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

Sponsor
Shandong University (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT06064669
Collaborator
Ren Ji Hospital of Shanghai Jiao Tong University (Other), Women's Hospital of Zhejiang University (Other), Shengjing Hospital (Other), Women's Hospital of Nanjing Medical University (Other), General Hospital of Ningxia Medical University (Other), West China Second University Hospital (Other), Maternal and Child Health Hospital of Henan Province (Other), Qingdao women's and children's Hospital (Other)
988
Enrollment
1
Location
4
Arms
51
Anticipated Duration (Months)
19.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
  • Drug: Metformin pretreatment before ovarian stimulation
  • Drug: Placebo pretreatment before ovarian stimulation
  • Drug: Metformin pretreatment before endometrial preparation for frozen embryo transfer
  • Drug: Placebo pretreatment before endometrial preparation for frozen embryo transfer
 N/A

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 Design

Study Type:
Interventional
Anticipated Enrollment :
988 participants
Allocation:
Randomized
Intervention Model:
Factorial Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Anticipated Study Start Date :
Oct 1, 2023
Anticipated Primary Completion Date :
Dec 31, 2026
Anticipated Study Completion Date :
Dec 31, 2027

Arms and Interventions

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: 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

    • 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: 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 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

    • 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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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

    7. 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

    8. 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

    9. Number of oocyte retrieved [From the date of randomization until the day of oocyte retrieved, up to 12 weeks]

      the number of oocyte retrieved

    10. 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

    11. 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

    12. 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

    13. Clinical pregnancy [30-35 days after the first frozen embryo transfer]

      defined as the ultrasound confirmation of at least one intrauterine gestational sac

    14. Singleton or twin pregnancy [30-35 days after the first frozen embryo transfer]

      the number of intrauterine gestational sacs

    15. 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.

    16. 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

    17. 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.

    18. Gestational weight gain [at delivery]

      maternal weight gain during pregnancy

    19. Birth weight [at delivery]

      birth weight of the newborn at delivery

    20. LGA [at delivery]

      defined as the birthweight above the 90th percentile for gestational age based on a sex-specific reference

    21. SGA [at delivery]

      defined as the birthweight below the 10th percentile for gestational age based on a sex-specific reference

    22. LBW [at delivery]

      the infant born weighing less than 2500g

    23. Macrosomia [at delivery]

      the infant born weighing larger than 4000g

    24. 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)

    25. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years to 40 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    Yes
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Shandong University Jinan Shandong China

    Sponsors and Collaborators

    • Shandong University
    • 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

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Chen Zi-Jiang, Academician, Shandong University
    ClinicalTrials.gov Identifier:
    NCT06064669
    Other Study ID Numbers:
    • MELT-PreDM
    First Posted:
    Oct 3, 2023
    Last Update Posted:
    Oct 3, 2023
    Last Verified:
    Sep 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Prediabetic State
    Glucose Intolerance
    Metformin

    Study Results

    No Results Posted as of Oct 3, 2023