Oral GDC-0077 in Premature Ovarian Insufficiency

This is a single-center, single-arm, exploratory clinical trial evaluating the safety and potential effect of oral GDC-0077 on ovarian function in women with premature ovarian insufficiency (POI). GDC-0077 is an oral, highly selective PI3Kα inhibitor. Preclinical data from this research group showed that PI3Kα inhibition increased secondary and antral follicle counts in aged mice and promoted follicle development in cultured mouse ovaries. Twelve participants with POI will receive GDC-0077 9 mg orally three times weekly (Monday, Wednesday, Friday) for 3 weeks. The primary safety focus includes hyperglycemia, stomatitis/mucositis, and diarrhea. Ovarian function will be assessed by change in antral follicle count (AFC) from baseline at 3 months after treatment initiation, along with FSH, AMH, ovarian volume, and return of spontaneous menses.

Inclusion Criteria: * Female, aged 20-40 years inclusive. Diagnosis of POI: Serum basal FSH \>25 IU/L on two occasions ≥4 weeks apart, measured on cycle days 2-4 or randomly during amenorrhea. Willing to provide written informed consent. Has a desire for future fertility, or does not exclude future fertility. Exclusion Criteria: * Known chromosomal abnormality in the participant. Iatrogenic POI: prior chemotherapy, radiotherapy, or ovarian surgery (except unilateral oophorectomy with preservation of at least part of the ovarian tissue). Abnormal liver or renal function. Diabetes mellitus, impaired fasting glucose, or insulin resistance. Pregnant or lactating women. Known hypersensitivity to GDC-0077 or any of its excipients. Participation in another interventional clinical trial within 3 months before enrollment. Any condition that, in the investigator's judgment, makes the participant unsuitable for the study (e.g., psychiatric disorder, substance abuse, poor adherence).