Objective: To compare the effect of a hysteroscopic niche resection with a Levenorgestrel-releasing intrauterine device (LNG-IUD) on postmenstrual spotting in women with a symptomatic niche in the uterine cesarean scar. Design: Single center, prospective cohort study. Setting: A hospital affiliated to a medical college in China. Population: Women diagnosed with a niche by MRI scan and postmenstrual spotting of at least two days. Method: Women were allocated to two groups based on the shared medical decision-making approach, and were followed up for 1 year after treatment. Main outcome measures: The primary outcome was effectiveness in reducing postmenstrual spotting. Secondary outcomes were menstrual characteristics, direct medical costs, complications and side effects. Results: Effectiveness of LNG-IUD was significantly higher than a hysteroscopic niche resection during the first year, based on linear mixed models (P=0.009), and the effectiveness increased overtime within 1 year. Postmenstrual spotting reduced statistically in both groups. More slight side effects, although not statistically significant, were reported in LNG-LUD group at obviously lower direct medical costs. Conclusion：LNG-IUD is more effective in the treatment of postmenstrual spotting from the 6th month onwards than a hysteroscopic niche resection in women with a symptomatic niche at lower direct costs. Key Words：Niche, uterine cesarean scar, hysteroscopy niche resection, LNG-IUD, postmenstrual spotting, amenorrhea Tweetable abstract: LNG-IUD is more effective in the treatment of postmenstrual spotting related to a niche than hysteroscopic niche resection.

Background: The optimal duration of magnesium administration postpartum for prevention of eclampsia has not yet been established. Objective: To investigate the effect of early discontinuation of postpartum magnesium on the rates of postpartum eclampsia when compared to continuation for 24-hour postpartum. Search Strategy: Searches were performed using keywords related to “preeclampsia” and “magnesium sulfate” from inception of database until March 2019. Selection Criteria: Randomized controlled trials of women with preeclampsia receiving magnesium prior to delivery randomized to early discontinuation of magnesium postpartum. The control group was 24-hours of magnesium postpartum. Data Collection and Analysis: The primary outcome was the rate of postpartum eclampsia. Main Results: Eight RCTs with 2,183 women were included with five different magnesium administration time-frames. Eclampsia rates were not different between the two groups (5/1,088 (0.5%) after early discontinuation, versus 2/1,095 (0.2%) in the 24-hour group; RR 2.25, 95% CI 0.5-9.9, I2=0%, 8 studies, 2,183 participants). A number needed to treat was calculated; 370 women would need to receive 24-hours of magnesium postpartum to prevent one episode of postpartum eclampsia. The early discontinuation group had a significant decrease in time to ambulation and breastfeeding. Conclusions: Compared to continuation of magnesium for 24 hours postpartum, early magnesium discontinuation postpartum does not significantly increase the rate of postpartum eclampsia. The largest proportion of women did not receive magnesium postpartum after receiving at least 8 grams intrapartum, thus it is reasonable to consider discontinuation of magnesium postpartum if a woman has received similar adequate dose prior to delivery.

Dear Editor,We would like to comment on the systematic review by Li et al.(1)The use of steroid hormones in the first trimester is a serious issue as organogenesis takes place at this time and therefore there is the possibility of harm from not only congenital anomalies, but also long-term, and even inter-generational effects. Anyone investigating the use of steroid hormones in the first trimester should remember the diethylstilbestrol legacy of devastating harm. Oestrogen (C18H24O2) and diethylstilbestrol (C18H20O2) have similar molecular composition, but their effects are poles apart. In this review, the authors have combined progesterone with progestogens; however they are not the same, in the same way that oestrogen and diethylstilbestrol are not the same. Vaginal micronized progesterone, which we used in our large and high-quality trials (the PROMISE (2) and PRISM (3) trials), has identical molecular structure to natural progesterone, but the other drugs included in this review do not (Table 1). We chose to study vaginal micronized progesterone, as it is identical in structure to natural progesterone, and the available evidence and expert opinion suggested that this is least likely to cause harm. It is important to note that there is evidence of potential harm from dydrogesterone, particularly congenital heart disease.(4)The authors make a bold statement in the abstract about the effects of dydrogesterone on live birth rate. However, they don’t fully address the weaknesses in the evidence. Therefore, we wish to highlight the significant deficiencies in the two trials that contributed live birth data that led to the assertion of beneficial effects from dydrogesterone. Both studies were single centre, open-label studies without placebo control. El-Zibdeh et al did not randomise participants, but instead allocated patients to dydrogesterone on Saturdays, Mondays and Wednesdays, and to no treatment on Sundays, Tuesdays and Thursdays. The trial by Pandian RU was not just a single-centre, but also a single-author study, with insufficient details of the methods to assess its quality. Thus, the effectiveness evidence from these trials cannot be considered reliable.Approximately 80% (4038 of 5056) of the data used in this systematic review come from our PRISM trial.(3) The PRISM trial is a prospectively-registered, randomised, placebo-controlled, multi-centre trial conducted to the highest standards in the UK. The trial found a 3% increase in live birth rate, but with borderline statistical significance (RR, 1.03; 95% CI, 1.00 to 1.07; P=0.08). A pre-specified subgroup analysis in women with the dual risk factors of current pregnancy bleeding and one or more previous miscarriages found a 5% increase in live birth rate (RR, 1.09; 95% CI, 1.03-1.15; P=0.003). In those with three or more previous miscarriages, a 15% increase in live birth rate was observed (RR, 1.28; 95% CI, 1.08 to 1.51; P=0.004).(3, 5) No short-term safety concerns were identified. Based on these data, our recommendation is to consider vaginal micronized progesterone for women with early pregnancy bleeding and one or more previous miscarriages. As for the role of dydrogesterone, we need not only high-quality, randomised trial evidence of its effects but also credible evidence of its safety. As dydrogesterone is a synthetic progesterone-like drug, i.e. a progestogen but not progesterone, the burden of proof to demonstrate short- and long-term safety rests on those promoting this drug.