Molecular Signatures Correlated With Poor IVF Outcomes: Insights From the mRNA and lncRNA Expression of Endometriotic Granulosa Cells.

The outcomes of in vitro fertilization (IVF) for endometriotic women are significantly worse than for patients without ovarian endometriosis (OEM), as shown by fewer retrieved oocytes. However, the exact pathophysiological mechanism is still unknown. Thus, we conducted a prospective study that analyzed mRNA and lncRNA transcriptome between granulosa cells (GCs) from patients with fewer retrieved oocytes due to OEM and GCs from controls with male factor (MF) infertility using an RNA sequencing approach. We found a group of significantly differentially expressed genes (DEGs), including NR5A2, MAP3K5, PGRMC2, PRKAR2A, DEPTOR, ITGAV, KPNB1, GPC6, EIF3A, and SMC5, which were validated to be upregulated and negatively correlated with retrieved oocyte numbers in GCs of patients with OEM, while DUSP1 demonstrated the opposite. The molecular functions of these DEGs were mainly enriched in pathways involving mitogen-activated protein kinase (MAPK) signaling, Wnt signaling, steroid hormone response, apoptosis, and cell junction. Furthermore, we performed lncRNA analysis and identified a group of differentially expressed known/novel lncRNAs that were co-expressed with the validated DEGs and correlated with retrieved oocyte numbers. Co-expression networks were constructed between the DEGs and known/novel lncRNAs. These distinctive molecular signatures uncovered in this study are involved in the pathological regulation of ovarian reserve dysfunction in OEM patients.

Meta-analysis of aspirin-heparin therapy for un-explained recurrent miscarriage.

Objective This study was designed to evaluate the efficacy and safety of aspirin-heparin treatment for un-explained recurrent spontaneous abortion (URSA). Methods Literatures reporting the studies on the aspirin-heparin treatment of un-explained recurrent miscarriage with randomized controlled trials (RCTs) were collected from the major publication databases. The live birth rate was used as primary indicator, preterm delivery, preeclampsia, intrauterine growth restriction, and adverse reactions (thrombocytopenia ) were used as the secondary indicators. The quality of the included studies was evaluated using RCT bias risk assessment tool in the Cochrane Handbook (v5.1.0). Meta-analysis was conducted using RevMan (v5.3) software. Subgroup analyses were conducted with an appropriately combined model according to the type of the treatments if heterogeneity among the selected studies was detected. Results Six publications of RCTs were included in this study. There were a total of 907 pregnant women with diagnosis of URSA, 367 of them were pooled in the study group with aspirin-heparin therapy and 540 women in the control group with placebo, aspirin or progesterone therapy. Meta-analysis showed that the live birth rate in the study group was significantly different from that in the control group [RR = 1.18, 95% CI (1.00-1.39), P=0.04]. Considering the clinical heterogeneity among the six studies, subgroup analysis were performed. Live birth rates in the aspirin-heparin treated groups and placebo groups were compared and no significant difference was found. There were no significant differences found between the two groups in the incidence of preterm delivery [RR=1.22, 95% CI (0.54-2.76), P=0.64], preeclampsia [RR=0.52, 95% CI (0.25-1.07), P=0.08], intrauterine growth restriction [RR=1.19, 95% CI (0.56-2.52), P=0.45] and thrombocytopenia [RR=1.17, 95% CI (0.09-14.42), P=0.90]. Conclusion This meta-analysis did not provide evidence that aspirin-heparin therapy had beneficial effect on un-explained recurrent miscarriage in terms of live birth rate, but it was relatively safe for it did not increase incidence of adverse pregnancy and adverse events. More well-designed and stratified double-blind RCT, individual-based meta-analysis regarding aspirin-heparin therapy are needed in future.