Pregnancies following assisted reproductive technology (ART) may have elevated potential risk of pregnancy loss (PL) when compared to natural conception. However, rare studies comprehensively analyzed the IVF/ICSI cycle-dependent factors for loss of clinical pregnancy. Therefore, we aimed to determine the ART subgroup-specific risks of PL throughout pregnancy and explore different risk factors for early miscarriage and late miscarriage among pregnancies conceived through ART. A retrospective cohort study was launched in two infertility treatment centers in Nanjing and Changzhou including 5485 IVF/ICSI embryo transfer cycles with known outcomes after clinical pregnancy by the end of 2015. Cox proportional hazards regression analysis was performed to estimate the hazard ratios and their 95% confidence intervals. The associations between survival time during pregnancy and demographics and clinical characteristics of clinical pregnancies were estimated using the Kaplan-Meier method and the Log-rank test. The overall PL rate in current ART population was 12.5%. Among the 685 pregnancy loss cycles, a total of 460 ended as early miscarriage, 191 as late miscarriage. We found couples in ART pregnancies demonstrated a significantly increased risk of PL as maternal age (HR = 1.31, Ptrend < 0.001) grows. Pregnancies received controlled ovarian hyperstimulation (COH) protocol like GnRH antagonist protocol (HR = 3.49, P < 0.001) and minimal stimulation protocol (HR = 1.83, P < 0.001) had higher risk of PL than GnRH-a long protocol. Notably, in contrast to fresh cycle, women who received frozen cycle embryo had a significant increased risk of early miscarriage (P < 0.001), while frozen cycle was linked with lower risk of late miscarriage (P = 0.045). In addition, four factors (maternal age, COH protocol, cycle type and serum hCG level 14 days after transfer) had independent impact on miscarriage mainly before 12 weeks of gestational age. With these findings in this study, clinicians may make it better to evaluate a patient’s risk of PL based on the maternal age at the time of treatment, COH protocol, cycle type and serum hCG level 14 days after transfer and the gestational week of the fetus, and we hope that it contributes to future study on its etiology and guide the clinical prevention and treatment.

Objective: Endometrial thickness is a prognostic factor for successful pregnancy. This meta-analysis aimed to examine the role of sildenafil citrate on infertile women with a thin endometrium. Methods: Two investigators independently searched the literature on sildenafil citrate and infertile women with a thin endometrium from PubMed, EMBASE, and the Cochrane Controlled Trials Register Database from inception to January 2019. Results: Nine studies involving 1452 patients were included for analysis in our study. We found that endometrial thickness in patients who received sildenafil citrate was significantly higher than that in the control group (placebo or no treatment) (weighted mean difference: 1.22; 95% confidence interval [CI]: 1.07–1.38). The radial artery resistance index was significantly lower (weighted mean difference: −0.12; 95% CI: −0.17 to −0.06), and the clinical pregnancy rate (risk ratio: 1.31; 95% CI: 1.11–1.53) and biochemical pregnancy rate (risk ratio: 1.45; 95% CI: 1.11–1.89) were significantly higher in the sildenafil citrate group compared with the control group. Conclusion: Sildenafil citrate is effective in improving endometrial thickness, the clinical pregnancy rate, and the biochemical pregnancy rate in women who have a thin endometrium. This treatment is a potential therapeutic intervention for a thin endometrium.

PAT1 homolog 2 (PATL2), encoding an RNA-binding protein, is a repressor involved in the translational regulation of maternal mRNAs during oocyte maturation. Previous studies have reported mutations inPATL2those led to female infertility with oocyte maturation arrest; however, the mechanisms by which mutations affected meiotic maturation remained unclear. Here, we identified several novel and recurrent mutations ofPATL2in patients with similar phenotype, and chose the missense mutation c.649 T>A p.Tyr217Asn inPATL2(PATL2^Y217N) as a typical to investigate the underlying mechanisms. We confirmed that this mutation disturbed oocyte maturation and observed morphological defects of large polar body, symmetrical division and abnormal spindle after microinjection of corresponding mutated mRNA. We further evaluated the effect of the PATL2^Y217Nmutation in 293T cells, and found this mutation decreased the ubiquitination level and degradation of PATL2. Then, abnormally increased PATL2 bound mRNAs of Mos, an upstream activator of mitogen activated protein kinase (MAPK), to regulate its translational activity and subsequently impaired MAPK signaling pathway and oocyte meiosis. These results dissented from the previous view thatPATL2mutations reduced their expression and highlight the role of PATL2 in translational regulation of Mos and its association with MAPK signaling pathway during oocyte meiotic maturation.