Recurrent pregnancy loss, also known as recurrent miscarriage, refers to the occurrence of three or more consecutive pregnancy losses before reaching the viability threshold (typically before 20 weeks of gestation or when the fetus weighs less than 500 grams). Losses that occur before 12 weeks are considered early miscarriages, while those that occur after 12 weeks are classified as late miscarriages. Approximately 89% of recurrent pregnancy losses occur in the first trimester. Clinically defined recurrent pregnancy loss is observed in around 1-3% of women who are actively trying to conceive, with approximately 15% of recognized pregnancies ending in miscarriage.
There are various possible etiological factors that can contribute to recurrent pregnancy loss. These factors include genetic causes (such as structural or numerical chromosomal abnormalities, single gene defects, carrier status for translocations or inversions; present in about 3-5% of cases), endocrine factors (luteal phase deficiency, polycystic ovary syndrome, diabetes mellitus, hyperprolactinemia, thyroid autoantibodies or thyroid disorders; present in about 15-60% of cases), uterine factors (uterine anomalies, fibroids, cervical incompetence, intrauterine adhesions; present in about 10-50% of cases), immunological factors (antiphospholipid antibody syndrome, alloimmune factors; present in about 5-15% of cases), thrombophilic disorders (associated with hereditary thrombophilias, such as factor V Leiden mutation, prothrombin gene mutation, protein S, protein C, and antithrombin deficiencies), as well as environmental factors (such as smoking, exposure to anesthetic agents), and diminished ovarian reserve. However, in most cases, no specific etiological factor can be identified. According to extensive studies on recurrent pregnancy loss cases, approximately 40% of cases do not exhibit a specific identifiable cause. Regardless of the underlying cause, approximately 70-75% of cases with identified or unexplained recurrent pregnancy loss can achieve successful pregnancy outcomes in subsequent pregnancies through supportive care alone.
When planning the treatment for recurrent pregnancy loss, the underlying etiology should be taken into consideration. If uncontrolled diabetes mellitus is present, blood sugar regulation should be managed. Thyroid hormone levels should be evaluated, and appropriate treatment should be provided if necessary. In cases of uterine anomalies, cervical cerclage may be a suitable treatment option. Progesterone is an essential hormone for endometrial preparation, implantation, and the maintenance of pregnancy. Progesterone deficiency also plays a role in the etiology of recurrent pregnancy loss. However, progesterone supplementation does not have an effect on sporadic cases of recurrent pregnancy loss where progesterone deficiency is not present. In cases where thrombophilia, antiphospholipid syndrome, or other coagulopathies are the underlying cause of recurrent pregnancy loss, low molecular weight heparin (LMWH) and aspirin (ASA) are important in the treatment. In conclusion, the etiology of recurrent pregnancy loss is multifactorial, and the cause of pregnancy loss remains unknown in most cases. As the number of early abortions increases, the recurrence rate also increases. The emotional impact of pregnancy loss and its subsequent impact on the woman’s mental state should be taken into consideration when providing treatment options for these women.
Alongside pregnancy-focused treatments, psychiatric support should also be provided. The treatment of recurrent pregnancy loss should be planned considering the underlying etiology. Progesterone, LMWH, ASA, and other medications have shown positive contributions to prognosis in appropriate indications and should be used in cases that fall within the specified indications.