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

September 26, 2023 updated by: Chen Zi-Jiang, Shandong University

Effect of Metformin on Healthy Live Birth After In-vitro Fertilization in Women With Prediabetes Mellitus: a Multicenter Double-blind Placebo Controlled Randomized Trial

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

988

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Shandong
      • Jinan, Shandong, China
        • Shandong University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Metformin pretreatment before ovarian stimulation
The enrolled patients will be prescribed metformin 850mg twice daily for at least 4 weeks prior to ovarian stimulation till oocyte retrieval.
Other Names:
  • Metformin before ovarian stimulation
Drug: Metformin pretreatment before endometrial preparation for frozen embryo transfer
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.
Other Names:
  • Metformin before endometrial preparation
Experimental: 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.
Drug: Metformin pretreatment before ovarian stimulation
The enrolled patients will be prescribed metformin 850mg twice daily for at least 4 weeks prior to ovarian stimulation till oocyte retrieval.
Other Names:
  • Metformin before ovarian stimulation
Drug: Placebo pretreatment before endometrial preparation for frozen embryo transfer
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.
Other Names:
  • Placebo before endometrial preparation
Experimental: 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.
Drug: Metformin pretreatment before endometrial preparation for frozen embryo transfer
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.
Other Names:
  • Metformin before endometrial preparation
Drug: Placebo pretreatment before ovarian stimulation
The enrolled patients will be prescribed placebo 850mg twice daily for at least 4 weeks prior to ovarian stimulation till oocyte retrieval.
Other Names:
  • Placebo before ovarian stimulation
Experimental: 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.
Drug: Placebo pretreatment before endometrial preparation for frozen embryo transfer
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.
Other Names:
  • Placebo before endometrial preparation
Drug: Placebo pretreatment before ovarian stimulation
The enrolled patients will be prescribed placebo 850mg twice daily for at least 4 weeks prior to ovarian stimulation till oocyte retrieval.
Other Names:
  • Placebo before ovarian stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
healthy live birth
Time Frame: 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.
From the date of randomization until delivery after the first embryo transfer, up to 16 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in BMI
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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.
From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks
Days of ovarian stimulation
Time Frame: From the date of randomization until the day of oocyte retrieved, up to 12 weeks
the duration of ovarian stimulation by exogenous gonadotropin
From the date of randomization until the day of oocyte retrieved, up to 12 weeks
Total dose of gonadotropins
Time Frame: 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
From the date of randomization until the day of oocyte retrieved, up to 12 weeks
Peak estradiol level
Time Frame: From the date of randomization until the day of oocyte retrieved, up to 12 weeks
the estradiol level on the day of hCG trigger
From the date of randomization until the day of oocyte retrieved, up to 12 weeks
Number of oocyte retrieved
Time Frame: From the date of randomization until the day of oocyte retrieved, up to 12 weeks
the number of oocyte retrieved
From the date of randomization until the day of oocyte retrieved, up to 12 weeks
Number of good-score embryos
Time Frame: From the date of randomization until the third day after oocyte retrieval, up to 12 weeks
the number of good-score embryos
From the date of randomization until the third day after oocyte retrieval, up to 12 weeks
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
the number of euploid embryos
From the date of randomization until the initiation of endometrial preparation for frozen embryo transfer, up to 20 weeks
OHSS
Time Frame: 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
From the day of oocyte retrieved until the initiation of endometrial preparation for the first frozen embryo transfer, up to 8 weeks
Clinical pregnancy
Time Frame: 30-35 days after the first frozen embryo transfer
defined as the ultrasound confirmation of at least one intrauterine gestational sac
30-35 days after the first frozen embryo transfer
Singleton or twin pregnancy
Time Frame: 30-35 days after the first frozen embryo transfer
the number of intrauterine gestational sacs
30-35 days after the first frozen embryo transfer
Pregnancy loss
Time Frame: 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.
From the date of confirmation of pregnancy until the date of pregnancy loss, up to 9 months
Live birth
Time Frame: 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
From the date of randomization until delivery after the first embryo transfer, up to 16 months
Incidences of obstetric and neonatal complications
Time Frame: 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.
From the establishment of clinically recognized pregnancy until six weeks after delivery after the first embryo transfer, up to 11 months
Gestational weight gain
Time Frame: at delivery
maternal weight gain during pregnancy
at delivery
Birth weight
Time Frame: at delivery
birth weight of the newborn at delivery
at delivery
LGA
Time Frame: at delivery
defined as the birthweight above the 90th percentile for gestational age based on a sex-specific reference
at delivery
SGA
Time Frame: at delivery
defined as the birthweight below the 10th percentile for gestational age based on a sex-specific reference
at delivery
LBW
Time Frame: at delivery
the infant born weighing less than 2500g
at delivery
Macrosomia
Time Frame: at delivery
the infant born weighing larger than 4000g
at delivery
Adverse events
Time Frame: 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)
From the date of randomization until six weeks after delivery after the first embryo transfer, up to 18 months
Cumulative live birth
Time Frame: 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.
From the date of randomization until delivery, up to 28 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shandong University

Collaborators

Shengjing Hospital
General Hospital of Ningxia Medical University
West China Second University Hospital
Women's Hospital of Nanjing Medical University
Maternal and Child Health Hospital of Henan Province
Ren Ji Hospital of Shanghai Jiao Tong University
Women's Hospital of Zhejiang University
Qingdao women's and children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2023

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

September 19, 2023

First Submitted That Met QC Criteria

September 26, 2023

First Posted (Actual)

October 3, 2023

Study Record Updates

Last Update Posted (Actual)

October 3, 2023

Last Update Submitted That Met QC Criteria

September 26, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MELT-PreDM

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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