Synthesized from ASRM (2023), RCOG Green‑top No. 17 (2023), ESHRE (2017, updates ongoing), and ACOG (2020)
1) Scope & Purpose
- Target users: Obstetricians/gynecologists, fertility specialists, early pregnancy units, and primary care clinicians.
- Population: Couples with recurrent pregnancy loss (RPL).
- Settings: Preconception, early pregnancy care, outpatient and inpatient gynecology.
2) Definitions
- Clinical pregnancy: Ultrasonographic evidence of an intrauterine gestational sac or histopathological confirmation.
- Recurrent Pregnancy Loss (RPL):
- ASRM/ESHRE/ACOG: ≥2 clinical pregnancy losses (not necessarily consecutive).
- RCOG: ≥3 consecutive clinical miscarriages (may offer evaluation after 2, especially with maternal age ≥35, prior fetal cardiac activity, or late loss).
- Exclude: Ectopic and molar pregnancies from the RPL count (manage separately).
- Classification: By gestation (early <10 weeks, late 10–20 weeks) and etiology (explained vs unexplained).
3) Epidemiology & Prognosis
- Miscarriage occurs in ~15–20% of clinically recognized pregnancies; RPL affects ~1–2% of couples.
- Prognosis: 60–80% will ultimately achieve a live birth even without specific therapy (after evaluation and supportive care).
4) Risk Factors For Recurrent Miscarriage
- In more than half of women with repeated miscarriages, no cause can be found.
4.1 Epidemiological factors
(Include maternal age, parity, lifestyle, prior obstetric history)
4.2 Thrombophilia
Acquired: Antiphospholipid syndrome (APS) – association between antiphospholipid antibodies (lupus anticoagulant, anticardiolipin [aCL], anti-β2-glycoprotein-I antibodies) and adverse pregnancy outcome or vascular thrombosis.
Adverse outcomes:
- ≥3 consecutive miscarriages <10 weeks
- ≥1 morphologically normal fetal loss after 10 weeks
- ≥1 preterm birth <34 weeks due to placental disease
Inherited: Factor V Leiden, protein C/S deficiencies, antithrombin deficiency, prothrombin gene mutation.
4.3 Genetic factors
- Parental chromosomal rearrangements: Balanced translocations
- Fetal chromosomal anomalies: Aneuploidy
4.4 Anatomical factors
- Congenital uterine anomalies: septate, bicornuate, arcuate
- Acquired uterine anomalies: myomas, endometrial polyps, intrauterine adhesions
- Cervical integrity: evaluate for cervical insufficiency
4.5 Endocrine
- Subclinical hypothyroidism (SCH), diabetes, PCOS
4.6 Immune factors
- Peripheral: HLA, cytokines, peripheral NK cells
- Uterine: uterine NK cells
4.7 Infective factors
- TORCH not recommended
- Bacterial vaginosis may increase second-trimester losses
- Chronic endometritis implicated, but criteria remain controversial
4.8 Male factors
- Consider sperm quality and DNA integrity in selected cases
5) Recommended Investigations
5.1 Thrombophilias
- Acquired: Test LA, aCL IgG/IgM, anti-β2-glycoprotein I IgG/IgM; repeat positive tests ≥12 weeks later; diagnose APS per clinical + lab criteria.
- Inherited: Test Factor V Leiden, prothrombin mutation, protein S deficiency in selected women; limited evidence for impact on outcomes.
