Can IVF Medications Cause Welts?
Yes, IVF medications can cause welts (urticaria) and injection site reactions, particularly with GnRH antagonists like cetrorelix and GnRH agonists like leuprolide, which are commonly used in controlled ovarian stimulation protocols.
Mechanism and Incidence
Cetrorelix (Cetrotide®), a GnRH antagonist used in IVF protocols, commonly causes local injection site reactions including redness, erythema, bruising, itching, swelling, and pruritus, which are typically transient, mild, and short-duration 1. Post-marketing surveillance has documented hypersensitivity reactions including anaphylactoid reactions with this medication 1.
Leuprolide acetate, a GnRH agonist alternative, reports urticaria (hives) and rash as documented adverse reactions during post-marketing surveillance 2. The drug label specifically notes that "rash, urticaria, and photosensitivity reactions have also been reported" along with symptoms consistent with anaphylactoid processes at an incidence rate of approximately 0.002% 2.
Critical Considerations in Patients with Urticarial Vasculitis History
In your specific context with a history of urticarial vasculitis and possible autoimmune disorders, several factors require attention:
Distinguish between simple urticaria and urticarial vasculitis: Individual wheals in ordinary urticaria last 2-24 hours, while urticarial vasculitis wheals persist for days 3. If welts last >24 hours, consider urticarial vasculitis flare rather than simple drug reaction 3.
Autoimmune associations: Thyroid autoimmunity occurs in 14% of patients with chronic ordinary urticaria versus 6% in controls 3. Given your possible autoimmune history, baseline thyroid function and autoantibodies should be checked 3.
Hypocomplementemic urticarial vasculitis: If you have documented low complement levels (C3/C4), this represents a more severe systemic disease with potential internal organ involvement 4, 5, 6.
Management Algorithm
For mild local injection site reactions:
- Continue IVF medications as these reactions are typically self-limited 1
- Apply cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) 3
- Consider oral antihistamines (cetirizine 10 mg daily or diphenhydramine 25-50 mg every 6 hours) 7
For systemic urticaria (welts beyond injection site):
- Stop the current IVF medication immediately 8
- Administer oral prednisone 20-40 mg daily for 2-3 days to prevent symptom recurrence 7
- Add cetirizine 10 mg or diphenhydramine 25-50 mg every 6 hours for 48-72 hours 7
- Switch to an alternative IVF protocol medication from a different class 7
For suspected anaphylaxis (systemic symptoms with respiratory/cardiovascular involvement):
- Administer epinephrine 0.3-0.5 mg intramuscularly immediately 8
- Call for emergency assistance 8
- Aggressive fluid resuscitation with normal saline 1-2 L IV 8
- Never restart the same medication after systemic hypersensitivity 8
Key Pitfalls to Avoid
Do not dismiss persistent welts: If individual welts last >24 hours, obtain lesional skin biopsy to evaluate for urticarial vasculitis, which shows leukocytoclastic vasculitis histologically 3.
Avoid routine premedication: Do not routinely premedicate with antihistamines/corticosteroids for future IVF injections, as this may mask early warning signs of severe reactions 8.
Screen complement levels: If urticarial vasculitis is confirmed or suspected, check serum C4 as screening test, then C3, C1-INH levels if abnormal 3. Hypocomplementemic disease carries worse prognosis with potential for intestinal ischemia and other systemic complications 9, 6.
Document drug allergy: If systemic reaction occurs, permanently document the specific IVF medication as a drug allergy in all medical records 10.
Treatment of Underlying Urticarial Vasculitis if Confirmed
If welts represent urticarial vasculitis flare rather than simple drug reaction:
- Corticosteroids are effective for skin symptoms in >80% of patients but require immunomodulatory agents for long-term control 6
- Dapsone (100 mg/day) shows excellent efficacy for hypocomplementemic urticarial vasculitis, achieving complete remission in documented cases 4, 5
- Colchicine (500 mcg daily) can provide dramatic response in normocomplementemic urticarial vasculitis 11
- H1-antihistamines alone are not effective in most urticarial vasculitis patients 6