What is the effect of antihistamines, such as loratadine (Claritin) or cetirizine (Zyrtec), on egg count and quality in women undergoing In Vitro Fertilization (IVF)?

Antihistamines Do Not Impair Egg Count or Quality in IVF

Current evidence shows no direct negative effect of antihistamines like loratadine or cetirizine on egg count or quality during IVF cycles, and these medications are safe to continue during ovarian stimulation and pregnancy. 1, 2, 3

Safety Profile During IVF and Pregnancy

Second-Generation Antihistamines Are Preferred

• Loratadine and cetirizine should be first-line choices during IVF cycles and pregnancy, including the first trimester when organogenesis occurs, as they have excellent safety records confirmed through large birth registries, case-control studies, and cohort studies. 1, 2, 3
• Both agents are FDA Pregnancy Category B with no evidence of fetal harm or teratogenic effects. 3
• These medications do not show any significant increase in congenital malformations when used during the first trimester. 1, 2

First-Generation Antihistamines Are Also Safe

• Chlorpheniramine has been specifically recommended as a first-choice agent during pregnancy due to its observed safety and longevity of use, though its sedative qualities may make it less desirable. 1, 2
• The main limitation is sedation and possible performance effects, not safety concerns regarding egg quality or pregnancy outcomes. 1, 2

Critical Timing Considerations for IVF

Ovulation and Follicle Development

• NSAIDs (not antihistamines) can interfere with ovulation by inducing luteinized unruptured follicle (LUF) syndrome through prostaglandin inhibition, which is not a mechanism of action for antihistamines. 1
• Women with difficulty conceiving should discontinue NSAIDs during periovulatory periods, but this recommendation does not apply to antihistamines. 1

Ovarian Stimulation Protocols

• Patients at risk for ovarian hyperstimulation syndrome may benefit from protocols incorporating aromatase inhibitors, but antihistamines are not contraindicated during these protocols. 1
• Continue necessary medications during ovarian stimulation for oocyte retrieval, with specific exceptions being cyclophosphamide and certain immunosuppressants—not antihistamines. 1

Medications That Actually Impair Egg Quality

Avoid These During IVF

• Low-dose aspirin administered empirically during IVF cycles may negatively affect both oocyte and embryo quality through COX 1-2 activity inhibition, showing higher numbers of immature oocytes and lower quality embryos in treated patients. 4
• Cyclophosphamide is associated with dose-related potential risk for irreversible infertility and should be discontinued at least 3 months prior to attempting conception. 1
• Methotrexate and mycophenolate should be discontinued before conception (methotrexate: 1-3 months; mycophenolate: 1.5 months). 1

Specific Antihistamines to Avoid

Hydroxyzine Is Contraindicated

• Hydroxyzine is the only antihistamine specifically contraindicated during early pregnancy based on animal data showing it induced fetal abnormalities in rats and mice at doses substantially above the human therapeutic range. 2, 3
• Cetirizine, the active metabolite of hydroxyzine, is recommended as a safer alternative with a long safety record. 2

Limited Data Agents

• Levocetirizine should be avoided during the first trimester due to limited safety data, though it is the active enantiomer of cetirizine. 3
• Desloratadine, azelastine, and fexofenadine have limited epidemiologic data in human pregnancy, though no reports of increased congenital malformations exist. 1

Common Pitfalls to Avoid

Do Not Combine with Oral Decongestants

• Oral decongestants (phenylephrine, pseudoephedrine) should be avoided during the first trimester due to conflicting reports of associations with gastroschisis and small intestinal atresia. 1, 2
• The risk of malformations increases when decongestants are combined with acetaminophen or salicylates. 1, 2
• Topical decongestants used short-term may have a better safety profile than oral agents for first trimester use. 1

Dose Optimization

• Use the lowest effective dose for the shortest possible time to minimize exposure during pregnancy. 2
• Cetirizine dose should be halved in moderate renal impairment and avoided in severe renal impairment (creatinine clearance < 10 mL/min). 2
• Loratadine should be used with caution in severe renal impairment. 2

Practical Algorithm for IVF Patients

Before and During Ovarian Stimulation

• Continue loratadine 10 mg daily or cetirizine 10 mg daily if already taking for allergic conditions. 3
• Do not empirically start low-dose aspirin, as this may negatively affect oocyte and embryo quality. 4
• Discontinue NSAIDs if using regularly, as these can interfere with ovulation. 1

During Pregnancy After IVF

• Continue the same antihistamine (loratadine or cetirizine) throughout pregnancy if needed for symptom control. 3
• Avoid switching to hydroxyzine at any point during pregnancy. 2, 3
• Avoid oral decongestant combinations, especially in the first trimester. 1, 2