Ultrashort GnRH Agonist/Antagonist Versus GnRH Antagonist IVF

Infertility Clinical Trial

Official title:

Ultrashort Flare GnRH Agonist Combined With Flexible Multidose GnRH Antagonist Versus Flexible Multidose GnRH Antagonist for Good-prognosis IVF Patients

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02173977
• Other study ID #: SHEBA-14-1078-RO-CTIL
• Status: Not yet recruiting
• Phase: Phase 2
• First received: June 2, 2014
• Last updated: June 23, 2014
• Start date: June 2014
• Est. completion date: May 2017

Study information

• Verified date: June 2014
• Source: Sheba Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the appropriate controlled ovarian hyperstimulation (COH) protocol in good prognosis patients undergoing IVF treatment. The stimulation characteristics of cycles which include ultrashort flare GnRH agonist combined with flexible multidose GnRH antagonist will be compared to the flexible multidose GnRH antagonist protocol.

The investigators hypothesized that combining the stimulatory effect of GnRH agonists and immediate suppression of the GnRH antagonist in a unique protocol may be a valuable new COH strategy for IVF patients, resulting in improved ART outcome.

Description:

The ultrashort flare GnRH agonist combined with flexible multidose GnRH antagonist protocol during COH cycle resulted in a significantly higher clinical pregnancy rate in patients with poor embryo quality, with repeated IVF failures and in poor responders. This protocol combines the effect of the microdose flare on endogenous follicle stimulating hormone (FSH) release with the benefit of an immediate luteinizing hormone suppression of the GnRH antagonist.

The basic hypothesis of this approach can also benefit IVF patients with good prognosis without compromising the ability to use gonadotrophin-releasing hormone (GnRH) agonist to effectively trigger ovulation, while completely eliminating any threat of clinically significant ovarian hyperstimulation syndrome (OHSS).

The purpose of the study is to compare cycles consisting of ultrashort flare GnRH agonist combined with flexible multidose GnRH antagonist with those using the flexible multidose GnRH antagonist protocol

1. To compare the IVF outcome variables and ongoing pregnancy rates.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: May 2017
• Est. primary completion date: May 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years to 35 Years

Eligibility

Inclusion Criteria:

• Up to three previous IVF attempts

Exclusion Criteria:

• Patients with poor or no response in previous COH for IVF cycles

• Abnormal ovarian reserve test i.e. anti-mullerian hormone (AMH), Antral follicle test

• Risk factor for Diminished Ovarian Reserve

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infertility

Intervention

Other:
• ARM A- Agonist/Antagonist protocol
In vitro fertilization (IVF/ICSI)
• ARM B- Antagonist protocol
In vitro fertilization (IVF/ICSI)

Locations

Country	Name	City	State
Israel	Sheba Medical Center- IVF unit	Ramat Gan

Sponsors (1)

Lead Sponsor	Collaborator
Sheba Medical Center

Country where clinical trial is conducted

Israel, 

References & Publications (5)

Orvieto R, Kruchkovich J, Rabinson J, Zohav E, Anteby EY, Meltcer S. Ultrashort gonadotropin-releasing hormone agonist combined with flexible multidose gonadotropin-releasing hormone antagonist for poor responders in in vitro fertilization/embryo transfer programs. Fertil Steril. 2008 Jul;90(1):228-30. Epub 2007 Aug 6. — View Citation

Orvieto R, Meltcer S, Liberty G, Rabinson J, Anteby EY, Nahum R. A combined approach to patients with repeated IVF failures. Fertil Steril. 2010 Nov;94(6):2462-4. doi: 10.1016/j.fertnstert.2010.03.057. Epub 2010 May 7. — View Citation

Orvieto R, Nahum R, Rabinson J, Gemer O, Anteby EY, Meltcer S. Ultrashort flare GnRH agonist combined with flexible multidose GnRH antagonist for patients with repeated IVF failures and poor embryo quality. Fertil Steril. 2009 Apr;91(4 Suppl):1398-400. doi: 10.1016/j.fertnstert.2008.04.064. Epub 2008 Aug 3. — View Citation

Orvieto R, Nahum R, Zohav E, Liberty G, Anteby EY, Meltcer S. GnRH-agonist ovulation trigger in patients undergoing controlled ovarian hyperstimulation for IVF with ultrashort flare GnRH-agonist combined with multidose GnRH-antagonist protocol. Gynecol Endocrinol. 2013 Jan;29(1):51-3. doi: 10.3109/09513590.2012.705376. Epub 2012 Aug 3. — View Citation

Orvieto R. The ultrashort flare GnRH-agonist/GnRH-antagonist protocol enables cycle programming and may overcome the "detrimental effect" of the oral contraceptive. Fertil Steril. 2012 Sep;98(3):e17-8; author reply e19. doi: 10.1016/j.fertnstert.2012.06.053. Epub 2012 Jul 26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Positive Pregnancy Test		2 Years	Yes
Primary	Ongoing pregnancy rates		2 years	Yes
Secondary	Total gonadotropin use		2 Years	Yes
Secondary	Biochemical pregnancy	Positive pregnancy test without documentation of intrauterine or extrauterine pregnancy	2 Years	Yes
Secondary	Clinical pregnancy	Positive pregnancy test with documentation of intrauterine or extrauterine pregnancy	2 Years	Yes
Secondary	Multiple pregnancy rate		2 Years	Yes
Secondary	Miscarriage rate		2 Years	Yes
Secondary	Fertilization rate		2 Years	Yes
Secondary	Number of oocytes		2 years	Yes
Secondary	OHSS rates		2 Years	Yes
Secondary	Embryo quality	Grading of a day 3 embryo based on the number of cells that make up the embryo, the amount of fragmentation, and the symmetry of each of the embryo's cells (blastomeres).; E.g. good quality embryos: embryos that reach the eight-cell stage with less than 20% fragmentation on day 3	2 Years	Yes