Efficacy of Long- Versus Short-term Metformin Protocol in Infertile Anovulatory PCOS Patients
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Pregnancy rate
研究概览
简要总结
Metformin, an oral biguanide administrated for treating type-2 diabetes mellitus, is a safe and effective drug recently experimented also in patients with polycystic ovary syndrome (PCOS). The administration of metformin induces ovulatory cycles in CC-resistant or -nonresistant patients with PCOS, and improves the ovulation rate as an additional treatment in women who received CC.
To date, it is unknown the best protocol for metformin administration. In particular, it is not known how long patients who ovulate under metformin should continue treatment before switching to second-line ovulation induction therapy. In this regard, in a recent study by the Kaplan-Meier survival analysis we demonstrated that the first pregnancy occurred late after metformin with an estimated median of seven months.
Based on these considerations, the aim of the present study will be to evaluate the clinical efficacy of metformin according to its duration of administration in infertile PCOS patients ovulating under treatment.
详细描述
Infertile PCOS patients having three ovulatory cycles under metformin, administered using tailored protocol, will be enrolled and randomized in two groups (groups A and B). Patients of group A will continue metformin administration for further three cycles followed by six months of progestogens cyclically administered, whereas patients of group B will continue metformin therapy for further nine cycles.
All patients eligible will undergo baseline assessment consisting of anthropometric, hormonal, and ultrasonographic evaluations. During the study, the clinical and reproductive outcomes, and the adverse experience will be evaluated in each patient.
Data will be analyzed using the intention-to-treat principle and a P value of 0.05 or less will be considered significant. Continuous variables will be analyzed with the unpaired t test and general linear model for repeated measures analysis with Bonferroni test for the post-hoc analysis as required. For categorical variables, the Pearson chi-square and Fisher's exact tests will be used. Cumulative pregnancy rate, our primary end-point, will be calculated by the Kaplan-Maier method, and the differences between the two groups will be assessed with the log-rank test. Cox proportional-hazards model will be used to calculate the hazard ratio for new pregnancy in both groups.
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
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Polycystic ovary syndrome (using NIH criteria)
- •Anovulatory infertility (using WHO criteria)
- •Ovulatory cycles under metformin (three cycles)
排除标准
- •Age <18 or >35 years
- •Severe obesity (BMI >35)
- •Neoplastic, metabolic, hepatic, and cardiovascular disorders or other concurrent medical illnesses
- •Hypothyroidism, hyperprolactinemia, Cushing's syndrome, and non-classical congenital adrenal hyperplasia
- •Current or previous (within the last six months) use of oral contraceptives, glucocorticoids, antiandrogens, antidiabetic and anti-obesity drugs or other hormonal drugsPrevious use of ovulation induction agents
- •Intention to start a diet or a specific program of physical activity
- •Organic pelvic diseases
- •Previous pelvic surgery
- •Suspected peritoneal factor infertility
- •Tubal or male factor infertility or sub-fertility
研究组 & 干预措施
Group A
Short protocol
干预措施: Metformin (Drug)
Group B
Long protocol
干预措施: Metformin (Drug)
结局指标
主要结局
Pregnancy rate
时间窗: 12 months
次要结局
- Ovulation rate Abortion rate Live-birth rate Adverse events(21 months)
研究者
Stefano Palomba
Associate Professor
University Magna Graecia