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Why IVF increases APD risk IVF protocols commonly require progesterone injections, suppositories, or oral formulations at doses much higher than those produced during a natural cycle Exogenous progesterone bypasses the bodys normal regulatory mechanisms, increasing the likelihood of mast cell activation and histamine release Repeated exposure during fertility treatment may unmask previously undiagnosed APD or worsen existing symptoms When progesterone desensitization is used Desensitization protocols may be recommended before or during IVF for individuals with known or suspected APD These protocols involve carefully supervised, incremental exposure to progesterone to reduce immune reactivity Desensitization is most often used when progesterone cannot be avoided, such as during luteal support or early pregnancy Role of antihistamines and corticosteroids during IVF Antihistamines (such as H1 and H2 blockers) are commonly used to blunt histamine-mediated symptoms during progesterone exposure Short-term corticosteroids may be prescribed to control severe inflammatory or allergic reactions during treatment cycles These medications do not treat the underlying hypersensitivity but can help protect patient safety and treatment continuity In some cases, clinicians may also consider antioxidant support such as NAC to help manage inflammatory stress during fertility treatment or pregnancy , though this should always be individualized