What is the Following Step to Improve Fertility in Infertile PCOS Patients Ovulating Under Clomiphene Citrate or Metformin? A Randomized Controlled Clinical Study.
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Pregnancy rate
研究概览
简要总结
Several data demonstrated that both clomiphene citrate (CC) and metformin are two safe and valid first-step options to induce ovulation in infertile anovulatory PCOS patients. Notwithstanding a high percentage of patients ovulate under treatment, only ~40% and 60% of subjects obtain a pregnancy after CC and metformin, respectively.
For these patients, controlled ovarian stimulation (COS) followed by intrauterine insemination (IUI) could be the next therapeutic step before assisted reproductive techniques since IUI improves significantly the fertility in couples with unexplained infertility. Furthermore, to date it is not defined if COS should be obtained using the same ovulatory agent (CC or metformin) or switching the treatment to gonadotropins.
In this view, the aim of the present study will be to evaluate the best management of infertile PCOS patients ovulating after CC or metformin.
详细描述
Infertile PCOS patients who ovulated under CC or metformin without pregnancy achievement will be enrolled and treated with three trials of COS plus IUI. All patients will be randomly allocated into two different groups (groups A and B). In group A, COS will be obtained using the same ovulatory agent (CC or metformin) employed in the previous ovulatory cycles, whereas in group B using gonadotropins in a low-dose step-up regimen.
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 and the will be analyzed also categorizing the patients according to ovulatory agent used for COS (CC or metformin).
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)
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 drugs
- •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
Continuing treatment
干预措施: Clomiphene citrate, metformin, highly purified urinary FSH (Drug)
Group B
Gonadotrophins
干预措施: Clomiphene citrate, metformin, highly purified urinary FSH (Drug)
结局指标
主要结局
Pregnancy rate
时间窗: one year
次要结局
- Ovulation rate Abortion rate Live-birth rate Adverse events(one year)
研究者
Stefano Palomba
Associate Professor
University Magna Graecia