Back to resultsEffect of Metformin on Healthy Live Birth in Women With Prediabetes (MELT-PreDM)
Primary Purpose
Metformin, Prediabetes, In-Vitro Fertilization
Status
Not yet recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Metformin pretreatment before ovarian stimulation
Placebo pretreatment before ovarian stimulation
Metformin pretreatment before endometrial preparation for frozen embryo transfer
Placebo pretreatment before endometrial preparation for frozen embryo transfer
Sponsored by
About this trial
This is an interventional treatment trial for Metformin
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Sites / Locations
- Shandong University
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Metformin-Metformin Group
Metformin-Placebo Group
Placebo-Metformin Group
Placebo-Placebo Group
Arm 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.
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 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 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.
Outcomes
Primary Outcome Measures
healthy live birth
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
Change in BMI
change in body mass index (BMI) from baseline to the establishment of clinical pregnancy.
Change in fasting glucose level
change in fasting glucose level from baseline to the establishment of clinical pregnancy.
Change in fasting insulin level
change in fasting insulin level from baseline to the establishment of clinical pregnancy.
Change in 2-h levels of glucose after 75-g OGTT
change in 2-h levels of glucose after 75-g OGTT from baseline to the establishment of clinical pregnancy.
Change in 2-h levels of insulin after 75-g OGTT
change in 2-h levels of insulin after 75-g OGTT from baseline to the establishment of clinical pregnancy.
Days of ovarian stimulation
the duration of ovarian stimulation by exogenous gonadotropin
Total dose of gonadotropins
the total dose of exogenous gonadotropin used during ovarian stimulation
Peak estradiol level
the estradiol level on the day of hCG trigger
Number of oocyte retrieved
the number of oocyte retrieved
Number of good-score embryos
the number of good-score embryos
Number of euploid embryos
the number of euploid embryos
OHSS
ovarian hyperstimulation syndrome was defined according to the Golan criteria
Clinical pregnancy
defined as the ultrasound confirmation of at least one intrauterine gestational sac
Singleton or twin pregnancy
the number of intrauterine gestational sacs
Pregnancy loss
defined as pregnancies that eventuate in a spontaneous abortion or therapeutic abortion that occurred throughout pregnancy.
Live birth
defined as the delivery of any neonate with signs of life at ≥ 28 weeks of gestation
Incidences of obstetric and neonatal complications
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.
Gestational weight gain
maternal weight gain during pregnancy
Birth weight
birth weight of the newborn at delivery
LGA
defined as the birthweight above the 90th percentile for gestational age based on a sex-specific reference
SGA
defined as the birthweight below the 10th percentile for gestational age based on a sex-specific reference
LBW
the infant born weighing less than 2500g
Macrosomia
the infant born weighing larger than 4000g
Adverse events
adverse event (AE) and serious adverse event (SAE)
Cumulative live birth
define as women achieving live birth after all the cycles of embryo transfer per oocyte retrieval that performed within one year after randomization.
Full Information
NCT ID
NCT06064669
First Posted
September 19, 2023
Last Updated
September 26, 2023
Sponsor
Shandong University
Collaborators
Ren Ji Hospital of Shanghai Jiao Tong University, Women's Hospital of Zhejiang University, Shengjing Hospital, Women's Hospital of Nanjing Medical University, General Hospital of Ningxia Medical University, West China Second University Hospital, Maternal and Child Health Hospital of Henan Province, Qingdao women's and children's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT06064669
Brief Title
Effect of Metformin on Healthy Live Birth in Women With Prediabetes
Acronym
MELT-PreDM
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 1, 2023 (Anticipated)
Primary Completion Date
December 31, 2026 (Anticipated)
Study Completion Date
December 31, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shandong University
Collaborators
Ren Ji Hospital of Shanghai Jiao Tong University, Women's Hospital of Zhejiang University, Shengjing Hospital, Women's Hospital of Nanjing Medical University, General Hospital of Ningxia Medical University, West China Second University Hospital, Maternal and Child Health Hospital of Henan Province, Qingdao women's and children's Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metformin, Prediabetes, In-Vitro Fertilization
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
988 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Metformin-Metformin Group
Arm Type
Experimental
Arm 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.
Arm Title
Metformin-Placebo Group
Arm Type
Experimental
Arm 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.
Arm Title
Placebo-Metformin Group
Arm Type
Experimental
Arm 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.
Arm Title
Placebo-Placebo Group
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Metformin pretreatment before ovarian stimulation
Other Intervention Name(s)
Metformin before ovarian stimulation
Intervention Description
The enrolled patients will be prescribed metformin 850mg twice daily for at least 4 weeks prior to ovarian stimulation till oocyte retrieval.
Intervention Type
Drug
Intervention Name(s)
Placebo pretreatment before ovarian stimulation
Other Intervention Name(s)
Placebo before ovarian stimulation
Intervention Description
The enrolled patients will be prescribed placebo 850mg twice daily for at least 4 weeks prior to ovarian stimulation till oocyte retrieval.
Intervention Type
Drug
Intervention Name(s)
Metformin pretreatment before endometrial preparation for frozen embryo transfer
Other Intervention Name(s)
Metformin before endometrial preparation
Intervention Description
After oocyte retrieval, the enrolled patients will be prescribed metformin 850mg twice daily for at least 4 weeks before endometrial preparation for frozen embryo transfer and till the establishment of clinical pregnancy (7-8 weeks gestation) after the first frozen embryo transfer.
