Effect of Metformin on Healthy Live Birth in Women With Prediabetes
- Conditions
- MetforminPrediabetesIn-Vitro Fertilization
- Interventions
- Drug: Placebo pretreatment before ovarian stimulationDrug: Placebo pretreatment before endometrial preparation for frozen embryo transfer
- Registration Number
- NCT06064669
- Lead Sponsor
- Shandong University
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 988
- Women who are diagnosed with prediabetes by ADA criteria, including either IFG, IGT, or HbA1C 5.7-6.4%.
- Women aged 20-40 years.
- Women who plan to undergo a new cycle of IVF, ICSI, or PGT-A.
- 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.
- 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.
- Women with un-corrected hyperthyroidism or hypothyroidism.
- Women with congenital or acquired abnormal uterine cavity including septate uterus, unicornous uterus, uterus duplex, and intrauterine adhesions.
- Women with a diagnosis of adenomyosis.
- Women with untreated hydrosalpinx.
- Women who plan to undergo PGT-SR or PGT-M.
- Women with major medical comorbidities, such as known liver disease, known renal disease, or known significant anemia.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Metformin-Metformin Group Metformin pretreatment before endometrial preparation for frozen embryo transfer 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. Placebo-Metformin Group Metformin pretreatment before endometrial preparation for frozen embryo transfer 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. Metformin-Metformin Group Metformin pretreatment before ovarian stimulation 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. Metformin-Placebo Group Metformin pretreatment before ovarian stimulation 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. Placebo-Placebo Group Placebo pretreatment before endometrial preparation for frozen embryo transfer 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. Placebo-Metformin Group Placebo pretreatment before ovarian stimulation 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. Metformin-Placebo Group Placebo pretreatment before endometrial preparation for frozen embryo transfer 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. Placebo-Placebo Group Placebo pretreatment before ovarian stimulation 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.
- Primary Outcome Measures
Name Time Method healthy live birth From the date of randomization until delivery after the first embryo transfer, up to 16 months defined as a singleton live birth at ≥37 weeks, with infant birth weight between 2500 and 4000g and without a major congenital anomaly.
- Secondary Outcome Measures
Name Time Method Gestational weight gain at delivery maternal weight gain during pregnancy
Change in 2-h levels of glucose after 75-g OGTT From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks change in 2-h levels of glucose after 75-g OGTT from baseline to the establishment of clinical pregnancy.
Days of ovarian stimulation From the date of randomization until the day of oocyte retrieved, up to 12 weeks the duration of ovarian stimulation by exogenous gonadotropin
Change in BMI From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks change in body mass index (BMI) from baseline to the establishment of clinical pregnancy.
Pregnancy loss From the date of confirmation of pregnancy until the date of pregnancy loss, up to 9 months defined as pregnancies that eventuate in a spontaneous abortion or therapeutic abortion that occurred throughout pregnancy.
Live birth From the date of randomization until delivery after the first embryo transfer, up to 16 months defined as the delivery of any neonate with signs of life at ≥ 28 weeks of gestation
OHSS From the day of oocyte retrieved until the initiation of endometrial preparation for the first frozen embryo transfer, up to 8 weeks ovarian hyperstimulation syndrome was defined according to the Golan criteria
LBW at delivery the infant born weighing less than 2500g
Change in fasting glucose level From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks change in fasting glucose level from baseline to the establishment of clinical pregnancy.
Change in fasting insulin level From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks change in fasting insulin level from baseline to the establishment of clinical pregnancy.
Peak estradiol level From the date of randomization until the day of oocyte retrieved, up to 12 weeks the estradiol level on the day of hCG trigger
Number of euploid embryos From the date of randomization until the initiation of endometrial preparation for frozen embryo transfer, up to 20 weeks the number of euploid embryos
Clinical pregnancy 30-35 days after the first frozen embryo transfer defined as the ultrasound confirmation of at least one intrauterine gestational sac
Change in 2-h levels of insulin after 75-g OGTT From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks change in 2-h levels of insulin after 75-g OGTT from baseline to the establishment of clinical pregnancy.
Total dose of gonadotropins From the date of randomization until the day of oocyte retrieved, up to 12 weeks the total dose of exogenous gonadotropin used during ovarian stimulation
Number of oocyte retrieved From the date of randomization until the day of oocyte retrieved, up to 12 weeks the number of oocyte retrieved
Number of good-score embryos From the date of randomization until the third day after oocyte retrieval, up to 12 weeks the number of good-score embryos
LGA at delivery defined as the birthweight above the 90th percentile for gestational age based on a sex-specific reference
Macrosomia at delivery the infant born weighing larger than 4000g
Singleton or twin pregnancy 30-35 days after the first frozen embryo transfer the number of intrauterine gestational sacs
Incidences of obstetric and neonatal complications From the establishment of clinically recognized pregnancy until six weeks after delivery after the first embryo transfer, up to 11 months including gestational diabetes mellitus, pre-eclampsia, premature rupture of membrane, placenta previa, placental abruption, congenital anomalies, postpartum hemorrhage, stillbirth, neonatal respiratory distress syndrome, neonatal jaundice, neonatal infection, neonatal death.
SGA at delivery defined as the birthweight below the 10th percentile for gestational age based on a sex-specific reference
Birth weight at delivery birth weight of the newborn at delivery
Adverse events From the date of randomization until six weeks after delivery after the first embryo transfer, up to 18 months adverse event (AE) and serious adverse event (SAE)
Cumulative live birth From the date of randomization until delivery, up to 28 months define as women achieving live birth after all the cycles of embryo transfer per oocyte retrieval that performed within one year after randomization.
Trial Locations
- Locations (1)
Shandong University
🇨🇳Jinan, Shandong, China