MetforminMELT-PreDMNCT06064669
Effect of Metformin on Healthy Live Birth in Women With Prediabetes
A study testing Metformin pretreatment before ovarian stimulation and Metformin pretreatment before endometrial preparation for frozen embryo transfer in people with Metformin and Prediabetes, run by Shandong University at 1 site in China.
Trial summary
To evaluate the efficacy and safety of metformin pretreatment on reproductive outcomes in infertile women with prediabetes. Read more about this study
- Who is it for?
- Ages 20 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Metformin, Prediabetes, In-Vitro Fertilization
- What is being tested?
- Metformin pretreatment before ovarian stimulation and Metformin pretreatment before endometrial preparation for frozen embryo transfer
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 988 participants
- Where
- 1 siteChina
- Study dates
- 22 Feb 2024to 31 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Shandong University
Jinan, Shandong
Zi-Jiang Chen, Professor, +0086 531 85651190, chenzijiang@vip.163.com
Daimin Wei, Professor, +0086 531 86561172, sdweidaimin@163.com
About this study
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
To evaluate the efficacy and safety of metformin pretreatment on reproductive outcomes in infertile women with prediabetes.
Read the 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.
- Conditions
- Metformin, Prediabetes, In-Vitro Fertilization
- Being tested
- 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
- Medical subject headings
- Prediabetic State
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin pretreatment before ovarian stimulationDrug
Also called Metformin 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 stimulationDrug
Also called Placebo 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 transferDrug
Also called Metformin before endometrial preparation
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 transferDrug
Also called Placebo before endometrial preparation
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.
| Study group | Role | What they receive |
|---|---|---|
| Metformin-Metformin Group | Experimental | 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. Receives: Drug: Metformin pretreatment before ovarian stimulation; Drug: Metformin pretreatment before endometrial preparation for frozen embryo transfer |
| Metformin-Placebo Group | Experimental | 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. Receives: Drug: Metformin pretreatment before ovarian stimulation; Drug: Placebo pretreatment before endometrial preparation for frozen embryo transfer |
| Placebo-Metformin Group | Experimental | 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. Receives: Drug: Placebo pretreatment before ovarian stimulation; Drug: Metformin pretreatment before endometrial preparation for frozen embryo transfer |
| Placebo-Placebo Group | Experimental | 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. Receives: Drug: Placebo pretreatment before ovarian stimulation; Drug: Placebo pretreatment before endometrial preparation for frozen embryo transfer |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From the date of randomization until delivery after the first embryo transfer, up to 16 months
Secondary outcomes (25)
Change in BMI
change in body mass index (BMI) from baseline to the establishment of clinical pregnancy.
Measured: 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
change in fasting glucose level from baseline to the establishment of clinical pregnancy.
Measured: 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
change in fasting insulin level from baseline to the establishment of clinical pregnancy.
Measured: 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
change in 2-h levels of glucose after 75-g OGTT from baseline to the establishment of clinical pregnancy.
Measured: 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
change in 2-h levels of insulin after 75-g OGTT from baseline to the establishment of clinical pregnancy.
Measured: From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks
Days of ovarian stimulation
the duration of ovarian stimulation by exogenous gonadotropin
Measured: From the date of randomization until the day of oocyte retrieved, up to 12 weeks
Total dose of gonadotropins
the total dose of exogenous gonadotropin used during ovarian stimulation
Measured: From the date of randomization until the day of oocyte retrieved, up to 12 weeks
Peak estradiol level
the estradiol level on the day of hCG trigger
Measured: From the date of randomization until the day of oocyte retrieved, up to 12 weeks
Number of oocyte retrieved
the number of oocyte retrieved
Measured: From the date of randomization until the day of oocyte retrieved, up to 12 weeks
Number of good-score embryos
the number of good-score embryos
Measured: From the date of randomization until the third day after oocyte retrieval, up to 12 weeks
Number of euploid embryos
the number of euploid embryos
Measured: From the date of randomization until the initiation of endometrial preparation for frozen embryo transfer, up to 20 weeks
OHSS
ovarian hyperstimulation syndrome was defined according to the Golan criteria
Measured: From the day of oocyte retrieved until the initiation of endometrial preparation for the first frozen embryo transfer, up to 8 weeks
Clinical pregnancy
defined as the ultrasound confirmation of at least one intrauterine gestational sac
Measured: 30-35 days after the first frozen embryo transfer
Singleton or twin pregnancy
the number of intrauterine gestational sacs
Measured: 30-35 days after the first frozen embryo transfer
Pregnancy loss
defined as pregnancies that eventuate in a spontaneous abortion or therapeutic abortion that occurred throughout pregnancy.
