A Multicenter, Prospective, Randomized Study to Assess the Effect of Metformin Supplementation on IVF Outcome and Intrafollicular Environment in Patients With Polycystic Ovarian Syndrome Undergoing In Vitro Fertilization/Embryo Transfer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Number of mature(MII) oocyte
研究概览
简要总结
This study was performed to investigate the effects of metformin on controlled ovarian stimulation (COS), in vitro fertilization (IVF) outcomes, pregnancy outcomes, and comparison of serum and follicular fluid cytokines and hormones in patients with polycystic ovary syndrome (PCOS) undergoing IVF using gonadotropin-releasing hormone(GnRH) antagonist protocol.
详细描述
Polycystic ovary syndrome is the common cause of the female infertility that features insulin resistance and hyperinsulinemia participate in the reproductive as well as metabolic disturbances.
In many studies, metformin treatment reduces androgen levels and attenuates hyperinsulinemia in women with PCOS. This favorable effect on insulin and androgens levels, justifies the use of metformin in reproductive disturbances in PCOS women. Metformin treatment was shown to diminish ovarian androgen secretion, while lowering insulin levels in women with PCOS.
In women with PCOS, metformin treatment may increase ovulation, improve menstrual cyclicity, and reduce seum androgen levels. Metformin has direct effects on the ovary and also reduces the level of insulin that act upon the ovary. It has been indicated that metformin has direct, insulin-independent actions on theca cell steroidogenesis, because in human ovarian theca-like tumor cells, metformin suppressed androstenedione production. Metformin also exert a direct effect on granulosa cells and subsequent reduction of steroid production.
Metformin was shown to improve endothelium dependent vasodilation in insulin resistant patients and potentially protect against atherogenesis and cardiovascular disease.
Considering gonadotropin ovulation induction or IVF in women with PCOS, metformin coadministration improves the pregnancy outcome and reduces the risk of ovarian hyperstimulation syndrome. Metformin therapy throughout pregnancy can reduce the risk of early miscarriage or the incidence of gestational diabetes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •PCOS diagnostic criteria
- •2003 American Society for Reproductive Medicine(ARSM)/European Society of Human Reproduction and Embryology(ESHRE) consensus meeting guideline
- •include two out of three
- •Oligo - or anovulation
- •Clinical or/and biochemical hyperandrogenism
- •Polycystic ovaries on ultrasound, exclusion of other etiologies( ≥ 12 follicles(2-9 mm diameter) in each ovary or ovarian volume(0.5 x length x width x thickness) ≥ 10cm3)
- •Anatomical normal uterus
- •Normal level of thyroid hormone
排除标准
- •Severe endometriosis(stageIII, IV)
- •Endometrial thickness less than 7mm in late follicular phase
- •Severe male infertility factor, non-obstructive azoospermia
- •History of ectopic pregnancy or abortion over the last 3 months
- •Unexplained abnormal uterine bleeding
- •Congenital adrenal hyperplasia
- •Androgen secreting tumor
- •Cushing syndrome
- •Concurrent administration of metformin, ovulation induction drugs, oral contraceptives within previous 3 months
- •Chronic disease(liver, kidney, severe heart failure, DM)
- •Any pathology of genital tract
- •History of alcohol abuse
- •Refuse of study participate consent
研究组 & 干预措施
Placebo
Placebo(identical in appearance to metformin), every 12 hours, from the first day of oral contraceptive pills taken to the day of oocyte retrieval
干预措施: Metformin (Drug)
Metformin
Metformin 500mg tablet by mouth, every 12 hours, from the first day of oral contraceptive pills taken to the day of oocyte retrieval
干预措施: Metformin (Drug)
结局指标
主要结局
Number of mature(MII) oocyte
时间窗: Day1(from the day of oocyte retrieval to fertilization confirmation)
using polarized light microscopy
次要结局
- Miscarriage rate in %(Pregnancy test was carried out at 11 days after embryo transfer and was classified as positive when the serum beta-human chorionic gonadotropin(hCG) level was over 5 IU/L. Than follow up to 20 weeks of gestation.)
- Total duration of FSH used(day)(average of 10 days, From the day of stimulation start with FSH to the day of oocyte retrieval)
- Number of frozen 2 pronucleus(2PN) embryos(Day1((from the day of oocyte retrieval to fertilization confirmation))
- Clinical pregnancy rate in %(Pregnancy test was carried out at 11 days after embryo transfer and was classified as positive when the serum beta-human chorionic gonadotropin(hCG) level was over 5 IU/L. Than follow up to 12 weeks of gestation.)
- Serum TNF-α level in pg/ml and serum Adiponectin level in pg/ml and serum Interleukin-6 level in pg/ml and serum AMH level in pg/ml and serum Testosterone level in pg/ml and serum Estradiol level in pg/ml(Day 1)
- Total dose of follicle-stimulating hormone(FSH) used(IU)(average of 10 days, From the day of stimulation start with FSH to the day of oocyte retrieval)
- Number of oocytes retrieved(Day1(the day of oocyte retrieval))
- Follicular fluid Tumor necrosis factor(TNF)-α level in pg/ml and follicular fluid Adiponectin level in pg/ml and follicular fluid Interleukin-6 level in pg/ml and follicular fluid Anti-mullerian hormone(AMH) level in pg/ml(Day 1)
研究者
Chung-Hoon Kim
Asan Medical Center
Asan Medical Center