

confidence: 99%

Age‐ and endometrial microbiota‐related delay in development of endometrial receptivity

Fujii¹,

Oguchi²

2023

Reprod Medicine & Biology

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PurposeWe evaluated factors affecting the development of endometrial receptivity according to age and changes in the endometrial microbiota.MethodsWe recruited patients with infertility who underwent transcriptomic analyses of endometrial receptivity and the endometrial microbiome prior to frozen embryo transfer. An endometrial biopsy was performed 108 h after initial progesterone administration.ResultsIn 185 tests from 185 eligible patients, the results of endometrial receptivity analysis were receptive in 111 (60.0%) patients and pre‐receptive in 74 (40.0%) patients. Compared with receptive patients, pre‐receptive patients had significantly older ages (36.0 ± 0.5 vs. 38.2 ± 0.5, p = 0.0021), a smaller proportion of normal Lactobacillus‐dominant microbiota (27.9% vs. 12.2%), and a greater proportion of microbiota with ultralow biomass (22.5% vs. 41.9%) (p = 0.0074). Patient age (adjusted odds ratio: 1.08, 95% confidence interval: 1.01–1.16, p = 0.0351) and a microbiome with ultralow biomass (adjusted odds ratio: 3.82, 95% confidence interval: 1.49–9.82, p = 0.0039) were independent predictive factors for pre‐receptive endometrium.ConclusionsOlder age was accompanied by a decrease in Lactobacillus‐dominant microbiota; aging and endometrial microbiota with ultralow biomass were significantly associated with pre‐receptive endometrium. Our findings suggest that the quantity (rather than proportion) of Lactobacillus in the endometrium is important in the development of endometrial receptivity.

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Uterine microbiota plasticity during the menstrual cycle: Differences between healthy controls and patients with recurrent miscarriage or implantation failure

Cited by 24 publications

References 36 publications

Diagnostic factors for recurrent pregnancy loss: an expanded workup

Diagnostic factors for recurrent pregnancy loss: an expanded workup

Female reproductive tract microbiome and early miscarriages

Age‐ and endometrial microbiota‐related delay in development of endometrial receptivity

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