What are the main causes of recurrent miscarriage?

Approximately 50% of cases have an identifiable cause: genetic (chromosomal abnormalities in embryos, parental balanced translocations) accounts for the largest share; anatomical (uterine septum, fibroids, polyps, adhesions); immune (antiphospholipid syndrome, less commonly other autoimmune conditions); endocrine (uncontrolled thyroid, diabetes, very high prolactin); thrombophilia (clotting disorders, controversial). The remaining 50% remain 'unexplained' — though many of these are likely embryonic chromosomal abnormalities not investigated.

Does PGT-A help with recurrent miscarriage?

For couples with a history of recurrent miscarriage where embryonic chromosomal abnormality is the suspected cause, PGT-A (preimplantation genetic testing for aneuploidy) reduces miscarriage rates by selecting only euploid embryos for transfer. Evidence is strongest for women over 35 and for couples where prior miscarriage karyotyping showed aneuploid losses. PGT-A is less helpful when the cause is anatomical, immune, or unexplained.

What is antiphospholipid syndrome and how is it treated?

Antiphospholipid syndrome (APS) is an autoimmune condition where antibodies cause clots, including in placental blood vessels — leading to recurrent miscarriage, especially in the second trimester. Diagnosis requires positive lupus anticoagulant, anticardiolipin, or anti-β2-glycoprotein-I antibodies on two tests at least 12 weeks apart, plus clinical history. Treatment is low-dose aspirin (75 mg daily) plus low-molecular-weight heparin (LMWH) from positive pregnancy test through delivery. This protocol substantially reduces miscarriage in confirmed APS.

What about thrombophilia testing?

Inherited thrombophilias (Factor V Leiden, prothrombin gene mutation, MTHFR) are tested in some recurrent miscarriage workups but the evidence for treatment is weak. ASRM and RCOG both note that thrombophilia testing in recurrent miscarriage is controversial and treatment with anticoagulants in inherited thrombophilia (without APS) does not consistently reduce miscarriage. Some clinics still offer LMWH; others do not. This is an area where second opinions are useful.

What lifestyle factors matter for recurrent miscarriage?

Strongest evidence: stop smoking (both partners), reduce alcohol, maintain BMI 19–30, control thyroid function and diabetes well, and consider stopping caffeine over 200 mg/day. Less established but reasonable: vitamin D supplementation if deficient, folic acid (5 mg high-dose for some indications). The female partner's age is the largest single factor and not modifiable; this is information not advice.

When should I consider IVF specifically for recurrent miscarriage?

IVF with PGT-A is most useful when: the couple has had 2–3 losses with documented chromosomal abnormalities, the female partner is over 35–37, a parental balanced translocation is identified (PGT-SR for selecting balanced embryos), or other workup is negative and chromosomal abnormality is the probable cause. IVF without PGT-A rarely improves miscarriage rates over natural conception. IVF is not always the answer — sometimes the answer is anatomical correction (septum resection) or APS treatment, with natural conception.

Recurrent Miscarriage and IVF: Causes, Workup, Protocols, and What Actually Helps

Recurrent miscarriage is one of the most painful and least clearly explained presentations in fertility care. Roughly half of cases have an identifiable cause; the rest are labelled "unexplained", which often means "not investigated thoroughly". This guide walks through what the workup should include, what each finding means for treatment, and where IVF (with or without PGT-A) actually helps versus where it does not.

The honest message: many recurrent miscarriage cases are driven by embryonic chromosomal abnormalities — particularly in women over 35 — and PGT-A meaningfully reduces miscarriage rates in this group. But IVF is not always the right answer. Anatomical correction, APS treatment, or simply patience with appropriate workup can matter as much.

When should I be investigated for recurrent miscarriage?

Most specialists begin investigation after two consecutive miscarriages. After two losses, recurrence risk approaches 30–40%, well above the baseline ~15%. ESHRE explicitly recommends investigation at two; ASRM and RCOG also support investigation at two. Do not wait for three losses unless you and your specialist agree the workup before then would not change management.

What investigations are done for recurrent miscarriage?

Standard workup: pelvic ultrasound and saline sonogram or hysteroscopy (anatomical), parental karyotypes (chromosomal translocations), antiphospholipid antibody panel (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein-I), thyroid function and prolactin (endocrine), and a karyotype of any miscarriage product if available. Inherited thrombophilia testing is sometimes added but is controversial. Immune testing beyond APS (NK cells, cytokine panels) is offered at some clinics but evidence is weaker.

What Counts as Recurrent Miscarriage

RCOG (UK): Three or more consecutive miscarriages — though investigation often offered after two
ASRM (US): Two or more pregnancy losses
ESHRE: Recommends investigation after two consecutive losses
The trend across all major bodies is investigating earlier (at two losses) rather than waiting

Main Causes

Category	Examples	Approx. share of identified causes
Genetic / chromosomal	Embryo aneuploidy, parental translocations	~50%
Anatomical	Septum, fibroids, polyps, adhesions	~10–20%
Immune (APS)	Antiphospholipid syndrome	~10–15%
Endocrine	Thyroid, diabetes, prolactin	~5–10%
Thrombophilia (inherited)	Factor V Leiden, prothrombin	Disputed; treatment evidence weak

Approximately 50% of recurrent miscarriage cases remain unexplained after standard workup. Many of these are likely chromosomal abnormalities not investigated — which is one reason miscarriage karyotyping (cytogenetic analysis of pregnancy tissue) is so valuable when feasible.

