Risk Factors Associated with Recurrent Pregnancy Loss and Outcome of Pre-Implantation Genetic Screening of Affected Couples
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ABSTRACT: Background:
Recurrent pregnancy loss (RPL) is a multifactorial disorder which affects up to 5% of couples around
SUBMITTER: Fatemi N
PROVIDER: S-EPMC8530214 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This retrospective cohort study explores whether noninvasive chromosome screening (NICS) for aneuploidy can improve the clinical outcomes of patients with recurrent pregnancy loss (RPL) or repeated implantation failure (RIF) in assisted reproductive technology. A total of 273 women with a history of RPL or RIF between 2018 and 2021 were included in this study. We collected data of all oocyte retrieval cycles and single blastocyst resuscitation transfer cycles. For the patients experiencing RPL, NICS reduced the miscarriages rate per frozen embryo transfer (FET), improved the ongoing pregnancies rate and live birth rate: 17.9% vs 42.6%, adjusted OR 0.39, 95% CI 0.16-0.95; 40.7% vs 25.0%, adjusted OR 2.00, 95% CI 1.04-3.82; 38.9% vs 20.6%, adjusted OR 2.53, 95% CI 1.28-5.02, respectively. For the patients experiencing RIF, the pregnancy rates per FET in the NICS group were significantly higher than those in the non-NICS group (46.9% vs. 28.7%, adjusted OR 2.82, 95% CI 1.20-6.66). This study demonstrated that the selection of euploid embryos through NICS can reduce the miscarriage rate of patients experiencing RPL and improve the clinical pregnancy rate of patients experiencing RIF. Our data suggested NICS could be considered as a possibly useful screening test in clinical practice.
| S-EPMC9253989 | biostudies-literature
Project description:T helper 17 (TH17) cells have been identified as a new lineage of helper T cells and have been shown to be important in host defense against extracellular infectious agents, autoimmune disease and chronic inflammatory diseases. Recently, TH17 cells have also been shown to participate in successful pregnancy, as well as in the pathogenesis of diseases of pregnancy, such as recurrent spontaneous abortion (RSA) and pre-eclampsia (PE). Here, we review our current knowledge of TH17 cells in human RSA and PE. We also discuss how the local uterine microenvironment affects the differentiation of TH17 cells and the mechanisms that regulate TH17 cells during pregnancy. Research into TH17 cells will not only advance our understanding of TH17-related pregnancy complications, but will also facilitate the design of novel therapies for reproductive diseases.
| S-EPMC4220838 | biostudies-other
Project description:Recurrent pregnancy loss is a frequently occurring human infertility-related disease affecting ~1% of women. It has been estimated that the cause remains unexplained in >50% cases which strongly suggests that genetic factors may contribute towards the phenotype. Concerning its molecular aetiology numerous studies have had limited success in identifying the disease's genetic causes. This might have been due to the fact that hundreds of genes are involved in each physiological step necessary for guaranteeing reproductive success in mammals. In such scenario, next generation sequencing provides a potentially interesting tool for research into recurrent pregnancy loss causative mutations. The present study involved whole-exome sequencing and an innovative bioinformatics analysis, for the first time, in 49 unrelated women affected by recurrent pregnancy loss. We identified 27 coding variants (22 genes) potentially related to the phenotype (41% of patients). The affected genes, which were enriched by potentially deleterious sequence variants, belonged to distinct molecular cascades playing key roles in implantation/pregnancy biology. Using a quantum chemical approach method we established that mutations in MMP-10 and FGA proteins led to substantial energetic modifications suggesting an impact on their functions and/or stability. The next generation sequencing and bioinformatics approaches presented here represent an efficient way to find mutations, having potentially moderate/strong functional effects, associated with recurrent pregnancy loss aetiology. We consider that some of these variants (and genes) represent probable future biomarkers for recurrent pregnancy loss.
| S-EPMC5634651 | biostudies-literature
Project description:BackgroundInternational guidelines recommend to offer supportive care during a next pregnancy to couples affected by recurrent pregnancy loss (RPL). In previous research, several options for supportive care have been identified and women's preferences have been quantified. Although it is known that RPL impacts the mental health of both partners, male preferences for supportive care have hardly been explored.MethodsA cross-sectional study was conducted in couples who visited a specialized RPL clinic in the Netherlands between November 2018 and December 2019. Both members of the couples received a questionnaire that quantified their preferences for supportive care in a next pregnancy and they were asked to complete this independently from each other. Preferences for each supportive care option were analysed on a group level (by gender) and on a couple level, by comparing preferences of both partners.ResultsNinety-two questionnaires (completed by 46 couples) were analysed. The overall need for supportive care indicated on a scale from 1 to 10 was 6.8 for men and 7.9 for women (P = 0.002). Both genders preferred to regularly see the same doctor with knowledge of their obstetric history, to make a plan for the first trimester and to have frequent ultrasound examinations. A lower proportion of men preferred a doctor that shows understanding (80% of men vs. 100% of women, P = 0.004) and a doctor that informs on wellbeing (72% vs. 100%, P = ≤0.000). Fewer men preferred support from friends (48% vs. 74%, P = 0.017). Thirty-seven percent of men requested more involvement of the male partner at the outpatient clinic, compared to 70% of women (P = 0.007). In 28% of couples, partners had opposing preferences regarding peer support.ConclusionsWhile both women and men affected by RPL are in need of supportive care, their preferences may differ. Current supportive care services may not entirely address the needs of men. Health care professionals should focus on both partners and development of novel supportive care programs with specific attention for men should be considered.
