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Recurrent Pregnancy Loss (RPL) affects 2-4% of couples, and with increasing numbers of pregnancy losses the risk of miscarrying a euploid pregnancy is increased, suggesting RPL is a pathology distinct from sporadic miscarriage that is due largely to lethal embryonic aneuploidy. There are a number of conditions associated with RPL including unspecified "immune" pathologies; one of the strongest candidates for dysregulation remains T regulatory cells as depletion in the very early stages of pregnancy in mice leads to pregnancy loss. Human endometrial Treg and conventional CD4T cells were isolated during the peri-implantation period of the menstrual cycle in normal women. We identified an endometrial Treg transcriptomic signature and validated an enhanced regulatory phenotype compared to peripheral blood Treg. Parous women had an altered endometrial Treg transcriptome compared to nulliparity, indicating acquired immune memory of pregnancy within the Treg population, by comparison endometrial conventional CD4T cells were not altered. We compared primary and secondary RPL to nulliparous or parous controls respectively. Both RPL subgroups displayed differentially expressed Treg gene transcriptomes compared to controls. We found increased cell surface S1PR1 and decreased TIGIT protein expression by Treg in primary RPL, confirming the presence of altered Treg in the peri-implantation RPL endometrium., (© 2021. The Author(s).)

This review and meta-analysis aim to assess the effect of prolonged progesterone support on pregnancy outcomes in women undergoing fresh embryo transfer after IVF/intracytoplasmic sperm injection (ICSI). Two independent authors searched Embase, MEDLINE and grey literature from inception to January 2019 for randomized controlled trials (RCT) of prolonged progesterone support versus early cessation. Risk of bias was assessed. Outcome measures were live birth, miscarriage and ongoing pregnancy rate. The study was registered with PROSPERO (CRD42018088605). Seven trials involving 1627 participants were included: three reported live birth rate (672/830), seven the miscarriage rate (178/1627) and seven the ongoing pregnancy rate (1351/1627). Clinical outcomes were similar between early progesterone cessation versus progesterone continuation: live birth rate (risk ratio [RR] 0.94, 95% confidence interval [CI] 0.88-1.00), miscarriage rate (RR 0.91, 95% CI 0.69-1.20) and ongoing pregnancy rate (RR 0.98, 95% CI 0.91-1.05). Ongoing pregnancy rates were similar when analyses were restricted to those with cessation of progesterone on the day of a positive human chorionic gonadotrophin (RR 0.93, 95% CI 0.83-1.06). This meta-analysis suggests that prolonged progesterone support may be unnecessary after fresh embryo transfer. Further larger RCT would be useful to corroborate and lead to standardized duration of progesterone luteal phase support across IVF/ICSI centres., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Vaginal progesterone via capsule, gel or tablet is the most common route for luteal phase support (LPS) in Europe. Although there is a wealth of data comparing products used at other stages of assisted reproductive technology cycles, there is a lack of systematically identified evidence comparing the wide range of vaginal progesterone products. This systematic review queried the MEDLINE, Embase and Cochrane Library databases on 30 June 2016 to identify head-to-head randomized controlled trials (RCTs) comparing the efficacy or safety of vaginal progesterone preparations (Crinone, Cyclogest, Lutigest or Utrogestan Vaginal) for LPS in assisted reproductive technology cycles. Of 1914 results, 18 RCTs were included. No significant difference in clinical pregnancy rate was identified in comparisons of Utrogestan Vaginal with Crinone. Utrogestan Vaginal and Lutigest were non-inferior to Crinone in ongoing pregnancy rate comparisons. Differences in patient-reported perineal irritation with Crinone and Lutigest were not significantly different to Cyclogest. In studies comparing varying timing or dosage of Utrogestan Vaginal or Crinone, no significant differences were observed. These results suggest Crinone, Cyclogest, Lutigest and Utrogestan Vaginal represent equally safe and effective choices of vaginal progesterone for LPS in assisted reproductive technology cycles. Future quantitative analyses could provide further support for these findings., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A diagnostic test to confirm pre-eclampsia would be beneficial for the clinical management of the syndrome. The Triage PlGF test is able to confirm pre-eclampsia with high accuracy, with the greatest efficacy at <35weeks gestation. We recently found that the anti-inflammatory protein sST2 is elevated in the plasma of pre-eclamptic women compared to normal controls. Here sST2 and PlGF are compared in early-onset and late-onset pre-eclamptic women. sST2 was found to be an equally good diagnostic tool for early-onset (sST2 AUC 0.944 versus PlGF AUC 0.995; not significant) but not late-onset disease., (Copyright © 2013 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)