Recurrent MiscarriageGreen-top Guideline No. 17

Abstract

In this guideline, recurrent miscarriage has been defined as three or more first trimester miscarriages. However, clinicians are encouraged to use their clinical discretion to recommend extensive evaluation after two first trimester miscarriages, if there is a suspicion that the miscarriages are of pathological and not of sporadic nature. Women with recurrent miscarriage should be offered testing for acquired thrombophilia, particularly for lupus anticoagulant and anticardiolipin antibodies, prior to pregnancy. [Grade C] Women with second trimester miscarriage may be offered testing for Factor V Leiden, prothrombin gene mutation and protein S deficiency, ideally within a research context. [Grade C] Inherited thrombophilias have a weak association with recurrent miscarriage. Routine testing for protein C, antithrombin deficiency and methylenetetrahydrofolate reductase mutation is not recommended. [Grade C] Cytogenetic analysis should be offered on pregnancy tissue of the third and subsequent miscarriage(s) and in any second trimester miscarriage. [Grade D] Parental peripheral blood karyotyping should be offered for couples in whom testing of pregnancy tissue reports an unbalanced structural chromosomal abnormality [Grade D] or there is unsuccessful or no pregnancy tissue available for testing. [GPP] Women with recurrent miscarriage should be offered assessment for congenital uterine anomalies, ideally with 3D ultrasound. [Grade B] Women with recurrent miscarriage should be offered thyroid function tests and assessment for thyroid peroxidase (TPO) antibodies. [Grade C] Women with recurrent miscarriage should not be routinely offered immunological screening (such as HLA, cytokine and natural killer cell tests), infection screening or sperm DNA testing outside a research context. [Grade C] Women with recurrent miscarriage should be advised to maintain a BMI between 19 and 25 kg/m² , smoking cessation, limit alcohol consumption and limit caffeine to less than 200 mg/day. [Grade D] For women diagnosed with antiphospholipid syndrome, aspirin and heparin should be offered from a positive test until at least 34 weeks of gestation, following discussion of potential benefits versus risks. [Grade B] Aspirin and/or heparin should not be given to women with unexplained recurrent miscarriage. [Grade B] There are currently insufficient data to support the routine use of PGT-A for couples with unexplained recurrent miscarriage, while the treatment may carry a significant cost and potential risk. [Grade C] Resection of a uterine septum should be considered for women with recurrent first or second trimester miscarriage, ideally within an appropriate audit or research context. [Grade C] Thyroxine supplementation is not routinely recommended for euthyroid women with TPO who have a history of miscarriage. [Grade A] Progestogen supplementation should be considered in women with recurrent miscarriage who present with bleeding in early pregnancy (for example 400 mg micronised vaginal progesterone twice daily at the time of bleeding until 16 weeks of gestation). [Grade B] Women with unexplained recurrent miscarriage should be offered supportive care, ideally in the setting of a dedicated recurrent miscarriage clinic. [Grade C].