Clinical trial NCT06064669: Effect of Metformin on Healthy Live Birth in Women With Prediabetes
Official title: Effect of Metformin on Healthy Live Birth After In-vitro Fertilization in Women With Prediabetes Mellitus: a Multicenter Double-blind Placebo Controlled Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Metformin
Prediabetes
In-Vitro Fertilization
Lead sponsor: Shandong University
Sponsor class: OTHER
Collaborators: name: Ren Ji Hospital of Shanghai Jiao Tong University
name: Women's Hospital of Zhejiang University
name: Shengjing Hospital
name: Nanjing Medical University
name: General Hospital of Ningxia Medical University
name: West China Second University Hospital
name: Maternal and Child Health Hospital of Henan Province
name: Qingdao women's and children's Hospital
First posted: 2023-10-03
Enrollment: 988
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: healthy live birth
timeFrame: From the date of randomization until delivery after the first embryo transfer, up to 16 months
Secondary outcomes:
measure: Change in BMI
timeFrame: From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks
measure: Change in fasting glucose level
timeFrame: From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks
measure: Change in fasting insulin level
timeFrame: From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks
measure: Change in 2-h levels of glucose after 75-g OGTT
timeFrame: From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks
measure: Change in 2-h levels of insulin after 75-g OGTT
timeFrame: From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks
measure: Days of ovarian stimulation
timeFrame: From the date of randomization until the day of oocyte retrieved, up to 12 weeks
measure: Total dose of gonadotropins
timeFrame: From the date of randomization until the day of oocyte retrieved, up to 12 weeks
measure: Peak estradiol level
timeFrame: From the date of randomization until the day of oocyte retrieved, up to 12 weeks
measure: Number of oocyte retrieved
timeFrame: From the date of randomization until the day of oocyte retrieved, up to 12 weeks
measure: Number of good-score embryos
timeFrame: From the date of randomization until the third day after oocyte retrieval, up to 12 weeks
measure: Number of euploid embryos
timeFrame: From the date of randomization until the initiation of endometrial preparation for frozen embryo transfer, up to 20 weeks
measure: OHSS
timeFrame: From the day of oocyte retrieved until the initiation of endometrial preparation for the first frozen embryo transfer, up to 8 weeks
measure: Clinical pregnancy
timeFrame: 30-35 days after the first frozen embryo transfer
measure: Singleton or twin pregnancy
timeFrame: 30-35 days after the first frozen embryo transfer
measure: Pregnancy loss
timeFrame: From the date of confirmation of pregnancy until the date of pregnancy loss, up to 9 months
measure: Live birth
timeFrame: From the date of randomization until delivery after the first embryo transfer, up to 16 months
measure: Incidences of obstetric and neonatal complications
timeFrame: From the establishment of clinically recognized pregnancy until six weeks after delivery after the first embryo transfer, up to 11 months
measure: Gestational weight gain
timeFrame: at delivery
measure: Birth weight
timeFrame: at delivery
measure: LGA
timeFrame: at delivery
measure: SGA
timeFrame: at delivery
measure: LBW
timeFrame: at delivery
measure: Macrosomia
timeFrame: at delivery
measure: Adverse events
timeFrame: From the date of randomization until six weeks after delivery after the first embryo transfer, up to 18 months
measure: Cumulative live birth
timeFrame: From the date of randomization until delivery, up to 28 months
Other outcomes:
Locations:
city: Jinan
country: China
facility: Shandong University
state: Shandong
Study officials:
affiliation: Shandong University
name: Zi-Jiang Chen, Professor
role: PRINCIPAL_INVESTIGATOR
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