PATERNAL EXPOSURES AND EFFECTS ON PREGNANCY OUTCOME

A significantly increased risk of fetal malformation following paternal exposure to drugs and/or chemicals is generally thought to be unlikely unless the compound in question is a mutagen with the potential to induce genetic alterations in exposed sperm, in which case an increased risk of adverse pregnancy outcome is theoretically possible. The potential for non-mutagenic exposures to induce epigenetic changes in sperm that impact on fetal development or offspring health later on in life is widely debated. For most medicines, fetal outcome following paternal exposure has not been studied, however, the limited available data for known human teratogens or medications with known/suspected genotoxic effects, do not suggest a major increased risk, if any, to the fetus. Although still limited, there is currently no evidence of recognised teratogenic effects (i.e. those described for maternal exposures) occurring after peri-conception paternal exposure to medications such as mycophenolate mofetil and methotrexate, which may be present in seminal fluid. Despite this, prevention of pregnancy is still advised and readers are advised to consult current regulatory guidance for individual exposures. Paternal transmission of viral teratogens during sexual intercourse may, however, result in maternal and, subsequently, fetal infection and teratogenic effects, as has been documented for zika.

In general, men who are exposed to cytotoxic or mutagenic substances are advised to wait about six months (two sperm cycles) before attempting conception. However, recommendations regarding conception following paternal treatment will depend on the drug in question. Where available, an overview of the available paternal exposure data with regard to pregnancy outcome is included in the paternal section of each UKTIS monograph, which should be used, in conjunction with this overview document, where an individual patient risk assessment is required.

At present there is insufficient evidence to justify routine termination of an otherwise wanted pregnancy following paternal exposures, including to agents that are known human teratogens. However, it is advisable that each case is considered on its own merit and the available data and guidance discussed with the patient. Where there is concern due to a paternal exposure prior to conception, or where information for the purpose of planning a pregnancy is required for men on long-term medication, please contact UKTIS for patient-specific advice. Other risk factors which independently increase the risk of adverse pregnancy outcome may be present in individual cases. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.

Links to key monographs are provided below. Please note, however, that this list is not exhaustive. Where available, additional drug specific paternal exposure data is included in the ‘paternal’ section of each UKTIS monograph.