Recurrent pregnancy loss (RPL) is defined as two or more pregnancy losses before 20 weeks. It affects 1–2% of couples trying to conceive. In about 50% of cases, a specific cause can be identified through testing: chromosomal abnormalities (most common), uterine abnormalities, blood clotting disorders, hormonal issues, or immune factors. IVF with PGT-A genetic testing can significantly reduce loss rates for couples with chromosomal causes.
- Chromosomal abnormalities in the embryo cause 50–60% of all pregnancy losses, and the rate increases with maternal age
- A comprehensive RPL workup includes karyotype analysis, uterine imaging, thrombophilia screening, hormonal panel, and immune testing
- IVF with PGT-A can identify chromosomally normal embryos before transfer, reducing miscarriage risk from 30–40% to under 10% per transfer
- Treatable causes include antiphospholipid syndrome (blood thinners), uterine septum (surgical correction), thyroid disorders (medication), and progesterone deficiency (supplementation)
- In 50% of RPL cases, no cause is found — but the prognosis is still favorable, with 60–75% of couples achieving a successful pregnancy with supportive care alone
When Pregnancy Loss Becomes “Recurrent”
The American Society for Reproductive Medicine (ASRM) defines recurrent pregnancy loss as two or more clinical pregnancy losses documented by ultrasound or histopathology. Previously, the threshold was three losses, but most reproductive endocrinologists now initiate testing after two.
Understanding the scope: approximately 15–20% of recognized pregnancies end in miscarriage. Having one miscarriage does not significantly increase your risk of another. Having two losses raises the recurrence risk to approximately 25–30%. After three losses, the recurrence risk rises to 30–40%.
Early losses confirmed by positive pregnancy tests (chemical pregnancies) are increasingly recognized in RPL evaluations, especially when they occur repeatedly. If you’ve had two or more chemical pregnancies, discuss with your RE whether a workup is warranted — even if the losses occurred before ultrasound confirmation.
The RPL Workup: What Tests to Expect
| Test Category | Specific Tests | What It Rules Out |
|---|---|---|
| Genetic (both partners) | Peripheral blood karyotype | Balanced translocation or other chromosomal rearrangement (found in 3–5% of RPL couples) |
| Uterine anatomy | Saline sonohysterogram (SHG), hysteroscopy, or MRI | Uterine septum, fibroids, polyps, Asherman’s syndrome |
| Thrombophilia | Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-beta2 glycoprotein I), Factor V Leiden, Prothrombin G20210A | Antiphospholipid syndrome (APS), inherited clotting disorders |
| Hormonal | TSH, prolactin, hemoglobin A1c, progesterone | Thyroid dysfunction, diabetes, luteal phase deficiency |
| Immune (controversial) | Natural killer (NK) cell assay, cytokine panels | Immune dysregulation (evidence is limited; see our NK Cell Testing article) |
Causes and Treatments
Chromosomal Abnormalities (50–60% of losses)
The most common cause of any pregnancy loss — and the most common identifiable cause of RPL — is aneuploidy (wrong number of chromosomes in the embryo). This is largely age-related: at 35, about 30% of embryos are aneuploid; by 40, it’s over 60%; by 43, over 80%.
Treatment: IVF with PGT-A (preimplantation genetic testing for aneuploidy) allows selection of chromosomally normal embryos before transfer. This reduces per-transfer miscarriage rates to under 10%, compared to 30–40% without testing. For couples where one partner carries a balanced translocation, IVF with PGT-SR (structural rearrangement) can identify embryos with the correct chromosomal complement.
Antiphospholipid Syndrome (APS)
APS is an autoimmune condition that causes blood clots in the placental vessels, leading to pregnancy loss — typically in the late first or second trimester. It is diagnosed when antiphospholipid antibodies are found on two tests at least 12 weeks apart.
Treatment: Low-dose aspirin (81mg daily) plus heparin injections starting at positive pregnancy test. This combination reduces loss rates from approximately 50–70% to 20–30% in APS patients.
Uterine Abnormalities
A uterine septum (a wall dividing the uterine cavity) is the most common structural cause of RPL. Fibroids distorting the cavity and intrauterine adhesions (Asherman’s syndrome) can also contribute.
Treatment: Hysteroscopic surgery to remove the septum, fibroids, or adhesions. This is typically outpatient with a 2–4 week recovery period. Post-surgical pregnancy rates improve significantly — septal resection reduces miscarriage rates from approximately 60% to 15%.
Thyroid Disorders
Both overt and subclinical hypothyroidism are associated with increased miscarriage risk. The ASRM recommends TSH levels below 2.5 mIU/L for women trying to conceive.
Treatment: Levothyroxine (thyroid hormone replacement). Dosing is adjusted to maintain TSH in the optimal range throughout pregnancy.
Unexplained RPL (50% of cases)
When the full workup reveals no identifiable cause, the diagnosis is “unexplained RPL.” This is frustrating but not hopeless. The prognosis for unexplained RPL is actually favorable: 60–75% of couples will achieve a successful pregnancy with supportive care (close monitoring, early ultrasounds, progesterone supplementation, and emotional support).
IVF with PGT-A is not automatically recommended for all RPL patients. It is most beneficial when: the woman is over 37 (higher aneuploidy rates), a parental balanced translocation has been identified, or multiple losses have occurred despite treating other identified causes. For younger couples with unexplained RPL, trying naturally with close monitoring may be equally effective and far less invasive.