Effect of Metformin on Healthy Live Birth in Women With Prediabetes

Prediabetes Clinical Trial

— 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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06064669
• Other study ID #: MELT-PreDM
• Status: Not yet recruiting
• Phase: N/A
• Start date: October 1, 2023
• Est. completion date: December 31, 2027

Study information

• Verified date: September 2023
• Source: Shandong University
• Contact: Zi-Jiang Chen, Professor
• Phone: +0086 531 85651190
• Email: chenzijiang[@]vip.163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 988
• Est. completion date: December 31, 2027
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years to 40 Years

Eligibility

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, a-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.

Related Conditions & MeSH terms

• Glucose Intolerance
• In-Vitro Fertilization
• Metformin
• Prediabetes
• Prediabetic State

Intervention

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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
China	Shandong University	Jinan	Shandong

Sponsors (9)

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

Country where clinical trial is conducted

China, 

References & Publications (66)

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* Note: There are 66 references in all — Click here to view all references

Outcome

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