Vitrification Versus Slow Cooling of Human Cleavage Stage Embryos - Full Text View

Sponsors and Collaborators:	UMC Utrecht Acad. Hosp. of Brussels; Dep.Reproductive Med.; Laarbeekelaan 100; 1090 Brussels, Belgium
Information provided by:	UMC Utrecht
ClinicalTrials.gov Identifier:	NCT00886431

Purpose

Human embryos can be preserved for later transfers by freezing. Traditionally the slow cooling method has been used. About 70% of the embryos remain fully intact after thawing. However, the remaining 30% of the embryos become (partially) damaged, and this freezing damage reduces their chance to implant. Recently an ultra rapid freezing method, called vitrification has been developed. During vitrification no damaging ice crystals are formed and the embryo freezes in a glass like state. It appears that the freezing damage is reduced when embryos are vitrified. Observational studies in humans indicate that embryos are successfully preserved by vitrification, as indicated by promising pregnancy rates following thawing. However, the effectiveness of vitrification in relation to slow cooling with respect to pregnancy rates has so far not been evaluated by a randomised, controlled trial. The aim of this study is to investigate whether vitrification significantly improves embryo survival and ongoing pregnancy rates when compared to embryos frozen by slow cooling.

Condition	Intervention
Infertility	Other: embryo vitrification

MedlinePlus related topics: Infertility Methamphetamine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver), Parallel Assignment, Efficacy Study
Official Title:	A Double Blinded, Randomised Controlled Trial Comparing the Effectiveness of Vitrification to Slow Cooling in Cryopreserving Human Preimplantation Embryos

Further study details as provided by UMC Utrecht:

Primary Outcome Measures:

The percent change of the ongoing pregnancy rate per patient/couple who use their thawed embryos (following a fesh embryo transfer which did not result in an ongoing pregnancy) from baseline (slow cooling) to end point (vitrification). [ Time Frame: ongoing pregnancy is established 10 weeks following the transfer of a frozen embryo ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

post-thaw embryo survival rate [ Time Frame: 1 hour after thawing ] [ Designated as safety issue: No ]
ongoing pregnancy rate per patient using their thawed embryos (independent of whether they became pregnant following a fresh embryo transfer or not [ Time Frame: 10 weeks following transfer of frozen thawed embryo ] [ Designated as safety issue: No ]
implantation rate per thawed embryo [ Time Frame: 10 weeks after transfer of thawed embryo ] [ Designated as safety issue: No ]
implantation rate per transferred thawed embryo [ Time Frame: 10 weeks after transfer of thawed embryo ] [ Designated as safety issue: No ]
cumulative implantation rate per cryopreservation [ Time Frame: 10 weeks after thawed embryo transfer ] [ Designated as safety issue: No ]
ongoing pregnancy rate per frozen-thaw cycle [ Time Frame: 10 weeks following thawed embryo transfer ] [ Designated as safety issue: No ]
average number of frozen-thawed cycles per patient [ Time Frame: is variable ] [ Designated as safety issue: No ]
post thaw development (categorial) per thawed embryo [ Time Frame: 24 hours following thawing ] [ Designated as safety issue: No ]
average number of cryo-thaw cycles to ongoing pregnancy [ Time Frame: variable, up to 3 years ] [ Designated as safety issue: No ]
average number of thawed embryos to ongoing implantation [ Time Frame: variable, up to 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	626
Study Start Date:	May 2009
Estimated Primary Completion Date:	May 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Vitrification: Experimental The embryos of patients allocated to this arm will be cryopreserved by vitrification.	Other: embryo vitrification Ultra rapid cooling of embryos by immersion in liquid nitrogen. The formation of potentially damaging ice crystals is prevented by briefly incubating the embryos in high concentrations of a mix of cryoprotectants.
Slow cooling: No Intervention The embryos of patients allocated to this arm will be cryorpeserved by the slow cooling method, which is the standard method (=no intervention)

Detailed Description:

time of allocation: following embryo selection

type of embryos: cleavage stage -, morula stage or early blastocyst stage embryo (day3 - day4 after oocyte collection)

cryoprotectants: sucrose, dimethylsuloxide, ethyleneglycol

vitrification storage device: high security vitrification straws

Eligibility

Ages Eligible for Study:	18 Years to 35 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

female patient age 35 years or less
embryos are obtained by in vitro fertilization (IVF) or intra cytoplasmatic spermatozoon injection (ICSI)
single embryo transfer
1rst IVF/ICSI treatment with an embryo transfer
availability of cryopreservable embryos

Exclusion Criteria:

female patient age is 36 years or older
participants of oocyte donation program
participants of percutaneous spermatozoon aspiration (PESA) program
couples with a finite source of spermatozoa
absence of cryopreservable embryos

