Hydroxychloroquine and Prednisone for Elevated Immune Markers in IVF
Hydroxychloroquine (Plaquenil) combined with prednisone can effectively reduce elevated TNF-α/IL-10 ratios, IFN-γ/IL-10 ratios, and normalize CD56+ NK cell levels in women with recurrent implantation failure undergoing IVF, with hydroxychloroquine specifically demonstrating significant immunomodulatory effects on these parameters. 1
Evidence for Hydroxychloroquine Effects on Immune Markers
Hydroxychloroquine directly reduces the specific immune markers you're asking about:
TNF-α/IL-10 ratio: Hydroxychloroquine (400 mg orally daily) significantly decreased serum TNF-α levels (p < 0.0001) and significantly increased IL-10 levels (p < 0.0001) in women with RIF who had elevated TNF-α/IL-10 ratios (≥30.6), effectively lowering this ratio 1
IFN-γ levels: Hydroxychloroquine treatment significantly decreased IFN-γ immunoreactivity in endometrial tissue (p < 0.05), which would improve the IFN-γ/IL-10 ratio 1
CD56+ NK cells: Women with elevated CD56+ cells who received immunomodulatory treatment (including hydroxychloroquine) showed significantly improved IVF outcomes, with implantation rates of 45% versus 22% without treatment (p = 0.0032) 2
CD19 (B cells): While not directly studied with hydroxychloroquine in the IVF context, hydroxychloroquine is pregnancy-compatible and strongly recommended for continuation before conception, during pregnancy, and while breastfeeding 3
Mechanism of Action
Hydroxychloroquine shifts the immune balance from Th1 to Th2 dominance:
- Down-regulates T-bet (Th1 transcription factor) expression 1
- Up-regulates GATA-3 (Th2 transcription factor) expression 1
- Increases IL-10 and IL-4 (Th2 cytokines) immunoreactivity in endometrial tissue (p < 0.05 and p < 0.001 respectively) 1
- Decreases TNF-α and IFN-γ (Th1 cytokines) immunoreactivity in endometrial tissue (p < 0.05) 1
Combined Immunomodulatory Treatment Outcomes
Prednisone combined with other immunomodulatory agents significantly improves IVF success:
Women with RPL and RIF receiving immunomodulatory treatment (prednisone alone or prednisone plus IVIG) plus anticoagulation showed pregnancy rates of 48.2% versus 33.0% in historical controls (p < 0.001) 4
Live birth rates improved dramatically: 39.6% versus 1.8% in historical controls (p < 0.001) 4
For women with both RPL and RIF (≥3 failures), pregnancy rates were 33.3% versus 11.0% (p < 0.005) and live birth rates were 33.3% versus 2.5% (p < 0.001) 4
Safety During IVF and Pregnancy
Both medications are pregnancy-compatible and can be continued throughout conception attempts:
Hydroxychloroquine: Strongly recommended for continuation before conception, during pregnancy, and during breastfeeding (++ rating in all phases) 3
Prednisone: Compatible with pregnancy but should be tapered to ≤5 mg/day when possible, or maintained at <20 mg/day during pregnancy 3
Prednisone doses >20 mg/day require careful consideration due to risks of gestational diabetes, preterm birth, and maternal infections, though doses ≤5 mg/day are associated with low risk 3
Treatment Protocol Considerations
Specific dosing based on available evidence:
Hydroxychloroquine: 400 mg orally daily, started during the implantation window 1
Prednisone: Typically used in combination protocols, with doses varying but ideally maintained at ≤20 mg/day during conception attempts 3, 4
Treatment should be initiated before the IVF cycle to allow time for immune parameter normalization 1
Anticoagulation Requirement
If you have antiphospholipid antibodies or thrombophilia, prophylactic anticoagulation is essential:
Low molecular weight heparin (enoxaparin 40 mg daily) should be started at the beginning of ovarian stimulation 3, 5, 4
Anticoagulation is withheld 24-36 hours prior to oocyte retrieval and resumed following retrieval 3, 5
Continue throughout pregnancy if conception occurs 4
Critical Pitfall to Avoid
Do not use these medications without baseline immune testing confirmation: The benefit of immunomodulatory therapy is specifically seen in women with documented immune abnormalities (elevated Th1:Th2 ratios, elevated CD56+ cells, elevated TNF-α/IL-10 ratios) 2, 1. Women with normal immune parameters showed no additional benefit from IVIG therapy (69% pregnancy rate with treatment versus 71% without, p = 0.48) 2, suggesting that treatment should be targeted to those with confirmed abnormalities.