Search

In Brief: The causes of subfertility and recurrent pregnancy loss are often unclear. This study shows that endometrial gland cilia from women with subfertility have ultrastructural defects., Abstract: Endometrial glands secrete products into the endometrium and are necessary for embryo implantation and successful pregnancy. However, structural and functional abnormalities in endometrial gland cilia from women with reproductive failure remain poorly understood. This was a cross-sectional study where endometrial biopsies were collected at days 19-23 of the menstrual cycle from women with unexplained recurrent pregnancy loss (n = 15), unexplained subfertility (n = 11) or from egg donor control participants (n = 10). Endometrial gland cilia ultrastructure was imaged by transmission electron microscopy and cilia defects assessed by an electron-microscopist from a national primary ciliary dyskinesia diagnostic centre. Endometrial glands were isolated, and the cilia beat frequency recorded by high speed video. Subfertile women have proportionately lower ultrastructurally normal cilia (P < 0.05); higher frequency of absent dynamin arms (P < 0.01) or inner arm defects (P < 0.01) and lower cilia beat frequency (P < 0.05). The mechanisms underlying these obversions have yet to be determined. Recent studies have identified cilia related gene expression changes associated with reproductive failure and this study adds to the growing body of literature revealing structural and functional changes. The observation that cilia defects occurred at a higher frequency in endometrial glands of subfertile women raises the question of its mechanistic role in implantation.

Introduction: Biological rhythms, the innate cycle of changes in the body's physiological functions, are circadian if they have a 24-hour period. It is known that sleep is a key feature of human circadian rhythm but the relation between sleep and female fertility is largely unknown. This paucity of research is surprising given that circadian rhythms are paramount to human physiology and sleep is related to major female reproductive events. This study was designed to investigate whether there is a difference between the sleep and activity parameters of women with poor reproductive outcome compared with healthy, fertile parous women (comparator group) using subjective (questionnaires) and objective (actigraphy and light exposure) measures., Material and Methods: A prospective cohort study in a tertiary in vitro fertilization referral center in the UK; composed of three study groups: women diagnosed with recurrent implantation failure, women with recurrent miscarriage (RM) and a comparison group (fertile women without endometrial pathology). Comparison women were selected gynecology patients without endometrial disease (ie perineal complaints or altruistic egg donors). Primary outcome was differences in objective length of sleep in each of the participant groups using actigraphy. Secondary outcomes were subjective sleep quality and quantity, using participant questionnaires, light exposure, and the feasibility of machine learning in activity-pattern interpretation., Results: Women with recurrent implantation failure slept daily on average for 7 hours 35 minutes (± 57 min), 53 minutes less than the comparison group (P = .03), although quality of their objective sleep, and quantity of their subjective sleep, were not significantly different. Women with recurrent miscarriage slept less that the comparison women (36 minutes less/night) but more than women with recurrent implantation failure (17 minutes more/night). No difference in light exposure was found between recurrent miscarriage and the recurrent implantation failure and comparison groups., Conclusions: This study demonstrates an objective observation of sleep time reduction in women with subfertility, although it is not yet clear if this association is casual. Given our increased understanding of the internal body clock and circadian rhythm on fertility, our observation warrants further investigation., (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To investigate how women experience the initial period of a new pregnancy after suffering recurrent miscarriage (RM)., Design: A qualitative study, nested within a randomised controlled feasibility study of a coping intervention for RM, used semi-structured face-to-face interviews. Interviews were audio-recorded, transcribed verbatim and analysed using a thematic network approach., Setting: Participants were recruited from the Recurrent Miscarriage Clinic and Early Pregnancy Unit in two tertiary referral hospitals in the UK., Participants: 14 women with RMs and who had previously participated in the randomised controlled trial (RCT) feasibility component of the study were recruited., Results: Seven organising themes emerged from the data: (1) turmoil of emotions, (2) preparing for the worst, (3) setting of personal milestones, (4) hypervigilance, (5) social isolation, (6) adoption of pragmatic approaches, (7) need for professional affirmation., Conclusions: The study established that for women with a history of RM, the waiting period of a new pregnancy is a traumatic time of great uncertainty and emotional turmoil and one in which they express a need for emotional support. Consideration should be given to the manner in which supportive care is best delivered within the constraints of current health service provision., Trial Registration Number: ISRCTN43571276., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: Progesterone is essential to maintain a healthy pregnancy. Guidance from the Royal College of Obstetricians and Gynaecologists and a Cochrane review called for a definitive trial to test whether or not progesterone therapy in the first trimester could reduce the risk of miscarriage in women with a history of unexplained recurrent miscarriage (RM). The PROMISE trial was conducted to answer this question. A concurrent cost-effectiveness analysis was conducted., Design and Setting: A randomised, double-blind, placebo-controlled, international multicentre study, with economic evaluation, conducted in hospital settings across the UK (36 sites) and in the Netherlands (nine sites)., Participants and Interventions: Women with unexplained RM (three or more first-trimester losses), aged between 18 and 39 years at randomisation, conceiving naturally and giving informed consent, received either micronised progesterone (Utrogestan(®), Besins Healthcare) at a dose of 400 mg (two vaginal capsules of 200 mg) or placebo vaginal capsules twice daily, administered vaginally from soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) until 12 completed weeks of gestation (or earlier if the pregnancy ended before 12 weeks)., Main Outcome Measures: Live birth beyond 24 completed weeks of gestation (primary outcome), clinical pregnancy at 6-8 weeks, ongoing pregnancy at 12 weeks, miscarriage, gestation at delivery, neonatal survival at 28 days of life, congenital abnormalities and resource use., Methods: Participants were randomised after confirmation of pregnancy. Randomisation was performed online via a secure internet facility. Data were collected on four occasions of outcome assessment after randomisation, up to 28 days after birth., Results: A total of 1568 participants were screened for eligibility. Of the 836 women randomised between 2010 and 2013, 404 received progesterone and 432 received placebo. The baseline data (age, body mass index, maternal ethnicity, smoking status and parity) of the participants were comparable in the two arms of the trial. The follow-up rate to primary outcome was 826 out of 836 (98.8%). The live birth rate in the progesterone group was 65.8% (262/398) and in the placebo group it was 63.3% (271/428), giving a relative risk of 1.04 (95% confidence interval 0.94 to 1.15; p = 0.45). There was no evidence of a significant difference between the groups for any of the secondary outcomes. Economic analysis suggested a favourable incremental cost-effectiveness ratio for decision-making but wide confidence intervals indicated a high level of uncertainty in the health benefits. Additional sensitivity analysis suggested the probability that progesterone would fall within the National Institute for Health and Care Excellence's threshold of £20,000-30,000 per quality-adjusted life-year as between 0.7145 and 0.7341., Conclusions: There is no evidence that first-trimester progesterone therapy improves outcomes in women with a history of unexplained RM., Limitations: This study did not explore the effect of treatment with other progesterone preparations or treatment during the luteal phase of the menstrual cycle., Future Work: Future research could explore the efficacy of progesterone supplementation administered during the luteal phase of the menstrual cycle in women attempting natural conception despite a history of RM., Trial Registration: Current Controlled Trials ISRCTN92644181; EudraCT 2009-011208-42; Research Ethics Committee 09/H1208/44., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 41. See the NIHR Journals Library website for further project information.

