Recurrent Miscarriage
Definition
Recurrent miscarriage is defined as three or more first-trimester miscarriages, consistent with previous RCOG editions. Clinicians are encouraged to use clinical discretion and offer extensive evaluation after two first-trimester losses if there is suspicion of a pathological (rather than sporadic) cause — for example, a loss following a pregnancy with a normal karyotype or NIPT result. The definition is not restricted to consecutive losses, and is not restricted to losses with the same partner, since many relevant maternal pathologies are unaffected by paternal identity. Note that ESHRE's 2017/2022 guidance instead defines recurrent pregnancy loss as two or more losses — an important point of guideline divergence for exam purposes. Sporadic miscarriage (usually due to random fetal chromosomal anomalies) is a distinct entity from recurrent miscarriage, which persists even when the fetal karyotype is normal.
Investigations
- Acquired thrombophilia (antiphospholipid syndrome): offer testing for lupus anticoagulant and anticardiolipin antibodies prior to pregnancy [Grade C]. Antiphospholipid antibodies are present in ~15% of women with recurrent miscarriage.
- Second-trimester loss: may offer testing for Factor V Leiden, prothrombin gene mutation, and protein S deficiency, ideally within a research context [Grade C]
- Inherited thrombophilia: has only a weak association with recurrent miscarriage — routine testing for protein C, antithrombin deficiency, and MTHFR mutation is not recommended [Grade C]
- Cytogenetic analysis should be offered on pregnancy tissue of the third and subsequent miscarriage, and of any second-trimester miscarriage [Grade D]
- Parental peripheral blood karyotyping should be offered if pregnancy tissue testing reports an unbalanced structural chromosomal abnormality [Grade D], or if tissue testing is unsuccessful/unavailable [GPP]
- Congenital uterine anomalies: offer assessment, ideally with 3D ultrasound [Grade B]
- Thyroid function tests and TPO antibodies should be offered [Grade C]
- Immunological screening (HLA, cytokine, NK cell tests), infection screening, and sperm DNA testing should not be routinely offered outside a research context [Grade C]
- Insufficient data currently support routine PGT-A for unexplained recurrent miscarriage [Grade C]
Management
- Antiphospholipid syndrome: offer aspirin and heparin from a positive test until at least 34 weeks of gestation, after discussion of benefits versus risks [Grade B]
- Aspirin and/or heparin should not be given for unexplained recurrent miscarriage [Grade B]
- Uterine septum: resection should be considered for women with recurrent first- or second-trimester miscarriage, ideally within an audit or research context [Grade C]
- Subclinical hypothyroidism/TPO positivity: thyroxine supplementation is not routinely recommended for euthyroid women with TPO antibodies and a history of miscarriage [Grade A]
- Progestogen supplementation should be considered for women with recurrent miscarriage who present with bleeding in early pregnancy (e.g. 400mg micronised vaginal progesterone twice daily at the time of bleeding until 16 weeks) [Grade B] — there is no evidence progesterone prevents miscarriage in the absence of bleeding
- Lifestyle advice: maintain BMI 19–25 kg/m², smoking cessation, limit alcohol, limit caffeine to <200mg/day [Grade D]
- Unexplained recurrent miscarriage: offer supportive care, ideally in a dedicated recurrent miscarriage clinic [Grade C]
- Cervical cerclage for second-trimester loss/cervical insufficiency is addressed separately in Green-top Guideline No. 75, not duplicated here
High-Yield Exam Points
- RCOG definition = 3+ first-trimester losses, non-consecutive counted, any partner; ESHRE differs at 2+ losses — a common trap in exam MCQs
- Cytogenetics on products of conception: from the 3rd miscarriage onward (or any 2nd-trimester loss) — parental karyotyping only follows an unbalanced result
- Uterine assessment first-line = 3D ultrasound, Grade B
- APS management = aspirin + heparin to 34 weeks (Grade B); do not use aspirin/heparin for unexplained RM (Grade B) — a frequently tested contrast
- Thyroxine is not indicated for euthyroid TPO-positive women (Grade A) — do not confuse with treating overt/subclinical hypothyroidism
- Progesterone only indicated with early pregnancy bleeding, not as blanket prophylaxis
- Routine inherited thrombophilia, immunology, infection, and sperm DNA screening are all not recommended outside research — a repeated "don't over-investigate" theme
Source: RCOG Green-top Guideline No. 17 (June 2023 (4th edition; Regan, Rai, Saravelos, Li — BJOG 2023;130:e9–e39))
Read the original on rcog.org.uk
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