Effectiveness and Safety Study of Fixed Versus Flexible of Gonadotropin-releasing Hormone Antagonist Protocol
NCT ID: NCT02635607
Last Updated: 2015-12-21
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
NA
200 participants
INTERVENTIONAL
2016-01-31
2017-03-31
Brief Summary
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Detailed Description
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Statistical Methods For the primary endpoint, mean and standard deviation (SD) on the number of oocytes will be presented. The between-group difference and corresponding 95% confidence interval (CI) (Day-5 fixed protocol - flexible protocol) will be calculated by using a two-sample t-test under the assumption that the sample data are normally distributed. A test for normality will be performed prior to the analysis on primary endpoint and possible nonparametric adjustment will be made for skewed data in terms of primary analyses. The non-inferiority will be established if the lower bound of the 95%CI in the treatment difference between two groups (Day-5 fixed protocol - flexible protocol) does not exceed -3.0. The superiority may be claimed for the Day-5 fixed protocol if the lower bound of 95%CI for the treatment difference is above 0.0.
For the secondary endpoints on categorical variables, the number and percentage of the event will be calculated and displayed. Clinical and ongoing pregnancy rates will be separately calculated and presented. Between-group comparisons will be made by Chi-square test and the corresponding 95%CI will be presented by using Miettinen-Nurminen method if the number of the observed events is at least 4. Mean and SD will be summarized for continuous variables in terms of secondary outcome measures. A treatment difference between study groups will be made by using two-sample t-test or nonparametric test whenever appropriate.
The number of subjects who have reported adverse experiences (AE) and the incidence of individual AEs will be counted and presented. Fisher's exact test will be performed to compare between treatment groups.
Demographics and the subject's relevant medical history will be summarized by descriptive statistics.
All statistical analyses will be two-sided and at a significant level of a p value less than 0.05, unless otherwise specified.
Sample Size:
A sample size of 200 (1:1 allocation) achieves 80% power to detect non-inferiority of the Day-5 fixed-dose regimen as compared with the flexible protocol by a margin at -3 oocytes retrieved (3 oocytes fewer than the controlled group), using a one-sided, two-sample t-test with Mann-Whitney test adjustment at the significance level at 0.025. The true difference between the means is assumed to be 0.0 and the standard deviation of both intervention arms to be 6.8. The pre-mature discontinuation rate is set at approximately 15% for this study.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Fixed Protocol
Patients will start Follitropin beta stimulation on menstrual cycle day 3 and the daily dose will be fixed for the first 5 days of stimulation, a modification of the rFSH dose will be allowed from stimulation day 6 onward. Ganirelix will start fixedly on stimulation Day 5. rhCG will be administered to induce final oocyte maturation as soon as at least three follicles of ≥17 mm were observed, and triptorelin trigger will be used as a replacement in case of OHSS high risk
Follitropin Beta
Patients will start stimulation with a daily s.c. injection of 150IU follitropin beta on menstrual cycle day 3. A modification of the rFSH dose will be allowed from stimulation day 6 onward in case that a high ovarian response occurs at the discretion of the investigator.
Ganirelix
Ganirelix 0.25mg daily s.c. will start after 4 days of rFSH stimulation
rhCG
An amount of 250ug rhCG will be administered to induce final oocyte maturation as soon as at least three follicles of ≥17 mm were observed
triptorelin
0.2mg triptorelin will replace rHCG to trigger in case of high risk of overstimulation
Flexible protocol
Patients will start Follitropin beta stimulation on menstrual cycle day 3 and the daily dose will be fixed for the first 5 days of stimulation, a modification of the rFSH dose will be allowed from stimulation day 6 onward. Ganirelix will start flexibly by the promissory criterion in the flexible group. rhCG will be administered to induce final oocyte maturation as soon as at least three follicles of ≥17 mm were observed, and triptorelin trigger will be used as a replacement in case of OHSS high risk
Follitropin Beta
Patients will start stimulation with a daily s.c. injection of 150IU follitropin beta on menstrual cycle day 3. A modification of the rFSH dose will be allowed from stimulation day 6 onward in case that a high ovarian response occurs at the discretion of the investigator.
Ganirelix
Ganirelix 0.25mg daily s.c. will start when at least one of the following criteria are fulfilled: (i) the presence of at least one follicle measuring≥12 mm; (ii) serum E2 levels\>600 pg/ml; and (iii) serum LH levels\>10 IU/l.
rhCG
An amount of 250ug rhCG will be administered to induce final oocyte maturation as soon as at least three follicles of ≥17 mm were observed
triptorelin
0.2mg triptorelin will replace rHCG to trigger in case of high risk of overstimulation
Interventions
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Follitropin Beta
Patients will start stimulation with a daily s.c. injection of 150IU follitropin beta on menstrual cycle day 3. A modification of the rFSH dose will be allowed from stimulation day 6 onward in case that a high ovarian response occurs at the discretion of the investigator.
