Effect of Metformin on Healthy Live Birth in Women With Prediabetes

Shandong University988 enrolled

Overview

To evaluate the efficacy and safety of metformin pretreatment on reproductive outcomes in infertile women with prediabetes.

To evaluate the efficacy and safety of metformin pretreatment on reproductive outcomes in infertile women with prediabetes and to determine whether either starting metformin pretreatment before ovarian stimulation (aiming at improving the quality of oocyte/embryo) or starting before frozen embryo transfer (FET) (aiming at improving the receptivity of endometrium) could increase the chance of a healthy live birth compared with placebo.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

988

Conditions

Metformin Prediabetes In-Vitro Fertilization

Interventions

Metformin pretreatment before ovarian stimulationDRUG

The enrolled patients will be prescribed metformin 850mg twice daily for at least 4 weeks prior to ovarian stimulation till oocyte retrieval.

Placebo pretreatment before ovarian stimulationDRUG

The enrolled patients will be prescribed placebo 850mg twice daily for at least 4 weeks prior to ovarian stimulation till oocyte retrieval.

Metformin pretreatment before endometrial preparation for frozen embryo transferDRUG

After oocyte retrieval, the enrolled patients will be prescribed metformin 850mg twice daily for at least 4 weeks before endometrial preparation for frozen embryo transfer and till the establishment of clinical pregnancy (7-8 weeks gestation) after the first frozen embryo transfer.

Eligibility

Sex: FEMALEMin age: 20 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Women who are diagnosed with prediabetes by ADA criteria, including either IFG, IGT, or HbA1C 5.7-6.4%. 2. Women aged 20-40 years. 3. Women who plan to undergo a new cycle of IVF, ICSI, or PGT-A. Exclusion Criteria: 1. Women who are diagnosed with diabetes according to the ADA criteria11,12, which is meeting one of the following criteria: fasting plasma glucose ≥7.0mmol/L, 2-h plasma glucose during 75-g OGTT ≥11.1mmol/L, HbA1c≥6.5%, or a random plasma glucose≥11.1mmol/L. 2. Women who are taking medicine that interfere with glucose metabolism, such as metformin, oral anti-diabetic agents (sulfonylureas, glinides, thiazolidinediones, α-glycosidase inhibitors, GLP-1 receptor agonist, etc.), weight loss drugs (i.e.orlistat, etc.), glucocorticoids, and growth hormones within 2 months before enrollment. 3. Women with un-corrected hyperthyroidism or hypothyroidism. 4. Women with congenital or acquired abnormal uterine cavity including septate uterus, unicornous uterus, uterus duplex, and intrauterine adhesions. 5. Women with a diagnosis of adenomyosis. 6. Women with untreated hydrosalpinx. 7. Women who plan to undergo PGT-SR or PGT-M. 8. Women with major medical comorbidities, such as known liver disease, known renal disease, or known significant anemia.

Locations (1)

Shandong University

Jinan, Shandong, China

RECRUITING

Outcomes

Primary Outcomes

healthy live birth

defined as a singleton live birth at ≥37 weeks, with infant birth weight between 2500 and 4000g and without a major congenital anomaly.

Time frame: From the date of randomization until delivery after the first embryo transfer, up to 16 months