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).