Is prednisolone (corticosteroid) contraindicated during In Vitro Fertilization (IVF)?

Prednisolone Use During IVF: Benefits and Risks

Prednisolone is not routinely recommended during IVF as there is insufficient evidence supporting its benefit and potential risks of congenital anomalies have been identified. 1

Evidence Assessment

Potential Risks

The most recent and highest quality evidence raises significant concerns about prednisolone use during IVF:

• A large 2022 retrospective cohort study of 12,426 live births found that maternal exposure to corticosteroids during IVF/ICSI treatment was associated with increased risk of:

  • Talipes equinovarus (clubfoot) (adjusted IRR = 4.30)
  • Hypospadias (adjusted IRR = 5.90)
  • Cryptorchidism (undescended testicles) (adjusted IRR = 5.53) 1

• The same study found that corticosteroid exposure during fresh embryo transfers altered the sex ratio, favoring males 1

Theoretical Mechanism of Harm

• Corticosteroid therapy during conception may impede essential immune processes:
  • Controlled inflammation and immune activation are necessary for embryo implantation
  • The immune response actively promotes endometrial receptivity and tolerance of the embryo
  • Perturbing immune adaptation at implantation may adversely influence placental development 2

Limited Evidence for Benefit

Some older, smaller studies suggested potential benefits:

• A 1986 study reported higher pregnancy rates with prednisolone (7.5 mg daily) supplementation to Clomid/gonadotrophin stimulation 3
• A 1998 study found improved implantation rates with prednisolone (10 mg/day) plus low-dose aspirin in women with autoimmune conditions 4
• A 2005 study suggested improved implantation and clinical pregnancy rates with prednisolone in women with antinuclear antibodies 5

Clinical Approach

General Recommendation

• For most women undergoing IVF without specific autoimmune conditions, prednisolone should be avoided due to potential risks of congenital anomalies 1

Special Considerations

For women with specific autoimmune conditions:

1. Antiphospholipid Syndrome (APS):

   • For women with obstetric APS undergoing ART, prophylactic anticoagulation with heparin or LMWH is strongly recommended 6
   • Prednisolone is not specifically recommended in these guidelines

2. Systemic Lupus Erythematosus (SLE):

   • The American College of Rheumatology conditionally recommends against empiric dosage increases of prednisone during ART procedures in patients with SLE 6
   • Instead, careful monitoring and treating flares if they occur is suggested

3. Inflammatory Conditions:

   • For patients with inflammatory conditions requiring corticosteroids during pregnancy, prednisolone is preferred over dexamethasone 7
   • If needed, taper to ≤5 mg/day maintenance dose when possible to minimize maternal-fetal complications 6

Important Caveats

• If prednisolone is deemed necessary for maternal conditions during IVF/pregnancy:

  • Use the lowest effective dose for the shortest duration possible 7
  • Be aware that higher doses are associated with pregnancy-associated osteoporosis, gestational diabetes, serious maternal infections, and preterm birth 6
  • Counsel patients about the potential increased risk of urogenital congenital anomalies 1

• For women undergoing IVF egg extraction who are already on long-term prednisolone therapy:

  • Stress-dose steroids may be required during the procedure (hydrocortisone 100 mg intravenously on induction) 6

Conclusion

Based on the most recent evidence, prednisolone should not be routinely used during IVF due to potential risks of congenital anomalies. For women with specific autoimmune conditions, treatment decisions should be based on the underlying condition rather than the IVF procedure itself, with careful consideration of risks versus benefits.