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Identification of Uterine Microbiota in Infertile Women Receiving in vitro Fertilization With and Without Chronic Endometritis.

ABSTRACT: In vitro fertilization (IVF) is an important assisted reproductive technology in treating infertility, whose failure rate is still high. Studies suggested that uterine microbiota are related to women's reproductive diseases and persisting intrauterine bacterial infectious conditions, such as chronic endometritis (CE), impairing the pregnant processes. However, the relationship between uterine microbiota and IVF outcomes is still an open question. In the present study, 94 patients diagnosed with infertility were enrolled and were divided into CE (E group, n = 25) and non-CE (NE group, n = 69) groups depending on the hysteroscopy and immunohistochemistry. Subsequently, E (Ep, n = 8 and Enp, n = 17) and NE (NEp, n = 41 and NEnp, n = 28) groups were divided into pregnancy and non-pregnancy groups depending on the IVF outcomes, respectively. The uterine fluids were collected and microbial profiles were examined through the V4 region of 16S rRNA gene high-throughput sequencing. The results demonstrated that patients with CE had significantly lower clinical pregnancy rate compared with the non-CE patients (32 vs. 58.42%, p = 0.0014). The relative abundances of Proteobacteria and Acidobacteria were higher in the non-CE group, whereas high abundances of Actinobacteria and Fusobacteria were observed in the CE group at the phylum level. At the genus level, high relative abundances of Gardnerella were observed in the CE group and non-pregnancy groups, which significantly referred to the negative IVF outcome. In conclusion, CE may be a key factor for the negative outcome after IVF, of which the uterine microbiota plays a pivotal role, and the microbial diversity in uterine may serve as a biomarker to forecast the success of IVF outcome.

SUBMITTER: Chen W

PROVIDER: S-EPMC8409574 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:To explore the association between uterine volume and in vitro fertilization (IVF) reproductive outcomes of infertile patients with adenomyosis, we performed a retrospective cohort study of infertile patients with adenomyosis who underwent IVF from January 2009 to December 2019 in our clinical center. Patients were divided into five groups according to the uterine volume before the IVF cycle. A line graph was drawn to demonstrate the linear trend of IVF reproductive outcomes with uterine volume. Univariate and multivariate analyses were used to explore the association between uterine volume of adenomyosis patients and IVF reproductive outcomes in first fresh embryo transfer (ET) cycle, first frozen-thawed embryo transfer (FET) cycle, and per ET cycle. Kaplan-Meier curves and Cox regression were conducted to evaluate the association between uterine volume and cumulative live birth. A total of 1155 infertile patients with adenomyosis were included. Clinical pregnancy rate showed no significant correlation with uterine volume in first fresh ET cycle, first FET cycle, and per ET cycle; miscarriage rate showed an upward trend with uterine volume increasement, in which the uterine volume turning point was 8 weeks of gestation; live birth rate showed a downward trend with turning point of 10 weeks of gestation. Subsequently, patients were divided into two groups (uterine volume ≤ 8 weeks of gestation vs. uterine volume > 8 weeks of gestation). Univariate and multivariate analyses showed that patients with a uterus larger than 8 weeks of gestation had a higher miscarriage rate and a lower live birth rate in all ET cycles. Kaplan-Meier curves and Cox regression demonstrated lower cumulative live birth rate in patients with a uterine volume larger than 8 weeks of gestation. IVF reproductive outcome gets worse as uterine volume increases in infertile patients with adenomyosis. Adenomyosis patients with a uterus larger than 8 weeks of gestation had a higher miscarriage rate and a lower live birth rate.

Project description:BackgroundThe previous researches show that infertile patients have a higher incidence of endometritis and endometrial polyps, and the occurrence of these two diseases is related to changes in the microbiota of the genital tract. We aim to determine the composition and changing characteristics of the microbiota in the genital tract (especially the endometrium) of infertile patients with chronic endometritis or endometrial polyps, and find the correlation between it and the occurrence of diseases.MethodsThis is a prospective study. We collected genital tract biopsy samples from 134 asymptomatic infertile patients receiving assisted reproductive therapy before embryo transfer. Through pathological examination and 16S ribosomal RNA(16S rRNA) sequencing, we determined the distribution of chronic endometritis and endometrial polyps in these patients, as well as their distribution of reproductive tract microorganisms.ResultsCompared with the normal control group, the microbial group of reproductive tract in patients with chronic endometritis and endometrial polyps is changed, and there are significant species differences and relative abundance differences in the vagina, cervix and uterine cavity. Lactobacillus, the dominant flora of female genital tract, showed a change in abundance in patients with endometrial diseases. Endometrial microbiota composed of Staphylococcus, Gardnerella, Atopobium, Streptococcus, Peptostreptococcus, Chlamydia, Fusobacterium, Acinetobacter, etc. are related to chronic endometritis and endometrial polyps.ConclusionThe results showed that, compared with the normal control group, the endometrial microbiota of infertile patients with chronic endometritis or endometrial polyps did have significant changes in the relative abundance distribution of species, suggesting that changes in local microecology may be an important factor in the occurrence of disease, or even adverse pregnancy outcomes. The further study of endometrial microecology may provide a new opportunity to further improve the diagnosis and treatment strategy of chronic endometritis.

Project description:BackgroundThe fertility of females with advanced age declines with aging. Therefore, for medical and social reasons, it is important to establish mechanisms to protect and improve the fertility of such populations. With widespread use of traditional Chinese medicine (TCM) in in vitro fertilization (IVF), studies have evaluated their impact on improving the fertility of females with advanced age. In this study, we performed proteomic analysis of follicular fluid to reveal mechanisms of the Erzhi Tiangui (EZTG) granule (Chinese herbs for replenishing vital essence to tonify the kidney) in improving the outcomes of IVF in infertile women with advanced age.MethodsThis was a randomized, double-blind, and placebo-controlled trial in which 100 patients with advanced age were divided into the EZTG group and the placebo group by the random number table plus envelope method. Both groups were subjected to controlled ovarian stimulation with a GnRH antagonist regimen. Differences between the two groups were evaluated, including the TCM syndrome score after treatment, gonadotrophin (Gn) days and Gn doses, the number of retrieved oocytes, 2 pronucleus (PN) fertilization, 2PN cleavage, and high-quality embryos. Differentially expressed proteins were identified using the LC-MS/MS method, and their functions were determined through bioinformatics analyses.ResultsThe number of high-quality embryos in the placebo group was significantly lower than that in the EZTG group (2.88 ± 1.85 vs. 4.13 ± 2.83, p=0.011). Eleven differentially expressed proteins were identified between the two groups. Four proteins were highly expressed, whereas seven were suppressed in the control group, compared to the EZTG group. The overall trend suggested that the apoptotic effect in the follicular fluid of the EZTG group was downregulated.ConclusionTreatment with the EZTG granule can improve embryo quality in IVF of advanced age females with both kidney Qi and Yin deficiency syndromes. The mechanism is attributed to downregulation of apoptotic-effector protein expressions in the follicular fluid. This trial is registered with ChiCTR1900025139.

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Identification of Uterine Microbiota in Infertile Women Receiving in vitro Fertilization With and Without Chronic Endometritis.

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