Evaluation and Management of Recurrent Pregnancy Loss
Both partners require concurrent evaluation when recurrent pregnancy loss (RPL) is identified, with the male partner assessment being essential in all couples with ≥2 pregnancy losses. 1, 2, 3
Initial Diagnostic Workup for Both Partners
Female Partner Evaluation
Perform parental karyotyping on the female partner to identify chromosomal rearrangements, which cause 5-7% of RPL. 1, 2, 3
Screen for antiphospholipid antibodies (APLAs) in all patients with recurrent early pregnancy loss (≥3 miscarriages before 10 weeks), as this represents an established treatable cause. 2, 3, 4
Test products of conception when available, as chromosomal errors account for 50-60% of early losses. 2, 5
Begin anatomical evaluation with transvaginal ultrasound (TVUS) as the initial screening tool, then proceed to sonohysterography (SIS) for superior assessment of uterine cavity abnormalities. 2, 3, 5
Measure thyroid function tests (TSH, free T4), as thyroid dysfunction contributes to pregnancy loss and requires optimization before conception. 2, 3, 5
Evaluate for polycystic ovary syndrome (PCOS), which is associated with higher rates of pregnancy loss. 2, 3, 5
Assess ovarian reserve (AMH levels), as severely diminished ovarian reserve may be associated with increased miscarriage risk. 2, 5
For patients with recurrent complete hydatidiform moles, consider genetic testing for mutations in NLRP7 and KHDC3L genes, as these cause familial recurrent hydatidiform mole. 2, 5
Male Partner Evaluation
The 2024 AUA/ASRM guideline now mandates evaluation of the male partner in all couples with ≥2 pregnancy losses, representing a critical shift in RPL management. 1, 2, 3
Perform karyotype testing on the male partner to identify chromosomal abnormalities that may contribute to RPL. 1, 2, 3
Consider sperm DNA fragmentation testing, as increasing evidence links elevated sperm DNA fragmentation with recurrent pregnancy loss and failed IVF cycles. 1, 2, 3
Male reproductive experts should conduct the evaluation, including complete history, physical examination, and semen analysis. 1
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. 2, 3, 4
Chromosomal Abnormalities
Couples with parental chromosomal rearrangements require genetic counseling regarding options including preimplantation genetic testing. 2, 6
Patients with recurrent anembryonic pregnancies due to NLRP7 and KHDC3L gene mutations may benefit from ovum donation rather than conventional IVF. 2, 5
Anatomical Abnormalities
Surgical correction may be appropriate for certain uterine malformations, intrauterine synechiae, or cervical incompetence. 2, 4
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, 7
Lifestyle Modifications
Counsel on smoking cessation, alcohol avoidance, and elimination of recreational drugs, as these are modifiable risk factors. 2, 3, 5
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, 3, 5
Optimize nutrition and maintain healthy weight before attempting conception. 2, 3
Management of Subsequent Pregnancies
Confirm viable intrauterine pregnancy with early ultrasound as soon as pregnancy is detected, and provide regular prenatal visits with serial ultrasound monitoring throughout the pregnancy. 2, 3, 5
Screen for gestational diabetes in current pregnancies, as glucose intolerance may contribute to pregnancy loss. 2, 3, 5
Monitor for and promptly treat any endocrine conditions, such as thyroid dysfunction. 2, 5
Critical Caveats
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, 4
Do NOT routinely screen for inherited thrombophilias (factor V Leiden, prothrombin G20210A mutation, protein C/S deficiency) in women with recurrent pregnancy loss. 3, 4
Anembryonic pregnancies should be counted when calculating recurrent pregnancy losses for workup purposes, as they represent confirmed early pregnancy losses meeting diagnostic criteria. 2, 5
The majority of RPL cases (up to 75%) remain idiopathic despite thorough evaluation, but the long-term prognosis is good with most couples eventually achieving a healthy live birth. 8, 6