Glucose Metabolism and Live Birth Outcomes in PCOS

Impact of Glucose Metabolism Abnormalities on Live Birth Rate in South-East Asian Women With Polycystic Ovary Syndrome

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.

Study Overview

• Status: Completed
• Conditions: Diabetes; Infertility; PreDiabetes; PCOS
• Intervention / Treatment: Diagnostic test: Oral glucose tolerance test

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

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.

• Study Type: Observational
• Enrollment (Actual): 1208

Contacts and Locations

Study Locations

• Vietnam
  • Ho Chi Minh City, Vietnam
    • My Duc Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Infertile PCOS women; All Vietnamese, infertile women, diagnosed with PCOS according to the Rotterdam criteria (2003) at IVFMD Tan Binh and IVFMD Phu Nhuan will be enrolled to the study.

Diagnostic test: Oral glucose tolerance test; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth rate at 24 months following enrollment into the study	Live birth was defined as the delivery of a live infant after 22 weeks of gestation, regardless of the method of conception.	From enrollment until delivery (up to 24 months after enrollment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gestational diabetes mellitus	Diagnosis based on standard criteria recorded in medical records.	From enrollment until delivery (up to 24 months after enrollment).
Hypertensive disorders of pregnancy	Includes gestational hypertension, preeclampsia, and eclampsia.	From enrollment until delivery (up to 24 months after enrollment).
Miscarriage	Pregnancy loss before 22 weeks of gestation.	From enrollment until delivery (up to 24 months after enrollment).
Preterm birth	Delivery before 37 completed weeks of gestation.	From enrollment until delivery (up to 24 months after enrollment).
Birthweight	Neonatal birthweight measured in grams at delivery; categorized as low birthweight (<2500 g) or macrosomia (≥4000 g).	At delivery (up to 24 months after enrollment).
Gestational age at birth	Gestational age in completed weeks at delivery.	At delivery (up to 24 months after enrollment).
Neonatal Intensive Care Unit (NICU) admission	Admission to NICU after birth (yes/no).	At delivery (up to 24 months after enrollment).
Neonatal respiratory distress	Clinical diagnosis of respiratory distress requiring intervention.	At delivery (up to 24 months after enrollment).
Baseline glycemic status (diabetes, prediabetes, or normal glucose tolerance before infertility treatment)	Glycemic status will be determined before initiation of infertility treatment, based on the 75-g oral glucose tolerance test (OGTT), fasting plasma glucose, and HbA1c, according to the American Diabetes Association (ADA) 2023 criteria. Participants will be categorized into: Diabetes mellitus, Prediabetes, Normal glucose tolerance. Unit of Measure: Number of participants (%) in each category.	At baseline (at enrollment, before treatment).

Collaborators and Investigators

• Sponsor: Mỹ Đức Hospital
• Investigators: Principal Investigator: Lan TN Vuong, MS, PhD, Mỹ Đức Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): August 31, 2022
• Study Completion (Actual): August 31, 2022

Study Registration Dates

• First Submitted: April 24, 2020
• First Submitted That Met QC Criteria: April 24, 2020
• First Posted (Actual): April 27, 2020

Study Record Updates

• Last Update Posted (Actual): August 24, 2025
• Last Update Submitted That Met QC Criteria: August 21, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility
• Other Study ID Numbers: 08/20/ĐĐ-BVMD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No