Intervention Type
Drug
Intervention Name(s)
Placebo pretreatment before endometrial preparation for frozen embryo transfer
Other Intervention Name(s)
Placebo before endometrial preparation
Intervention Description
After oocyte retrieval, the enrolled patients will be prescribed placebo 850mg twice daily for at least 4 weeks 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 Measure Information:
Title
healthy live birth
Description
defined as a singleton live birth at ≥37 weeks, with infant birth weight between 2500 and 4000g and without a major congenital anomaly.
Time Frame
From the date of randomization until delivery after the first embryo transfer, up to 16 months
Secondary Outcome Measure Information:
Title
Change in BMI
Description
change in body mass index (BMI) from baseline to the establishment of clinical pregnancy.
Time Frame
From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks
Title
Change in fasting glucose level
Description
change in fasting glucose level from baseline to the establishment of clinical pregnancy.
Time Frame
From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks
Title
Change in fasting insulin level
Description
change in fasting insulin level from baseline to the establishment of clinical pregnancy.
Time Frame
From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks
Title
Change in 2-h levels of glucose after 75-g OGTT
Description
change in 2-h levels of glucose after 75-g OGTT from baseline to the establishment of clinical pregnancy.
Time Frame
From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks
Title
Change in 2-h levels of insulin after 75-g OGTT
Description
change in 2-h levels of insulin after 75-g OGTT from baseline to the establishment of clinical pregnancy.
Time Frame
From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks
Title
Days of ovarian stimulation
Description
the duration of ovarian stimulation by exogenous gonadotropin
Time Frame
From the date of randomization until the day of oocyte retrieved, up to 12 weeks
Title
Total dose of gonadotropins
Description
the total dose of exogenous gonadotropin used during ovarian stimulation
Time Frame
From the date of randomization until the day of oocyte retrieved, up to 12 weeks
Title
Peak estradiol level
Description
the estradiol level on the day of hCG trigger
Time Frame
From the date of randomization until the day of oocyte retrieved, up to 12 weeks
Title
Number of oocyte retrieved
Description
the number of oocyte retrieved
Time Frame
From the date of randomization until the day of oocyte retrieved, up to 12 weeks
Title
Number of good-score embryos
Description
the number of good-score embryos
Time Frame
From the date of randomization until the third day after oocyte retrieval, up to 12 weeks
Title
Number of euploid embryos
Description
the number of euploid embryos
Time Frame
From the date of randomization until the initiation of endometrial preparation for frozen embryo transfer, up to 20 weeks
Title
OHSS
Description
ovarian hyperstimulation syndrome was defined according to the Golan criteria
Time Frame
From the day of oocyte retrieved until the initiation of endometrial preparation for the first frozen embryo transfer, up to 8 weeks
Title
Clinical pregnancy
Description
defined as the ultrasound confirmation of at least one intrauterine gestational sac
Time Frame
30-35 days after the first frozen embryo transfer
Title
Singleton or twin pregnancy
Description
the number of intrauterine gestational sacs
Time Frame
30-35 days after the first frozen embryo transfer
Title
Pregnancy loss
Description
defined as pregnancies that eventuate in a spontaneous abortion or therapeutic abortion that occurred throughout pregnancy.
Time Frame
From the date of confirmation of pregnancy until the date of pregnancy loss, up to 9 months
Title
Live birth
Description
defined as the delivery of any neonate with signs of life at ≥ 28 weeks of gestation
Time Frame
From the date of randomization until delivery after the first embryo transfer, up to 16 months
Title
Incidences of obstetric and neonatal complications
Description
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.
Time Frame
From the establishment of clinically recognized pregnancy until six weeks after delivery after the first embryo transfer, up to 11 months
Title
Gestational weight gain
Description
maternal weight gain during pregnancy
Time Frame
at delivery
Title
Birth weight
Description
birth weight of the newborn at delivery
Time Frame
at delivery
Title
LGA
Description
defined as the birthweight above the 90th percentile for gestational age based on a sex-specific reference
Time Frame
at delivery
Title
SGA
Description
defined as the birthweight below the 10th percentile for gestational age based on a sex-specific reference
Time Frame
at delivery
Title
LBW
Description
the infant born weighing less than 2500g
Time Frame
at delivery
Title
Macrosomia
Description
the infant born weighing larger than 4000g
Time Frame
at delivery
Title
Adverse events
Description
adverse event (AE) and serious adverse event (SAE)
Time Frame
From the date of randomization until six weeks after delivery after the first embryo transfer, up to 18 months
Title
Cumulative live birth
Description
define as women achieving live birth after all the cycles of embryo transfer per oocyte retrieval that performed within one year after randomization.
Time Frame
From the date of randomization until delivery, up to 28 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zi-Jiang Chen, Professor
Phone
+0086 531 85651190
Email
chenzijiang@vip.163.com
Facility Information:
Facility Name
Shandong University
City
Jinan
State/Province
Shandong
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Yes
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Effect of Metformin on Healthy Live Birth in Women With Prediabetes
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