What is the recommended lab workup and treatment for a woman experiencing back-to-back early miscarriages?

From the Guidelines

For women experiencing back-to-back early miscarriages, the recommended initial step is to undergo a comprehensive lab workup, including tests for antiphospholipid antibodies, thyroid function, and parental karyotyping to check for chromosomal abnormalities, as identified causes can guide specific treatments 1. The lab workup should also consider testing for thrombophilias and hormonal imbalances, as these can contribute to recurrent pregnancy loss. Additional testing may include:

• Pelvic ultrasound to evaluate uterine structure
• Hysteroscopy to assess the uterine cavity
• Testing for diminished ovarian reserve, although the evidence for its association with miscarriage risk is still emerging and not conclusively defined 1 Treatment depends on the identified causes, and may include:
• Antiphospholipid syndrome treatment with low-dose aspirin and prophylactic heparin during pregnancy
• Thyroid disorder management with levothyroxine to maintain TSH below 2.5 mIU/L
• Uterine abnormality correction through surgery
• Progesterone supplementation for luteal phase defects
• Lifestyle modifications, such as maintaining a healthy weight, avoiding smoking and excessive alcohol, and taking prenatal vitamins with folic acid Psychological support is crucial for women experiencing recurrent pregnancy loss, as it can cause significant emotional distress. Early monitoring with serial hCG measurements and early ultrasounds in subsequent pregnancies provides both medical surveillance and emotional reassurance. It is essential to note that the evidence for certain tests and treatments, such as diminished ovarian reserve, is still limited and requires further research 1. However, based on the most recent and highest-quality study available, the recommended approach prioritizes a comprehensive lab workup and individualized treatment based on identified causes, while also considering lifestyle modifications and psychological support.

From the Research

Definition and Prevalence of Recurrent Miscarriage

• Recurrent miscarriage is a common clinical problem in reproduction, occurring in approximately 1% of reproductive-aged women 2.
• The prevalence of women who have had one miscarriage is 10·8% (10·3-11·4%), two miscarriages is 1·9% (1·8-2·1%), and three or more miscarriages is 0·7% (0·5-0·8%) 3.
• Recurrent pregnancy loss is a complex health challenge with no universally accepted definition, and the true incidence is difficult to estimate due to the heterogeneity of definitions and criteria applied by international guidelines 4.

Causes and Risk Factors of Recurrent Miscarriage

• Known causes of recurrent miscarriage include abnormal chromosomes, endocrinological disorders, and uterine abnormalities 5.
• Risk factors for miscarriage include very young or older female age, older male age, very low or very high body-mass index, Black ethnicity, previous miscarriages, smoking, alcohol, stress, working night shifts, air pollution, and exposure to pesticides 3.
• The exact etiology of recurrent pregnancy loss remains questionable, and up to 75% of cases remain unexplained 4.

Diagnostic Approach and Management

• The diagnostic approach and management of recurrent pregnancy loss largely depend on the etiology and risk factors taken into consideration by a healthcare professional 4.
• Antiphospholipid syndrome and some recurrent miscarriage-related endocrinological disorders can be effectively treated 5.
• New therapeutic approaches and the pleiotropic effects of old ones have led to improved fetal-maternal outcomes 5.
• Maternal age, history of miscarriage, and embryonic/fetal size are associated with cytogenetic results of spontaneous early miscarriages 6.

Psychological and Social Consequences

• Miscarriage, and especially recurrent miscarriage, is a sentinel risk marker for obstetric complications and a predictor of longer-term health problems, such as cardiovascular disease and venous thromboembolism 3.
• The consequences of miscarriage are both physical and psychological, including increases in the risk of anxiety, depression, post-traumatic stress disorder, and suicide 3.
• Underestimation of social and health consequences of recurrent pregnancy loss leads to compromised reproductive health and psychological well-being of women after miscarriage 4.