Recurrent Miscarriage: Why It Happens and What Can Be Done
The Difference Between One and Recurrent
One miscarriage affects 15–20% of recognised pregnancies and is usually a random chromosomal error — unlikely to recur.
Recurrent pregnancy loss (RPL) — two or more losses — affects 1–2% of couples. A systematic cause is more likely to be found and, in approximately 50% of RPL cases, a specific treatable cause is identified.
The Most Important Causes
1. Antiphospholipid Syndrome (APS) — Most Treatable Found in ~15% of RPL. Autoimmune antibodies cause placental blood clots. Test: lupus anticoagulant, anticardiolipin IgG/IgM, anti-beta-2-glycoprotein IgG/IgM — twice at least 12 weeks apart.
Treatment: low-dose aspirin 75mg/day + LMWH heparin from positive pregnancy test. Live birth rate improves from ~10% without treatment to 70–75% with treatment.
2. Uterine Anatomical Abnormalities Uterine septum: 65–70% miscarriage rate untreated; drops to ~15% after hysteroscopic resection. Submucous fibroids, polyps, and Asherman's syndrome also impair implantation. Detected by SIS or hysteroscopy — not standard ultrasound.
3. Thyroid Disease TSH >2.5 mIU/L and positive thyroid antibodies (even with normal TSH) both increase miscarriage risk 2–3×. Simple blood test, simple treatment — levothyroxine to maintain TSH <2.5 mIU/L.
4. Parental Chromosomal Translocations One partner carries a balanced translocation — undetected in them but producing unbalanced embryos. Found in 3–5% of RPL couples. Test: peripheral karyotype of both partners. Management: IVF + PGT-SR (structural rearrangement testing).
5. Progesterone Deficiency The PROMISE trial (large UK RCT) showed vaginal progesterone 400mg twice daily from positive pregnancy test significantly improved live birth rates in unexplained RPL with early pregnancy bleeding. ESHRE 2023 recommends progesterone supplementation for unexplained RPL.
6. Sperm DNA Fragmentation Elevated paternal DNA fragmentation (>25% DFI) impairs embryo development and causes early pregnancy loss even after implantation. Standard semen analysis does not test this.
7. Age-Related Aneuploidy In women over 37, most embryos are chromosomally abnormal — multiple losses may simply reflect multiple aneuploid pregnancies. IVF + PGT-A selects chromosomally normal embryos for transfer.
Essential Tests After 2 Miscarriages
- Peripheral karyotype (both partners)
- APS antibody panel (×2, ≥12 weeks apart)
- TSH + anti-TPO antibodies
- SIS or hysteroscopy (uterine cavity)
- AMH (guides IVF/PGT-A discussion if DOR suspected)
- Sperm DNA fragmentation index (if unexplained)
- POC chromosomal microarray (if tissue available from the loss)
Not recommended routinely (ESHRE 2023): NK cell testing, HLA typing, full thrombophilia screen beyond APS.
Unexplained RPL: Still Good News
50% of RPL couples have no identified cause. The spontaneous live birth rate in the next pregnancy with supportive care alone is 50–75%. "Tender loving care" programmes — early pregnancy monitoring with frequent ultrasound and psychological support — improve outcomes above expectant management.
Reference: ASRM 2020 — Evaluation and Treatment of RPL. ESHRE 2023 — Recurrent Pregnancy Loss. PROMISE Trial 2015.
Frequently Asked Questions
What causes recurrent miscarriage?▾
In ~50% of RPL cases, a specific treatable cause is found. The most important treatable causes are: antiphospholipid syndrome (APS — treated with aspirin + heparin), uterine anatomical abnormalities like a septum (corrected by hysteroscopy), thyroid disease (levothyroxine), and parental chromosomal translocations (IVF + PGT-SR). The remaining 50% is unexplained — still carrying a 50–75% chance of live birth in the next pregnancy with supportive care.
Does progesterone prevent miscarriage?▾
For women with unexplained recurrent pregnancy loss, vaginal progesterone (400mg twice daily from a positive pregnancy test) significantly improves live birth rates — shown in the PROMISE RCT. ESHRE 2023 recommends it for unexplained RPL. However, progesterone does not prevent miscarriage caused by chromosomal abnormalities, APS, or other structural causes.
How many miscarriages before investigation?▾
ASRM 2020 and ESHRE 2023 both recommend investigation after 2 losses. The old threshold of 3 losses caused unnecessary suffering and delayed diagnosis of treatable causes. Investigation should be offered earlier if you are over 35, had a late loss (>10 weeks), or have other risk factors.