Is Endometrial Withdrawal Bleeding Necessary Prior to Ovulation Induction With Clomiphene Citrate? A Randomized Controlled Trial and Feasibility Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 3
- 主要终点
- Time to pregnancy
研究概览
简要总结
Rationale:
There is some information suggesting that a progesterone-induced withdrawal bleeding before the start of ovulation induction in women suffering from oligo- or amenorrhea reduces pregnancy and live birth rate.
Objective:
To evaluate the effects of withholding progesterone-induced endometrial withdrawal bleeding before ovulation induction on the time to pregnancy and the ongoing pregnancy rate.
Study design:
Prospective multicenter randomized controlled feasibility study
Study population:
Women with oligomenorrhea or amenorrhea according to WHO classification category 2
Intervention:
Patients will be randomized to receive one of the following two treatments:
Stair step group: blind start ovulation induction (no progesterone induced withdrawal bleeding and stair step protocol in case of treatment failure.
Control: standard care; a progesterone induced withdrawal bleeding in case of no spontaneous menses before starting an ovulation induction cycle and in between anovulatory cycles.
Main study parameters/endpoints:
The primary endpoints are the time to pregnancy and ongoing pregnancy rate within a treatment horizon of 3 cycles. Secondary endpoints include time to ovulation, endometrial thickness, multiple pregnancy and the incidence of treatment failure.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
The number of site visits or physical examinations will not differ from accepted clinical practice.
详细描述
OBJECTIVES
Primary objective:
To demonstrate whether withholding progesterone induced endometrial shedding prior to ovulation induction improves the ongoing pregnancy rate per cycle compared to not withholding progesterone treatment and to demonstrate its impact on the time to pregnancy.
Secondary objectives:
To elucidate the impact of the two study protocols on time to ovulation, endometrial thickness, multiple follicle growth, multiple pregnancy and the incidence of treatment failure. Furthermore, in accordance to the proposed areas of focus addressed by feasibility studies [Bowen et al (2009)], the number of eligible patients, the number of protocol violations and the number of drop-outs will be recorded.
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 41 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •WHO classification category 2 PCOS or non-PCOS
- •Age between 18 - 41 years
- •Patent Fallopian tubes, proven by hysterosalpingography (HSG), a negative Chlamydia antibody titre (CAT) or diagnostic laparoscopy combined with tubal testing (DLS and TT), depending on the local protocol.
- •BMI < 40 kg/m2
排除标准
- •BMI > 40 kg/m2
- •Previous unsuccessful ovulation induction cycles with CC
- •Double-sided tubal pathology
- •Presence of ovarian cysts on ultrasound
- •Moderate - severe male infertility (TMSC < 3 million)
- •Grade III/IV endometriosis
- •Thrombosis
- •Severe liver disease
研究组 & 干预措施
Standard group
Intervention:Medroxyprogesterone acetate (Provera) 10 mg daily for 10 days will be used prior to starting ovulation induction with clomiphene citrate (CC) and between anovulatory cycles. On cycle day (CD) 3 CC 50 mg is administered daily for 5 days. Follicle growth will be monitored by ultrasound, starting from CD11. Anovulatory patients (defined as no follicle ≥ 14 mm) on CD20, will receive Provera 10mg daily for 10 days. The CC dosage will be increased in the next cycle. On CD3 patients will receive CC 100 mg daily for 5 days with ultrasounds performed from CD11 onwards. Anovulatory patients will receive Provera 10mg daily for 10 days. In the next cycle the CC dose will be increased to 150 mg, starting from CD3, daily for 5 days with ultrasounds starting from CD11-20.
干预措施: Medroxyprogesterone Acetate 10 MG (Drug)
Stair Step group
Intervention: Stair step protocol without medroxyprogesterone acetate 10 mg prior to ovulation induction with clomiphene citrate (CC), nor in between anovulatory cycles. After performing an ultrasound to check for the presence of cysts or any other abnormalities and a negative pregnancy test, patients will receive CC 50 mg daily for 5 days. Ultrasounds will be performed on CD11-14. If there is no response on CD14 (no follicle ≥ 14 mm), the dose of CC is immediately increased to 100 mg CC daily for 5 days and an ultrasound is performed 1 week following the last ultrasound. If there is no response, 150 mg CC daily is initiated immediately for 5 days and the ultrasound is repeated 1 week after the previous ultrasound.
干预措施: Stair step protocol without Medroxyprogesterone Acetate (Other)
结局指标
主要结局
Time to pregnancy
时间窗: duration of 1 cycle: 28-35 days, a maximum of 3 cycles will be performed (pregnancy test will be performed at the end of the cycle if there is no menstruation)
the time between obtaining informed consent and the presence of a positive pregnancy test after treatment
Ongoing pregnancy rate per cycle
时间窗: in case of pregnancy: 8 weeks after the start of each cycle, (maximum of 3 cycles, duration of 1 cycle: 28-35 days)
Ongoing pregnancy is defined as the presence of at least one intra uterine fetus with heartbeat at 8 weeks of gestation
次要结局
- Endometrial thickness on the last day of ultrasonography(maximum of 3 cycles (each 28-35 days))
- Time to ovulation(3 cycles of 28-35 days, calculated as 14 days before the start of menstruation or 14 days before a positive pregnancy test)
- The incidence of multiple follicle growth on the last day of ultrasonography(maximum of 3 cycles (each 28-35 days))
- The incidence of treatment failure(maximum of 3 cycles (each 28-35 days))
- The number of protocol violations(duration: maximum of 3 cycles (each 28-35 days))
- The number of eligible patients(Inclusion 16 months, follow-up 3 months.)
- The incidence of multiple pregnancy(in case of pregnancy: 8 weeks after the start of a treatment cycle (maximum of 3 cycles; each 28-35 days))