Objective: To identify, besides maternal age and the number of previous pregnancy losses, additional characteristics of couples with unexplained recurrent pregnancy loss (RPL) that improve the prediction of an ongoing pregnancy. Design: Hospital-based cohort study in couples who visited specialized RPL units of two academic centers between 2012 and 2020. Setting: Two academic centers in the Netherlands. Patients: Clinical data from 526 couples with unexplained RPL were used in this study. Intervention(s): None. Main Outcome Measures: The final model to estimate the chance of a subsequent ongoing pregnancy was determined using a backward selection process and internally validated using bootstrapping. Model performance was assessed in terms of calibration and discrimination (area under the receiver operating characteristic curve). Results: Subsequent ongoing pregnancy was achieved in 345 of 526 couples (66%). The number of previous pregnancy losses, maternal age, paternal age, maternal body mass index, paternal body mass index, maternal smoking status, and previous in vitro fertilization/intracytoplasmic sperm injection treatment were predictive of the outcome. The optimism-corrected area under the receiver operating characteristic curve was 0.63 compared with 0.57 when using only the number of previous pregnancy losses and maternal age. Conclusions: The identification of additional predictors of a subsequent ongoing pregnancy after RPL, including male characteristics, is significant for both clinicians and couples with RPL. At the same time, we showed that the predictive ability of the current model is still limited and more research is warranted to develop a model that can be used in clinical practice.

Differentiation of human-induced pluripotent stem cells (hiPSCs) into vascular endothelium is of great importance to tissue engineering, disease modeling, and use in regenerative medicine. Although differentiation of hiPSCs into endothelial-like cells (hiPSC-derived endothelial cells [hiPSC-ECs]) has been demonstrated before, controversy exists as to what extent these cells faithfully reflect mature endothelium. To address this issue, we investigate hiPSC-ECs maturation by their ability to express von Willebrand factor (VWF) and formation of Weibel-Palade bodies (WPBs). Using multiple hiPSCs lines, hiPSC-ECs failed to form proper VWF and WPBs, essential for angiogenesis, primary and secondary homeostasis. Lowering the increased intracellular pH (pHi) of hiPSC-ECs with acetic acid did result in the formation of elongated WPBs. Nuclear magnetic resonance data showed that the higher pHi in hiPSC-ECs occurred in association with decreased intracellular lactate concentrations. This was explained by decreased glycolytic flux toward pyruvate and lactate in hiPSC-ECs. In addition, decreased expression of monocarboxylate transporter member 1, a member of the solute carrier family (SLC16A1), which regulates lactate and H+ uptake, contributed to the high pHi of hiPSC-EC. Mechanistically, pro-VWF dimers require the lower pH environment of the trans-Golgi network for maturation and tubulation. These data show that while hiPSC-ECs may share many features with mature EC, they are characterized by metabolic immaturity hampering proper EC function.

Introduction: The pathophysiology of endometriosis-induced pain is complex and current pain management is often inadequate. As a consequence, the quality of life of endometriosis patients is reduced due to persistent and often recurrent severe pain, affecting emotional well-being. Case description: In this case report, we present a 28-year-old patient with deep endometriosis and severe pain resistant to conventional therapy, who experienced, after an 8-h infusion with esketamine, no pain symptoms for 8 weeks. Discussion: Current treatment options to suppress chronic pain symptoms in patients with (deep) endometriosis are often inadequate. Esketamine targets key components of the condition (inflammation, pain, depression), but the use of this drug in the treatment of chronic pain due to endometriosis has not been reported yet. Future trials are necessary to assess the effect of esketamine in the treatment of chronic pain due to endometriosis. Conclusion: This case report highlights the potential of esketamine infusion therapy in the treatment of endometriosis patients with persistent pain despite conventional therapy.