Measured: From the date of confirmation of pregnancy until the date of pregnancy loss, up to 9 months
Live birth
defined as the delivery of any neonate with signs of life at ≥ 28 weeks of gestation
Measured: From the date of randomization until delivery after the first embryo transfer, up to 16 months
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.
Measured: From the establishment of clinically recognized pregnancy until six weeks after delivery after the first embryo transfer, up to 11 months
Gestational weight gain
maternal weight gain during pregnancy
Measured: at delivery
Birth weight
birth weight of the newborn at delivery
Measured: at delivery
LGA
defined as the birthweight above the 90th percentile for gestational age based on a sex-specific reference
Measured: at delivery
SGA
defined as the birthweight below the 10th percentile for gestational age based on a sex-specific reference
Measured: at delivery
LBW
the infant born weighing less than 2500g
Measured: at delivery
Macrosomia
the infant born weighing larger than 4000g
Measured: at delivery
Adverse events
adverse event (AE) and serious adverse event (SAE)
Measured: From the date of randomization until six weeks after delivery after the first embryo transfer, up to 18 months
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.
Measured: From the date of randomization until delivery, up to 28 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2023
- Study start22 Feb 2024
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (66)Papers the sponsor has linked to this study.
- Other trials for MetforminStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 988 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shandong University
- Sponsor type
- University, hospital or other
- Collaborators
- Ren Ji Hospital of Shanghai Jiao Tong University, Women's Hospital School Of Medicine Zhejiang University, Shengjing Hospital, Nanjing Medical University, General Hospital of Ningxia Medical University, West China Second University Hospital, Henan Provincial Maternal and Child Health Care Hospital, Qingdao women's and children's Hospital
- Responsible party
- Principal investigator, Chen Zi-Jiang, Shandong University
- Investigators
- Zi-Jiang Chen, Professor, Principal investigator, Shandong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06064669
- Sponsor's protocol ID
- MELT-PreDM
- Acronym
- MELT-PreDM
- Status last verified
- May 2024
- First submitted
- 19 Sep 2023
- Last updated
- 29 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified participant data
Publications
Wei Y, Xu Q, Yang H, Yang Y, Wang L, Chen H, Anderson C, Liu X, Song G, Li Q, Wang Q, Shen H, Zhang Y, Yan D, Peng Z, He Y, Wang Y, Zhang Y, Zhang H, Ma X. Preconception diabetes mellitus and adverse pregnancy outcomes in over 6.4 million women: A population-based cohort study in China. PLoS Med. 2019 Oct 1;16(10):e1002926. doi: 10.1371/journal.pmed.1002926. eCollection 2019 Oct.
PubMed 31574092Macintosh MC, Fleming KM, Bailey JA, Doyle P, Modder J, Acolet D, Golightly S, Miller A. Perinatal mortality and congenital anomalies in babies of women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based study. BMJ. 2006 Jul 22;333(7560):177. doi: 10.1136/bmj.38856.692986.AE. Epub 2006 Jun 16.
PubMed 16782722Egan AM, Dow ML, Vella A. A Review of the Pathophysiology and Management of Diabetes in Pregnancy. Mayo Clin Proc. 2020 Dec;95(12):2734-2746. doi: 10.1016/j.mayocp.2020.02.019. Epub 2020 Jul 28.
PubMed 32736942Bianco ME, Josefson JL. Hyperglycemia During Pregnancy and Long-Term Offspring Outcomes. Curr Diab Rep. 2019 Nov 21;19(12):143. doi: 10.1007/s11892-019-1267-6.
