What investigations should be performed in recurrent miscarriage?

ASRM (2026) presents a stepwise algorithm rather than a fixed panel, with the sequence determined by the chromosome result of the most recent miscarriage. Step one — array-based chromosome testing of miscarriage tissue, offered to all patients at their second loss. This is the highest-yield single investigation and its position first is deliberate: identifying a sporadic aneuploid event explains the loss, avoids an expensive workup, and reduces the couple's guilt and self-blame. Aneuploidy accounts for 50–60% of first-trimester losses — around 50% of tested miscarriages in women under 35 and 75% in women over 40. Then, depending on that result: Aneuploid — consider uterine cavity assessment and TSH. Unbalanced translocation — parental karyotypes, plus consider cavity assessment and TSH. Euploid — uterine cavity assessment, TSH, APS testing and additional testing as indicated by history. No testing performed — cavity assessment, parental karyotypes, TSH, APS and additional testing by history. Note that a single euploid early miscarriage has not been shown to increase the risk of a second loss, so reflex testing for other causes is not indicated after one euploid loss. Not recommended: inherited thrombophilia screening including MTHFR, thyroid antibodies, NK cell and other autoimmune testing outside APS, endometrial receptivity testing, microbiome testing including mycoplasma and ureaplasma, routine ovarian reserve testing. Worth raising in counselling: cohort data show women with RPL have elevated later-life risk of cardiovascular disease, stroke, diabetes, autoimmune and mental health disorders, which is why ASRM frames complete maternal and paternal health evaluation as part of RPL care.