Table 1 The predefined eligibility criteria based on population, intervention, comparator, outcome, and study design (PICOS)

Population

Animal models of POI. No weight or animal species limitations were defined.

Intervention

Extracellular vesicles derived from mesenchymal stem cells. No administration route, dose, timing, or particle size limitations were defined.

Comparator

Animal models of primary ovarian insufficiency that have not received any treatment, or have been administered a placebo.

Outcome

Fertility parameters (Follicle count, pregnancy rate, number of offspring, and serum levels of hormones related to ovarian function namely estradiol (E2), anti-Müllerian hormone (AMH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH)).

Study design

Controlled studies with at least two separate untreated POI and EV-treated POI arms.