5.2 Genetic
- Cytogenetic analysis on pregnancy tissue for 3rd+ miscarriage or second-trimester loss
- Parental karyotyping if pregnancy tissue shows unbalanced rearrangement
- Offer parental karyotyping if tissue unavailable or testing fails
5.3 Uterine Anatomy
- 3D USG, saline infusion sonohysterography, HSG, diagnostic hysteroscopy
- MRI/endoscopy for complex anomalies
5.4 Endocrine & Metabolic
- TSH (target <2.5 mIU/L), treat overt hypo/hyperthyroidism
- HbA1c/fasting glucose, optimize preconception
- Prolactin if cycle disturbance/galactorrhea
- Address PCOS/obesity/metabolic syndrome
5.5 Immune
- Routine screening not recommended outside research
5.6 Infective
- Routine screening not recommended outside research
5.7 Male factors
- Routine sperm DNA testing not recommended outside research
5.8 Tests Not Routinely Recommended
- Inherited thrombophilia panels without history
- TORCH or chronic endometritis without clinical indication
- Immune assays (NK, HLA, IVIG, intralipids) outside APS
6) Evidence-Based Management
6.1 Lifestyle modifications
- Maintain BMI 19–25 kg/m², quit smoking, limit alcohol, caffeine <200 mg/day
6.2 Thrombophilias
Acquired: Aspirin + LMWH in APS; avoid in unexplained RPL
Inherited: Individualized discussion; routine treatment not supported
6.3 Genetic factors
- Options: natural conception, PGT-SR, gamete donation
- Routine PGT-A not recommended in unexplained RPL
6.4 Anatomical factors
- Congenital anomalies: septum resection if recurrent miscarriage
- Acquired anomalies: individualized counseling
- Cervical integrity: vaginal progesterone or cerclage if history + short cervix
6.5 Endocrine factors
- Thyroxine for moderate SCH; not routine in mild SCH
- Regular TSH monitoring 7–9 weeks gestation
- Progesterone if early bleeding
6.6 Immune factors
- Immunotherapy (IVIG, paternal cell immunization) not recommended
6.7 Male factors
- No evidence to recommend treatments
6.8 Unexplained RPL
- Offer supportive care in dedicated clinic
- Endometrial scratch not recommended
6.9 Adjuncts & What Not to Use
- Avoid steroids, IVIG, intralipids, aspirin alone, anticoagulation for inherited thrombophilia outside APS
- Metformin only for glycemic/PCOS indications
7) Preconception & Lifestyle Optimization
- Folic acid ≥400 μg daily (4–5 mg if diabetes/NTD risk)
- BMI 19–25, diet/exercise programs, sleep, stress management
- Smoking cessation, avoid alcohol/drugs, caffeine <200 mg/day
- Review medications; avoid teratogens; ensure vaccinations
8) Care Pathway & Follow-up
- Evaluation after 2 losses (earlier if age ≥35 or late miscarriage)
- Written plan for next pregnancy: contact, LDA/LMWH, progesterone, early scans
- Early Pregnancy Unit access for reassurance, triage
- Psychological support, bereavement services
- Document prognosis and safety-net advice
9) Special Situations
- Second-trimester or recurrent late loss: evaluate cervical/fetal/placental/maternal factors; consider cerclage
- Assisted reproduction: luteal support per ART, PGT for structural rearrangements
- Secondary RPL: similar evaluation; note age-related aneuploidy
10) Documentation & Communication
- Summarize prior pregnancies, tests, results, and interpretations
- Record patient preferences and shared decisions
- Provide concise patient-held plan for next conception
11) Quality Indicators (Audit)
- APS panel and uterine imaging completion rate
- Referral to work-up completion time (≤8–12 weeks)
- Documentation of counseling and written plan
- Live-birth rate within 12–24 months of evaluation
12) Medication Dosing Summary (Quick Reference)
- Low-dose aspirin: 75–100 mg orally daily
- LMWH prophylactic: enoxaparin 40 mg SC daily (start positive test, continue pregnancy)
- LMWH therapeutic: enoxaparin 1 mg/kg SC twice daily
- Progesterone: micronized vaginal 200–400 mg/day or dydrogesterone 10 mg twice daily until 12–16 weeks
- Levothyroxine: per TSH; recheck every 4–6 weeks
13) Patient Information
- Most couples will conceive and carry a healthy pregnancy
- Stepwise evaluation targets causes with proven treatments
- Healthy lifestyle, early contact on positive test, and supportive care improve outcomes
References & Source Guidelines
- ASRM Committee Opinion: Evaluation and Treatment of Recurrent Pregnancy Loss (2023)
- RCOG Green‑top Guideline No. 17: Recurrent Miscarriage (2023)
- ESHRE Guideline on Recurrent Pregnancy Loss (2017; updates ongoing)
- ACOG Practice Bulletin: Early Pregnancy Loss/Management Considerations (2020)
Compiled By:
Dr. Sumaiya Binte Asif
Contributors
- Prof Fawzia Hossain
- Prof Farhna Dewan
- Prof Salma Begum
- Prof Rashida Begum
- Prof Tabassum Parveen
- Dr Rubina Akter
- Dr Sumaiya Binte Asif
- Dr Taslima Akter
- Dr Maniza
- Dr Chyochyo Nancy
- Dr Aklima Zakaria Zinan
- Dr Sharmin Alam Leena
- Dr Sadia Shormin
- Dr Sumaiya Binte Asif
- Dr Asma Habib