Evidence of an association between skewed X chromosome inactivation (SXCI) and idiopathic recurrent spontaneous abortion (RSA) is conflicting. No consensus has been reached on the degree of SXCI and the number of pregnancy losses in patients who have experienced RSA. In this systematic review and meta-analysis, different degrees of skewing and definitions of RSA are used to establish an association between SXCI and idiopathic RSA. Twelve studies comprising 1594 women who had experienced RSA and 1924 controls were included. No significant association was found between SXCI and RSA when 80 or 90% was used as cut-off value of skewing; more stringent 95% or greater SXCI was significantly higher in women who had experienced RSA than in controls (odds ratio [OR] = 4.27, 95% confidence interval [CI] 1.46 to 12.46). A significantly higher incidence of SXCI when defined as greater than 90% (or ≥90%) was found in women who had experienced RSA with three or more pregnancy losses (OR = 2.31, 95% CI 1.41, 3.78); significance diminished when RSA was defined as two or more losses. Extreme skewing of SXCI is associated with idiopathic RSA with three or more losses. More studies are needed to validate the potential genetic mechanism.

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Background To evaluate the differences in pregnancy outcomes between assisted reproductive technology (ART) patients and natural pregnant women in Shanghai, China in the past 6 years objectively. And to assess the feasibility of the research method of registry-database linkage in mainland China. Methods This retrospective study was conducted using registry-database linkage. A total of 8102 pregnancies with ART and 8096 parturients with spontaneous conception (SC) from 10 reproductive centers and 111 hospitals composed our retrospective study. The primary outcomes were the rates of obstetric complications (pregnancy-induced hypertention [PIH], gestational diabetes mellitus [GDM], placenta previa, mode of delivery, preterm birth [PTB], low birth weight [LBW], and macrosomia). The prenatal outcomes were compared between ART and SC parturients, frozen-thawed embryo transfer (FET) and fresh embryo transfer, and in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). We calculated odds ratios (ORs) and 95% confidence intervals (CIs). Results The final matching rate of the target population was 92% by using registry linkage. ART resulted in a higher rate of multiple birth, PTB, LBW, cesarean section, placenta previa and GDM compared with SC in the singleton cohort. In ART patients, pregnant women with FET had a significantly higher risk of PIH than those with fresh embryo transfer (14.1% Vs 9.3%, AOR1.528, 95% CI 1.303–1.793), but there was no difference between IVF and ICSI. FET is also related to the severity of PIH. Conclusions ART increased the rate of complications during pregnancy, the risk and severity of PIH in patients with FET was higher than that in patients with fresh embryo transfer. The registry-database linkage study is an objective and feasible research method in mainland China.

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IntroductionPregnancy loss (PL) is an adverse life event, and there is no proven effective treatment for recurrent PL (RPL). Preimplantation genetic screening (PGS) can be performed to reduce the risks of PL; however, there is still no solid scientific evidence that PGS improves outcomes for couples experiencing RPL. Comprehensive chromosome screening (PGS2.0) has become a routine practice in in vitro fertilisation (IVF) clinics. Previous studies based on PGS1.0 with a focus on RPL couples where the female is of advanced maternal age have reported contradictory results. Hence, a multicentre randomised trial is needed to provide evidence for the clinical benefits of PGS2.0 treatment for RPL couples.Methods and analysisOverall, 268 RPL couples undergoing IVF cycles will be enrolled. Couples will be randomised according to a unique grouping number generated by a random digital software into (1) PGS2.0 group and (2) non-PGS (conventional embryo morphology evaluation) group. This study aims to investigate whether the live birth rate (LBR) per initiated cycle after PGS2.0 is superior to the LBR per initiated cycle after conventional embryo evaluation (non-PGS group). Live birth will be defined as a live baby born after a gestation period of >28 weeks, with a birth weight of more than 1000 g. A multivariate logistic regression model will be used to adjust for confounding factors.Ethics and disseminationEthical approval has been granted by the Ethics Committee of Obstetrics and Gynecology Hospital, Fudan University and the participating hospitals. Written informed consent will be obtained from each couple before any study procedure is performed. Data from this study will be stored in the Research Electronic Data Capture. The results of this trial will be presented and published via peer-reviewed publications and presentations at international conferences.Trial registration numberNCT03214185; Pre-results.