Cellular therapies in primary ovarian insufficiency and poor ovarian reserve: a systematic review.

PURPOSE

To evaluate the efficacy, safety, and limitations of cellular therapy in primary ovarian insufficiency (POI) and poor ovarian response (POR).

METHODS

A comprehensive search was conducted through the PubMed, Scopus, Web of Science, and Cochrane databases. The study type was limited to clinical trials, pilot studies, and case reports performed on human patients. Animal experiments, in vitro studies, correlational and longitudinal studies, and study designs and protocols were excluded. Twenty-seven studies with 694 patients from 2014 were found by May 2025.

RESULTS

Most studies (59.3%) were from Asia, and 77.8% lacked control groups. Autologous bone marrow mesenchymal stem/stromal cells (MSCs) were used in 37% of studies, rising to 51.8% when combined with platelet-rich plasma. Intraovarian injection was the most common delivery method (70.3%), administered laparoscopically (29.6%), or transvaginally (37%). Follow-up durations of 7-12 months were most common (40.7%). Pregnancy outcomes were reported in 59.2% of studies with control groups. Of the 522 patients treated, 60 (11.7%) became pregnant, compared to 13 (7.6%) of 172 controls. In two-arm studies (22.2% of all), the pregnancy rate was 22.6% (40 patients). Menstruation resumed in 37 (7.1%) of 522 treated patients, dropping to 5.1% in controlled studies.

CONCLUSION

Variability in sample sizes and protocols affects the reliability of findings. Larger trials and standardized protocols for cell type, delivery, and outcomes are essential. Seven to twelve months of follow-up seems suitable for evaluating efficacy but may not be optimal for evaluating the safety. Stratifying patients by age, cause, and reserve could improve outcomes.

TRIAL REGISTRATION

Prospero (ID: CRD420251047104).