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00886431

Contacts

Contact: Dagmar R Gutknecht, PhD	0031887555555	d.r.gutknecht@umcutrecht.nl
Contact: Bart C Fauser, Prof, PhD, MD	0031887555555	b.c.fauser@umcutrecht.nl

Locations

Belgium
Academic Hospital of Brussels
Brussels, Belgium, 1090
Netherlands
University Medical Center of Utrecht
Utrecht, Netherlands, 3584 CX

Sponsors and Collaborators

UMC Utrecht

Acad. Hosp. of Brussels; Dep.Reproductive Med.; Laarbeekelaan 100; 1090 Brussels, Belgium

Investigators

Principal Investigator:

Bart C Fauser, Prof.,MD,PhD

UMC Utrecht

More Information

Publications:

Boonkusol D, Gal AB, Bodo S, Gorhony B, Kitiyanant Y, Dinnyes A. Gene expression profiles and in vitro development following vitrification of pronuclear and 8-cell stage mouse embryos. Mol Reprod Dev. 2006 Jun;73(6):700-8.

Burns WN, Gaudet TW, Martin MB, Leal YR, Schoen H, Eddy CA, Schenken RS. Survival of cryopreservation and thawing with all blastomeres intact identifies multicell embryos with superior frozen embryo transfer outcome. Fertil Steril. 1999 Sep;72(3):527-32.

Desai N, Blackmon H, Szeptycki J, Goldfarb J. Cryoloop vitrification of human day 3 cleavage-stage embryos: post-vitrification development, pregnancy outcomes and live births. Reprod Biomed Online. 2007 Feb;14(2):208-13.

Edgar DH, Bourne H, Speirs AL, McBain JC. A quantitative analysis of the impact of cryopreservation on the implantation potential of human early cleavage stage embryos. Hum Reprod. 2000 Jan;15(1):175-9.

Kasai M, Mukaida T. Cryopreservation of animal and human embryos by vitrification. Reprod Biomed Online. 2004 Aug;9(2):164-70. Review.

Mukaida T, Nakamura S, Tomiyama T, Wada S, Kasai M, Takahashi K. Successful birth after transfer of vitrified human blastocysts with use of a cryoloop containerless technique. Fertil Steril. 2001 Sep;76(3):618-20.

Rama Raju GA, Haranath GB, Krishna KM, Prakash GJ, Madan K. Vitrification of human 8-cell embryos, a modified protocol for better pregnancy rates. Reprod Biomed Online. 2005 Oct;11(4):434-7.

Salumets A, Suikkari AM, Mäkinen S, Karro H, Roos A, Tuuri T. Frozen embryo transfers: implications of clinical and embryological factors on the pregnancy outcome. Hum Reprod. 2006 Sep;21(9):2368-74. Epub 2006 May 9.

Sheehan CB, Lane M, Gardner DK. The CryoLoop facilitates re-vitrification of embryos at four successive stages of development without impairing embryo growth. Hum Reprod. 2006 Nov;21(11):2978-84. Epub 2006 Sep 1.

Stehlik E, Stehlik J, Katayama KP, Kuwayama M, Jambor V, Brohammer R, Kato O. Vitrification demonstrates significant improvement versus slow freezing of human blastocysts. Reprod Biomed Online. 2005 Jul;11(1):53-7.

Takahashi K, Mukaida T, Goto T, Oka C. Perinatal outcome of blastocyst transfer with vitrification using cryoloop: a 4-year follow-up study. Fertil Steril. 2005 Jul;84(1):88-92.

Al-Hasani S, Ozmen B, Koutlaki N, Schoepper B, Diedrich K, Schultze-Mosgau A. Three years of routine vitrification of human zygotes: is it still fair to advocate slow-rate freezing? Reprod Biomed Online. 2007 Mar;14(3):288-93.

Liebermann J, Tucker MJ. Comparison of vitrification and conventional cryopreservation of day 5 and day 6 blastocysts during clinical application. Fertil Steril. 2006 Jul;86(1):20-6. Epub 2006 Jun 8.

Yokota Y, Sato S, Yokota M, Yokota H, Araki Y. Birth of a healthy baby following vitrification of human blastocysts. Fertil Steril. 2001 May;75(5):1027-9.

Responsible Party:	UMC Utrecht ( Prof. Dr. B.C. Fauser )
Study ID Numbers:	Vitrification study, CCMO NL23499.000.08, METC 08/183
Study First Received:	April 22, 2009
Last Updated:	April 22, 2009
ClinicalTrials.gov Identifier:	NCT00886431 History of Changes
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by UMC Utrecht:

IVF
embryo cryopreservation
vitrification
slow cooling

slow freezing
surplus embryos
Human Reproduction

Study placed in the following topic categories:

Genital Diseases, Female
Infertility
Methamphetamine
Amphetamine
Genital Diseases, Male

Additional relevant MeSH terms:

Genital Diseases, Female
Infertility
Genital Diseases, Male

ClinicalTrials.gov processed this record on May 06, 2009