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Association of the Cervical Microbiota With Pregnancy Outcome in a Subfertile Population Undergoing In Vitro Fertilization: A Case-Control Study.

ABSTRACT: The microorganisms of the reproductive tract have been implicated to affect in vitro fertilization (IVF) outcomes. However, studies on the reproductive tract microbiota of infertile women are limited and the correlation between cervical microbiota and IVF outcome remains elusive. This study aimed to characterize the cervical microbiota of IVF patients undergoing embryo transfer (ET) and assess associations between the cervical microbiota and pregnancy outcomes while exploring the underlying contributing factors. We launched a nested case-control study of 100 patients with two fresh or frozen-thawed cleavage embryos transferred per IVF cycle. Cervical swabs were collected on the day of ET and divided into four groups according to clinical pregnancy outcomes. Variable regions 3 and 4 (V3-V4) of the 16S rRNA gene were amplified and sequenced on the Illumina MiSeq platform. In fresh IVF-ET cycles, the clinical pregnancy group (FP, n = 25) demonstrated higher α diversity (P = 0.0078) than the non-pregnancy group (FN, n = 26). Analysis of similarity (ANOSIM) revealed a significant difference in β diversity between the two groups (R = 0.242, P = 0.001). In frozen-thawed ET cycles, though not significant, similar higher α diversity was found in the clinical pregnancy group (TP, n = 27) compared to the non-pregnancy group (TN, n = 22) and ANOSIM analysis showed a significant difference between the two groups (R = 0.062, P = 0.045). For patients in fresh IVF-ET groups, Lactobacillus, Akkermansia, Desulfovibrio, Atopobium, and Gardnerella showed differentially abundance between pregnant and non-pregnant women and they accounted for the largest share of all taxa investigated. Among them, Lactobacillus was negatively correlated with the other genera and positively correlated with serum estradiol levels. Logistic regression analysis suggested that the composition of the cervical microbiota on the day of ET was associated with the clinical pregnancy in fresh IVF-ET cycles (P = 0.030). Our results indicate that cervical microbiota composition has an impact on the outcome of assisted reproductive therapy.

SUBMITTER: Hao X

PROVIDER: S-EPMC8495128 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundUnicornuate uterus, a congenital uterine malformation resulting from unilateral maldevelopment of Mullerian duct, is more prevalent in women with infertility. Owing to relative rarity of the condition, the evidence on the associated reproductive outcomes is derived from small heterogeneous studies that report different clinical endpoints and often do not account for the anatomical variations of unicornuate uterus. The aim of this study was to evaluate the embryological and clinical outcomes following IVF-ICSI treatment in women with unicornuate uterus without rudimentary functional cavity (ESHRE-ESGE class IVb).MethodsRetrospective nested case-control study comprised 342 women with unicornuate uterus and 1026 matched controls who underwent IVF-ICSI cycles between October 2012 and October 2016. Cumulative live birth rate upon one complete IVF cycle, including transfers of all resulting embryos was considered as a primary outcome measure.ResultsBaseline characteristics were comparable between the unicornuate uterus and control groups except for higher rate of primary infertility in unicornuate uterus. Ovarian response to stimulation did not differ between the groups. Transfer of day-3 embryos in fresh cycle resulted in lower clinical pregnancy rate (35.9% vs. 43.9%, p = 0.028) and live-birth rate (26.9% vs. 35.2%, p = 0.017) per transfer, but the difference was not observed when either cleavage frozen-thaw embryos or blastocysts were transferred. Implantation rate was lower and miscarriage rate was higher in women with unicornuate uterus but the difference between the groups did not reach statistical significance. Transfer of cleavage embryos resulted in significantly higher miscarriage rate and lower live-birth rate in fresh versus frozen-thaw cycles in each group, whereas fresh and frozen-thaw blastocyst embryos had comparable outcomes. Upon completion of one IVF-ICSI cycle, the cumulative pregnancy rate (53.1% vs. 65.7, p < 0.001) and cumulative live birth rate (42.4% vs. 54.6%, p < 0.001) were significantly lower in women with unicornuate uterus compared to those in women with normal uterus. Cumulative outcomes were superior when embryos were cultured to blastocyst stage.ConclusionsWomen with unicornuate uterus have lower clinical pregnancy and live birth rate after IVF-ICSI treatment compared to women with normal uterus. The treatment outcomes are improved with blastocyst culture, which warrants evaluation in prospective setting.

