Effect of Metformin on Healthy Live Birth in Women With Prediabetes

Effect of Metformin on Healthy Live Birth After In-vitro Fertilization in Women With Prediabetes Mellitus: a Multicenter Double-blind Placebo Controlled Randomized Trial

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.

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.