Low-Dose Aspirin During FET Preparation
For women with recurrent pregnancy loss or antiphospholipid syndrome undergoing frozen embryo transfer, low-dose aspirin (75-150 mg daily) is safe and recommended, starting during FET preparation and continuing through delivery if pregnancy is achieved. 1
Safety Profile in Pregnancy
Low-dose aspirin has an established safety record throughout pregnancy, including during the periconception period and FET preparation:
- No increased risk of placental abruption, postpartum hemorrhage, fetal intracranial bleeding, or congenital anomalies 2, 3
- No increased perinatal mortality with aspirin use 2
- Safe continuation through delivery without stopping at predetermined gestational ages 1
Specific Indications for Your Patient Population
Recurrent Pregnancy Loss
Women with history of recurrent pregnancy loss benefit from aspirin prophylaxis, particularly when combined with other risk factors 2. The mechanism involves improved uteroplacental blood flow during critical placentation periods 1.
Antiphospholipid Syndrome
This is a clear indication for aspirin therapy:
- Low-dose aspirin is well-established for preventing obstetric complications in antiphospholipid syndrome 4
- When combined with heparin, recurrent fetal loss rates drop below 30% 4
- Aspirin desensitization can be safely performed even during pregnancy for aspirin-sensitive patients with antiphospholipid syndrome 5
Dosing Recommendations
Optimal dosing is 100-150 mg daily rather than the traditional 81 mg:
- Meta-analyses demonstrate aspirin ≥100 mg initiated before 16 weeks is significantly more effective than lower doses (RR 0.33,95% CI 0.19-0.57) 1
- The American Diabetes Association recommends 100-150 mg daily for high-risk pregnancies 1
- International guidelines increasingly favor 150 mg daily for high-risk women 1
Timing Protocol
Start aspirin during FET preparation (ideally at cycle initiation):
- Begin between 12-16 weeks equivalent (or at FET cycle start if earlier) 3, 1
- Continue daily through pregnancy testing 6
- If pregnancy achieved, continue until delivery 1
- Do not stop at 36 weeks—this removes protection during a high-risk period 1
Important Caveats
Evidence Specific to FET Cycles
Critical distinction: While aspirin is clearly beneficial for women with antiphospholipid syndrome or recurrent pregnancy loss, studies examining aspirin's effect on FET success rates in unselected populations show no improvement in pregnancy rates 7, 8, 6:
- A 2023 study of 4,454 programmed FET cycles found no elevation in live birth rates with 50 mg aspirin 7
- A 2020 randomized trial showed no improvement in implantation or clinical pregnancy rates 8
- A 1998 matched study found lower pregnancy rates in the aspirin group (11.1% vs 33.3%) 6
However, these studies examined unselected populations. Your patient has specific high-risk features (recurrent pregnancy loss or antiphospholipid syndrome) that constitute clear indications for aspirin independent of FET outcomes.
Combination Therapy for Antiphospholipid Syndrome
For antiphospholipid syndrome specifically, consider adding low-molecular-weight heparin to aspirin:
- Combined aspirin-heparin therapy reduces recurrent fetal loss more effectively than aspirin alone 4
- LMWH is advised in patients with history of venous thrombosis 2
Practical Implementation
Prescribe aspirin 100-150 mg daily:
- Start at FET cycle initiation
- Take at bedtime for optimal effectiveness 1
- Continue through pregnancy testing
- If positive pregnancy test, continue until delivery
- Monitor for standard pregnancy complications but expect no aspirin-related adverse effects
The rationale: While aspirin may not improve FET implantation rates in general populations, your patient's underlying thrombophilic condition (antiphospholipid syndrome) or history of recurrent loss creates a separate, well-established indication for aspirin therapy that supersedes FET-specific considerations 2, 4.