Project description:ObjectiveTo determine whether prophylactic azithromycin is associated with the vaginal bacterial microbiome and clinical outcomes in subfertile women undergoing in vitro fertilization (IVF).DesignProspective exploratory cohort study.SettingSingle academic fertility center.PatientsSubfertile women aged 18-43 years undergoing their first IVF cycle and fresh embryo transfer.InterventionPrimary exposure to prophylactic azithromycin (1 g orally) once at baseline.Main outcome measuresThe primary outcome was the effect of azithromycin on the vaginal microbiome compared with a no-azithromycin group at 3 time points throughout the IVF cycle (baseline, retrieval, and embryo transfer). The secondary outcomes were associations of vaginal bacterial communities with clinical outcomes.ResultsA planned a priori exploratory cohort of 27 subjects (12 in the azithromycin treatment group and 15 in the no-azithromycin group) contributed 79 vaginal swabs for the analysis as part of an ongoing randomized, controlled noninferiority trial. No specific taxa were associated with azithromycin or pregnancy at any time point. Azithromycin did not affect alpha diversity or community stability. Although there were trends of a lower bacterial load and higher percentage of Lactobacillus species in the azithromycin group at the time of transfer, these were not statistically significant. In women who did not become pregnant, the percentage of Lactobacillus species was lower (P = .048; Hodges-Lehmann estimate of difference, 0.41; 95% confidence interval, 0.08-0.65) and the change in community composition over time was higher. The percentage of Lactobacillus species at baseline was not predictive of the percentage of Lactobacillus species at the time of embryo transfer.ConclusionsProphylactic azithromycin at baseline is not associated with changes in vaginal bacterial communities. Bacterial community features at the time of embryo transfer are associated with pregnancy. Bacterial community structures at baseline are not predictive of those at the time of embryo transfer.Clinical trial registration numberNCT03386227.

Project description:BackgroundEvidence from animal studies suggests that exposure to organophosphate flame retardants (PFRs) can disrupt endocrine function and impair embryo development. However, no epidemiologic studies have been conducted to evaluate effects on fertility and pregnancy outcomes.ObjectivesWe evaluated associations between urinary concentrations of PFR metabolites and outcomes of in vitro fertilization (IVF) treatment among couples recruited from an academic fertility clinic.MethodsThis analysis included 211 women enrolled in the Environment And Reproductive Health (EARTH) prospective cohort study (2005-2015) who provided one or two urine samples per IVF cycle. We measured five urinary PFR metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate (tb-PPP), and bis(1-chloro-2-propyl) phosphate (BCIPP)] using negative electrospray ionization liquid chromatography tandem mass spectrometry (LC-MS/MS). Molar concentrations of the urinary PFR metabolites were summed. We used multivariable generalized linear mixed models to evaluate the association of the PFR metabolites with IVF outcomes, accounting for multiple IVF cycles per woman.ResultsDetection frequencies were high for BDCIPP (87%), DPHP (94%), and ip-PPP (80%), but low for tb-PPP (14%) and BCIPP (0%). We observed decreased success for several IVF outcomes across increasing quartiles of both summed and individual PFR metabolites (DPHP and ip-PPP) in our adjusted multivariable models. Significant declines in adjusted means from the lowest to highest quartile of ?PFR were observed for the proportion of cycles resulting in successful fertilization (10% decrease), implantation (31%), clinical pregnancy (41%), and live birth (38%).ConclusionsUsing IVF to investigate human reproduction and pregnancy outcomes, we found that concentrations of some urinary PFR metabolites were negatively associated with proportions of successful fertilization, implantation, clinical pregnancy, and live birth. https://doi.org/10.1289/EHP1021.

