Medications, Environmental Exposures, and Lifestyle Factors to Avoid When Trying to Conceive
Women attempting pregnancy must discontinue methotrexate (1-3 months before conception), mycophenolate (1.5 months before), and cyclophosphamide (3 months before) due to proven teratogenicity and embryotoxicity 1.
Critical Medications to Avoid
Teratogenic Drugs Requiring Preconception Discontinuation
The 2025 EULAR guidelines establish clear timelines for stopping teratogenic antirheumatic drugs 1:
- Methotrexate: Stop 1-3 months before attempting conception
- Mycophenolate: Stop 1.5 months before conception
- Cyclophosphamide: Stop 3 months before conception
These drugs cause miscarriage and major birth defects when exposure occurs during the first trimester. Effective contraception is mandatory while taking these medications 1.
NSAIDs and Ovulation Interference
Women with difficulty conceiving should discontinue NSAIDs entirely during the periovulatory period 1. Continuous NSAID exposure around ovulation induces luteinised unruptured follicle (LUF) syndrome, directly reducing fecundability by interfering with prostaglandin-dependent ovulation 1. This is a common pitfall—many women take NSAIDs for menstrual cramps without realizing the impact on conception.
If NSAIDs are needed for inflammatory conditions after conception occurs, use only short-acting agents (ibuprofen preferred) at the lowest dose for ≤7-10 days, and stop completely by gestational week 28 to prevent oligohydramnios and ductus arteriosus complications 1.
Lifestyle and Environmental Factors to Avoid
Substance Use
Based on 2025 evidence on male and female fertility 2, 3:
- Smoking: Increases sperm DNA fragmentation by ~10%, alters hormonal profiles, and impairs female fertility—complete cessation is essential
- Alcohol: Chronic use raises sperm DNA fragmentation by ~10%, disrupts the hypothalamic-pituitary-gonadal axis, and may cause testicular atrophy—limit or eliminate intake
- Cannabis and opioids: Suppress fertility through hormonal disruption—avoid completely
- Anabolic steroids: Severely impair spermatogenesis—discontinue well before conception attempts
Weight and Metabolic Factors
Obesity impairs spermatogenesis through aromatase-mediated hormonal imbalance and inflammation—even modest weight loss improves sperm parameters 2. Maintaining a healthy BMI is critical for both partners.
Environmental Exposures
Avoid or minimize 2:
- Heat exposure: Prolonged heat (hot tubs, saunas, laptops on lap) reduces semen quality
- Fine particulate matter (air pollution): Reduces semen quality and contributes to testicular dysgenesis
- Endocrine-disrupting chemicals: Found in plastics (BPA), pesticides, and personal care products—reduce exposure by choosing glass containers, organic produce when possible, and avoiding products with phthalates and parabens
Immunological Considerations
From a reproductive immunology perspective, excessive or unresolved innate immune activation contributes to infertility, recurrent pregnancy loss, preeclampsia, and preterm birth 4. While you cannot directly "avoid" immune dysregulation, you can avoid triggers:
- Chronic inflammation: Address underlying inflammatory conditions (endometriosis, chronic endometritis) as these alter endometrial receptivity 5
- Uncontrolled autoimmune disease: Active inflammatory disease impairs reproductive outcomes—disease control is crucial, but must be achieved with pregnancy-compatible medications 6
Safe Medications During Conception Attempts
For women requiring ongoing treatment 1:
- Hydroxychloroquine: Safe throughout pregnancy at standard doses
- Sulfasalazine: Safe up to 2 g/day (add folic acid supplementation due to folate absorption inhibition)
- Azathioprine: Safe up to 2 mg/kg/day in women with normal thiopurine metabolism
- Colchicine: Compatible at 1-2 mg/day
- Cyclosporine and tacrolimus: Safe at lowest effective dose
- Low-to-moderate dose corticosteroids (prednisone/prednisolone): Safe throughout pregnancy
Male Partner Considerations
Men taking methotrexate, sulfasalazine, cyclosporine, azathioprine, or leflunomide face risks of infertility and potential teratogenicity 7. While paternal medication safety data are less robust, the 2025 guideline review found only 66.7% agreement on preconception discontinuation timing for paternal exposure 6—err on the side of caution and discuss discontinuation 3 months before conception attempts.
Common Pitfalls
- Continuing NSAIDs for menstrual pain during conception attempts: This directly impairs ovulation
- Assuming "natural" supplements are safe: Many lack safety data in pregnancy
- Focusing only on female factors: Male lifestyle factors (smoking, alcohol, obesity, heat exposure) contribute to 50% of infertility cases 2
- Stopping disease-modifying drugs without guidance: Uncontrolled inflammatory disease itself impairs fertility—switch to pregnancy-compatible alternatives rather than stopping treatment entirely