Investigation of Ibuprofen in the Delay of Ovulation in NC-IVF (Natural Cycle in Vitro Fertilisation) Therapy With the Objective of Reducing Premature Ovulation and Thus Improving Effectivity (Off Label Use)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- Percentage of non ovulated follicles
研究概览
简要总结
During natural cycle in vitro fertilisation, no gonadotropin stimulation is used to stimulate oocyte production. Ovulation is induced with HCG (human chorionic gonadotropin) and the follicle is retrieved 36 hours later.
In this study the patient in the intervention group will receive Ibuprofen as a study intervention beginning at the same time as the HCG injection. The treatment dose will either be 400mg every 8 to 12 hours or 800mg every 8 to 12 hours until the follicle retrieval, totalling 5 tablets. Instead of the usual time period of 36 hours, the follicular punction will occur after 42 hours. Should the oocyte still be accessible after this time period, then it is proven that Ibuprofen delays ovulation. In this case the patient will continue the regular NC-IVF treatment cycle.
The study design is a admissible two-stage design. During stage 1, 8 cycles in 8 patients will be examined. Should it be the case that after these 8 patients have completed a cycle, 4 or more show a positive treatment effect from the Ibuprofen intake, then the study will continue to stage 2 with 17 more more patients, totalling 25.
Should it be the case however, that after 8 patients, 3 or less show an effect of the Ibuprofen intake, then the study will be stopped prematurely for futility. The study intervention will be increased to 800mg of Ibuprofen and the study will recommence with 8 more patients.
A control group will consist of women undergoing intrauterine insemination (IUI) or timed sexual intercourse (TSI). 42 hours after Beta-HCG injection, an ultrasound examination will be performed in order to determine the number of remaining follicles in the ovary. This examination is to verify and control the proposed time limit of 42 hours.
详细描述
Background
In vitro fertilisation can be performed without the use of gonadotropin-stimulating medication, = Natural Cycle-IVF or NC-IVF for short. The effectivity of NC-IVF is limited as pro treatment cycle only one follicle develops, which can ovulate prematurely. If this is the case, a follicle aspiration is no longer possible and the next cycle must be awaited. One possibility of preventing premature ovulation is the prescription of NSAID, which is common practice in many centres, even though up until now, the effectivity has not been proven.
To test the meaningfulness of the worldwide implementation of NSAIDs in NC-IVF, a proof of concept is needed. An exactly defined study outline will explore the use Ibuprofen in a dosage of 3x400mg/24h or 3x800mg/24h. At the lower dose, Ibuprofen did not show increased side effects in randomised placebo-controlled studies.
The primary purpose of the study is therefore to determine whether or not NSAIDs in the form of Ibuprofen can successfully delay ovulation in such a way that it would be useful for everyday application in NC-IVF. Secondary purposes are to measure the effect of Ibuprofen on the Prostaglandin-E2 levels in the fluid of the extracted follicles and also whether the number of oocytes obtained in the extracted follicles differs from regular IVF-treatment.
The study design is a prospective, non-randomised, single-arm, no-treatment controlled, proof-of-concept trial. The intervention to be studied is a dose of either 400mg Brufen® or a dose of 800mg Brufen® (Drug class: Ibuprofen), taken every 8h (at night up to 12 hours) equalling a daily dose of 1200mg/24h or 2400mg/24h. The intervention will continue for 42h, totalling 5 tablets. Patients recruited will enter the study and take part for the duration of one NC-IVF treatment cycle, roughly for 2 months. Each patient can take part once, for one treatment cycle. The control group will consist of females undergoing either IUI or TSI treatment. One ultrasound examination will be performed, to measure the number of naturally occuring delayed ovulation, 42h after HCG injection. Patients recruited can take part once, for one treatment cycle.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 42 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Indication for NC-IVF
- •Wish for NC-IVF
- •Menstruation every 26-32 days
- •Accessibility of both ovaries for a follicle aspiration
- •18-42 years of age
- •Written informed consent
- •Indication for IUI or TSI
- •Wish for IUI or TSI
- •Exclusion Criteria
- •<18 and >42 years of age
- •Gastro-intestinal diseases
- •Known Ibuprofen Intolerance
排除标准
- 未提供
研究组 & 干预措施
Intervention
2 Stage study design. Stage 1: 8 patients will be treated with the lower dose of 400mg of Ibuprofen. Should the efficacy be insufficient (3 or less patients) then the study will stop and stage 1 will recommence with 800mg.
Stage 2: 17 patients will be treated either with the lower dose of 400mg or the higher dose of 800mg of Ibuprofen should the respective stage 1 have been successful (4 or more patients showing an effect).
干预措施: Ibuprofen (Drug)
结局指标
主要结局
Percentage of non ovulated follicles
时间窗: 42 hours after HCG injection
The primary outcome of this study is whether Ibuprofen delays ovulation in the test subjects. It will be measured in the percentage of non-ovulated follicles exactly 42h after HCG administration with Ibuprofen.
次要结局
- E2 (Estradiol) concentration in the follicular fluid(42 hours after HCG injection)
- Percentage of oocytes obtained from aspirated follicles(42 hours after HCG injection)
- Incidence and severity of gastrointestinal and of other side effects(Throughout study duration, expected to be up to 11 months)
- Comparison of ovulation rates between the intervention and the control groups(42 hours after HCG injection, up to end of study duration.)