No increased risk of postpartum major depression (PPMD) was reported in women conceiving through assisted reproductive technologies (ART). However, ART may be associated with a higher risk of parenting difficulties in women with PPMD. In 359 women with a PPMD admitted to a Mother-Baby Unit (MBU), ART-women (4.2%) showed a 5-fold higher rate of parenting difficulties than those with spontaneous pregnancy (73.33% vs. 35.17%, multivariate ORa = 5.09 [1.48-17.48] p = 0.01). Specific support for mother-child relationship should be implemented in ART-women with PPMD.