Clinical trial NCT04364087: Impaired Glucose Tolerance in Vietnamese Infertile PCOS Women
Official title: Prevalence of Diabetes and Prediabetes in Vietnamese Infertile Women With Polycystic Ovarian Syndrome
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: PCOS
Infertility
Diabetes
PreDiabetes
Lead sponsor: Mỹ Đức Hospital
Sponsor class: OTHER
First posted: 2020-04-27
Enrollment: 1208
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
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.

Brief 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

Eligibility criteria: Inclusion Criteria:

* Vietnamese women with polycystic ovarian syndrome diagnosed followed by Rotterdam criteria (2003) having indications for infertility treatments

Exclusion Criteria:

* Endocrinal abnormalities including thyroid-stimulating hormone (TSH) \>5mIU/mL, serum prolactin (PRL) \>30ng/mL and any other concomitant endocrinopathy such as a history of hypothyroidism, Cushing's syndrome, premature ovarian insufficiency and late-onset or non-classic congenital adrenal hyperplasia will be excluded.

Primary outcomes:
measure: the prevalence of diabetes and prediabetes in infertile women with PCOS
timeFrame: Baseline
Secondary outcomes:
measure: Factors associated with diabetes and prediabetes
timeFrame: Baseline
Other outcomes:
Locations:
city: Ho Chi Minh City
country: Vietnam
facility: My Duc Hospital
Study officials:
affiliation: Mỹ Đức Hospital
name: Lan TN Vuong, MS, PhD
role: PRINCIPAL_INVESTIGATOR
References: