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IntroductionWomen with repeated implantation failure (RIF) and unexplained recurrent miscarriage (RM) are proposed to be at opposite ends of the implantation spectrum, with RM representing an overly receptive endometrium (implantation of genetically aberrant or poor-quality embryos) versus RIF representing an overly selective endometrium (no implantation even with good quality embryos). In both cases, often no explanation for reproductive failure can be found and although promising add-on treatments have been introduced, therapeutic options are frequently limited to supportive care. Both RM and RIF are multifactorial and research indicates that the interplay between steroidogenesis, uterine natural killer (uNK) cells and the microbiome determine the capacity of the endometrium to be a biosensor for invading embryos. Our objective is to elucidate whether there is a difference in endometrial receptivity parameters (ie, steroid metabolism, uNK cells and the microbiome) between women aged 18–38 years with reproductive failure (RIF and RM), and fertile controls.Methods and analysisSingle-centre, observational cohort study. Endometrial biopsies, vaginal swabs and peripheral blood will be collected during the window of implantation and menstrual blood in the subsequent menstruation. The study parameters are the steroid profile (steroid levels and mRNA levels, protein expression and activity of steroid enzymes) in endometrial tissue and peripheral blood, as well as the activating or inhibitory phenotype of uNK cells based on receptor expression in menstrual blood and endometrial tissue and determination of the vaginal and endometrial microbiome using the inter spacer bacterial profiling technique.Ethics and disseminationThe protocol is approved by the local medical ethical review committee at the Maastricht University Medical Centre. Findings from this study will be shared with the academic and medical community and the patient organisations to optimise and individualise medical care of patients with implantation failure and miscarriages.Trial registration numberNTR7571, registered 28 February 2019.

Background Studies have shown an association between Chlamydia trachomatis infection (chlamydia) and an increased risk for tubal factor infertility (TFI) in women. To assess if this association also result in fewer pregnancies, we aimed to investigate the proportion of pregnancies in women with and without a previous chlamydia infection in women participating in the Netherlands Chlamydia Cohort Study (NECCST). Methods NECCST is a cohort of 5704 women of reproductive age all tested for chlamydia by PCR in a chlamydia screening study between 2008–11. Women were re-invited for NECCST in 2015–16. Chlamydia-status (positive/negative) was defined using results from the screening, chlamydia IgG presence in serum and/or self-reported chlamydia infections. Data on pregnancies was collected via questionnaires in 2015–16 and 2017–18. Pregnancies, intended and unintended, were compared between chlamydia positive and chlamydia negative women who ever tried to become pregnant using logistic regression analyses. Results Of 5704 women enrolled, 1717 (30.1%) were chlamydia positive and 3146 (55.2%) tried to become pregnant or had been pregnant at least once. In preliminary results, of those 3146 women, 980 (31.2%) were CT positive and 2166 (68.8%) were CT negative. Of CT positive women, 90% (n=882) got pregnant compared to 91% (n=1973) of CT negative women, p=0.329. Excluding unintended pregnancies, CT positive women got pregnant less often (82% versus 89%, p Conclusion The proportion of women who were ever pregnant did not differ between chlamydia positive and negative women. However, an intended pregnancy was less common in women with a previous chlamydia infection. Disclosure No significant relationships.

Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 checklist: recommended items to address in a clinical trial protocol and related documents. (DOC 53 kb)