About 15–20% of clinically recognised pregnancies end in miscarriage. Chromosome abnormalities are the most common cause, accounting for over 60% of losses.
Causes of recurrent pregnancy loss
RPL has been linked to genetic abnormalities, uterine anatomy problems, antiphospholipid syndrome, endocrine, hormonal or metabolic disorders, infections, sperm quality and lifestyle factors. A cause can be identified and managed in only about 50% of patients; the rest are classed as idiopathic (unexplained).
Challenges in managing RPL
- Telling sporadic miscarriages apart from true RPL.
- Patient-reported pregnancy losses may be inaccurate.
- Many recommended investigations are supported by low-quality evidence.
- Treating unexplained (idiopathic) cases, about 50%, is difficult.
- Counselling is hard when no definite cause is found.
Chromosome abnormalities in pregnancy loss
60–80%Numerical (aneuploidy)
Trisomies and monosomies; monosomy X and trisomies 16 and 22 are the most common.
~20%Abnormal fertilisation
Triploidy, tetraploidy and polyploidy.
2–5%Structural
Balanced and unbalanced translocations and inversions.
How aneuploidy arises
Segregation errors (non-disjunction) during meiosis I and II in egg and sperm development.
Balanced translocations
Balanced translocations occur in 2–5% of couples with recurrent miscarriage and should be ruled out before planning another pregnancy.
Robertsonian translocation
Involves acrocentric chromosomes (13, 14, 15, 21, 22). Carriers may have reduced fertility and a risk of unbalanced offspring, including higher risks of Down syndrome or Patau syndrome for some carrier types.
Reciprocal translocation
An exchange of material between chromosomes, usually with no loss, so carriers are typically healthy. It can produce aneuploid gametes leading to recurrent loss. Seen in about 0.2% of newborns and 0.6% of infertile men.
What professional guidelines recommend
- ASRM: peripheral karyotyping of both partners to detect balanced structural abnormalities; karyotyping of products of conception (POC) may help during ongoing RPL therapy.
- ACOG: chromosomal microarray on fetal tissue after intrauterine fetal death or stillbirth; pre- and post-test genetic counselling is essential.
- ESHRE: array CGH / microarray strongly recommended for pregnancy tissue as it reduces maternal cell contamination.
A recent study testing POC with a 24-chromosome microarray alongside the standard ASRM workup found a probable cause in most RPL patients. The authors recommend offering genetic evaluation of tissue from the second and later losses; the proposed algorithm identifies a probable or definitive cause in over 90% of miscarriages.
Comparison of methods for pregnancy tissue
| Method | Detects | Resolution | Turnaround | Guidelines | Cost (INR) |
|---|---|---|---|---|---|
| Microarray (CGH) | Aneuploidy, triploidy, unbalanced structural changes; no culture failure or maternal contamination | 100–400 kb | 10–12 days | Yes | 15,000–18,000 |
| Karyotype | Number changes, balanced & unbalanced translocations; 10–20% culture failure | 5–10 Mb | 14–21 days | Yes | 7,000–8,000 |
| FISH | Targeted, probe-limited | Moderate | 24–48 hours | No | 6,000–7,000 |
| QF-PCR | Aneuploidy of 13, 18, 21, X, Y, 15, 16, 22 | — | < 24 hours | No | 4,000–6,000 |
| NGS | Many genes | < 50 kb | 21–28 days | No | 20,000–25,000 |
RPL investigations & costs
| Test | Specimen | Cost (INR) | Turnaround |
|---|---|---|---|
| Couple karyotype (both partners) | 2–4 ml blood, sodium heparin | 4,500 | 10–15 days |
| Microarray on POC (315K) | 25–50 mg fetal/placental tissue | 14,000 | 10–15 days |
| Karyotype / FISH on POC | 25–50 mg fetal/placental tissue | 6,000 | 7–21 days |
| Antiphospholipid panel (lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein) | Serum and citrated blood | 4,500 | 7 days |
| Inherited thrombophilia profile (Factor V Leiden, Factor II G20210A) | 2–4 ml EDTA blood | 12,500 | 15–21 days |
| MTHFR two-mutation test | 2–4 ml EDTA blood | 7,000 | 7 days |
| Fetal autopsy with placental pathology | Fetal & placental tissue with signed consent | 12,000 | 3–4 weeks |
| Genetic counselling | — | 600 | 60 minutes |
Specimens are generally stable for 24–72 hours and are transported at ambient temperature with a cool pack (2–8 °C), except fetal autopsy samples, which travel at room temperature. Prices are indicative; please call to confirm.