Pregnancy Clinical Trial
— IbudelayOfficial 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)
NCT number | NCT02571543 |
Other study ID # | 015/15 |
Secondary ID | |
Status | Recruiting |
Phase | Phase 2 |
First received | |
Last updated | |
Start date | January 2016 |
Est. completion date | March 2020 |
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.
Status | Recruiting |
Enrollment | 68 |
Est. completion date | March 2020 |
Est. primary completion date | March 2020 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Female |
Age group | 18 Years to 42 Years |
Eligibility |
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 |
Country | Name | City | State |
---|---|---|---|
Switzerland | Department of Obstetrics and Gynecology, Bern University Hospital | Bern |
Lead Sponsor | Collaborator |
---|---|
University Hospital Inselspital, Berne | Merck Sharp & Dohme Corp. |
Switzerland,
Bata MS, Al-Ramahi M, Salhab AS, Gharaibeh MN, Schwartz J. Delay of ovulation by meloxicam in healthy cycling volunteers: A placebo-controlled, double-blind, crossover study. J Clin Pharmacol. 2006 Aug;46(8):925-32. — View Citation
Diao HL, Zhu H, Ma H, Tan HN, Cong J, Su RW, Yang ZM. Rat ovulation, implantation and decidualization are severely compromised by COX-2 inhibitors. Front Biosci. 2007 May 1;12:3333-42. — View Citation
Edelman AB, Jensen JT, Doom C, Hennebold JD. Impact of the prostaglandin synthase-2 inhibitor celecoxib on ovulation and luteal events in women. Contraception. 2013 Mar;87(3):352-7. doi: 10.1016/j.contraception.2012.07.004. Epub 2012 Aug 16. — View Citation
Espey LL. Current status of the hypothesis that mammalian ovulation is comparable to an inflammatory reaction. Biol Reprod. 1994 Feb;50(2):233-8. Review. — View Citation
Gaytán M, Bellido C, Morales C, Sánchez-Criado JE, Gaytán F. Effects of selective inhibition of cyclooxygenase and lipooxygenase pathways in follicle rupture and ovulation in the rat. Reproduction. 2006 Oct;132(4):571-7. — View Citation
Gaytán M, Morales C, Bellido C, Sánchez-Criado JE, Gaytán F. Non-steroidal anti-inflammatory drugs (NSAIDs) and ovulation: lessons from morphology. Histol Histopathol. 2006 May;21(5):541-56. doi: 10.14670/HH-21.541. Review. — View Citation
Jesam C, Salvatierra AM, Schwartz JL, Croxatto HB. Suppression of follicular rupture with meloxicam, a cyclooxygenase-2 inhibitor: potential for emergency contraception. Hum Reprod. 2010 Feb;25(2):368-73. doi: 10.1093/humrep/dep392. Epub 2009 Nov 19. — View Citation
Kadoch IJ, Al-Khaduri M, Phillips SJ, Lapensée L, Couturier B, Hemmings R, Bissonnette F. Spontaneous ovulation rate before oocyte retrieval in modified natural cycle IVF with and without indomethacin. Reprod Biomed Online. 2008 Feb;16(2):245-9. — View Citation
Kawachiya S, Matsumoto T, Bodri D, Kato K, Takehara Y, Kato O. Short-term, low-dose, non-steroidal anti-inflammatory drug application diminishes premature ovulation in natural-cycle IVF. Reprod Biomed Online. 2012 Mar;24(3):308-13. doi: 10.1016/j.rbmo.2011.12.002. Epub 2011 Dec 15. — View Citation
Pall M, Fridén BE, Brännström M. Induction of delayed follicular rupture in the human by the selective COX-2 inhibitor rofecoxib: a randomized double-blind study. Hum Reprod. 2001 Jul;16(7):1323-8. — View Citation
Rijken-Zijlstra TM, Haadsma ML, Hammer C, Burgerhof JG, Pelinck MJ, Simons AH, van Echten-Arends J, Arts JG, Land JA, Groen H, Hoek A. Effectiveness of indometacin to prevent ovulation in modified natural-cycle IVF: a randomized controlled trial. Reprod Biomed Online. 2013 Sep;27(3):297-304. doi: 10.1016/j.rbmo.2013.05.009. Epub 2013 May 22. — View Citation
Tanaka N, Espey LL, Kawano T, Okamura H. Comparison of inhibitory actions of indomethacin and epostane on ovulation in rats. Am J Physiol. 1991 Feb;260(2 Pt 1):E170-4. — View Citation
* Note: There are 12 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Percentage of non ovulated follicles | 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. | 42 hours after HCG injection | |
Secondary | Comparison of ovulation rates between the intervention and the control groups | Measured using ultrasound. | 42 hours after HCG injection, up to end of study duration. | |
Secondary | Percentage of oocytes obtained from aspirated follicles | Compared to whether this differs from regular NC-IVF without the investigational product | 42 hours after HCG injection | |
Secondary | E2 (Estradiol) concentration in the follicular fluid | To assess whether Ibuprofen has altered these levels | 42 hours after HCG injection | |
Secondary | Incidence and severity of gastrointestinal and of other side effects | To assess whether Ibuprofen has caused these known side effects | Throughout study duration, expected to be up to 11 months |
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