Anti-Depressants
There has been a rise in the use of antidepressants amongst men and women of childbearing age over the last decade. More so, patients who suffer with subfertility are vulnerable to the associated psychological and emotional sequelae associated with the diagnosis of subfertility and subsequent demanding and time-consuming process of ART, which can often exacerbate underlying mental health instability (12). Selective serotonin reuptake inhibitors (SSRI) are often first line for medical treatment of depression (13). Women are counselled in pregnancy about the risks of SSRIs including a small increased risk of persistent pulmonary hypertension in the new-born and poor neonatal adaptation syndrome (14). However, these risks are often outweighed by the potential risks of untreated depression on the pregnant woman, such as deteriorating mental health and suicide, and fetal risks, such as miscarriage, preterm labour and low birthweight(15).
One Swedish cohort study of 23,557 patients undergoing their first ART cycle over a 5-year period found that there was no statistically significant difference in ART outcomes of patient’s on SSRI’s, however there was a decrease in live birth rates in patients on other medications such as tricyclic antidepressants. The study lacked sufficient information on patient compliance, or whether patients were taking medication prescribed outside of the hospital environment such as in primary care or by psychiatrists working in the private sector (16). A retrospective case review of 950 patients found that patients’ on SSRIs had a higher cycle cancellation rate, but no statistically significant difference in pregnancy or live birth rate (17). This study was limited by its small sample size, as well as lack of data on length of SSRI treatment. Another questionnaire-based study of over 3200 men and women found that women taking non-SSRI anti-depressants (e.g. amitriptyline) were associated with an increased risk of first trimester loss (18). However, SSRI anti-depressant use was not associated with a statistically significant difference in first trimester loss or live birth rates. Similar results were seen in a retrospective study of 698 patients (19).
These studies suggest that there is no convincing evidence of an effect on reproductive outcomes for patients taking SSRIs prior to or during ART, however there may be some demonstrable effect on other antidepressant’s such as tricyclics. Antidepressant use prior to and during ART should be considered on a case-by-case basis after careful counselling with the couple. There is an argument that mental health of patients should be optimised prior to undergoing ART, and if a patient is on SSRI’s then a risk-benefit analysis of continuing the medication versus stopping it at the risk of relapse, should be carried out. Non-pharmaceutical management including cognitive behavioural therapy (CBT)) should be considered. More information on the prevalence of antidepressant use during ART including dosage, duration of treatment and associated reproductive outcomes including successful clinical pregnancy and live birth rates are required. ART can have an overwhelming, yet often overlooked, impact on the mental health of male partners too especially if investigations are associated with diagnoses of severe male factor infertility, genetic conditions with risk of vertical transmission and the potential consequence of not being able to father a child biologically resulting in the necessary use of donor sperm (20) . Further research is required on the consequences of poor mental health of male partners and the effect of antidepressant use has on associated reproductive outcomes. This will help guide clinical advice and appropriate management of these patients throughout what is often a difficult physical and emotional journey (21).