Off-Label Drug Use in Gynecology Evidence-Based Applications for Fertility and Pregnancy

Off-label drug use is common in women’s reproductive healthcare, particularly when approved therapeutic options are limited, although the strength of supporting evidence varies substantially across drugs and indications. This narrative review aimed to synthesize and compare evidence on the off-label use of filgrastim, methotrexate, sildenafil citrate, misoprostol, letrozole, and pentoxifylline in fertility-, pregnancy-, and gynecology-related care. Relevant literature was identified from major biomedical databases and clinical trial registries and qualitatively synthesized according to study design, consistency of findings, clinical outcomes, safety findings, and methodological limitations. Methotrexate and letrozole showed comparatively well-established evidence for selected reproductive indications, particularly medical management of ectopic pregnancy and ovulation induction in women with polycystic ovary syndrome. Filgrastim and sildenafil demonstrated potential benefits for thin endometrium and implantation-related outcomes, although findings were heterogeneous and improvements in pregnancy outcomes were inconsistent. Misoprostol has extensive evidence-based reproductive and obstetric use despite variation in regulatory approval across settings. Pentoxifylline showed potential benefits for endometrial insufficiency and endometriosis-associated infertility, but evidence for sustained pregnancy and live-birth outcomes remains limited. Overall, off-label use in reproductive healthcare encompasses interventions with markedly different levels of evidentiary support. Appropriate prescribing should therefore consider evidence quality, indication-specific benefit–risk balance, patient selection, safety, and clinical monitoring.