In this issue of BJOG, many different types of studies and approaches were used to answer important clinical questions. These range from case–control and cohort epidemiologic studies, animal models, systematic reviews, and randomized clinical trials. There is also a focus on novelty and innovation. One of the most original studies is the use of umbilical cord mesenchymal stromal cells as a patch to improve outcomes with in-utero repair of meningomyeloceles (MMC) in a sheep model. Atheil and colleagues report higher Sheep Locomotor Rating Scores, higher large neutron density, less amyotrophy, and less fibrosis in lambs receiving the stromal cells compared to controls. This paper is accompanied by an excellent mini commentary by Anna David, highlighting the potential of stem cell therapy.

It is rare for me to describe a systematic review as exciting. However, Melo and coworkers performed an SR on trials using progesterone intended to reduce the risk of pregnancy loss or preterm birth. The trials were heterogenous regarding the population studied, dosing of progesterone, timing of treatment, and outcomes assessed. Nonetheless, they noted a significant decrease in risk of hypertensive disorders of pregnancy in people treated with progesterone in the first trimester. The review was prompted by similar observations by the authors in some of the individual studies. When started in the first trimester, the risk of hypertensive disorders of pregnancy with progesterone was 0.71 (0.53–0.93), and of preeclampsia was 0.61 (0.41. – 0.92). The authors outline convincing biologic plausibility and progesterone is extremely attractive as an intervention due to safety, low cost, and wide availability. However, results must be considered as hypothesis generating given the small number of trials included, varied study designs, and the fact that hypertensive disorders of pregnancy were secondary outcomes in each of the studies.

Another novel study evaluated markers of arterial vascular health in people with and without unexplained recurrent pregnancy loss. Donckers et al found increased carotid intima thickness and decreased brachial endothelial dependent flow-mediated vasodilation in individuals with pregnancy loss compared to controls. These parameters improved with exercise in people with pregnancy loss. The authors' data provide insight into mechanisms involved in subsequent cardiovascular and metabolic disease in patients with adverse pregnancy outcomes including pregnancy loss. Importantly, their findings suggest that exercise may potentially modify risks. These findings should motivate further research on the benefits of exercise in people with adverse pregnancy outcomes.

Several studies assessed biomarkers and adverse pregnancy outcomes. The group at King's College evaluated placental growth factor (PlGF) at 19 to 23 weeks' gestation as a predictor of subsequent outcomes when combined with clinical risk factors. They found that mid-pregnancy PlGF did not improve the poor predictive value of clinical risk assessment for prediction of adverse outcomes. Sovio and colleagues at Cambridge tested the association between numerous biomarkers in the first trimester and adverse pregnancy outcomes. They tested analytes associated with placental function including PlGF, PAPP-A, sFlt-1, and AFP with subsequent complications including preeclampsia, small for gestational age fetus, preterm birth, and stillbirth. Several of these biomarkers were associated with adverse pregnancy outcomes. Importantly, different analytes were associated with different outcomes, suggesting some variation in pathophysiology among conditions.

Further important observations were noted in a series of epidemiologic studies. Van't Oever and colleagues used a population-based cohort in the Netherlands to assess subsequent pregnancies in people with RhD alloimmunization requiring intrauterine transfusion. They noted that the risk of recurrence was very high and that the first transfusion in subsequent pregnancies occurred about three weeks earlier in gestation than in the index pregnancy. These data are useful for counseling families desiring more pregnancies after RhD alloimmunization. Using a Swedish cohort, Kogner et al assessed the relationship between duration of the first stage of labor and maternal postpartum complications. They noted that increasing duration of first stage of labor was associated with increased risk of severe perineal lacerations and postpartum infection. Tsamantioti and colleagues also used a Swedish cohort to assess trends in severe maternal morbidity (SMM). They noted an Increase in SMM between 1999 and 2006, followed by a decrease through 2019. This was mostly due to similar trends in severe postpartum hemorrhage. In a sobering but important study, Legasse and coworkers report a considerable increase in maternal mortality in the Tigray region of Ethiopia associated with wartime. These data underscore the exponential adverse consequences of war and societal disruption.

Finally, there is a small but valuable randomized clinical trial comparing a non-ablative dual YAG laser treatment with topical steroids for lichen sclerosis. Zivanovic and coworkers reported that outcomes and patient satisfaction were superior with the laser treatment, indicating promise for this novel therapy.

