Recurrent pregnancy loss (RPL) — defined by ASRM as two or more failed clinical pregnancies — affects approximately 1-2% of couples trying to conceive. It is one of the most emotionally devastating fertility challenges, compounded by the fact that in roughly 50% of cases, no clear cause is ever identified.
But "unexplained" does not mean "untreatable." This guide covers the known causes, the testing that matters, and the evidence-based treatments that improve outcomes.
When Does Miscarriage Become "Recurrent"?
A single miscarriage is common — occurring in 15-25% of recognized pregnancies. ACOG and ASRM recommend a diagnostic workup after two consecutive losses, though some clinicians still wait until three. If you have experienced two losses, requesting a workup is clinically appropriate.
Known Causes
Chromosomal abnormalities (50-60% of cases)
The most common cause of any individual miscarriage is embryonic aneuploidy — the embryo has an incorrect number of chromosomes. In RPL, this can be random bad luck (especially over age 35) or, in about 3-5% of couples, one partner carries a balanced chromosomal translocation that increases the risk of aneuploid embryos.
Uterine structural issues (10-15%)
Septate uterus, large fibroids (especially submucosal), significant adhesions (Asherman syndrome), or cervical insufficiency can prevent implantation or cause second-trimester losses. Many of these are surgically correctable.
Thrombophilia and antiphospholipid syndrome (5-15%)
Antiphospholipid syndrome (APS) is the most treatable cause of RPL. Diagnosed by specific antibody tests (anticardiolipin, lupus anticoagulant, anti-beta-2 glycoprotein I), it causes blood clots in the placental vasculature. Treatment with low-dose aspirin and heparin improves live birth rates from ~10% to ~70%.
Endocrine disorders (5-10%)
Uncontrolled thyroid disease (especially hypothyroidism with elevated TSH), unmanaged diabetes, and progesterone insufficiency (luteal phase defect) are modifiable risk factors.
Immunological factors (under investigation)
NK cell testing, cytokine panels, and treatments like intralipids, IVIG, and prednisone remain controversial. ASRM does not recommend routine immune testing or empiric immune therapy outside of clinical trials.
The Recommended Workup
| Test | What It Checks | ASRM Recommended? |
|---|---|---|
| Karyotype (both partners) | Balanced translocations | Yes |
| Antiphospholipid antibodies | APS/clotting disorder | Yes |
| TSH, free T4 | Thyroid function | Yes |
| Uterine imaging (SHG/HSG/MRI) | Structural abnormalities | Yes |
| Hemoglobin A1c | Diabetes screening | If indicated |
| Prolactin | Hyperprolactinemia | If indicated |
| Products of conception testing | Chromosomal cause of each loss | Recommended when available |
| NK cell / immune panels | Immune factors | Not recommended routinely |
Evidence-Based Treatments
APS-positive: Low-dose aspirin (81mg) plus prophylactic heparin, started before or at positive pregnancy test. This is the most clearly effective RPL treatment.
Uterine septum: Hysteroscopic resection. Studies show improved pregnancy outcomes, though the evidence is less robust than previously thought.
Thyroid optimization: Targeting TSH below 2.5 mIU/L in early pregnancy with levothyroxine when indicated.
Progesterone supplementation: The PRISM trial (2020) showed benefit for women with early pregnancy bleeding and a history of recurrent loss. Vaginal progesterone 400mg twice daily from positive test through 16 weeks.
IVF with PGT-A: For couples with recurrent aneuploidy-related losses or balanced translocations, IVF with preimplantation genetic testing can select chromosomally normal embryos before transfer.
The Emotional Weight
Recurrent loss carries a psychological burden that is fundamentally different from other fertility challenges. Grief compounds with each loss. The anxiety of early pregnancy after RPL can be overwhelming. Partners often grieve differently and on different timelines.
Professional support — a therapist experienced in perinatal loss, a support group like Share Pregnancy and Infant Loss Support, or peer communities — is not optional self-care. It is a core part of treatment.
The Bottom Line
A thorough workup identifies a treatable cause in approximately half of RPL cases. For the other half, the prognosis is still favorable — even with unexplained RPL, the chance of a successful next pregnancy is 60-75% with supportive care alone. Work with an RE or RPL specialist rather than a general OB-GYN, and ensure every loss is tested (products of conception karyotype) to build a clearer clinical picture over time.
Related Reading
Explore More Resources
Tracking and Timing
Cycle tracking tools and guides for every phase of your TTC journey.
FertileStart →Supplements That Help
Evidence-based prenatal vitamins, CoQ10, and fertility supplement reviews.
LifeFertile →The Full Picture
Fertility news, research, and your starting point for the TTC journey.
HowToHaveABaby →