PubMed 31754898Farrar D, Simmonds M, Bryant M, Sheldon TA, Tuffnell D, Golder S, Dunne F, Lawlor DA. Hyperglycaemia and risk of adverse perinatal outcomes: systematic review and meta-analysis. BMJ. 2016 Sep 13;354:i4694. doi: 10.1136/bmj.i4694.
PubMed 27624087HAPO Study Cooperative Research Group; Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, Hadden DR, McCance DR, Hod M, McIntyre HD, Oats JJ, Persson B, Rogers MS, Sacks DA. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008 May 8;358(19):1991-2002. doi: 10.1056/NEJMoa0707943.
PubMed 18463375Armengaud JB, Ma RCW, Siddeek B, Visser GHA, Simeoni U. Offspring of mothers with hyperglycaemia in pregnancy: The short term and long-term impact. What is new? Diabetes Res Clin Pract. 2018 Nov;145:155-166. doi: 10.1016/j.diabres.2018.07.039. Epub 2018 Aug 6.
PubMed 30092235Kitzmiller JL, Buchanan TA, Kjos S, Combs CA, Ratner RE. Pre-conception care of diabetes, congenital malformations, and spontaneous abortions. Diabetes Care. 1996 May;19(5):514-41. doi: 10.2337/diacare.19.5.514. No abstract available.
PubMed 8732721Correa A, Gilboa SM, Besser LM, Botto LD, Moore CA, Hobbs CA, Cleves MA, Riehle-Colarusso TJ, Waller DK, Reece EA. Diabetes mellitus and birth defects. Am J Obstet Gynecol. 2008 Sep;199(3):237.e1-9. doi: 10.1016/j.ajog.2008.06.028. Epub 2008 Jul 31.
PubMed 18674752Faerch K, Vaag A, Holst JJ, Hansen T, Jorgensen T, Borch-Johnsen K. Natural history of insulin sensitivity and insulin secretion in the progression from normal glucose tolerance to impaired fasting glycemia and impaired glucose tolerance: the Inter99 study. Diabetes Care. 2009 Mar;32(3):439-44. doi: 10.2337/dc08-1195. Epub 2008 Dec 3.
PubMed 19056613Li R, Wu J, He J, Wang Y, Liu X, Chen X, Tong C, Ding Y, Su Y, Chen W, Zhang C, Gao R. Mice endometrium receptivity in early pregnancy is impaired by maternal hyperinsulinemia. Mol Med Rep. 2017 May;15(5):2503-2510. doi: 10.3892/mmr.2017.6322. Epub 2017 Mar 14.
PubMed 28447735Chang EM, Han JE, Seok HH, Lee DR, Yoon TK, Lee WS. Insulin resistance does not affect early embryo development but lowers implantation rate in in vitro maturation-in vitro fertilization-embryo transfer cycle. Clin Endocrinol (Oxf). 2013 Jul;79(1):93-9. doi: 10.1111/cen.12099. Epub 2013 Apr 19.
PubMed 23176069Via Y Rada R, Daniel N, Archilla C, Frambourg A, Jouneau L, Jaszczyszyn Y, Charpigny G, Duranthon V, Calderari S. Identification of the Inner Cell Mass and the Trophectoderm Responses after an In Vitro Exposure to Glucose and Insulin during the Preimplantation Period in the Rabbit Embryo. Cells. 2022 Nov 25;11(23):3766. doi: 10.3390/cells11233766.
PubMed 36497026Jungheim ES, Moley KH. The impact of type 1 and type 2 diabetes mellitus on the oocyte and the preimplantation embryo. Semin Reprod Med. 2008 Mar;26(2):186-95. doi: 10.1055/s-2008-1042957.
PubMed 18302110Catalano PM, Shankar K. Obesity and pregnancy: mechanisms of short term and long term adverse consequences for mother and child. BMJ. 2017 Feb 8;356:j1. doi: 10.1136/bmj.j1.
