What treatments are available to prevent first trimester miscarriages?

Treatments to Prevent First Trimester Miscarriages

For women with recurrent miscarriage, progesterone supplementation should be considered, especially for those who present with bleeding in early pregnancy (400 mg micronized vaginal progesterone twice daily until 16 weeks of gestation). 1

Recurrent Miscarriage Prevention

Progesterone Therapy

• Progesterone supplementation is recommended for women with recurrent miscarriage who present with bleeding in early pregnancy 1
• The recommended dosage is 400 mg micronized vaginal progesterone twice daily at the time of bleeding until 16 weeks of gestation 1
• However, for women with unexplained recurrent miscarriage without bleeding, progesterone supplementation probably has little to no effect on outcomes in subsequent pregnancies 2

Antiphospholipid Syndrome Management

• For women diagnosed with antiphospholipid syndrome, aspirin and heparin should be offered from a positive test until at least 34 weeks of gestation 1
• This combination therapy has shown significant benefit in preventing miscarriage in women with antiphospholipid syndrome, with over 98% having normal term deliveries when treated appropriately 3
• The treatment must be discussed with patients regarding potential benefits versus risks 1

Thyroid Management

• Women with recurrent miscarriage should be offered thyroid function tests and assessment for thyroid peroxidase (TPO) antibodies 1
• However, thyroxine supplementation is not routinely recommended for euthyroid women with TPO antibodies who have a history of miscarriage 1
• Levothyroxine may be considered in women with subclinical hypothyroidism 4

Important Considerations for Rh-Negative Women

• For Rh-negative women experiencing first trimester miscarriage, RhD immune globulin (RhIg) should be administered within 72 hours 5
• A dose of 50 μg RhIg is adequate for first trimester losses; if unavailable, the standard 300 μg dose should be used 5
• Fetal red blood cells display RhD antigens from as early as 6 weeks of gestation, making maternal sensitization possible even in early pregnancy 5
• Prevention of RhD alloimmunization is critical given its substantial impact on pregnancy outcomes in subsequent pregnancies 5

Diagnostic Evaluation for Recurrent Miscarriage

• Testing for acquired thrombophilia, particularly for lupus anticoagulant and anticardiolipin antibodies, should be offered prior to pregnancy 1
• Cytogenetic analysis should be performed on pregnancy tissue of the third and subsequent miscarriage(s) 1
• Assessment for congenital uterine anomalies should be offered, ideally with 3D ultrasound 1
• Parental peripheral blood karyotyping should be offered when pregnancy tissue reports an unbalanced structural chromosomal abnormality 1

Lifestyle Modifications

• Women with recurrent miscarriage should be advised to maintain a BMI between 19 and 25 kg/m² 1
• Smoking cessation is strongly recommended 1
• Limiting alcohol consumption is advised 1
• Caffeine intake should be limited to less than 200 mg/day 1

Treatments Not Recommended

• Aspirin and/or heparin should not be given to women with unexplained recurrent miscarriage (without antiphospholipid syndrome) 1
• Routine immunological screening (such as HLA, cytokine, and natural killer cell tests) is not recommended outside a research context 1
• Infection screening or sperm DNA testing should not be routinely offered outside a research context 1
• There is insufficient data to support the routine use of preimplantation genetic testing for aneuploidy (PGT-A) for couples with unexplained recurrent miscarriage 1

Supportive Care

• Women with unexplained recurrent miscarriage should be offered supportive care, ideally in the setting of a dedicated recurrent miscarriage clinic 1
• This supportive care approach has been shown to improve outcomes even when specific treatments are not available 1

Common Pitfalls to Avoid

• Failing to administer RhIg to Rh-negative women with first trimester miscarriage, as fetal RBCs display red cell antigens from as early as 6 weeks gestation 5
• Using aspirin and/or heparin in women with unexplained recurrent miscarriage without antiphospholipid syndrome 1
• Prescribing thyroxine supplementation for euthyroid women with TPO antibodies who have a history of miscarriage 1
• Delaying surgical intervention when clinically indicated, as surgery should never be postponed if deemed crucial in the management plan 6