Aim: To evaluate serum soluble fms-like tyrosine kinase-1, proangiogenic protein placental growth factor, and niacin levels in women with premature ovarian insufficiency (POI) and to compare the results with those of healthy subjects.

Methods: This prospective study will be included 45 women with idiopathic premature ovarian insufficiency and 45 controls. The blood for analysis will be obtained at the early follicular phase of the menstrual cycle and serum soluble fms-like tyrosine kinase-1, proangiogenic protein placental growth factor, and niacin levels will be measured using a commercially available ELISA kit.

This will be an observational prospective cohort study conducted at Obstetrics and Gynecology Department of Cengiz Gokcek Obstetrics and Children's Hospital between November 2020 and April 2021. The investigators will be recruited 45 subjects with idiopathic POI, and 45 healthy patients were selected for the control group. All patients will be given their oral and written informed consent before their inclusion in the study. The protocol was approved by the Ethics Committee for Clinical Research of Gaziantep University (Reference number: 2020/320). The study strictly will be adhered to the principles of the Declaration of Helsinki.

Women between the ages of 18-39 will be included. A volunteer group of healthy women who will be visited the gynecology clinic for routine examinations and women who will be admitted for pre-pregnancy tests will be invited randomly to this research as a control group. Healthy women, who will be returned during their early follicular phase of the menstrual cycle, will be recruited as the control group subjects. The exclusion criteria will be as follows: women with evidence for karyotypic, metabolic, toxic, or iatrogenic cause of the ovarian insufficiency and any women who use any medication for POI treatment. At enrollment, for both groups, the investigators will be collected data about age, height, weight, BMI, age of menarche, obstetrics history, history of smoking, regular exercise and family history of POI. At enrolment, all patients will be underwent vaginal ultrasonography for the assessment of antral follicle count (AFC) and venous blood sample from the antecubital veins for measuring serum concentration of soluble fms-like tyrosine kinase-1, proangiogenic protein placental growth factor, and niacin, Follicle-stimulating hormone (FSH), E2, anti-mullerian hormone (AMH) and complete blood count (CBC). In control subjects venous blood samples and AFC will be collected during the early follicular phase of the menstrual cycle. The serum samples will be stored in aliquots at -80°C prior to the analyses of sFlt- 1, PIGF, and niacin. The serum soluble fms-like tyrosine kinase-1, proangiogenic protein placental growth factor, and niacin level will be measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Then, this study will be determined maternal serum soluble fms-like tyrosine kinase-1, proangiogenic protein placental growth factor, and niacin levels in women with POI (n=45) compared to those of volunteer healthy women (n=45). Then, these three markers levels will be compared in both group.

Inclusion Criteria:

• women with POI
• Healthy women

Exclusion Criteria:

1. women with any systemic condition (such as chronic hypertension, renal disease)
2. history of using any medication
3. drug user
4. history/presence of malignancy
5. history of Radiotherapy/chemotherapy
6. polycystic ovary syndrome
7. women who had any other acute/chronic infection or fever
8. Patients whose chromosome analysis result is not normal
9. history of ovarian surgery
10. Ovarian cysts/mass
11. pregnancy
12. lactation

POI is a clinical syndrome defined by loss of ovarian activity before the age of 40 years. POI is characterized by menstrual disturbance (amenorrhea or oligomenorrhea) with raised gonadotrophins and low estradiol. It is estimated to affect 1% of women under the age of 40, 0.1% under 30 and 0.01% under 20.

The investigators consecutively will be recruited 45 subjects with POI, and 45 healthy women will be selected for the control group.