Granulocyte colony-stimulating factor treatment in women with premature ovarian insufficiency: a pilot clinical study of biological activity and menstrual resumption

BACKGROUND: Women are born with a limited number of eggs, which decline over time. Premature ovarian insufficiency (POI) occurs when this decline happens before age 40, causing infertility. Bone marrow (BM) stem cells may help restore ovarian function, as some women conceive after BM transplants. Studies suggest that mobilizing stem cells with Granulocyte Colony-Stimulating Factor (G-CSF) can improve ovarian response in women with diminished ovarian reserve, possibly without needing ovarian infusion. Our study aimed to evaluate if G-CSF injections alone could improve ovarian function in women with POI. METHODS: This was a pilot, non-randomized, open-label clinical trial including 11 women aged 25-40 years with clinical POI and menopausal symptoms, defined by elevated follicle-stimulating hormone (FSH) on two occasions, low anti-Müllerian hormone (AMH), and reduced antral follicle count (AFC). Participants received up to three rounds of subcutaneous G-CSF administered daily for four days per month over 60 days. Ovarian reserve markers (FSH, AMH, AFC), menstruation resumption, and menopausal symptoms were assessed at baseline and multiple follow-up points over 12 months. RESULTS: The mean age of participants was 34.1 ± 5.2 years (BMI 23.96 ± 4.0 kg/m²). GCS-F injections resulted in significant increases in white blood cells and mild elevation of liver enzymes which returned to baseline within one month. By four months, significant improvements in menopausal symptoms were reported. Exploratory analyses did not identify consistent correlations between clinical response and baseline characteristics. Mean FSH decreased from 54.3 ± 24.6 IU/L at baseline to 29.0 ± 8.1 IU/L at six months (p = 0.008). AMH and AFC rose modestly (0.21 ± 0.15 to 0.49 ± 1.13 pmol/L; 1.09 ± 1.0 to 2.18 ± 2.60) but did not reach statistical significance. Menstruation resumed in 7 of 11 women (63.6%, p = 0.031). One participant showed marked response including retrieval of three mature oocytes. CONCLUSIONS: G-CSF injections were associated with menstrual resumption and symptom relief in most women with POI, suggesting biological activity. Although improvements in ovarian reserve markers were modest and disappointing in terms of the potential for assisted reproduction, these findings may support further evaluation of G-CSF in larger, controlled trials to clarify its clinical benefit and therapeutic potential. TRIAL REGISTRATION: NCT06117982. https://clinicaltrials.gov/study/NCT06117982?cond=The%20Impact%20of%20Granulocyte%20Colony%20Stimulating%20Factor%20on%20Premature%20Ovarian%20Insufficiency&rank=1 .