Recurrent Pregnancy Loss (RPL)

Recurrent pregnancy loss is defined by the ASRM as two or more failed clinical pregnancies — a threshold lowered from the historical three-loss criterion to enable earlier evaluation and treatment. The most common underlying cause is chromosomal aneuploidy in the embryo: random errors in meiosis produce embryos with incorrect chromosome numbers, which fail to develop beyond the first trimester. This explains why RPL risk increases with maternal age — aneuploidy rates rise steeply after 35, when chromosomal segregation errors become more frequent. Approximately 50% of all individual miscarriages are aneuploid, and this proportion is reflected in RPL cohorts as well.

Beyond embryonic chromosomal errors, several treatable maternal causes must be systematically excluded. Antiphospholipid syndrome (APS) — diagnosed when antiphospholipid antibodies (lupus anticoagulant, anticardiolipin IgG/IgM, anti-β2 glycoprotein I) are persistently elevated on two tests 12 weeks apart — is the most clinically important identifiable cause, found in 5–20% of RPL patients. APS causes recurrent thrombosis in the placental vasculature, impairing placentation and leading to fetal growth restriction and pregnancy loss. Low-dose aspirin combined with therapeutic-dose heparin (low molecular weight heparin, LMWH) reduces loss rates from approximately 90% to 25–30% in APS-associated RPL (Rai et al., Lancet 1997; Empson et al., Cochrane 2005). Uterine structural abnormalities — most commonly a uterine septum, which is associated with RPL due to impaired implantation and reduced vascularity — are found in 10–15% of patients and are correctable by operative hysteroscopy.

Parental chromosomal rearrangements (balanced translocations or inversions) are found in 2–5% of RPL couples. Although the parents themselves are phenotypically normal, their rearranged chromosomes can produce unbalanced gametes, resulting in aneuploid embryos. Preimplantation genetic testing for structural rearrangements (PGT-SR) with IVF allows selection of chromosomally balanced embryos and significantly reduces pregnancy loss rates in this group. For RPL patients with normal karyotypes and no identifiable cause — the majority — prognosis is still favorable: large observational studies show 60–70% live birth rates in subsequent pregnancies, particularly with supportive monitoring and progesterone supplementation in the luteal phase (Coomarasamy et al., NEJM 2015).