Understanding Premature Ovarian Insufficiency: Observations from Multiple Hospitals

Women with POI

1. Inclusion Criteria 1.1 Age at Diagnosis: Less than 40 years of age. 1.2 Diagnosis of POI: Met one of the following diagnostic criteria based on ESHRE guidelines: Spontaneous POI: Oligomenorrhea or amenorrhea for at least 4 months, combined with elevated FSH levels (\> 25 IU/L) on two occasions at least 4 weeks apart.

   Iatrogenic POI: Documented history of bilateral oophorectomy, or ovarian failure resulting from chemotherapy or radiotherapy.

   1.3 Informed Consent: Willing to participate in the study, provide biological samples, and complete long-term follow-up assessments.
2. Exclusion Criteria 2.1 Current Pregnancy or Lactation: Women who were pregnant or breastfeeding at the time of enrollment.

2.2 Severe Systemic Conditions: Presence of severe somatic or psychiatric diseases (e.g., active malignancy not related to POI, severe heart/renal failure, or cognitive impairment) that would preclude adherence to the study protocol or long-term follow-up.

Control

1. Inclusion Criteria:

   1.1 Age: 18-50 years. 1.2 Menstrual History: Regular menstrual cycles (21-35 days) for the past 12 months.

   1.3 Consent: Willingness to participate, provide biological samples, and provide written informed consent.
2. Exclusion Criteria:

2.1 Physiological Status: Pregnancy, breastfeeding, or clinical perimenopause/postmenopause.

2.2 Reproductive Disorders: History of PCOS, endometriosis, or other reproductive pathologies.

2.3 Iatrogenic \& Toxic Factors: Prior ovarian surgery (e.g., cystectomy), chemotherapy, or radiotherapy.

2.4 Systemic Diseases: History of endocrine (e.g., thyroid dysfunction), autoimmune, cardiovascular, liver, kidney, or hematological diseases, or malignancy.

2.5 Genetic \& Familial Background: First-degree relatives with POI or early menopause (\< 45 years). Family history of hereditary diseases. 2.6 Medication: Use of hormonal drugs or contraceptives within the last 6 months.

Ovarian Surgery group

1. Inclusion Criteria:

   1.1 Age: 18-60 years. 1.2 Patients with ovarian surgery: women scheduled to undergo ovarian surgery for gynecological disease.

   1.3 Informed Consent: Willing to participate in the study, provide biological samples, and sign the informed consent.
2. Exclusion Criteria:

2.1 Reproductive Disorders: History of PCOS, endometriosis, or other reproductive pathologies.

2.2 Medication: Use of hormonal drugs or contraceptives within the last 6 months.

2.3 Genetic or chromosomal abnormalities: Turner syndrome, or other genetic disease.

2.4 Physiological Status: Pregnancy, breastfeeding, or seeking the help of assisted reproductive technology.

2.5 Severe systemic Diseases: History of endocrine (e.g., thyroid dysfunction), autoimmune, cardiovascular, liver, kidney, hematological diseases, malignancy, or cognitive impairment.

Oophorectomy group

1. Inclusion Criteria:

   1.1 Age: 45-65 years. 1.2 Patients with oophorectomy: women scheduled to undergo oophorectomy due to gynecological diseases and met criteria for being menopausal.

   1.3 Menopausal status: at least 12 consecutive months of amenorrhea without other medical causes.

   1.3 Informed Consent: Willing to participate in the study, provide biological samples, and sign the informed consent.
2. Exclusion Criteria:

2.1 Reproductive Disorders: History of PCOS, endometriosis, or other reproductive pathologies.

2.2 Medication: Use of hormonal drugs or contraceptives within the last 6 months.

2.3 Genetic or chromosomal abnormalities: Turner syndrome, or other genetic disease 2.4 Physiological Status: Pregnancy, breastfeeding, or seeking the help of assisted reproductive technology.

2.5 Severe systemic Diseases: History of endocrine (e.g., thyroid dysfunction), autoimmune, cardiovascular, liver, kidney, hematological diseases, malignancy, or cognitive impairment.