Standard Diagnostic Workup

Tests every recurrent miscarriage workup should include

• Pelvic ultrasound, saline sonogram, or hysteroscopy
• Both partners' karyotypes
• Antiphospholipid antibody panel — twice, 12 weeks apart
• Thyroid function (TSH, free T4) and TPO antibodies
• Prolactin
• HbA1c (diabetes screen)
• Karyotype of miscarriage tissue if collected

Tests that are sometimes added

• Inherited thrombophilia (Factor V Leiden, prothrombin) — controversial
• Sperm DNA fragmentation in male partner
• Endometrial biopsy for chronic endometritis
• Vitamin D level
• NK cell testing — limited evidence

A clinical reality

Some clinics routinely run extensive immune panels (NK cells, cytokine ratios, HLA typing) that lack strong evidence and lead to expensive treatments. Approach with skepticism unless the evidence base is clear. A clinic that recommends every test for every patient should be questioned, not trusted.

Your IVF journey, organised and free

IVFPath is built for IVF patients — track medications, appointments, lab results, and costs all in one place.

💊

Medication Reminders

Never miss a dose — log every injection and tablet

📅

Appointment Calendar

All your scans, retrievals and transfers in one view

💰

Cost Tracker

Track spending so nothing is a surprise

Start for free — no card needed

Free · No credit card · Works on any device

Antiphospholipid Syndrome

APS is one of the few clearly treatable causes of recurrent miscarriage with strong evidence.

Diagnosis: Lupus anticoagulant, anticardiolipin, or anti-β2-glycoprotein-I antibodies on two tests at least 12 weeks apart, plus clinical history (recurrent miscarriage, late fetal loss, or thrombosis)
Treatment: Low-dose aspirin (75 mg daily) from positive pregnancy test, plus low-molecular-weight heparin (LMWH) — typically through delivery
Outcomes: Live birth rates with treatment improve from approximately 10% to 70–80% in confirmed APS
Pre-pregnancy: Aspirin can be started before conception; LMWH typically starts at positive test

When IVF with PGT-A Helps

IVF + PGT-A is a strong tool for couples whose recurrent miscarriage is driven by embryonic chromosomal abnormality — but it is not the right answer for every case.

PGT-A typically helps when

• Female partner is over 35–37 (high baseline aneuploidy rate)
• Prior miscarriage karyotyping showed aneuploid losses
• A parental balanced translocation is identified (use PGT-SR)
• Other workup is negative and chromosomal cause is suspected

PGT-A is less useful when

• Cause is anatomical (uterine septum, fibroids) — fix the anatomy instead
• Cause is APS — treat the APS
• Female partner is under 35 with documented euploid losses
• Patient has very low ovarian reserve (few embryos to test)

When Everything Is Normal

Approximately 50% of recurrent miscarriage cases remain unexplained after thorough workup. This is real, deeply frustrating, and not the same as "there is no cause".

Live birth rate after unexplained recurrent miscarriage is still 65–75% with appropriate care
Many unexplained cases are likely chromosomal — PGT-A may help even without confirmed cause
Tender loving care (close monitoring, frequent reassurance scans) has a documented effect on outcomes — likely partly stress-mediated, partly via early detection
Empirical interventions (low-dose aspirin, progesterone) are sometimes used; evidence is mixed

Need a second opinion on your workup?

Recurrent miscarriage workup quality varies a lot between clinics. If you are uncertain whether your investigation has been thorough, Nestie's AI assistant can help you compare what you have been offered against guideline-recommended workup and surface gaps to discuss with your specialist.

Review your workup with Nestie →

Emotional and Decision Support

Recurrent miscarriage is one of the most psychologically demanding fertility presentations. The grief is repeated, the cause is often unclear, and family/social support is variable.

Specialised RPL counselling (separate from general fertility counselling) is available in many countries
The Miscarriage Association (UK) and SHARE (US) have peer-support communities specifically for recurrent loss
Couples therapy is often valuable — partners frequently grieve and cope differently
Take time between losses for physical and emotional recovery; do not rush back to TTC under pressure

Frequently Asked Questions

References

Guidance based on RCOG Green-top Guideline 17 (Recurrent Miscarriage), ASRM practice committee opinion on evaluation and treatment of recurrent pregnancy loss, ESHRE guideline on recurrent pregnancy loss (2023), and published meta-analyses on APS treatment and PGT-A outcomes. Workup recommendations evolve — verify current guidelines with your specialist.

Recurrent Miscarriage and IVF: Causes, Workup, and What Actually Helps