PubMed 28179267
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06064669
- Acronym / sponsor ID
- MELT-PreDM / MELT-PreDM
- Conditions
- Metformin, Prediabetes, In-Vitro Fertilization
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 988 participants (estimated)
- Lead sponsor
- Shandong UniversityUniversity, hospital or other
- Collaborators
- Ren Ji Hospital of Shanghai Jiao Tong University, Women's Hospital School Of Medicine Zhejiang University, Shengjing Hospital, Nanjing Medical University, General Hospital of Ningxia Medical University, West China Second University Hospital, Henan Provincial Maternal and Child Health Care Hospital, Qingdao women's and children's Hospital
- Study start
- 22 Feb 2024 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 3 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Metformin-Metformin Group | Experimental | Drug: Metformin pretreatment before ovarian stimulation, Drug: Metformin pretreatment before endometrial preparation for frozen embryo transferMetformin 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-Placebo Group | Experimental | Drug: Metformin pretreatment before ovarian stimulation, Drug: Placebo pretreatment before endometrial preparation for frozen embryo transferMetformin 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-Metformin Group | Experimental | Drug: Placebo pretreatment before ovarian stimulation, Drug: Metformin pretreatment before endometrial preparation for frozen embryo transferPlacebo 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-Placebo Group | Experimental | Drug: Placebo pretreatment before ovarian stimulation, Drug: Placebo pretreatment before endometrial preparation for frozen embryo transferPlacebo 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. |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin pretreatment before ovarian stimulationAlso: Metformin before ovarian stimulationThe enrolled patients will be prescribed metformin 850mg twice daily for at least 4 weeks prior to ovarian stimulation till oocyte retrieval. | Drug | Metformin-Metformin Group, Metformin-Placebo Group |
| Placebo pretreatment before ovarian stimulationAlso: Placebo before ovarian stimulationThe enrolled patients will be prescribed placebo 850mg twice daily for at least 4 weeks prior to ovarian stimulation till oocyte retrieval. | Drug | Placebo-Metformin Group, Placebo-Placebo Group |
| Metformin pretreatment before endometrial preparation for frozen embryo transferAlso: Metformin before endometrial preparationAfter 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. | Drug | Metformin-Metformin Group, Placebo-Metformin Group |
| Placebo pretreatment before endometrial preparation for frozen embryo transferAlso: Placebo before endometrial preparationAfter 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. | Drug | Metformin-Placebo Group, Placebo-Placebo Group |
Primary outcome
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.
25 secondary outcomes
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 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 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 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 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
Days of ovarian stimulation
Time frame: 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
Peak estradiol level
Time frame: 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
Number of good-score embryos
Time frame: 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
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
Clinical pregnancy
Time frame: 30-35 days after the first frozen embryo transfer
Singleton or twin pregnancy
Time frame: 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
Live birth
Time frame: 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
Gestational weight gain
Time frame: at delivery
Birth weight
Time frame: at delivery
LGA
Time frame: at delivery
SGA
Time frame: at delivery
LBW
Time frame: at delivery
Macrosomia
Time frame: 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
Cumulative live birth
Time frame: From the date of randomization until delivery, up to 28 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2024.
- Background: PubMed 31574092Wei Y, Xu Q, Yang H, Yang Y, Wang L, Chen H, Anderson C, Liu X, Song G, Li Q, Wang Q, Shen H, Zhang Y, Yan D, Peng Z, He Y, Wang Y, Zhang Y, Zhang H, Ma X. Preconception diabetes mellitus and adverse pregnancy outcomes in over 6.4 million women: A population-based cohort study in China. PLoS Med. 2019 Oct 1;16(10):e1002926. doi: 10.1371/journal.pmed.1002926. eCollection 2019 Oct.
- Background: PubMed 16782722Macintosh MC, Fleming KM, Bailey JA, Doyle P, Modder J, Acolet D, Golightly S, Miller A. Perinatal mortality and congenital anomalies in babies of women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based study. BMJ. 2006 Jul 22;333(7560):177. doi: 10.1136/bmj.38856.692986.AE. Epub 2006 Jun 16.
