Recurrent Miscarriage: Causes, Testing, and What Comes Next

Recurrent pregnancy loss (RPL) is defined as three or more consecutive miscarriages before 20 weeks. A cause is found in roughly 50% of cases — most commonly chromosomal, uterine, or immunological. In the remaining 50%, no identifiable cause is found, but 60–75% of couples with unexplained RPL still achieve a live birth in a subsequent pregnancy.

One miscarriage is heartbreaking. Two begins to feel like a pattern. Three or more — what clinicians call recurrent pregnancy loss (RPL) — demands investigation. If you are in this position, you deserve more than reassurance. You deserve answers, or at least the honest acknowledgment of where the science currently stands.

This article covers the known causes of RPL, what a standard diagnostic workup looks like, and what the data says about outcomes after evaluation.

Defining Recurrent Pregnancy Loss

The American College of Obstetricians and Gynecologists (ACOG) and the European Society of Human Reproduction and Embryology (ESHRE) define RPL as two or more pregnancy losses before 20 weeks. Some specialists use three as the threshold before beginning full evaluation, though two losses in women over 35, or two losses with an identifiable pattern, often warrant earlier workup.

Roughly 1–2% of couples trying to conceive experience RPL. About 15–20% of recognized pregnancies end in single losses, but the probability of three consecutive losses by chance alone is less than 1% — which is why a clinical investigation is appropriate rather than attributing it to bad luck.

Known Causes of RPL

A cause is identified in approximately 50% of RPL cases. Here are the main categories:

Chromosomal abnormalities (~50–60% of individual losses, lower in RPL patterns)

Most individual miscarriages are caused by chromosomal errors in the embryo. In RPL, random chromosomal errors are less likely to explain the pattern than in a single loss. However, one or both partners may carry a balanced chromosomal translocation — a structural rearrangement where genetic material is swapped between chromosomes. The total amount of DNA is normal, so the carrier is unaffected, but some eggs or sperm receive unbalanced chromosomal sets, resulting in repeated losses.

Uterine structural abnormalities (~10–15% of RPL cases)

A uterine septum — a wall of tissue dividing the uterine cavity — is the most common structural cause of RPL. Septums can reduce blood flow to an implanting embryo. Other structural causes include submucosal fibroids (benign tumors protruding into the cavity), Asherman's syndrome (intrauterine adhesions, often from prior surgery), and bicornuate or arcuate uterus. Most structural issues are identified by hysteroscopy, saline-infusion sonography, or MRI.

Antiphospholipid syndrome (APS) (~5–15% of RPL cases)

APS is an autoimmune condition where the immune system produces antibodies (anticardiolipin antibodies, lupus anticoagulant, anti-beta2 glycoprotein I) that interfere with normal placental function. It is one of the few treatable causes of RPL: low-dose aspirin plus low-molecular-weight heparin (LMWH) during pregnancy significantly reduces loss rates in women with APS. Testing requires two positive results at least 12 weeks apart to confirm.

Thyroid dysfunction (~5–10% of RPL cases)

Both hypothyroidism and hyperthyroidism affect implantation and early placental development. Subclinical hypothyroidism (TSH above 2.5 mIU/L) is now recognized as a possible RPL contributor, and many specialists treat to a TSH target below 2.5 in women with RPL. Simple thyroid function testing (TSH, free T4) is included in all standard RPL workups.

Other causes

Diabetes (poorly controlled), inherited thrombophilias (factor V Leiden, prothrombin gene mutation), and luteal phase deficiency have been proposed as RPL causes, though evidence for some is mixed. Progesterone supplementation is often used empirically even where the evidence for benefit is not definitive, given its low risk profile.

The Standard Diagnostic Workup

If you have experienced two or more losses, the following tests are typically ordered:

• Karyotyping of both partners (peripheral blood chromosomes) — looks for balanced translocations
• Antiphospholipid antibody panel (anticardiolipin antibodies, lupus anticoagulant, anti-beta2 glycoprotein I)
• Thyroid function (TSH, free T4)
• Uterine evaluation (saline-infusion sonography, office hysteroscopy, or pelvic MRI)
• Hormonal evaluation (fasting glucose, prolactin, day-3 FSH/LH/estradiol if relevant)

If products of conception from the losses are available, chromosomal analysis of the lost pregnancy tissue (conceptus karyotyping or microarray) can determine whether the loss was chromosomally abnormal. This is valuable information: if three losses all show different chromosomal abnormalities, that suggests bad luck rather than a maternal cause.

Unexplained RPL: What the Prognosis Looks Like

Half of RPL cases have no identifiable cause after full workup. This is frustrating, but the prognosis is not as bleak as the history might suggest.

Studies of women with unexplained RPL show live birth rates of 60–75% in subsequent pregnancies without any specific treatment — including women with three, four, or five prior losses. The live birth rate is somewhat lower in women over 40, where chromosomal factors are more likely to be at play, but still meaningful.

Progesterone supplementation (vaginal progesterone from the time of positive pregnancy test) is increasingly offered empirically in women with unexplained RPL, based on the results of the PROMISE and PRISM trials. The PRISM trial (2019, N=4,153) found a modest but significant improvement in live birth rates in women with a history of three or more losses. The benefit was most pronounced in women with bleeding in early pregnancy.

Finding the Right Specialist

RPL evaluation should ideally involve a reproductive endocrinologist or a maternal-fetal medicine specialist with RPL experience. Not all OB/GYNs are trained in the full RPL workup or familiar with newer evidence-based treatments.

After your diagnosis, our miscarriage risk calculator can help you track how your personal risk estimate changes week by week in a subsequent pregnancy. The prior-loss multiplier in the calculator reflects the elevated risk from prior losses, but a confirmed heartbeat and increasing gestational age still shift the numbers meaningfully in the right direction.

If you have been through RPL and are navigating a new pregnancy, our article on trying again after miscarriage covers timing, monitoring, and what to expect emotionally and clinically.

Sources: ACOG Practice Bulletin No. 200: Early Pregnancy Loss (2018). ESHRE RPL Guideline (2022). Brigham SA et al. (1999). A longitudinal study of pregnancy outcome following idiopathic RPL. Human Reproduction. Coomarasamy A et al. PRISM Trial (2019). Progesterone in women with bleeding in early pregnancy. NEJM.