In This article

• Many women undergoing IVF also require treatment for depression or anxiety, often with SSRIs.
• A large Danish ART cohort found no meaningful reduction in pregnancy or live birth rates among current or recent antidepressant users.
• A Swedish IVF cohort suggested that untreated depression or anxiety, but not SSRI treatment, may be associated with lower pregnancy and live birth rates.
• Existing studies focus mainly on pregnancy and live birth rates and provide limited data on earlier ART steps such as oocyte yield and fertilization.
• Overall, current evidence is reassuring that SSRIs do not substantially impair IVF success, while the impact of untreated depression remains an important concern.

Antidepressant treatment in women undergoing IVF or embryo transfer does not appear to substantially reduce the chance of achieving a pregnancy or live birth, based on current observational data. At the same time, there is some evidence that untreated depression or anxiety may be associated with lower pregnancy and live birth rates, although this relationship remains incompletely understood.

Antidepressants and ART: What Do We Tell Our Patients?

In our clinic at the Center for Women’s Mental Health, we see many women who present with depression and anxiety in the context of infertility treatment. For some, this is the first episode of depression or anxiety; for most, there is a history of mood or anxiety disorders that predates infertility and its treatment. In this population, we typically recommend psychotherapy and, when indicated, treatment with serotonin reuptake inhibitors (SRIs).

A common and important question is:

Will the medication affect my chances of getting pregnant?

Although the available data are still limited, the findings we have are reassuring and can help guide these conversations.

Antidepressants and IVF outcomes

Several studies have examined whether antidepressant use affects outcomes of in vitro fertilization (IVF) and other assisted reproductive technologies (ART).

The most recent is a Danish nationwide register-based cohort study that assessed all women undergoing ART between 2006 and 2019, including 44,542 women and 123,146 embryo transfers. The investigators compared three groups:

• Women using antidepressants at the time of embryo transfer (current users)
• Women who had discontinued antidepressants before embryo transfer (recent users)
• Women with no recorded antidepressant use (unexposed cohort)

The analysis included:

• 1,057 current users (median age 35) with 2,154 embryo transfers
• 1,580 recent users with 2,780 transfers
• 42,861 women without antidepressant use with 118,212 transfers

The use of antidepressants (either current or recent) did not appear to affect the chances of pregnancy or live birth. There are small differences but these are not statistically significant.

• For current users, the adjusted relative risk (aRR) was 0.96 (95% CI: 0.87–1.03) for clinical pregnancy and 0.96 (95% CI: 0.87–1.00) for live birth. 
• For recent users, the aRRs for clinical pregnancy and live birth were 0.94 (95% CI: 0.87–1.00) and 0.99 (95% CI: 0.85–1.14), respectively. adjusted RRs were 0.94 (95% CI: 0.86–1.01) for clinical pregnancy and 1.04 (95% CI: 0.90–1.20) for live birth.

Based on this nationwide analysis of more than a thousand women using antidepressants at the time of embryo transfer, current or recent use of antidepressants was not associated with a meaningful reduction in the chance of clinical pregnancy or live birth. These findings suggest that, for women treated with antidepressants, ART treatment appears to be as successful as for women without antidepressant exposure.

There are, however, important limitations to keep in mind. This study focuses on one component of the process: the success of embryo transfer. It does not provide information on how antidepressants might affect other aspects of ART, such as number of oocytes retrieved, oocyte or embryo quality, and fertilization rates. Thus, while the results regarding pregnancy and live birth are reassuring, we still lack detailed data on earlier steps in the ART process.

Impact of Untreated Depression on IVF Outcomes

Discussions often center on the potential reproductive risks of antidepressant medications, but we also need to consider the possible impact of untreated depression or anxiety on fertility and the likelihood of ART to succeed.

A nationwide register-based cohort study from Sweden (Cesta et al, 2016) examined associations between depression, anxiety, antidepressant treatment before IVF, and IVF outcomes. The study included nulliparous women undergoing their first IVF cycle recorded in the Swedish Quality Register of Assisted Reproduction (n = 23,557).

Key findings included:

• Overall, 4.4% of women had a diagnosis of depression and/or anxiety and/or had been treated with antidepressants before their first IVF cycle (1,044 women).
• In this group, the adjusted odds of pregnancy and live birth were modestly reduced (AOR for pregnancy = 0.86; 95% CI, 0.75–0.98; AOR for live birth = 0.83; 95% CI, 0.72–0.96) compared to women with no history of depression/anxiety or antidepressant treatment.
• Among women who had filled at least one prescription for an SSRI (n = 829), rates of pregnancy and live birth did not differ significantly from those in women without depression/anxiety or antidepressant use.
• In contrast, women with a diagnosis of depression or anxiety but no antidepressant treatment (n = 164) had substantially lower odds of pregnancy (AOR = 0.58; 95% CI, 0.41–0.82) and live birth (AOR = 0.60; 95% CI, 0.41–0.89).
• Among women who became pregnant (39.7%), there were no statistically significant associations between exposure and risk of miscarriage, except for women using non-SSRI antidepressants (n = 52), who had increased odds of miscarriage (AOR = 3.56; 95% CI, 1.06–11.9).

Taken together, this study suggests that:

• Untreated depression or anxiety may be associated with a lower likelihood of pregnancy and live birth after IVF.
• SSRI treatment, in contrast, was not associated with reduced rates of pregnancy or live birth in this sample.

The bottom line

This is still an understudied area, and more high-quality research is needed. However, the available data allow us to offer some clinically useful guidance:

• Current evidence does not indicate that SSRI antidepressants meaningfully reduce the chances of pregnancy or live birth in women undergoing IVF or embryo transfer.
• In at least one large cohort, women with depression or anxiety who were not treated with antidepressants had substantially lower odds of pregnancy and live birth compared to women without psychiatric illness, while women treated with SSRIs did not show this reduction.
• Although limitations in the existing studies prevent us from concluding that untreated depression directly impairs fertility, they underscore that focusing exclusively on potential medication risks may overlook the possible reproductive and emotional costs of leaving depression or anxiety untreated.

In practice, we can tell patients that antidepressants, particularly SSRIs, do not appear to adversely affect IVF outcomes based on current evidence. Treatment decisions should be individualized, weighing the benefits of maintaining mood stability against the still-limited but generally reassuring reproductive data.

—Ruta Nonacs, MD PhD