- Background: PubMed 32736942Egan AM, Dow ML, Vella A. A Review of the Pathophysiology and Management of Diabetes in Pregnancy. Mayo Clin Proc. 2020 Dec;95(12):2734-2746. doi: 10.1016/j.mayocp.2020.02.019. Epub 2020 Jul 28.
- Background: PubMed 31754898Bianco ME, Josefson JL. Hyperglycemia During Pregnancy and Long-Term Offspring Outcomes. Curr Diab Rep. 2019 Nov 21;19(12):143. doi: 10.1007/s11892-019-1267-6.
- Background: PubMed 27624087Farrar D, Simmonds M, Bryant M, Sheldon TA, Tuffnell D, Golder S, Dunne F, Lawlor DA. Hyperglycaemia and risk of adverse perinatal outcomes: systematic review and meta-analysis. BMJ. 2016 Sep 13;354:i4694. doi: 10.1136/bmj.i4694.
- Background: PubMed 18463375HAPO Study Cooperative Research Group; Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, Hadden DR, McCance DR, Hod M, McIntyre HD, Oats JJ, Persson B, Rogers MS, Sacks DA. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008 May 8;358(19):1991-2002. doi: 10.1056/NEJMoa0707943.
- Background: PubMed 30092235Armengaud JB, Ma RCW, Siddeek B, Visser GHA, Simeoni U. Offspring of mothers with hyperglycaemia in pregnancy: The short term and long-term impact. What is new? Diabetes Res Clin Pract. 2018 Nov;145:155-166. doi: 10.1016/j.diabres.2018.07.039. Epub 2018 Aug 6.
- Background: PubMed 8732721Kitzmiller JL, Buchanan TA, Kjos S, Combs CA, Ratner RE. Pre-conception care of diabetes, congenital malformations, and spontaneous abortions. Diabetes Care. 1996 May;19(5):514-41. doi: 10.2337/diacare.19.5.514. No abstract available.
- Background: PubMed 18674752Correa A, Gilboa SM, Besser LM, Botto LD, Moore CA, Hobbs CA, Cleves MA, Riehle-Colarusso TJ, Waller DK, Reece EA. Diabetes mellitus and birth defects. Am J Obstet Gynecol. 2008 Sep;199(3):237.e1-9. doi: 10.1016/j.ajog.2008.06.028. Epub 2008 Jul 31.
- Background: PubMed 19056613Faerch K, Vaag A, Holst JJ, Hansen T, Jorgensen T, Borch-Johnsen K. Natural history of insulin sensitivity and insulin secretion in the progression from normal glucose tolerance to impaired fasting glycemia and impaired glucose tolerance: the Inter99 study. Diabetes Care. 2009 Mar;32(3):439-44. doi: 10.2337/dc08-1195. Epub 2008 Dec 3.
- Background: PubMed 28447735Li R, Wu J, He J, Wang Y, Liu X, Chen X, Tong C, Ding Y, Su Y, Chen W, Zhang C, Gao R. Mice endometrium receptivity in early pregnancy is impaired by maternal hyperinsulinemia. Mol Med Rep. 2017 May;15(5):2503-2510. doi: 10.3892/mmr.2017.6322. Epub 2017 Mar 14.
- Background: PubMed 23176069Chang EM, Han JE, Seok HH, Lee DR, Yoon TK, Lee WS. Insulin resistance does not affect early embryo development but lowers implantation rate in in vitro maturation-in vitro fertilization-embryo transfer cycle. Clin Endocrinol (Oxf). 2013 Jul;79(1):93-9. doi: 10.1111/cen.12099. Epub 2013 Apr 19.
- Individual participant dataSharing planned: Yes. Deidentified participant data
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Zi-Jiang Chen, Professor principal investigator
Shandong University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Metformin pretreatment before ovarian stimulation and Metformin pretreatment before endometrial preparation for frozen embryo transfer in people with Metformin and Prediabetes, run by Shandong University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zi-Jiang Chen, Professor (+0086 531 85651190, chenzijiang@vip.163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
healthy live birth (time frame: From the date of randomization until delivery after the first embryo transfer, up to 16 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06064669, which also lists 66 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2024.