Background: Progesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain., Methods: We conducted a multicenter, double-blind, placebo-controlled, randomized trial to investigate whether treatment with progesterone would increase the rates of live births and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twice-daily vaginal suppositories containing either 400 mg of micronized progesterone or matched placebo from a time soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) through 12 weeks of gestation. The primary outcome was live birth after 24 weeks of gestation., Results: A total of 1568 women were assessed for eligibility, and 836 of these women who conceived naturally within 1 year and remained willing to participate in the trial were randomly assigned to receive either progesterone (404 women) or placebo (432 women). The follow-up rate for the primary outcome was 98.8% (826 of 836 women). In an intention-to-treat analysis, the rate of live births was 65.8% (262 of 398 women) in the progesterone group and 63.3% (271 of 428 women) in the placebo group (relative rate, 1.04; 95% confidence interval [CI], 0.94 to 1.15; rate difference, 2.5 percentage points; 95% CI, -4.0 to 9.0). There were no significant between-group differences in the rate of adverse events., Conclusions: Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages. (Funded by the United Kingdom National Institute of Health Research; PROMISE Current Controlled Trials number, ISRCTN92644181.).

Obstetric and neonatal outcomes of women who had a history of recurrent miscarriage were compared with a control population from 1 January 1992 to 30 June 1998. Amongst a total of 162 pregnancies which progressed beyond 24 weeks gestation in women with a history of recurrent miscarriage, there were four perinatal deaths and 16 babies were admitted to the special care baby unit. The rates of preterm delivery (13%), small-for-gestational-age (13%), perinatal loss (2.5%) and Caesarean section (36%) were significantly (P < 0.05) higher than those of the control group (3.9, 2.1, 1 and 16.7% respectively). The ratio of male to female babies was equal. There was no significant difference in the incidence of hypertension or diabetes between the two groups. Patients with recurrent miscarriage represent a population at high risk of obstetric problems and close surveillance in the antenatal period is therefore required.