P-727 The impact of antidepressants and anxiolytics on assisted reproductive technology treatment outcomes
Authors: Jølving L  R , Munk-Olsen T , Torseth O , Fedder J , Nørgård B , Larsen M  D 
Published: July 2024

Abstract

Study question
Does antidepressant and anxiolytic use impact the chance of live birth after assisted reproductive technology (ART) treatment?

Summary answer
For women using antidepressants, ART treatment is as successful as for others. However, concomitant anxiolytic use was associated with failure to succeed.

What is known already
Infertility and depression are prevalent disorders in women of reproductive age and may occur coincidently. Antidepressants constitute the mainstay in treatment for moderate-severe depression, and selective serotonin reuptake inhibitors (SSRIs) are among the most commonly used antidepressants because they, in general, cause few side effects. However, antidepressant use in women undergoing ART treatment may be considered to balance the possible risks of untreated depression against fetal drug exposure and the efficacy of ART treatment. Furthermore, up to 50% of patients with depression also meet the criteria for anxiety disorders and may be treated with anxiolytics.

Study design, size, duration
This is an observational cohort study based on the Danish health registries. The use of antidepressants, i.e. as current or recent users, and anxiolytics or hypnotics at embryo transfer was obtained from the prescription register and information on all ART treatments and childbirths between 2006 and 2019 from the Danish ART register and the Danish birth register.

Participants/materials, setting, methods
The study population included 130,170 embryo transfers in 48,156 women undergoing ART treatment. A total of 1505 women were exposed to antidepressants at the time of embryo transfer, and 1160 women were recent users who discontinued before embryo transfer. We used mixed-effects logistic regression analyses. The association between antidepressants and anxiolytics respectively and ART was analyzed taking potential confounders into account estimating the odds ratios(OR) of either a biochemical pregnancy, clinical pregnancy, or live birth.

Main results and the role of chance
The adjusted OR(aOR) and corresponding 95% confidence interval (CI) of a biochemical-, and clinical pregnancy in women with current use of antidepressants at time of embryo transfer were 0.87 (95% CI: 0.73-1.04) and 0.84 (95% CI: 0.57-1.20), respectively, and 0.90 (95% CI: 0.67-1.19) for live birth. For women who discontinued antidepressant use before embryo transfer (labeled recent users), the aORs for a biochemical-, clinical pregnancy and live birth were 0.95 (95% CI: 0.76-1.17), 0.71 (95% CI: 0.46-1.09) and 1.02 (95% CI: 0.72-1.45), respectively. When analyzing women who use or recently used antidepressants in combination with anxiolytics or hypnotics the chance of a live birth was decreased markedly with an aOR of 0.15 (95% CI: 0.04-0.51). Based on nationwide data from more than a decade of ART treatments, we found that the use of antidepressants at the time of embryo transfer was not associated with a decreased chance of biochemical or clinical pregnancy, or live birth. However, when women treated with antidepressants also used anxiolytics or hypnotics, the chance of a live birth was significantly decreased though based on a limited number of patients suggesting a point of further investigation and attention.

Limitations, reasons for caution
As in all observational studies, it can never be ensured that the patients take the medicine, but we used information on prescriptions for antidepressants/anxiolytics from the prescription register using at least two redeemed prescriptions within 182 days before, and until 182 days after the date of embryo transfer.

Wider implications of the findings
Use of antidepressants at the time of embryo transfer was not associated with a decreased chance of biochemical or clinical pregnancy, or live birth. However, when antidepressants are used concomitantly with anxiolytics or hypnotics, the chance of live birth is significantly decreased suggesting the need for further investigation and attention.

Trial registration number
The study was funded by The Region of Southern Denmark and Merck.