Recurrent miscarriage is not associated with a higher prevalence of inherited and acquired thrombophilia.

PROBLEM: Although not being recommended in guidelines, many physicians perform routine screening for thrombophilia in RM patients suspecting a higher prevalence in these patients. The aim of this study was to analyze the prevalence of inherited and acquired thrombophilia in a large cohort of RM patients. METHOD OF STUDY: Within a multicenter case-control study, n = 820 RM patients and n = 141 controls were included. The prevalence of inherited and acquired thrombophilia including deficiency of protein C/S and antithrombin, elevation of factor VIII activity, APC resistance including mutation in the factor V Leiden gene, mutation in the prothrombin gene and antiphospholipid antibodies were assessed. Further, we performed a meta-analysis of the prevalence of thrombophilia in RM patients including studies between 01/2000 and 01/2020. RESULTS: An antiphospholipid syndrome (APLS) was only present in RM patients. Increased factor VIII concentration was significantly more prevalent in controls (RM vs controls: 5.8% vs 11.0%). None of the other thrombophilia did differ significantly between RM patients and controls. The meta-analysis revealed no significant difference in the occurrence of these thrombophilia between RM patients and controls. CONCLUSION: The prevalence of inherited thrombophilia does not differ between RM patients and controls. When analyzing rare events like thrombophilia, a high number of patients are needed to obtain reliable results, which might explain contradictory findings in previous studies analyzing small cohorts of RM patients. Despite being less prevalent than previously described, we still recommend screening for APLS as it is associated with severe pregnancy complications.

Recurrent pregnancy loss: a shared stressor---couple-orientated psychological research findings.

OBJECTIVE: To compare the psychological impact of recurrent pregnancy loss (RPL) on affected men and women and to determine risk and protective factors in both partners. DESIGN: Cross-sectional study. SETTING: University-affiliated fertility center. PATIENT(S): Ninety female/male couples and 14 women. INTERVENTION(S): Participants completed a questionnaire covering psychological risk factors (ScreenIVF), experience of pregnancy losses, coping strategies, and partnership satisfaction. MAIN OUTCOME MEASURE(S): Comparison of psychological risk factors, perception of RPL, and coping strategies between both partners and analysis of the influence of risk and protective factors. RESULT(S): In the ScreenIVF, 47.7% of women versus 19.1% of men showed a risk for anxiety, 51.7% versus 19.1% a risk for depression, and 28.1% versus 30.7% a risk for limited social support. The use of avoiding coping styles seems to be less favorable with regard to the psychological risk than active strategies. Having a child together and a satisfying partnership correlated with a lower risk for depression. Sharing the experience of RPL with others and being in a satisfying relationship correlated with a higher social support. CONCLUSION(S): Both men and women affected by RPL show high risks for developing depression and anxiety, underlining the importance of also including the male partners. The factors of communication with others, a satisfying relationship, and already having a child together correlate with decreased psychological risks. We advocate for health care professionals to implement screening for anxiety, depression, and social support for both partners and support them in dealing with RPL. REGISTRATION NUMBER: The study is registered in the German Clinical Trials Register (DRKS), number DRKS00014965.

Two of a kind? Immunological and clinical risk factors differ between recurrent implantation failure and recurrent miscarriage.

Recurrent miscarriage (RM) and recurrent implantation failure (RIF) are unsolved challenges in reproductive medicine. Whether RIF patients share the same risk factors as RM patients is a matter of debate. Besides clinical factors, immune alterations are discussed in both conditions. The scope of this study was to compare the prevalence of clinical and immunological risk factors in a large cohort of RM and RIF patients. Between 11/2011 and 02/2019, 613 RM and 185 RIF patients were included. A screening for anatomical malformations, endocrine, autoimmune, prothrombotic and parental chromosomal disorders was performed. The immune status was assessed using flow cytometry analysis of peripheral lymphocyte subpopulations and uterine natural killer cells (uNK cells) using immunohistochemistry. RM patients showed a higher rate of intrauterine adhesions and elevated antinuclear antibodies ≥ 1:160 (p < 0.05). A higher prevalence of submucous fibroids and increased factor VIII levels were observed in RIF patients (p < 0.05). The prevalence of an antiphospholipid syndrome (APLS) was low and did not differ between the two groups. RIF patients had higher numbers of peripheral regulatory T-cells (p < 0.05). Significant more RIF patients were diagnosed with elevated uNK cells (p < 0.05). Differences in clinical and immunological risk factors of RM and RIF patients reflect different entities. Lower Tregs in RM and higher uNK cells in RIF patients might be related to the previous exposure of the immune system to fetal cells. The low prevalence of an APLS indicates a potential overestimation of this factor in the pathophysiology of RM and RIF.

Progesterone for the Prevention of Preterm Birth - an Update of Evidence-Based Indications.

The prevention and treatment of preterm birth remains one of the biggest challenges in obstetrics. Worldwide, 11% of all children are born prematurely with far-reaching consequences for the children concerned, their families and the health system. Experimental studies suggest that progesterone inhibits uterine contractions, stabilises the cervix and has immunomodulatory effects. Recent years have seen the publication of numerous clinical trials using progestogens for the prevention of preterm birth. As a result of different inclusion criteria and the use of different progestogens and their methods of administration, it is difficult to draw comparisons between these studies. A critical evaluation of the available studies was therefore carried out on the basis of a search of the literature (1956 to 09/2018). Taking into account the most recent randomised, controlled studies, the following evidence-based recommendations emerge: In asymptomatic women with singleton pregnancies and a short cervical length on ultrasound of ≤ 25 mm before 24 weeks of gestation (WG), daily administration of vaginal progesterone (200 mg capsule or 90 mg gel) up until 36 + 6 WG leads to a significant reduction in the preterm birth rate and an improvement in neonatal outcome. The latest data also suggest positive effects of treatment with progesterone in cases of twin pregnancies with a short cervical length on ultrasound of ≤ 25 mm before 24 WG. The study data for the administration of progesterone in women with singleton pregnancies with a previous preterm birth have become much more heterogeneous, however. It is not possible to make a general recommendation for this indication at present, and decisions must therefore be made on a case-by-case basis. Even if progesterone use is considered to be safe in terms of possible long-term consequences, exposure should be avoided where it is not indicated. Careful patient selection is crucial for the success of treatment.