Recurrent pregnancy loss (RPL) is defined as two or more clinical pregnancy losses. An identifiable cause is found in approximately 50% of cases. The most important tests: parental karyotyping, antiphospholipid antibody panel, uterine anatomy evaluation (SHG or hysteroscopy), thyroid function, and progesterone levels. Many of these have straightforward treatments that dramatically improve outcomes in subsequent pregnancies.
When to Get Tested
ASRM recommends evaluation after two clinical pregnancy losses (confirmed by ultrasound or rising hCG, not just a chemical pregnancy/very early loss). Some clinicians initiate workup after a single loss if the patient is over 35 or has other risk factors, since time is limited.
Do not accept “it's just bad luck” after two losses without investigation. While chromosomal abnormality in the embryo is the single most common cause of miscarriage (especially in women over 35), a full workup identifies treatable causes in roughly half of RPL cases.
The Complete Testing Panel
1. Parental Karyotyping
A blood test on both partners to check for balanced chromosomal translocations — structural chromosome rearrangements that don't affect the carrier's health but can produce chromosomally unbalanced embryos. Found in approximately 3–5% of RPL couples. If detected, IVF with PGT-SR (preimplantation genetic testing for structural rearrangements) can select balanced embryos for transfer.
2. Antiphospholipid Antibody Panel
Tests for antiphospholipid syndrome (APS), an autoimmune condition where antibodies attack placental blood vessels, causing clotting and pregnancy loss. Found in 5–15% of women with RPL. The panel includes lupus anticoagulant, anticardiolipin antibodies (IgG and IgM), and anti-beta-2 glycoprotein I antibodies. Must be positive on two occasions 12 weeks apart for diagnosis.
APS is treatable
Treatment is baby aspirin (81 mg daily) plus heparin injections (typically enoxaparin/Lovenox) starting at positive pregnancy test. This combination increases live birth rates from approximately 10% to 70–80% in confirmed APS. It's one of the most dramatic treatment successes in reproductive medicine.
3. Uterine Anatomy Evaluation
A sonohysterogram (SHG), hysteroscopy, or MRI to check for structural uterine abnormalities:
- Uterine septum: A wall of tissue dividing the uterine cavity, present in 3–5% of women. Reduces blood supply to the implantation site. Surgical removal (hysteroscopic septoplasty) significantly reduces miscarriage rates.
- Submucosal fibroids: Fibroids that protrude into the uterine cavity can distort the implantation surface. Hysteroscopic removal improves outcomes.
- Endometrial polyps: Benign growths that can interfere with implantation. Easily removed hysteroscopically.
- Asherman's syndrome: Intrauterine adhesions (scar tissue), often from prior D&C procedures. Can be surgically lysed.
4. Thyroid Function (TSH + Free T4)
Both overt and subclinical hypothyroidism increase miscarriage risk. Optimal TSH for pregnancy is under 2.5 mIU/L. Treatment with levothyroxine is simple, safe, and effective.
5. Progesterone Assessment
Mid-luteal progesterone below 10 ng/mL may indicate inadequate luteal support. While controversial as a standalone diagnosis, progesterone supplementation in early pregnancy has shown benefit in the PRISM trial (2019, NEJM) for women with history of recurrent miscarriage: vaginal progesterone reduced miscarriage rate from 24% to 17% in women with RPL and first-trimester bleeding.
| Test | What It Detects | Found in % of RPL | Treatment If Positive |
|---|---|---|---|
| Parental karyotype | Balanced translocation | 3–5% | IVF with PGT-SR to select balanced embryos |
| Antiphospholipid panel | APS / clotting tendency | 5–15% | Baby aspirin + heparin in pregnancy |
| Uterine anatomy (SHG/hysteroscopy) | Septum, fibroids, polyps, adhesions | 10–15% | Hysteroscopic surgical correction |
| TSH + free T4 | Thyroid dysfunction | 5–10% | Levothyroxine to normalize TSH |
| Progesterone (7 DPO) | Luteal phase deficiency | 5–10% | Vaginal or oral progesterone supplementation |
| Factor V Leiden / prothrombin mutation | Inherited thrombophilia | 5–8% | Controversial; some doctors prescribe anticoagulants |
| Glucose / HbA1c | Uncontrolled diabetes | 2–5% | Blood sugar management |
| Prolactin | Hyperprolactinemia | 2–5% | Cabergoline or bromocriptine |
| Products of conception testing (POC) | Embryo chromosomal abnormality | 50–60% of losses | Guides prognosis; if recurrent aneuploidy, IVF + PGT-A may help |
What to ask for at your appointment
- Full antiphospholipid panel (not just one antibody)
- Parental karyotype for both partners
- SHG or office hysteroscopy (more detailed than standard ultrasound)
- TSH, free T4, and thyroid antibodies (TPO)
- If the next loss occurs: request chromosomal analysis of the products of conception (POC karyotype or microarray) — this is the single most informative test and is often not offered unless you ask
When IVF with PGT-A May Help
For recurrent loss caused by embryo aneuploidy, IVF with preimplantation genetic testing can select chromosomally normal embryos before transfer.
Learn About PGT-A