Are Genetic Results Improving RPL Management? A Clinical Audit

Objective: ASRM recently updated recurrent pregnancy loss (RPL) guidelines to prioritize chromosomal analysis of products of conception (POC) as the first step in evaluating all RPL patients. The new guidelines recommend no additional workup for aneuploid losses, and selective workup for euploid losses. We sought to identify what portion of individuals with euploid POC met criteria for RPL and determine if subsequent evaluation for other etiologies of pregnancy loss differed between those with and without RPL. Design: Single-site retrospective cohort analysis Materials and Methods: We included all individuals with singleton pregnancy losses before 20 weeks gestational age who underwent cytogenetic analysis of POC and were found to have euploid POC from 2022 to 2025. Our independent variable was meeting the diagnostic criteria for RPL. We examined completion of the RPL workup recommended by ASRM: endocrine (HbA1c, prolactin, and TSH levels), immunologic (anti-phospholipid syndrome (APLS) testing), anatomical (saline sonogram or hysteroscopy), and genetic (parental karyotype). Results: 119 individuals were available for analysis. Of these, 66 (55%) met criteria for RPL. There were low levels of subsequent workup completion in the RPL group: 48 A1c (73%), 41 TSH (62%), 11 prolactin (17%), 46 (70%) immunologic, 15 (23%) anatomical, and 12 (18%) genetic workup. Workup completion rates in the group without RPL were similar: 33 A1c (66%), 27 TSH (51%), 11 prolactin (21%), 19 (37%) immunologic, 6 (12%) anatomical, and 2 (4%) genetic workup. 4 individuals with RPL and 0 without RPL received a complete evaluation. Only the completion of immunologic workup differed between those with RPL and those without (p=0.001). Conclusions: Our findings suggest poor adherence to guidelines for pregnancy loss evaluation. While karyotypic testing is only recommended for those with RPL, nearly half of those tested did not meet RPL criteria. Completion of additional workup was low across both groups. Only immunologic (APLS) testing was performed significantly more frequently in patients with RPL. These results suggest that although clinicians may appropriately identify individuals with RPL, they remain unaware of the full scope of recommended diagnostic evaluation. Further work is needed to identify barriers to workup and develop interventions to ensure patients with RPL receive comprehensive evaluation.