Prognosis in unexplained recurrent pregnancy loss: a systematic review and quality assessment of current clinical prediction models

Objective: To identify models predicting live birth or ongoing pregnancy in couples with unexplained recurrent pregnancy loss (RPL) and evaluate the risk of bias, performance, generalizability, and applicability of these models. Evidence Review: A systematic literature search was performed in PubMed, Embase, Web of Science, and Cochrane Library until December 2020. Studies were eligible for inclusion if they were original studies predicting pregnancy outcome in patients with unexplained RPL and presented a tool that allowed for individual predictions. The risk of bias and applicability of the studies were assessed using the Prediction model Risk of Bias Assessment Tool. The Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis statement was used to assess reporting quality. Results: The search yielded 1,170 unique articles that were screened on the basis of the title and abstract. Seven studies were included: 1 prospective cohort study and 6 retrospective cohort studies. The recommended steps for the development of a prediction model were not followed by any of the studies, although 6 were published before the Prediction model Risk of Bias Assessment Tool and Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines. The included studies had a high risk of bias and were not externally validated. Conclusion: International guidelines recommend supportive care programs with prognostic counseling for couples with unexplained RPL. This information manages the expectations of couples and improves their ability to make an informed decision regarding further pregnancy attempts. On the basis of the results of this study, we cannot recommend the use of any of the studied prediction models in clinical practice to prevent overestimation of chances and false belief

HLA associations and HLA sharing in recurrent miscarriage : A systematic review and meta-analysis

Problem: The aim of this meta-analysis was to evaluate whether specific maternal HLA alleles and HLA sharing of couples are associated with the occurrence of recurrent miscarriage (RM). Method of study: A systematic literature search was performed for studies that evaluated the association between HLA alleles, HLA sharing and RM. RM was defined as three or more consecutive unexplained miscarriages and a control group was included of women with at least one live birth and no miscarriages in their history. Meta-analyses were performed and the pooled odds ratio (OR) was calculated. Results: We included 41 studies. Selection bias was present in 40 studies and information bias in all studies. Meta-analyses showed an increased risk of RM in mothers carrying a HLA-DRB1*4 (OR 1.41, 95% CI 1.05-1.90), HLA-DRB1*15 (OR 1.57, 95% CI 1.15-2.14), or a HLA-E*01:01 allele (OR 1.47, 95% CI 0.20-1.81), and a decreased risk with HLA-DRB1*13 (OR 0.63, 95% CI 0.45-0.89) or HLA-DRB1*14 (OR 0.54, 95% CI 0.31-0.94). Pooling results for HLA sharing showed that HLA-B sharing (OR 1.39, 95% CI 1.11-1.75) and HLA-DR sharing (OR 1.57, 95% CI 1.10-1.25) were both associated with the occurrence of RM. Conclusion: Although the present systematic review and meta-analysis demonstrates that specific HLA alleles and HLA sharing are associated with RM, a high degree of bias was present and therefore observed results should be interpreted carefully

Stronger T-Cell Alloreactivity and Diminished Suppressive Capacity of Peripheral Regulatory T Cells in Infertile Women Undergoing In Vitro Fertilization

ProblemIncreasing evidence suggests modulation of the maternal immune response to be essential for successful pregnancy. We studied the immunophenotypic profile and function of peripheral blood T lymphocytes in infertile women undergoing in vitro fertilization (IVF) and fertile control population. MethodWe collected peripheral blood mononuclear cells (PBMC) from infertile patients with recurrent implantation failure (RIF), infertile patients with successful IVF (IVFs), and normal fertile women. Cells were phenotypically analyzed, and the proliferative response and cytokine production were studied in mixed lymphocyte cultures (MLC), using lymphocytes of the own partner, or a third-party male as stimulators cells. To examine the suppressive capacity of regulatory regulatory T cells (Tregs), we performed MLC studies with a CD45(+) fraction depleted for CD4(+)CD25(bright) T cells. ResultsNo significant differences in proportions of subsets of circulating T lymphocytes were observed. The proliferative allo-immune response of PBMC of IVF women (RIF and IVFs) was significantly higher, with higher production of T-helper cells (Th1) and Th2 cytokines, compared to the fertile women. This difference in proliferation and cytokine production was associated with a diminished suppressive capacity of Tregs in these women. ConclusionThe higher allo-immune response of the IVF women compared to fertile women might be the result of a diminished suppressive capacity of Tregs and emphasizes the important role of Tregs during conception