What is the management approach for recurrent pregnancy loss?

Management of Recurrent Pregnancy Loss: A Comprehensive Approach

Recurrent pregnancy loss (RPL) requires a systematic evaluation of potential causes and evidence-based management strategies to improve outcomes, with up to 75% of cases remaining unexplained despite thorough investigation. 1

Definition and Epidemiology

• RPL is commonly defined as three or more consecutive pregnancy losses before 24 weeks of gestation, affecting approximately 1-5% of couples attempting pregnancy 1, 2
• The inconsistency in definitions (two versus three losses) and inclusion criteria (types of pregnancy and gestational age) makes true incidence difficult to determine 1

Evaluation of Potential Causes

Genetic Factors

• Parental chromosomal abnormalities should be evaluated in couples with RPL 2
• Genetic testing of products of conception can provide an explanation for the miscarriage and valuable prognostic information 3
• Some patients with recurrent complete hydatidiform moles may have mutations in NLRP7 and KHDC3L genes 4

Anatomical Factors

• Uterine cavity abnormalities can interfere with implantation and cause recurrent pregnancy loss 5
• Müllerian anomalies, intrauterine synechiae, and cervical incompetence should be evaluated 5
• Imaging studies such as transvaginal ultrasound (TVUS), sonohysterography (SIS), or hysterosalpingography (HSG) can help identify structural abnormalities 5

Endocrine Factors

• Diminished ovarian reserve may be associated with increased miscarriage risk, particularly with severely reduced AMH levels 4
• Screening for thyroid disorders should be considered, with levothyroxine indicated for overt hypothyroidism 2
• Polycystic ovary syndrome (PCOS) is associated with higher rates of pregnancy loss and should be evaluated 5

Thrombophilias

• Certain thrombophilias may increase risk of pregnancy loss 4
• Women with homozygous factor V Leiden or prothrombin 20210A mutation with positive family history for venous thromboembolism (VTE) should receive antepartum prophylaxis with prophylactic or intermediate-dose low molecular weight heparin (LMWH) 4
• Antiphospholipid syndrome (APS) is a well-established cause of RPL and should be screened for in all cases 2, 6

Management Strategies

Evidence-Based Treatments

• Low-dose aspirin plus heparin is indicated for the treatment of antiphospholipid syndrome 2
• Levothyroxine is recommended for overt hypothyroidism 2
• Genetic counseling is required in cases of abnormal parental karyotype 2

Treatments Not Recommended

• There is no evidence supporting the use of low-molecular-weight heparin for the sole indication of prevention of recurrent fetal growth restriction 5
• Sildenafil and activity restriction are not recommended for in utero treatment of fetal growth restriction 5
• Immunotherapy and anticoagulants are not recommended for unexplained RPL 2

Lifestyle Modifications

• Regular physical activity within guidelines is unlikely to increase the risk of pregnancy loss in women with RPL 5, 7
• Exercise may actually benefit factors that increase miscarriage risk, such as insulin resistance and obesity 7
• A recent meta-analysis demonstrated no increased odds of miscarriage or perinatal mortality in otherwise healthy pregnant women who exercised compared with those who did not 7

Male Factor Evaluation

• In couples with recurrent pregnancy losses (two or more), clinicians should evaluate the male partner 5
• Male partners should be evaluated by reproductive experts, with consideration for karyotype and sperm DNA fragmentation testing 5
• An increasing number of studies have linked recurrent pregnancy loss with abnormal male partner karyotype and elevated levels of sperm DNA fragmentation 5

Prognosis and Support

• Despite the cause of RPL, patients should be reassured that the prognosis for live birth with an evidence-based approach is excellent for most patients 3
• Psychological support is essential as RPL can have significant impacts on mental health and well-being 1

Management Algorithm for Current Pregnancy with History of RPL

1. Confirm viable intrauterine pregnancy with early ultrasound
2. For patients with APS: initiate low-dose aspirin plus heparin 2
3. For patients with thyroid disorders: optimize thyroid function with appropriate medication 2
4. For patients with history of cervical insufficiency: consider cerclage based on previous reproductive history 2
5. Regular prenatal visits with serial ultrasound monitoring
6. Provide emotional support and counseling throughout pregnancy 1

The management of RPL remains challenging, particularly for unexplained cases. A systematic approach to diagnosis and evidence-based treatments offer the best chance for successful outcomes.