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The rising rate of cesarean deliveries has led to an increased incidence of long long-term complications, including niche formation in the uterine scar. Niche development is associated with various gynecologic complaints and complications in subsequent pregnancies, such as uterine rupture and placenta accreta spectrum disorders. Although uterine closure technique is considered a potential risk factor for niche development, consensus on the optimal technique remains elusive. We aimed to evaluate the effect of single-layer vs double-layer closure of the uterine incision on live birth rate at a 3-year follow-up with secondary objectives focusing on gynecologic, fertility, and obstetrical outcomes at the same follow-up. A multicenter, double-blind, randomized controlled trial was performed at 32 hospitals in the Netherlands. Women ≥18 years old undergoing a first cesarean delivery were randomly assigned (1:1) to receive either single-layer or double-layer closure of the uterine incision. The primary outcome of the long-term follow-up was the live birth rate; with secondary outcomes, including pregnancy rate, the need for fertility treatment, mode of delivery, and obstetrical and gynecologic complications. This trial is registered on the International Clinical Trials Registry Platform www.who.int (NTR5480; trial finished). Between 2016 and 2018, the 2Close study randomly assigned 2292 women, with 830 of 1144 and 818 of 1148 responding to the 3-year questionnaire in the single-layer and double-layer closure. No differences were observed in live birth rates; also there were no differences in pregnancy rate, need for fertility treatments, mode of delivery, or uterine ruptures in subsequent pregnancies. High rates of gynecologic symptoms, including spotting (30%–32%), dysmenorrhea (47%–49%), and sexual dysfunction (Female Sexual Function Index score, 23) are reported in both groups. The study did not demonstrate the superiority of double-layer closure over single-layer closure in terms of reproductive outcomes after a first cesarean delivery. This challenges the current recommendation favoring double-layer closure, and we propose that surgeons can choose their preferred technique. Furthermore, the high risk of gynecologic symptoms after a cesarean delivery should be discussed with patients. [ABSTRACT FROM AUTHOR]

Objective: Successful implantation and placentation depend on the interaction between the endometrium and the embryo. Angiogenesis is crucial at this time. In this article we investigate the direct influence of the human embryo on in vitro endometrial angiogenesis. Design: In vitro study. Setting: Human endometrial microvascular endothelial cells (hEMVEC) grown on an in vitro angiogenesis model. Intervention(s): Conditioned media (CM) of human embryos were used to stimulate in vitro angiogenesis. Main Outcome Measure(s): In vitro angiogenesis of hEMVEC. Result(s): Conditioned media of human embryos, containing significant amounts of vascular endothelial growth factor (VEGF)–A, as determined by enzyme-linked immunosorbent assay (ELISA), caused an increase in hEMVEC tube formation. This effect was prevented by soluble VEGF receptor 1, which quenches VEGF-A activity. Recombinant EGF alone and leukemia inhibitory factor in combination with VEGF-A stimulated hEMVEC tube formation. None of the other tested recombinant mediators, which have been described as produced by the early embryo/trophoblast (interleukin (IL) 10, transforming growth factor (TGF) β, placental growth factor, hCG, colony-stimulating factor 1, interferon-γ, insulin-like growth factor I and II, IL-6, platelet-derived growth factor, and TGFα), had an effect on tube formation by hEMVEC. Conclusion(s): For the first time, it is shown that the human embryo is able to stimulate in vitro endometrial angiogenesis at the time of implantation, a process that is mediated by VEGF-A. [Copyright &y& Elsevier]

• This is the first prediction model for development of a niche, including important surgical factors, in a population with a first elective or emergency CS. • More attention should be paid to surgical factors (double-layer closure, less surgical experience, other suture material than Vicryl) given their effect on niche development. • Different factors contribute to development of a niche compared to development of a large niche. • This prediction model is, unfortunately, not usable in clinical practice due to lack of discriminative ability and accuracy. • Proper suturing and correct approximation rather than single- versus double-layer uterine closure could play an important role and needs attention during training of residents. • Clinicians should be aware that suture material influences niche development. To develop and internally validate a prognostic prediction model for development of a niche in the uterine scar after a first caesarean section (CS). Secondary analyses on data of a randomized controlled trial, performed in 32 hospitals in the Netherlands among women undergoing a first caesarean section. We used multivariable backward logistic regression. Missing data were handled using multiple imputation. Model performance was assessed by calibration and discrimination. Internal validation using bootstrapping techniques took place. The outcome was 'development of a niche in the uterus', defined as an indentation of ≥ 2 mm in the myometrium. We developed two models to predict niche development: in the total population and after elective CS. Patient related risk factors were: gestational age, twin pregnancy and smoking, and surgery related risk factors were double-layer closure and less surgical experience. Multiparity and Vicryl suture material were protective factors. The prediction model in women undergoing elective CS revealed similar results. After internal validation, Nagelkerke R2 ranged from 0.01 to 0.05 and was considered low; median area under the curve (AUC) ranged from 0.56 to 0.62, indicating failed to poor discriminative ability. The model cannot be used to accurately predict the development of a niche after a first CS. However, several factors seem to influence scar healing which indicates possibilities for future prevention such as surgical experience and suture material. The search for additional risk factors that play a role in development of a niche should be continued to improve the discriminative ability. [ABSTRACT FROM AUTHOR]