Effect of Metformin on Healthy Live Birth After In-vitro Fertilization in Women With Prediabetes Mellitus: a Multicenter Double-blind Placebo Controlled Randomized Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 988
- 试验地点
- 1
- 主要终点
- healthy live birth
研究概览
简要总结
To evaluate the efficacy and safety of metformin pretreatment on reproductive outcomes in infertile women with prediabetes.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Metformin-Metformin Group
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.
干预措施: Metformin pretreatment before ovarian stimulation (Drug)
Metformin-Metformin Group
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.
干预措施: Metformin pretreatment before endometrial preparation for frozen embryo transfer (Drug)
Metformin-Placebo Group
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.
干预措施: Metformin pretreatment before ovarian stimulation (Drug)
Metformin-Placebo Group
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.
干预措施: Placebo pretreatment before endometrial preparation for frozen embryo transfer (Drug)
Placebo-Metformin Group
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.
干预措施: Placebo pretreatment before ovarian stimulation (Drug)
Placebo-Metformin Group
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.
干预措施: Metformin pretreatment before endometrial preparation for frozen embryo transfer (Drug)
Placebo-Placebo Group
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.
干预措施: Placebo pretreatment before ovarian stimulation (Drug)
Placebo-Placebo Group
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.
干预措施: Placebo pretreatment before endometrial preparation for frozen embryo transfer (Drug)
结局指标
主要结局
healthy live birth
时间窗: 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.
次要结局
- 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)
- Days of ovarian stimulation(From the date of randomization until the day of oocyte retrieved, up to 12 weeks)
- Change in BMI(From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks)
- Pregnancy loss(From the date of confirmation of pregnancy until the date of pregnancy loss, up to 9 months)
- Live birth(From the date of randomization until delivery after the first embryo transfer, up to 16 months)
- Gestational weight gain(at delivery)
- OHSS(From the day of oocyte retrieved until the initiation of endometrial preparation for the first frozen embryo transfer, up to 8 weeks)
- LBW(at delivery)
- 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 insulin level(From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks)
- Peak estradiol level(From the date of randomization until the day of oocyte retrieved, up to 12 weeks)
- Number of euploid embryos(From the date of randomization until the initiation of endometrial preparation for frozen embryo transfer, up to 20 weeks)
- Clinical pregnancy(30-35 days after the first frozen embryo transfer)
- 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)
- Total dose of gonadotropins(From the date of randomization until the day of oocyte retrieved, up to 12 weeks)
- Number of oocyte retrieved(From the date of randomization until the day of oocyte retrieved, up to 12 weeks)
- Number of good-score embryos(From the date of randomization until the third day after oocyte retrieval, up to 12 weeks)
- LGA(at delivery)
- Macrosomia(at delivery)
- Singleton or twin pregnancy(30-35 days after the first frozen embryo transfer)
- 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)
- SGA(at delivery)
- Birth weight(at delivery)
- Adverse events(From the date of randomization until six weeks after delivery after the first embryo transfer, up to 18 months)
- Cumulative live birth(From the date of randomization until delivery, up to 28 months)
研究者
Chen Zi-Jiang
Academician
Shandong University