Impaired Glucose Tolerance in Vietnamese Infertile PCOS Women
Condition: PCOS; Infertility; Diabetes; PreDiabetes
MeSH terms: Infertility; Prediabetic State; Glucose Intolerance
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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
    

Intervention name(s): Oral glucose tolerance test
Intervention type(s): Diagnostic Test
Intervention description(s): Oral glucose tolerance test with 75 g glucose (75 g OGTT) will be performed to those with normal fasting glucose and HbA1C levels. Women will be recommended to have normal diet for 3 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).
Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        All Vietnamese, infertile women, aged 18 to 40, diagnosed with PCOS according to the
        Rotterdam criteria present at IVFMD Tan Binh and IVFMD Phu Nhuan will be enrolled to the
        study.