Recurrent Pregnancy Loss (RPL): Causes, Investigation & Treatment

Recurrent pregnancy loss

The definition changed

ASRM (2026) defines recurrent pregnancy loss as the spontaneous loss of two or more pregnancies under 22 weeks, excluding confirmed molar and ectopic pregnancies. Three points are easily missed:

• Pregnancies confirmed by a urine or blood hCG test are sufficient — ultrasound or tissue confirmation is not required
• Biochemical losses count, because they carry similar recurrence risk to clinical losses
• Losses do not need to be consecutive

If you have been told you need three losses before investigation, that reflects older guidance.

The most important thing to know first

50 to 80% of patients with unexplained recurrent loss succeed in a subsequent pregnancy with no specific intervention. ASRM frames conveying this as a provider responsibility, and expectant management should be discussed as a viable option.

Evaluation now starts with the miscarriage itself

ASRM recommends array-based chromosome analysis of miscarriage tissue as the first step, offered to all patients at their second miscarriage. Array-based testing is recommended over traditional karyotyping, which has 10 to 40% culture failure and cannot detect small changes.

At-home collection kits exist for those not having surgical management — ask about this at the time of a loss, not afterwards.

Why it comes first: around 50 to 60% of first-trimester miscarriages are due to embryonic aneuploidy — roughly 50% in women under 35 and 75% in women over 40. Finding a sporadic aneuploid event explains the loss, avoids an expensive workup, and reduces guilt and self-blame.

What else is recommended

For everyone: uterine cavity evaluation by HSG, saline sonogram or hysteroscopy.

In specific circumstances: parental karyotypes where miscarriage testing shows an unbalanced rearrangement or no testing was done; antiphospholipid antibodies where clinical criteria are met; TSH; HbA1c where diabetes risk factors are present; sperm DNA fragmentation in unexplained loss or concurrent infertility.

What is NOT recommended

This list matters, because these tests are commonly sold:

• Inherited thrombophilia screening, including factor V Leiden, prothrombin gene, MTHFR, protein C and S, antithrombin III. A systematic review found prevalence in women with RPL is the same as in the general population
• Thyroid antibodies — high-quality data show no benefit from treating euthyroid women with thyroid autoimmunity
• Natural killer cell testing and autoimmune testing outside APS
• Endometrial receptivity testing
• Microbiome testing, including mycoplasma and ureaplasma
• Routine ovarian reserve testing

Treatments proven ineffective

Empirical aspirin and anticoagulants without confirmed antiphospholipid syndrome. ASRM states this rests on high-quality evidence showing no benefit. One randomised trial in women with inherited thrombophilia found live birth rates of 72% treated versus 71% untreated.

Also listed as ineffective: treatment of inherited thrombophilia, IVIG, intralipids, prednisone, endometrial scratching, and G-CSF.

Worth knowing

Large cohort studies show women with RPL have an elevated later-life risk of cardiovascular disease, stroke, diabetes, autoimmune and mental health disorders — which is why ASRM frames complete health evaluation as part of RPL care.

Psychological support is described as an essential part of miscarriage care, not an optional extra.