Project description:Infertility is currently a growing problem observed around the world and is estimated to affect between 8 and 12% of reproductive-aged couples worldwide. Artificial reproductive techniques are the last chance for couples seeking their own child. Human leukocyte antigen (HLA)-G expression has been suggested as an immunomodulatory molecule that influences pregnancy outcome. The HLA-G gene encodes either membrane-bound or/and soluble proteins. The aim of this study was the evaluation of the role of soluble HLA-G (sHLA-G) and its gene polymorphism in successful implantation after in vitro fertilization embryo transfers (IVF-ETs) in different clinical protocols. We tested the HLA-G polymorphism in three positions: rs1632947: c.-964G>A; rs1233334: c.-725G>C/T in promoter region; rs371194629: c.*65_*66insATTTGTTCATGCCT in 3' untranslated region of exon 8, in 389 patients who underwent IVF-ETs and 320 women with healthy children born after natural conception. Among the patient group, 239 women were with recurrent implantation failure and 117 women had an ongoing pregnancy or a child born after IVF-ET. We found that certain rs1632947-rs1233334-rs371194629 HLA-G haplotypes and diplotypes were associated with infertility, while others were protective. The lowest secretors of sHLA-G were G-C-ins haplotype carriers (37.21 IU/ml), while the highest -G-C-del carriers (73.80 IU/ml). Other haplotype carriers were intermediate secretors. In our study, regardless of possessed haplotype by the patient, 59.73 IU/ml sHLA-G was the threshold value with the best sensitivity (58.82%) and specificity (66.10%) to discriminate patients who achieved and maintained pregnancy from those who did not conceive or they had miscarriage (p = 0.0085; likelihood ratio, 1.74; 95% CI = 0.55-0.78). However, we do not exclude that factors other than sHLA-G may also contribute to complications in pregnancy. In addition, we found that IVF patients in cycles when frozen/thawed embryo was transferred secreted higher soluble HLA-G levels than patients with fresh embryo transferred (p = 0.021). Moreover, correlation analysis of sHLA-G concentration measured before and after embryo transfer for particular patients indicated short ovarian stimulation with gonadotropin-releasing hormone antagonist as more beneficial than long protocol with gonadotropin-releasing hormone agonist. Our study confirms a role of HLA-G polymorphism in infertility and soluble HLA-G in the early stages of pregnancy.

Project description:BACKGROUND:Use of organophosphate flame retardants (PFRs) has increased over the past decade following the phase out of some brominated flame retardants, leading to increased human exposure. We recently reported that increasing maternal PFR exposure is associated with poorer pregnancy outcomes among women from a fertility clinic. Because a small epidemiologic study previously reported an inverse association between male PFR exposures and sperm motility, we sought to examine associations of paternal urinary concentrations of PFR metabolites and their partner's pregnancy outcomes. METHODS:This analysis included 201 couples enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2005-2015) who provided one or two urine samples per IVF cycle. In both the male and female partner, we measured five urinary PFR metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate (tb-PPP) and bis(1-chloro-2-propyl) phosphate (BCIPP)] using negative electrospray ionization liquid chromatography tandem mass spectrometry (LC-MS/MS). The sum of the molar concentrations of the urinary PFR metabolites was calculated. We used multivariable generalized linear mixed models to evaluate the association of urinary concentrations of paternal PFR metabolites with IVF outcomes, accounting for multiple in vitro fertilization (IVF) cycles per couple. Models were adjusted for year of IVF treatment cycle, primary infertility diagnosis, and maternal urinary PFR metabolites as well as paternal and maternal age, body mass index, and race/ethnicity. RESULTS:Detection rates were high for paternal urinary concentrations of BDCIPP (84%), DPHP (87%) and ip-PPP (76%) but low for tb-PPP (12%) and zero for BCIPP (0%). We observed a significant 12% decline in the proportion of fertilized oocytes from the first to second quartile of male urinary ?PFR and a 47% decline in the number of best quality embryos from the first to third quartile of male urinary BDCIPP in our adjusted models. An 8% decline in fertilization was observed for the highest compared to lowest quartile of urinary BDCIPP concentrations (95% CI: 0.01, 0.12, p-trend=0.06). CONCLUSIONS:Using IVF as a model to investigate human reproduction and pregnancy outcomes, we found that paternal urinary concentrations of BDCIPP were associated with reduced fertilization. In contrast to previously reported findings for the female partners, the paternal urinary PFR metabolites were not associated with the proportion of cycles resulting in successful implantation, clinical pregnancy, and live birth. These results indicate that paternal preconception exposure to TDCIPP may adversely impact successful oocyte fertilization, whereas female preconception exposure to ?PFRs may be more relevant to adverse pregnancy outcomes.

Dataset Information

Association of the Cervical Microbiota With Pregnancy Outcome in a Subfertile Population Undergoing In Vitro Fertilization: A Case-Control Study.

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