Management of Recurrent Pregnancy Loss
Screen all women with recurrent early pregnancy loss (≥3 miscarriages before 10 weeks) for antiphospholipid antibodies, and treat confirmed antiphospholipid syndrome with unfractionated heparin or LMWH plus low-dose aspirin. 1, 2
Initial Diagnostic Workup
The evaluation should begin after two clinically recognized first-trimester losses, not waiting for three. 3, 4
Essential Testing
Perform parental karyotyping on both partners to identify chromosomal rearrangements that could cause recurrent losses. 2, 5 Test products of conception when available, as chromosomal errors account for 50-60% of early losses. 2
Screen for antiphospholipid antibodies (APLAs) in all patients with recurrent early pregnancy loss (≥3 miscarriages before 10 weeks). 1 This is a Grade 1B recommendation from the American College of Chest Physicians. 1
Evaluate uterine anatomy starting with transvaginal ultrasound as initial screening, then proceed to sonohysterography for superior assessment of the uterine cavity. 2, 6 Three-dimensional sonohysterography has shown 100% accuracy in classification of uterine anomalies compared with hysteroscopy. 6
Measure thyroid function tests (TSH, free T4) as thyroid dysfunction contributes to pregnancy loss and requires optimization before conception. 2, 6
Assess for polycystic ovary syndrome (PCOS), which is associated with higher rates of pregnancy loss. 2, 6, 5
Evaluate ovarian reserve (AMH levels), as severely diminished ovarian reserve may be associated with increased miscarriage risk. 2, 5
Testing NOT Recommended
Do not screen for inherited thrombophilia in women with a history of pregnancy complications. 1 This is a Grade 2C recommendation from the American College of Chest Physicians. The evidence shows no benefit for antithrombotic prophylaxis in women with inherited thrombophilia and pregnancy complications. 1
Male Partner Evaluation
Evaluate the male partner in all couples with ≥2 pregnancy losses. 2, 5 Perform karyotype testing to identify chromosomal abnormalities. 2, 5 Consider sperm DNA fragmentation testing, as increasing evidence links elevated sperm DNA fragmentation with recurrent pregnancy loss. 2, 5
Treatment Based on Identified Causes
Antiphospholipid Syndrome
For women who meet laboratory criteria for APLA syndrome, treat with unfractionated heparin or LMWH plus low-dose aspirin. 1, 2 This is the only treatment for recurrent pregnancy loss with proven efficacy in properly controlled trials. 7
Genetic Causes
Patients with recurrent anembryonic pregnancies due to NLRP7 and KHDC3L gene mutations may benefit from ovum donation rather than conventional IVF. 2, 6
Couples with parental chromosomal rearrangements require genetic counseling regarding options including preimplantation genetic testing. 2
Anatomical Causes
Surgical correction may be appropriate for certain uterine malformations, intrauterine synechiae, or cervical incompetence. 2, 3 History-indicated cerclage should be reserved for individuals with classic historical features of cervical insufficiency or unexplained second-trimester loss in the absence of placental abruption. 2
Thrombophilia Management
For women with homozygous factor V Leiden or prothrombin 20210A mutation with positive family history for VTE, provide antepartum prophylaxis with prophylactic- or intermediate-dose LMWH. 1, 6, 5 However, for pregnant women with all other thrombophilias and no prior VTE who do not have a positive family history for VTE, use antepartum and postpartum clinical vigilance rather than pharmacologic prophylaxis. 1
Critical Caveat: What NOT to Do
For women with two or more miscarriages but without APLA or thrombophilia, do NOT use antithrombotic prophylaxis. 1 This is a Grade 1B recommendation against treatment. There is NO evidence supporting the use of LMWH for the sole indication of prevention of recurrent pregnancy loss outside of confirmed antiphospholipid syndrome. 2, 5
Lifestyle Modifications
Counsel on smoking cessation, alcohol avoidance, and elimination of recreational drugs, as these are modifiable risk factors. 2, 4
Regular physical activity within guidelines is safe and unlikely to increase pregnancy loss risk; it may actually benefit insulin resistance and obesity, which increase miscarriage risk. 2, 6, 5
Optimize nutrition and maintain healthy weight before attempting conception. 2
Management of Subsequent Pregnancies
Confirm viable intrauterine pregnancy with early ultrasound as soon as pregnancy is detected. 2, 6, 5
Provide regular prenatal visits with serial ultrasound monitoring throughout the pregnancy. 2, 6, 5
Screen for gestational diabetes in current pregnancies, as glucose intolerance may contribute to pregnancy loss. 2, 6
Monitor for and promptly treat any endocrine conditions, such as thyroid dysfunction. 2, 6
Consider vaginal progesterone supplementation in patients experiencing vaginal bleeding during the first trimester. 3
Special Considerations
Anembryonic Pregnancies
Anembryonic pregnancies should be counted when calculating recurrent pregnancy losses for workup purposes, as they represent confirmed early pregnancy losses meeting diagnostic criteria. 2, 6 An anembryonic pregnancy is defined as a gestational sac measuring ≥25 mm without an embryo. 6
Pre-eclampsia Risk
For women considered at risk for pre-eclampsia, use low-dose aspirin throughout pregnancy, starting from the second trimester. 1 This is a Grade 1B recommendation. 1
Prognosis
Most people with recurrent pregnancy loss, including those without identifiable risk factors, are expected to achieve a live birth within 5 years from the initial evaluation. 3 Even after a complete evaluation, the cause remains uncertain in over 50% of cases, but subsequent pregnancies have up to a 70% chance of success without treatment. 7