Abstract
Pregnancy loss is a common and devastating pregnancy complication. Recurrent early miscarriage (REM) isdefined as two or more consecutive pregnancy losses during the first trimester of pregnancy. It is a distinct entity and in approximately 50% of these patients, the underlying cause is never established. REM can be idiopathic, i.e. of unknown cause, be related to infections, anatomical or chromosomal abnormalities and can also be related to the presence of autoimmune connective tissue diseases or antiphospholipid antibodies (aPL). Hydroxychloroquine (HCQ) is an antimalarial immunomodulator and is currently being investigated for its role in the prevention of idiopathic REM and REM related to antiphospholipid antibodies (aPL). In this article we review the evidence that exists to date regarding the use of HCQ in the setting of unexplained REM and REM in relation to connective tissue diseases and aPL and antiphospholipid syndrome (APS).
Highlights
A sporadic 1st trimester miscarriage is clinically detected in approximately 10%–15% of pregnancies and is the most common complication in pregnancies
One of the drugs currently investigated for its role in the prevention of idiopathic Recurrent early miscarriage (REM) and REM related to antiphospholipid antibodies and antiphospholipid syndrome (APS) is hydroxychloroquine (HCQ)
REM has been associated to the presence of some autoimmiune connective tissue diseases, including systemic lupus erythematosus (SLE) and Undifferentiated connective tissue disease (UCTD), and is related to the persistent presence of aPL
Summary
A sporadic 1st trimester miscarriage is clinically detected in approximately 10%–15% of pregnancies and is the most common complication in pregnancies. There are trials on going such as HYPATIA which is looking at aPL positive women with randomization to a HCQ group or placebo for follow-up throughout preconception, pregnancy and delivery with an endpoint of the outcome of that pregnancy, including any complications encountered [38] Further prospective trials, such as HYDROSAPL and HIBISCUS will inform on the use of HCQ in the treatment of both thrombotic and obstetric APS hopefully in the foreseeable future [39,40]. Exclusion criteria include features of autoimmune disease and other known causes of miscarriage such as uterine cavity abnormalities, abnormal parental karyotypes, or infections, which should isolate truly unexplained miscarriages as much as possible as the study subjects Both trials are looking at the same two arms of HCQ treatment versus placebo [46,47]. When definitions were not unanimously detailed, we preferred to maintain the terminology used in each study
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