在本期 BJOG 中，使用了许多不同类型的研究和方法来回答重要的临床问题。这些范围包括病例对照和队列流行病学研究、动物模型、系统评价和随机临床试验。还注重新颖性和创新。最具原创性的研究之一是使用脐带间充质基质细胞作为补片，以改善绵羊模型中脑膜脊髓膨出 (MMC) 子宫内修复的结果。 Atheil 及其同事报告称，与对照组相比，接受基质细胞的羔羊的绵羊运动评分更高、大中子密度更高、肌萎缩更少、纤维化更少。本文附有 Anna David 的精彩迷你评论，强调了干细胞疗法的潜力。

我很少将系统评价描述为令人兴奋。然而，Melo 和同事对使用黄体酮的试验进行了 SR，旨在降低流产或早产的风险。这些试验在研究人群、黄体酮剂量、治疗时间和评估结果方面存在异质性。尽管如此，他们指出，在妊娠前三个月接受黄体酮治疗的人患妊娠期高血压疾病的风险显着降低。该审查是由作者在一些个别研究中的类似观察引发的。从妊娠早期开始，使用黄体酮的妊娠期高血压疾病的风险为 0.71（0.53-0.93），先兆子痫的风险为 0.61（0.41-0.92）。作者概述了令人信服的生物学合理性，并且由于安全性、低成本和广泛可用性，黄体酮作为干预措施极具吸引力。然而，鉴于纳入的试验数量较少、研究设计不同，以及妊娠期高血压疾病是每项研究的次要结果，结果必须被视为假设产生。

另一项新研究评估了有或没有不明原因反复流产的人群的动脉血管健康标志物。 Donckers等人发现，与对照组相比，妊娠失败的个体颈动脉内膜厚度增加，肱动脉内皮依赖性血流介导的血管舒张减少。流产患者的这些参数会随着锻炼而改善。作者的数据提供了对不良妊娠结局（包括流产）患者随后发生心血管和代谢疾病的机制的深入了解。重要的是，他们的研究结果表明锻炼可能会改变风险。这些发现应该会激发人们进一步研究运动对妊娠结局不良的人的益处。

几项研究评估了生物标志物和不良妊娠结局。国王学院的研究小组评估了妊娠 19 至 23 周时的胎盘生长因子 (PlGF)，与临床危险因素相结合，将其作为后续结果的预测因子。他们发现，妊娠中期 PlGF 并没有改善临床风险评估对不良结果预测的较差预测价值。索维奥和剑桥大学的同事测试了妊娠早期的多种生物标志物与不良妊娠结局之间的关联。他们测试了与胎盘功能相关的分析物，包括 PlGF、PAPP-A、sFlt-1 和 AFP，以及随后的并发症，包括先兆子痫、小于胎龄儿、早产和死产。其中一些生物标志物与不良妊娠结局相关。重要的是，不同的分析物与不同的结果相关，表明不同条件下的病理生理学存在一些差异。

一系列流行病学研究中还注意到了进一步的重要观察结果。 Van't Oever 及其同事利用荷兰的一个基于人群的队列来评估需要宫内输血的 RhD 同种异体免疫患者的后续妊娠情况。他们指出，复发的风险非常高，并且随后怀孕中的第一次输血发生在妊娠期比初次妊娠早约三周。这些数据对于咨询在 RhD 同种免疫后希望更多怀孕的家庭很有用。 Kogner 等人利用瑞典队列评估了第一产程持续时间与产妇产后并发症之间的关系。他们指出，第一产程持续时间的延长与会阴严重撕裂和产后感染的风险增加有关。 Tsamantioti 及其同事还利用瑞典队列来评估严重孕产妇发病率 (SMM) 的趋势。他们注意到 1999 年至 2006 年间 SMM 有所增加，随后到 2019 年有所下降。这主要是由于严重产后出血的类似趋势。在一项发人深省但重要的研究中，莱加塞和同事报告称，埃塞俄比亚提格雷地区的孕产妇死亡率因战时而大幅增加。这些数据强调了战争和社会破坏所带来的指数级不利后果。

最后，有一项小型但有价值的随机临床试验，比较了非剥脱性双 YAG 激光治疗与局部类固醇治疗地衣硬化的效果。 Zivanovic 及其同事报告说，激光治疗的结果和患者满意度均较高，这表明这种新型疗法的前景良好。