Clinical Effect of Follicular Preparation With Testosterone in Poor Ovarian Response: a Randomized Controlled Clinical Trial (TESTOPRIM)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 63
- 试验地点
- 2
- 主要终点
- Total number of mature oocytes obtained at follicular puncture.
研究概览
简要总结
Trial to determine the absolute and relative efficacy of two follicular preparation regimens with transdermal testosterone during the cycle (s) prior to the initiation of COS (controlled ovarian stimulation) in patients diagnosed with POR (poor ovarian response) for the increase in the number of mature oocytes recovered.
详细描述
POR is a challenge for reproductive medicine because of its impact on treatment outcomes and the lack of sufficiently proven therapeutic tools. According to recent publications based on retrospective studies of large registries, there is a correlation between the number of oocytes and LBR (live birth rate), so the investigators consider that variable mature oocytes are a reasonable compromise and a solid substitute for other outcome variables such as LBR or CPR (clinical pregnancy rate).
Regarding the duration of treatment, the investigators decided to include two groups of testosterone treatment (compared to the control group) with different duration. One will explore the role of testosterone in prolonged treatments (two full menstrual cycles). The other will test the pattern most commonly used in most studies, that is, testosterone in luteal phase of the previous cycle (about 10 days in short protocol with GnRH antagonist). In this way the investigators will establish an absolute comparison with the control group and relative between both treatment groups (long testosterone vs. short testosterone) to determine if / which of the two regimen (the two, only one or none) improves the number of mature oocytes recovered.
The product under investigation is testosterone gel, transdermal administration, 50 mg / single dose (Testim®, Ferring, Madrid, Spain). Regarding the dose, the investigators decided to keep the most used in the rest of studies (12.5 mg / day).
This study population will include only patients diagnosed with POR based on ESHRE Bologna criteria, in order to homogenize the population and allow comparisons with other studies in the future.
Regarding the dose, the investigators decided to keep the most used in the rest of studies (12.5 mg/day) which so far has been the only one proven effective. It is clearly possible that lower and more physiological doses are equally effective, but this yet has to be proven in well-designed studies. The gel is self-administered by the patients who are adequately instructed by a research nurse.
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
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Signed Informed consent prior to the completion of any procedure related to the clinical trial.
- •Female older than 18 years old at the time of randomization.
- •Prior diagnosis of poor ovarian response (POR) according to ESHRE Bologna criteria. Patients must meet at least 2 of the following:
- •Advanced maternal age (40 years or more) or any other risk factor for POR.
- •A previous POR (3 oocytes or less) with a conventional ovarian stimulation protocol.
- •Abnormal ovarian reserve test (RFA <5-7 or AMH 3.3-7.9 pmol / l).
排除标准
- •Presence of uterine malformations, corrected or not.
- •Presence of uterine pathology defined as submucous myomas or endometrial polyps, documented by transvaginal ultrasound.
- •Couples with severe male factor defined as REM <1 or azoospermia.
- •Hydrosalpinx unilateral or bilateral uncorrected.
- •Perimenopausal patients with irregular menstrual cycles.
- •Concurrent untreated endocrine disorders.
- •Patients who have participated in a clinical trial in a period of less than one month.
- •Known allergy to the drug.
- •Patients who have received androgen treatment within 3 months prior to inclusion in the study.
- •BMI> 35 kg / m2
研究组 & 干预措施
GROUP 1: Long testosterone
Application of testosterone in transdermal gel during the 2 cycles prior to initiation of controlled ovarian stimulation and until the onset of second menstruation (approximately 56 days). The COS begins the day after the last testosterone application.
干预措施: GROUP 1: Long testosterone (Drug)
GROUP 2: Short testosterone
Application of testosterone in transdermal gel begins on day 21 of menstrual cycle, from the luteal phase of the cycle prior to initiation of controlled ovarian stimulation and until menstruation (approximately 10 days). The COS begins the day after the last testosterone application.
干预措施: GROUP 2: Short testosterone (Drug)
GROUP 3: Control
The COS starts directly on the second day of the cycle without prior medication.
干预措施: GROUP 3: Control (Drug)
结局指标
主要结局
Total number of mature oocytes obtained at follicular puncture.
时间窗: 36 hours after induction of ovulation with recombinant HCG.
Determining whether a Follicular preparation with transdermal testosterone increases the number of mature oocytes retrieved in patients diagnosed with Poor Ovarian Response and which testosterone administration regimen is more effective for this purpose.
次要结局
- Initiation rate(Time E: prior to controlled ovarian stimulation (at the beginning of the third cycle after inclusion and randomization, approximately 56 days after Day 0))
- Number of days of stimulation duration(Time P (time of follicular puncture): 36 hours after the induction)
- Number of total follicles and greater than 16 mm(Time I (Day of induction): 10-12 days after controlled ovarian stimulation)
- Number of obtained embryos(6 days after ovarian puncture.)
- Number of antral follicles at the start of stimulation(Time E: prior to controlled ovarian stimulation (at the beginning of the third cycle after inclusion and randomization, approximately 56 days after Day 0))
- Fertilization rate(24 hours after the puncture)
- Rate of cycles that achieve embryo transfer(Time ET ( day of embryo transfer): 4-5 days after the stimulation)
- Number of cycles with supernumerary embryos to freeze(6 days after embryo transfer)
- Total dose of gonadotrophins used(Time I (Day of induction): 10-12 days after controlled ovarian stimulation)
- Cancellation rate due to lack of ovarian response(Time C: 10-12 days after controlled ovarian stimulation)
- Number of embryos transferred(Time ET (day of embryo transfer): 4-5 days after the stimulation)
- Ongoing pregnancy rate per cycle started and per transfer(70-75 days after embryo transfer)
- Clinical pregnancy rate per cycle started and per transfer(30-35 days after embryo transfer)
- Miscarriage rate(At 11-13 weeks of pregnancy, if there is no previous news of the patient (Trial completion time))
- Serum hormone levels(Day 0; Time I (day of induction): 10-12 days after controlled ovarian stimulation; and Time E (prior to controlled ovarian stimulation: at the beginning of the third cycle after inclusion and randomization, approximately 56 days after Day 0))
- Number of cumulus-oocyte complexes recovered on day of follicular puncture(Time P (time of follicular puncture): 36 hours after the induction)
- Number of good quality embryos available(48-72 hours after puncture)