Clinical overview
Recurrent pregnancy loss (RPL) is the loss of two or more pregnancies, and it is one of the most emotionally charged consultations in obstetrics. The couple in front of you have usually already grieved several times, may have been given conflicting advice, and frequently carry a heavy load of guilt and self-blame. Your task as a registrar is two-fold and inseparable: a systematic, evidence-based evaluation to find a treatable cause, and compassionate, honest counselling — because in roughly half of couples no cause is ever identified, and even then the prognosis for a future live birth is good.
Evaluating a woman with a history of RPL turns on assessment — what to ask, what to examine, what to test, how to interpret the results, and how to translate them into a management plan. RPL is not a single disease but a clinical phenotype with a heterogeneous set of contributors: genetic, anatomical, endocrine, thrombophilic (autoimmune), and a large idiopathic group. The discipline is to investigate appropriately, not exhaustively — to order the tests with evidence behind them, interpret them in context, and avoid the twin traps of over-investigation (false-positive findings driving unnecessary, sometimes harmful treatment) and under-investigation (missing the eminently treatable antiphospholipid syndrome). In the South African setting you must also frame loss against the background of the national maternal-mortality picture and ensure you are not missing an evolving complication such as an ectopic pregnancy or sepsis at the time of an acute loss.
Core knowledge
Definitions
There is no single global definition; the two most-cited differ:
- RCOG (GTG 17, recurrent miscarriage) traditionally defines recurrent miscarriage as three or more consecutive first-trimester losses, while accepting that investigation may reasonably begin after fewer.
- ESHRE (Recurrent Pregnancy Loss guideline, 2022 update) defines RPL as the loss of two or more pregnancies and explicitly includes non-visualised pregnancy losses (biochemical and pregnancy-of-unknown-location losses), while excluding ectopic and molar pregnancies. ESHRE recommends that the losses need not be consecutive.
The trend, reflected in the ESHRE 2022 position, is to start investigating after two clinically recognised losses, particularly where the woman is older or anxious, because the yield is reasonable and the wait for a third loss is hard to justify.
A useful subdivision is primary RPL (no previous live birth) versus secondary RPL (losses after a previous viable pregnancy), and early (pre-12 weeks, the majority) versus late (12 weeks to viability) loss — the latter shifting suspicion toward cervical, anatomical, and thrombotic causes.
Epidemiology and the chance factor
Sporadic miscarriage is common — affecting roughly one in five recognised pregnancies — so two or three losses can occur by chance alone. Most isolated early losses are due to sporadic embryonic aneuploidy, and the probability of a chromosomally abnormal loss falls with each successive miscarriage, whereas the probability of an underlying maternal cause rises. Advancing maternal age is the dominant risk factor for loss, driven by the exponential rise in oocyte aneuploidy; paternal age contributes more modestly. This frames every counselling conversation: even after three unexplained losses, the prognosis for a subsequent live birth with supportive care is encouraging.
Established and probable causes
Genetic. Two patterns. First, embryonic aneuploidy — sporadic and the commonest single cause of any individual early loss. Second, a parental structural chromosomal rearrangement (most often a balanced reciprocal or Robertsonian translocation) found in a small percentage of couples; the carrier is phenotypically normal but produces unbalanced gametes, causing repeated loss.
Anatomical. Congenital uterine anomalies (notably the septate uterus, the anomaly most consistently associated with loss) and acquired lesions — submucosal Fibroids, intrauterine adhesions (Asherman syndrome), and endometrial polyps. Cervical insufficiency classically presents as painless mid-trimester loss or rapid preterm delivery; see Cervical cerclage.
Endocrine and metabolic. Overt and poorly controlled diabetes and overt thyroid disease are associated with loss; thyroid autoimmunity and subclinical hypothyroidism are areas of genuine uncertainty. Polycystic ovary morphology and the associated metabolic milieu are linked epidemiologically. Obesity independently increases miscarriage risk.
Antiphospholipid syndrome (APS). This is the single most important treatable cause because effective therapy exists. APS is the association of persistent antiphospholipid antibodies with defined clinical events including recurrent early loss, one or more late losses, or severe early pre-eclampsia/placental insufficiency. The laboratory criteria require lupus anticoagulant, anticardiolipin antibodies, or anti-β2-glycoprotein-I antibodies, with the critical caveat that the abnormal result must be confirmed on a repeat sample, classically ≥12 weeks apart (standard teaching), because transient positivity is common after infection.