How should unexplained recurrent pregnancy loss be managed?

[Terminology: PCOS was renamed polyendocrine metabolic ovarian syndrome (PMOS) by global consensus in May 2026, published in The Lancet. The International Guideline now uses PMOS/PCOS in its recommendations and will use PMOS alone from 2028. Clinical content, diagnostic criteria and management are unchanged.]

Prognosis is the central message, and ASRM (2026) frames conveying it as a provider responsibility: 50–80% of patients with unexplained RPL succeed in their subsequent pregnancy attempt with no specific intervention. Expectant management should be discussed as a viable option. Standard recommended treatments per ASRM: preconception optimisation of maternal health conditions; psychological support; treatment of APS with heparin and low-dose aspirin; treatment of overt thyroid disease; treatment of uncontrolled diabetes; genetic counselling where a genetic cause is known; treatment of hyperprolactinaemia where symptomatic. Treatments of possible benefit with limited or conflicting evidence: correction of uterine cavity abnormalities; progesterone with first-trimester bleeding; empirical luteal progesterone; reproductive urology evaluation for elevated sperm DNA fragmentation; metformin in PCOS with insulin resistance; IVF for PGT-A or PGT-SR; donor gametes where a genetic cause is found or with advanced maternal age and diminished reserve. Proven ineffective or no evidence of benefit: empirical aspirin and thrombolytics without positive APS testing; treatment of endometriosis and adenomyosis; treatment of hyperprolactinaemia without ovulatory disorder; treatment of inherited thrombophilia; thyroid hormone in isolated TPO antibody positivity or TSH under 4 mIU/L; IVIG, intralipids or prednisone. ASRM also lists as showing no benefit: glucocorticoids, endometrial scratching, G-CSF, and lymphocyte immunisation therapy. The consultation challenge remains that "no specific treatment, good prognosis" can feel dismissive. Framing it as a favourable finding is worth the time.