Polycystic ovary syndrome (PCOS) is a common endocrine and reproductive disorder in which insulin resistance (IR) is proposed as a key pathophysiological feature of the disease's symptoms and consequences. Diabetes and rediabetes, a significant consequence of IR, are related to a higher risk of diabetes mellitus, future cardiovascular events, and adverse pregnancy outcomes.

All Vietnamese infertile women with PCOS, according to the Rotterdam criteria present at IVFMD, will be enrolled in the study. Phenotypes of PCOS are classified into A, B, C, and D due to hyperandrogenism (HA), ovulatory dysfunction (OD), and polycystic ovarian morphology (PCOM)

• A: HA + OD + PCOM
• B: HA + OD
• C: HA + PCOM
• D: OD + PCOM

All patients enrolled in this study will have:

• Standard anthropometric data will be done by professional and experienced physicians according to standard study protocol: Weight, height, waist and hip circumference, waist-to-hip ratio, and BMI calculated, followed by World Health Organization guidelines for Asian women. Trained midwives evaluated hirsutism and acanthosis nigricans, and fat mass was measured in the abdomen area using specific calipers (Accu-Measure®).
• Gynecologic ultrasound scan
• Blood tests:

A fasting blood sample was obtained. Luteinizing hormone (LH) (with a coefficient of variation [CV] 2.3%), follicle-stimulating hormone (FSH) (CV 3.5%), estradiol (CV 2.7%), progesterone (CV: 6.2%), prolactin (CV: 5.2%), sex hormone binding globulin (SHBG) (CV 5.6%), total testosterone (CV 8.4%) were measured by Elesys technique, Cobas e411 system. FAI was calculated using the formula: FAI = serum testosterone in nmol/L/serum SHBG in nmol/L × 100. Thyroid stimulating hormone (TSH) (CV 6.0%), free thyroxin (fT4) (CV 5.05%) were measured by Access 2 immunoassay system. High-density lipoprotein cholesterol (HDL-C) (CV 2.4%), low-density lipoprotein cholesterol (LDL-C) (CV 2.0%), and triglyceride (CV 1.76%) were measured by Beckman Coulter AU480 system. Fasting serum insulin (CV 2.8%) was measured by Elesys technique, Cobas e411 system. The Homeostasis Model Assessment of Insulin Resistance Index (HOMA-IR) was used to estimate insulin sensitivity. HOMA-IR was calculated as FPG in mmol/L × fasting insulin in mIU/mL/22.5 (Matthews et al., 1985). A 2 mL blood sample was withdrawn and stored in a vacutainer with nature oxalate and EDTA additive.

- Glucose tests:

+ After a fast of ≥4 hours, FPG (CV 0.9%) was measured by Beckman Coulter AU480 analyzer, and HbA1c (CV 1.00%) were measured by Tosoh HLC-723GX analyzer; participants who had not fasted for ≥4 hours were asked to return for measurement of FPG the next day.

Diagnosis of diabetes mellitus will be made when fasting glucose ≥126 mg/dL (7 nmol/L) or HbA1C ≥6.5% (48 mmol/mol) (American Diabetes Association, 2018). When glucose ≥126 mg/dL (7 nmol/L) or HbA1C ≥6.5% (48 mmol/mol) (American Diabetes Association, 2018).

• Oral glucose tolerance test with 75 g glucose (75 g OGTT) will be performed on those with normal fasting glucose and HbA1C levels. Women will be recommended to have a normal diet for three days and overnight fasting for at least 8 hours. The blood withdrawal will be performed twice: (i) fasting and (2i) 2 hours after solution administration. The volume of blood for each test is 2 ml. Impaired glucose tolerance will be diagnosed when two-hour glucose levels of 140 to 199 mg/dL (7.8 to 11.0 mmol/l) (American Diabetes Association, 2018).

  - Hyperandrogenism:

• Clinical hyperandrogenism: Hirsutism using the modified Ferriman Gallwey score (mFG) and severe acne

• Biochemical hyperandrogenism: free testosterone (normal range below 2,53nmol/ml), free testosterone index, SHBG

Following the assessment of glucose metabolism, all patients identified with preconception glucose metabolism disorders (e.g., prediabetes or diabetes) were referred to endocrinologists for specialized preconception care. This included lifestyle modifications and/or pharmacological interventions, aiming to optimize metabolic health before conception and potentially reduce adverse pregnancy outcome. Conception was achieved through various methods, including natural conception, ovulation induction combined with intrauterine insemination (OI/IUI), or in-vitro fertilization/ in-vitro maturation (IVF/IVM). These treatment options were counseled based on the recommendations from the 2023 international evidence-based guideline, in which first-line therapy involves optimizing preconception health and lifestyle, followed by OI with letrozole. Timed intercourse was recommended in the absence of male factor infertility, while IUI was offered in cases with mild male factor. IVF/IVM was indicated after failure of these initial approaches. Final decisions were individualized through shared decision-making, depending on clinical indications and patient preference (Teede et al., 2023b). Pregnancy outcomes, including pregnancy rates, live births and pregnancy outcomes, were tracked and documented over a 24-month follow-up period from the time of study enrollment.

Inclusion Criteria:

• Vietnamese women aged 18-40 years
• Diagnosed with polycystic ovary syndrome (PCOS) according to the Rotterdam criteria (2003)
• Having indications for infertility treatment

Exclusion Criteria:

• Thyroid-stimulating hormone (TSH) > 5 mIU/mL
• Serum prolactin (PRL) > 30 ng/mL
• History of hypothyroidism
• Cushing's syndrome
• Premature ovarian insufficiency
• Late-onset or non-classic congenital adrenal hyperplasia
• Any other concomitant endocrinopathy

Infertile Vietnamese women aged 18-40 years, diagnosed with polycystic ovary syndrome (PCOS) according to the Rotterdam 2003 criteria, who present for infertility treatment at IVFMD.