Effect of Metformin on Healthy Live Birth in Women With Prediabetes (MELT-PreDM)

Shandong University

Status: Enrolling

Conditions: Prediabetes; In-Vitro Fertilization; Metformin

Treatments: Drug: Placebo pretreatment before ovarian stimulation; Drug: Metformin pretreatment before ovarian stimulation; Drug: Metformin pretreatment before endometrial preparation for frozen embryo transfer; Drug: Placebo pretreatment before endometrial preparation for frozen embryo transfer

Study type: Interventional

Funder types: Other

Identifiers

NCT06064669

MELT-PreDM

Details and patient eligibility

About

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

Full description

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.

Enrollment: 988 estimated patients

Sex: Female

Ages: 20 to 40 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Triple Blind

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988 participants in 4 patient groups

Metformin-Metformin Group

Experimental group

Description:

Metformin pretreatment before ovarian stimulation till oocyte retrieval and cryopreservation of all embryos, and followed by metformin pretreatment before endometrial preparation for frozen embryo transfer and till the establishment of clinical pregnancy (7-8 weeks gestation) after the first frozen embryo transfer.

Treatment:

Drug: Metformin pretreatment before endometrial preparation for frozen embryo transfer

Drug: Metformin pretreatment before ovarian stimulation

Metformin-Placebo Group

Experimental group

Description:

Metformin pretreatment before ovarian stimulation till oocyte retrieval and cryopreservation of all embryos, and followed by placebo pretreatment before endometrial preparation for frozen embryo transfer and till the establishment of clinical pregnancy (7-8 weeks gestation) after the first frozen embryo transfer.

Treatment:

Drug: Placebo pretreatment before endometrial preparation for frozen embryo transfer

Drug: Metformin pretreatment before ovarian stimulation

Placebo-Metformin Group

Experimental group

Description:

Placebo pretreatment before ovarian stimulation till oocyte retrieval and cryopreservation of all embryos, and followed by metformin pretreatment before endometrial preparation for frozen embryo transfer and till the establishment of clinical pregnancy (7-8 weeks gestation) after the first frozen embryo transfer.

Treatment:

Drug: Metformin pretreatment before endometrial preparation for frozen embryo transfer

Drug: Placebo pretreatment before ovarian stimulation

Placebo-Placebo Group

Experimental group

Description:

Placebo pretreatment before ovarian stimulation till oocyte retrieval and cryopreservation of all embryos, and followed by placebo pretreatment before endometrial preparation for frozen embryo transfer and till the establishment of clinical pregnancy (7-8 weeks gestation) after the first frozen embryo transfer.

Treatment:

Drug: Placebo pretreatment before endometrial preparation for frozen embryo transfer

Drug: Placebo pretreatment before ovarian stimulation