| S-EPMC8630871 | biostudies-literature
Project description:Recurrent pregnancy loss (RPL) is a common complication in obstetrics, affecting about 5% of women of childbearing age. An increase in the number of abortions results in escalation in the risk of miscarriage. Although concentrated research has identified numerous causes for RPL, about 50% of them remain unexplained. Pregnancy is a complex process, comprising fertilization, implantation, organ and tissue differentiation, and fetal growth, which is effectively controlled by a number of both maternal and fetal factors. An example is the immune response, in which T cells and natural killer cells participate, and inflammation mediated by tumor necrosis factor or colony-stimulating factor, which hinders embryo implantation. Furthermore, vitamin D affects glucose metabolism and inhibits embryonic development, whereas microRNA has a negative effect on the gene expression of embryo implantation and development. This review examines the causes of RPL from multiple perspectives, and focuses on the numerous factors that may result in RPL.
| S-EPMC6629979 | biostudies-literature
Project description:The aim of this study was to identify the association of parental MTHFR C677T gene polymorphism in couples with and without RPL history.During the study, 21.4% (15/70) of Ala222Val polymorphism was observed among RPL couples while no polymorphism was seen among normal, healthy couples. Our study did not find any association between MTHFR C677T polymorphism and gender (p?>?0.05), gestational period (p?>?0.05), geographical region (p?>?0.05) and menstrual history (p?>?0.05). However, significant association was seen between MTHFR C677T polymorphism and number of losses (p?<?0.05), concluding that the risk of the polymorphism increased with the increase in number of losses. Significant variation in the MTHFR C677T genotype with number of losses among RPL couples were seen but not with other study variables.
| S-EPMC5887178 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-09-16 | E-GEOD-65102 | biostudies-arrayexpress
Project description:During the implantation window, the endometrium becomes poised to transition to a pregnant state, a process driven by differentiation of stromal cells into decidual cells (DC). Perturbations in this process, termed decidualization, leads to breakdown of the feto-maternal interface and miscarriage, but the underlying mechanisms are poorly understood. Here, we reconstructed the decidual pathway at single-cell level in vitro and demonstrate that stromal cells first mount an acute stress response before emerging as DC or senescent DC (snDC). In the absence of immune cell-mediated clearance of snDC, secondary senescence transforms DC into progesterone-resistant cells that abundantly express extracellular matrix remodelling factors. Additional single-cell analysis of midluteal endometrium identified DIO2 and SCARA5 as marker genes of a diverging decidual response in vivo. Finally, we report a conspicuous link between a pro-senescent decidual response in peri-implantation endometrium and recurrent pregnancy loss, suggesting that pre-pregnancy screening and intervention may reduce the burden of miscarriage.
| S-EPMC6972755 | biostudies-literature
Project description:Recurrent Pregnancy Loss (RPL) affects 2-4% of couples, and with increasing numbers of pregnancy losses the risk of miscarrying a euploid pregnancy is increased, suggesting RPL is a pathology distinct from sporadic miscarriage that is due largely to lethal embryonic aneuploidy. There are a number of conditions associated with RPL including unspecified "immune" pathologies; one of the strongest candidates for dysregulation remains T regulatory cells as depletion in the very early stages of pregnancy in mice leads to pregnancy loss. Human endometrial Treg and conventional CD4T cells were isolated during the peri-implantation period of the menstrual cycle in normal women. We identified an endometrial Treg transcriptomic signature and validated an enhanced regulatory phenotype compared to peripheral blood Treg. Parous women had an altered endometrial Treg transcriptome compared to nulliparity, indicating acquired immune memory of pregnancy within the Treg population, by comparison endometrial conventional CD4T cells were not altered. We compared primary and secondary RPL to nulliparous or parous controls respectively. Both RPL subgroups displayed differentially expressed Treg gene transcriptomes compared to controls. We found increased cell surface S1PR1 and decreased TIGIT protein expression by Treg in primary RPL, confirming the presence of altered Treg in the peri-implantation RPL endometrium.
| S-EPMC8732268 | biostudies-literature
Project description:Stress has been proposed as a cause of preterm birth (PTB) and small-for-gestational age (SGA), but stress does not have the same effects on all women. It may be that a woman's reaction to stress relates to her pregnancy health, and previous studies indicate that higher reactivity is associated with reduced birthweight and gestational age. The objective of this study was to examine the relationship between pre-pregnancy cardiovascular reactivity to stress and pregnancy outcome. The sample included 917 women in the Coronary Artery Risk Development in Young Adults Study who had cardiovascular reactivity measured in 1987-88 and at least one subsequent singleton livebirth within an 18-year period. Cardiovascular reactivity was measured using a video game, star tracing and cold pressor test. Gestational age and birthweight were based on the women's self-report, with PTB defined as birth <37 weeks' gestation and SGA as weight <10th percentile for gestational age. Linear and Poisson regression and generalised estimating equations were used to model the relationship between reactivity to stress and birth outcomes with control for confounders. Few associations were seen between reactivity and pregnancy outcomes. Higher pre-pregnancy diastolic blood pressure (adjusted relative risk 1.14; 95% confidence interval [CI] 0.98, 1.34) and mean arterial pressure reactivity (1.15; 0.98, 1.36) were associated with risk of PTB at first pregnancy, while SGA was associated with lower systolic blood pressure reactivity (0.76; 0.60, 0.95). No associations were seen with other measures of reactivity. Contrary to hypothesis, the association between heart rate reactivity and PTB in first pregnancy was stronger in whites (adjusted relative risk 1.39; 1.03, 1.88) than in blacks (1.00; 0.83, 1.20; P for interaction = 0.08). Similar results were found for mean arterial pressure. No strong associations were found between higher pre-pregnancy stress reactivity and SGA or PTB, and stress reactivity did not have a stronger association with birth outcomes in blacks than whites.
| S-EPMC3506123 | biostudies-literature