A pregnancy loss that occurs before 6 weeks of gestation, after a positive urinary human chorionic gonadotropin (hCG) or a raised serum β-hCG but before ultrasound or histological verification is defined as a ‘biochemical loss’.
The clinical term “miscarriage” is used when ultrasound examination has confirmed that an intrauterine pregnancy has existed. Miscarriages may be subdivided into early pregnancy losses (before gestational week 12) and late pregnancy losses (gestational weeks 12 to 21).
Three or more consecutive pregnancy losses before 22 weeks of gestation are considered as recurrent miscarriages. The incidence of early pregnancy loss is estimated to be 15% of conceptions with a significant variation according to age. Thus, the incidence ranges from 10% in women aged 20 to 24 years to 51% in women aged 40 to 44 years. Late losses between 12 and 22 weeks occur less frequently and constitute around 4% of pregnancy outcomes.
The major reason for early miscarriages is abnormalities in the embryo (75-85% of cases); however in recurrent miscarriages, there is a lower incidence of embryo abnormalities (29-60%). The exact causative agent(s) behind recurrent early miscarriages is unknown, but risk factors include uterine malformation, rejection of the implanted embryo by the woman’s immune system, tendency to thromboembolic events (hereditary or acquired) and thyroid dysfunction or thyroid autoimmunity.
Male factor also contributed to early pregnancy loss as DNA damages in sperm (DNA fragmentation) is a causative factor. A recent analysis has shown a significant link between DNA quality in sperm and recurrent miscarriages, 85% of the males in partners with recurrent miscarriages had DNA damage in sperm, versus 33% in fertile sperm donors. Miscarriages due to thrombosis are due to the formation of a blood clot in blood vessels in the placenta; hereditary factors include mutations or deficiency of antithrombin, protein C and protein S or carriage of the factor V Leiden or factor II (G20210A). Acquired factors include the presence of anti-phospholipid antibodies, lupus anticoagulant or anti-cardiolipin antibodies and hyperhomocysteinemia.
Since hyperhomocysteinemia is due to deficiencies of vitamin B6, folic acid (vitamin B9), and vitamin B12, it is treated by supplementation of these vitamins. Women who suffer from thrombosis are sometime treated with anti-coagulation therapy, such as low-dose heparin or aspirin. There is limited clinical evidence that treatment with low-dose heparin and aspirin during pregnancy increases the chance of live birth in recurrent miscarriages patients who have anti-phospholipid antibodies.
There is no evidence that anticoagulation therapy will improve the prognosis for recurrent miscarriages in women with hereditary thrombophilias or no thrombophilia factors at all, and results from relevant ongoing clinical trials are awaited.