Effect of Metformin on Healthy Live Birth in Women With Prediabetes

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 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.
• Препарат 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.
• Препарат 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.

Первичные конечные точки

• healthy live birth [Срок оценки: From the date of randomization until delivery after the first embryo transfer, up to 16 months]

Вторичные конечные точки (12)

• Change in BMI [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks]
• Days of ovarian stimulation [Срок оценки: From the date of randomization until the day of oocyte retrieved, up to 12 weeks]
• Total dose of gonadotropins [Срок оценки: From the date of randomization until the day of oocyte retrieved, up to 12 weeks]
• Peak estradiol level [Срок оценки: From the date of randomization until the day of oocyte retrieved, up to 12 weeks]
• Number of oocyte retrieved [Срок оценки: From the date of randomization until the day of oocyte retrieved, up to 12 weeks]
• Number of good-score embryos [Срок оценки: From the date of randomization until the third day after oocyte retrieval, up to 12 weeks]
• Number of euploid embryos [Срок оценки: From the date of randomization until the initiation of endometrial preparation for frozen embryo transfer, up to 20 weeks]
• OHSS [Срок оценки: From the day of oocyte retrieved until the initiation of endometrial preparation for the first frozen embryo transfer, up to 8 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Факторный дизайн

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shandong University — Цзинань

Публикации

• 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. PMID 31574092
• Macintosh 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. PMID 16782722
• Egan 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. PMID 32736942
• Bianco 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. PMID 31754898
• Farrar 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. PMID 27624087
• HAPO 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. PMID 18463375
• Armengaud 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. PMID 30092235
• Kitzmiller 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. PMID 8732721

Идентификаторы

NCT: NCT06064669 · MELT-PreDM

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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