Ganirelix
Ganirelix 0.25mg daily s.c. will start after 4 days of rFSH stimulation
Ganirelix
Ganirelix 0.25mg daily s.c. will start when at least one of the following criteria are fulfilled: (i) the presence of at least one follicle measuring≥12 mm; (ii) serum E2 levels\>600 pg/ml; and (iii) serum LH levels\>10 IU/l.
rhCG
An amount of 250ug rhCG will be administered to induce final oocyte maturation as soon as at least three follicles of ≥17 mm were observed
triptorelin
0.2mg triptorelin will replace rHCG to trigger in case of high risk of overstimulation
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. be \<35 years old;
3. have a BMI of 18-25kg/m2;
4. have a regular menstruation with a range of 24-35 days;
5. fulfill one of these three criteria as follow:
* the number of oocytes retrieved\>15 in previous COS cycle;
* Serum AMH (examined on the menstrual cycle day 2)\>3.52ng/ml;
* antral follicle count (AFC) (examined by ultrasonic on the menstrual cycle day 2)\>16
6. have willingness to give informed consent
Exclusion Criteria
2. Any difficulty on oocyte pick-up with abnormal condition of ovary and pelvic cavity;
3. Women have any clinically relevant pathology could impair embryo implantation or pregnancy continuation (uterine malformation, intermural uterine fibroids\>3cm, intrauterine adhesion,etc);
4. Women with polycystic ovary syndrome (PCOS) diagnosed by Rotterdam consensus criterion(Rotterdam, 2004)
5. Other known abnormal ovulation disorders (including but not limited to adrenal gland disease, thyroid disease and hyperprolactinemia);
6. A history of recurrent miscarriage or previous IVF cycles failure\>2;
7. A history of ovarian hypo-response in previous ovarian stimulation;
8. Women with other clinical/socio-economic factors precluding the completion of the study at the discretion of the investigator.
20 Years
35 Years
FEMALE
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
Chong Qing Reproducive and Genetic Institute
OTHER
Responsible Party
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Principal Investigators
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Hong Ye, bachelor
Role: STUDY_DIRECTOR
Genetic and Reproductive Institute, Chongqing Obstetrics and Gynecology Hospital
Central Contacts
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References
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Humaidan P, Quartarolo J, Papanikolaou EG. Preventing ovarian hyperstimulation syndrome: guidance for the clinician. Fertil Steril. 2010 Jul;94(2):389-400. doi: 10.1016/j.fertnstert.2010.03.028. Epub 2010 Apr 22.
Al-Inany HG, Youssef MA, Aboulghar M, Broekmans F, Sterrenburg M, Smit J, Abou-Setta AM. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2011 May 11;(5):CD001750. doi: 10.1002/14651858.CD001750.pub3.
Lainas TG, Sfontouris IA, Zorzovilis IZ, Petsas GK, Lainas GT, Alexopoulou E, Kolibianakis EM. Flexible GnRH antagonist protocol versus GnRH agonist long protocol in patients with polycystic ovary syndrome treated for IVF: a prospective randomised controlled trial (RCT). Hum Reprod. 2010 Mar;25(3):683-9. doi: 10.1093/humrep/dep436. Epub 2009 Dec 15.
Al-Inany H, Aboulghar MA, Mansour RT, Serour GI. Optimizing GnRH antagonist administration: meta-analysis of fixed versus flexible protocol. Reprod Biomed Online. 2005 May;10(5):567-70. doi: 10.1016/s1472-6483(10)61661-6.
Hamdine O, Eijkemans MJ, Lentjes EW, Torrance HL, Macklon NS, Fauser BC, Broekmans FJ. Ovarian response prediction in GnRH antagonist treatment for IVF using anti-Mullerian hormone. Hum Reprod. 2015 Jan;30(1):170-8. doi: 10.1093/humrep/deu266. Epub 2014 Oct 29.
Engmann L, DiLuigi A, Schmidt D, Nulsen J, Maier D, Benadiva C. The use of gonadotropin-releasing hormone (GnRH) agonist to induce oocyte maturation after cotreatment with GnRH antagonist in high-risk patients undergoing in vitro fertilization prevents the risk of ovarian hyperstimulation syndrome: a prospective randomized controlled study. Fertil Steril. 2008 Jan;89(1):84-91. doi: 10.1016/j.fertnstert.2007.02.002. Epub 2007 Apr 26.
Luo X, Pei L, Li F, Li C, Huang G, Ye H. Fixed versus flexible antagonist protocol in women with predicted high ovarian response except PCOS: a randomized controlled trial. BMC Pregnancy Childbirth. 2021 May 2;21(1):348. doi: 10.1186/s12884-021-03833-2.
Other Identifiers
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Merck-IISP-01
Identifier Type: -
Identifier Source: org_study_id