Can prednisone (corticosteroid) cause embryo implantation failure?

Prednisone Does Not Cause Embryo Implantation Failure

Based on the highest quality randomized controlled trial evidence, prednisone does not cause embryo implantation failure—in fact, it neither improves nor worsens implantation rates in women with recurrent implantation failure. 1

Key Evidence from Clinical Trials

The most definitive evidence comes from a 2023 multicenter, double-blind, placebo-controlled randomized trial involving 715 women with recurrent implantation failure undergoing frozen embryo transfer 1:

• No difference in live birth rates: 37.8% with prednisone versus 38.8% with placebo (RR 0.97,95% CI 0.81-1.17, P=0.78) 1
• No difference in implantation rates between prednisone and placebo groups 1
• Increased risk of biochemical pregnancy loss: 17.3% with prednisone versus 9.9% with placebo (RR 1.75, P=0.04) 1
• Increased risk of preterm delivery: 11.8% with prednisone versus 5.5% with placebo (RR 2.14, P=0.04) 1

Clinical Implications

Prednisone should not be used routinely to improve implantation in women undergoing IVF or with recurrent implantation failure, as it provides no benefit and may cause harm 1:

• The drug does not improve implantation success 1
• It increases the risk of early pregnancy loss 1
• It doubles the risk of preterm delivery 1
• No improvement in clinical pregnancy rates was observed 1

Understanding the Conflicting Evidence

While one smaller study from 2021 suggested prednisone might improve pregnancy outcomes by shifting immune balance toward regulatory T cells 2, this contradicts:

• The larger, higher-quality 2023 randomized trial showing no benefit 1
• A 2002 randomized study showing no improvement in pregnancy or implantation rates with low-dose prednisolone in routine ICSI patients 3
• Expert opinion that immune suppression during implantation may actually be harmful, as controlled inflammation is essential for normal embryo implantation 4

The theoretical rationale that immune activation prevents implantation is fundamentally flawed 4. Controlled immune activation is actually necessary for:

• Endometrial receptivity 4
• Embryo tolerance 4
• Vascular adaptation for placental development 4
• Establishing proper developmental trajectories 4

Safety During Established Pregnancy

If a woman is already pregnant and requires prednisone for a medical condition (such as autoimmune disease or severe asthma), the drug can be used safely 5:

• Prednisone is not associated with increased major birth defects when used for disease control 5
• Doses should be tapered to ≤5 mg/day when possible during pregnancy 5
• Higher doses carry dose-related risks including gestational diabetes, preterm birth, and maternal infections 5
• There is conflicting older data suggesting a possible 3-fold increased risk of cleft lip/palate with first-trimester use, though more recent studies have not confirmed this association 5, 6

Clinical Recommendation Algorithm

For women attempting conception or undergoing IVF:

• Do not prescribe prednisone to improve implantation 1
• Avoid routine corticosteroid use unless specific immune pathology is documented 4

For women with established autoimmune disease requiring prednisone:

• Continue prednisone if needed for disease control during pregnancy 5
• Use the lowest effective dose, ideally ≤5 mg/day 5
• Monitor for gestational diabetes, preterm labor, and maternal infections 5

Critical pitfall to avoid: Do not assume that immune suppression improves fertility outcomes—this "one-size-fits-all" approach lacks evidence and may interfere with the essential immune processes required for successful implantation 4.