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Can Ibuprofen Delay Ovulation in Natural Cycle-IVF? (Ibudelay)

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ClinicalTrials.gov Identifier: NCT02571543
Recruitment Status : Recruiting
First Posted : October 8, 2015
Last Update Posted : June 14, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Ovulation Ovulation Inhibition Ovulation Inhibition/Drug Effects Pregnancy Fertilization in Vitro/Methods Drug: Ibuprofen Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 68 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: 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)
Actual Study Start Date : January 2016
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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).

Drug: Ibuprofen
Beginning with 400mg Ibuprofen, 5 times. Depending on the outcome of stage 1 the treatment dose will increase to 800mg, 5 times.
Other Name: Brufen®

No Intervention: Control
The control group will consist of a no-treatment group of patients undergoing Intrauterine Insemination (IUI) or Timed Sexual intercourse (TSI), to verify the delay between LH-Peak onset and ovulation. 42h after Beta-HCG injection inducing LH-Peak, ovulation will be determined by ultrasound examination.



Primary Outcome Measures :
  1. Percentage of non ovulated follicles [ Time Frame: 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.


Secondary Outcome Measures :
  1. Comparison of ovulation rates between the intervention and the control groups [ Time Frame: 42 hours after HCG injection, up to end of study duration. ]
    Measured using ultrasound.

  2. Percentage of oocytes obtained from aspirated follicles [ Time Frame: 42 hours after HCG injection ]
    Compared to whether this differs from regular NC-IVF without the investigational product

  3. E2 (Estradiol) concentration in the follicular fluid [ Time Frame: 42 hours after HCG injection ]
    To assess whether Ibuprofen has altered these levels

  4. Incidence and severity of gastrointestinal and of other side effects [ Time Frame: Throughout study duration, expected to be up to 11 months ]
    To assess whether Ibuprofen has caused these known side effects



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Ages Eligible for Study:   18 Years to 42 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02571543


Contacts
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Contact: Michael von Wolff, Prof. Dr. 0316321301 michael.vonwolff@insel.ch
Contact: Monika Fäh, Dr. 0316321303 monika.faeh@insel.ch

Locations
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Switzerland
Department of Obstetrics and Gynecology, Bern University Hospital Recruiting
Bern, Switzerland, 3010 Bern
Contact: Gregory Reid       gregory.reid@students.unibe.ch   
Principal Investigator: Michael von Wolff         
Sub-Investigator: Monika Fäh         
Sub-Investigator: Alexandra Kohl         
Sponsors and Collaborators
University Hospital Inselspital, Berne
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Michael von Wolff, Prof. Dr. University of Bern

Publications:

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Responsible Party: University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT02571543     History of Changes
Other Study ID Numbers: 015/15
First Posted: October 8, 2015    Key Record Dates
Last Update Posted: June 14, 2019
Last Verified: June 2019
Keywords provided by University Hospital Inselspital, Berne:
Ibuprofen
IVF
minimal stimulation
modified natural-cycle
nonsteroidal anti-inflammatory drug (NSAID)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
Oocyte Retrieval
Ovarian Follicle/drug effects
Additional relevant MeSH terms:
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Ibuprofen
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action