Major depression, antidepressant use and male and female fertility

Among infertile couples, male depression is associated with lower pregnancy rates following non-assisted reproductive technology treatment. Female antidepressant use is associated with early pregnancy loss, which may be medication class dependent.

Volume 109, Issue 5, Pages 879–887


Emily A. Evans-Hoeker, M.D., Esther Eisenberg, M.D., Michael P. Diamond, M.D., Richard S. Legro, M.D., Ruben Alvero, M.D., Christos Coutifaris, M.D., Peter R. Casson, M.D., Gregory M. Christman, M.D., Karl R. Hansen, M.D., Ph.D., Heping Zhang, Ph.D., Nanette Santoro, M.D., Anne Z. Steiner, M.D., M.P.H. on behalf of the show Reproductive Medicine Network 



To determine if maternal major depression (MD), antidepressant use, or paternal MD are associated with pregnancy outcomes after non-IVF fertility treatments.


Cohort study.




Participants in two randomized trials: PPCOS II (clomiphene citrate versus letrozole for polycystic ovary syndrome), and AMIGOS (gonadotropins versus clomiphene citrate versus letrozole for unexplained infertility).


Female and male partners completed the Patient Health Questionnaire (PHQ-9). Female medication use was collected. PHQ-9 score ≥10 was used to define currently active MD.

Main Outcome Measure(s)

Primary outcome: live birth. Secondary outcomes: pregnancy, first-trimester miscarriage. Poisson regression models were used to determine relative risks after adjusting for age, race, income, months trying to conceive, smoking, and study (PPCOS II versus AMIGOS).


Data for 1,650 women and 1,608 men were included. Among women not using an antidepressant, the presence of currently active MD was not associated with poorer fertility outcomes (live birth, miscarriage), but rather was associated with a slightly increased likelihood of pregnancy. Maternal antidepressant use (n = 90) was associated with increased risk of miscarriage, and male partners with currently active MD were less likely to achieve conception.


Currently active MD in the female partner does not negatively affect non-IVF treatment outcomes; however, currently active MD in the male partner may lower the likelihood of pregnancy. Maternal antidepressant use is associated with first-trimester pregnancy loss, which may depend upon the type of antidepressant.

Clinical Trial Registration Numbers

NCT00719186 and NCT01044862.

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Go to the profile of Mary Samplaski
about 4 years ago

We know that SSRIs can increase DFI significantly. Were the authors able to differentiate between males who were taking SSRIs vs those that were treated with therapy only?

Go to the profile of Emily Evans-Hoeker
about 4 years ago

Thank you for your comment. The original studies from which our data was taken did not collect specific information about male SSRI use, so we are not able to determine which males were using an SSRI medication or which ones were undergoing therapy.