Vitrification Versus Slow Cooling of Human Cleavage Stage Embryos

Infertility Clinical Trial

Official title:

A Double Blinded, Randomised Controlled Trial Comparing the Effectiveness of Vitrification to Slow Cooling in Cryopreserving Human Preimplantation Embryos

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00886431
• Other study ID #: Vitrification study
• Secondary ID: CCMO NL23499.000
• Status: Terminated
• Phase: N/A
• First received: April 22, 2009
• Last updated: November 26, 2014
• Start date: May 2009

Study information

• Verified date: November 2014
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

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, dimethylsulfoxide, ethyleneglycol

vitrification storage device: high security vitrification straws

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 146
• Est. primary completion date: May 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 35 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infertility

Intervention

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.

Locations

Country	Name	City	State
Belgium	Academic Hospital of Brussels	Brussels
Netherlands	University Medical Center of Utrecht	Utrecht

Sponsors (2)

Lead Sponsor	Collaborator
UMC Utrecht	Vrije Universiteit Brussel

Countries where clinical trial is conducted

Belgium,  Netherlands, 

References & Publications (14)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).		ongoing pregnancy is established 10 weeks following the transfer of a frozen embryo	No
Secondary	post-thaw embryo survival rate		1 hour after thawing	No
Secondary	ongoing pregnancy rate per patient using their thawed embryos (independent of whether they became pregnant following a fresh embryo transfer or not		10 weeks following transfer of frozen thawed embryo	No
Secondary	implantation rate per thawed embryo		10 weeks after transfer of thawed embryo	No
Secondary	implantation rate per transferred thawed embryo		10 weeks after transfer of thawed embryo	No
Secondary	cumulative implantation rate per cryopreservation		10 weeks after thawed embryo transfer	No
Secondary	ongoing pregnancy rate per frozen-thaw cycle		10 weeks following thawed embryo transfer	No
Secondary	average number of frozen-thawed cycles per patient		is variable	No
Secondary	post thaw development (categorial) per thawed embryo		24 hours following thawing	No
Secondary	average number of cryo-thaw cycles to ongoing pregnancy		variable, up to 3 years	No
Secondary	average number of thawed embryos to ongoing implantation		variable, up to 3 years	No
Secondary	Life birth rate		9 month after pregnancy test	No