Unexplained Recurrent Miscarriage
Recurrent miscarriage is defined as the loss of all pregnancies detected in the intrauterine cavity. In human beings, the incidence of embryo wastage is estimated to be 30% before implantation, 30% before 6 weeks of gestation (biochemical pregnancy loss), and 10-15% of clinical pregnancies (miscarriages, mainly before 12 weeks of gestation). The accidental recurrent miscarriage rate can be estimated as a common clinical miscarriage rate, i.e. 10-15%. Patients with a history of recurrent miscarriage require screening for the risk factors for miscarriage.
Recurrent miscarriage is associated with a wide variety of risk factors. Interviewing patients about their pregnancy histories, lifestyle, and health behavior is particularly critical. Smoking, obesity, alcohol consumption, and caffeine intake are potential reasons for recurrent miscarriage. Ultrasonography can be used to detect uterine malformation and organic diseases, including uterine myoma and hysteroscopy, can identify intrauterine disorders such as endometrial polyps and chronic endometritis. Blood analyses include endocrinology, immunological, and chromosomal tests and thrombophilia screening.
Although the association between polycystic ovary syndrome (PCOS) and pregnancy loss remains controversial, diagnosing PCOS and examining patients for diabetes mellitus are critical. Immunological investigations mainly test for antiphospholipid antibody syndrome and include the following three antibodies: lupus anticoagulant, anticardiolipin antibody, and anti-β2-GP1 antibody. The presence of anti-phosphatidylethanolamine antibody should also be tested. Measurements of protein C and S and factor XII activity are also required during thrombophilia screening.
Patients with an unexplained recurrent miscarriage include those who do not achieve delivery due to accidental or undetectable causes of pregnancy loss. Given the association between the number of previous miscarriages and the miscarriage rate for the next pregnancy, 60-70% of patients with a history of 3 to 4 miscarriages eventually reach delivery without treatment, whereas the miscarriage rate in patients with 5 or more pregnancy losses is >50%, of which ≥60% losses of fetuses with a normal embryonic karyotype.
Thus, the frequency of miscarriages and the number of losses of fetuses with a normal embryonic karyotype increase with an increase in the number of pregnancy losses, which indicates that in patients with a history of recurrent pregnancy loss, the mother but not the fetus, have risk factors. Candidate risk factors in an unexplained recurrent miscarriage include unbalanced material immune tolerance for maintaining pregnancy, impaired intrauterine diseases at the local implantation site, and perturbation of the decidualization of uterine endometrium.
An unexplained recurrent miscarriage may be partial due to the lack of endometrial receptivity of the decidualized endometrium to preimplantation embryos that should have been wasted, while a low endometrial receptivity and excessive embryo selection of the uterine endometrium may result in recurrent implantation failure.
Most women with a history of an unexplained recurrent miscarriage become anxious during their subsequent pregnancies, and maternal stress is associated with an increased risk of pregnancy loss. The lack of specific risk factors for miscarriage is a source of further anxiety in patients with recurrent miscarriage, leading to a vicious cycle of pregnancy loss.
However, 75% of patients with an unexplained recurrent miscarriage can sustain pregnancy to delivery after proper evaluation and fertility treatment.
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