Comparison Between Three Freezing Protocols to Preserve Human Embryos

Human Embryo Cryopreservation Clinical Trial

Official title:

Randomized Comparison to Freeze Human Embryos by Either Vitrification or Slow Freezing Protocols

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00910390
• Other study ID #: VITR-1-EMBRYOS
• Status: Completed
• Phase: N/A
• First received: May 28, 2009
• Last updated: July 25, 2016
• Start date: April 2009
• Est. completion date: May 2011

Study information

• Verified date: July 2016
• Source: Erasme University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This randomized study compares three different freezing methods to store human in vitro fertilization (IVF) embryos: vitrification with two commercial kits or slow freezing. After information, all patients undergoing IVF treatment can be included in the study. If qualified, embryos at different developmental stages will be allocated between the three methods. At the end of the first year survival and developmental rates, and implantation and pregnancy rates will be analyzed in order to determine the best method.

Description:

Despite all the advances achieved in vitro fertilized treatments, it is known that the chances of implantation for fertilised in vitro embryo remain limited, at around 20%. Cryopreservation of supernumerary embryos produced during IVF cycles provides an opportunity for patients to increase the number of transfers per oocyte harvest cycle, increasing then their chances of conception.

The freezing technique may involve different media and methods, which lead to different survival and developmental rates after thawing.

Vitrification is a new freezing method, which consists in exposing cells to high concentrations of cryoprotectants and then cooling them ultra-rapidly; this induces an increase in viscosity which favours the formation of a vitreous state without any ice crystals formation. This method contrasts with the slow freezing method (currently employed), which is based on exposure to very low concentrations of cryoprotectants combined with long cooling times and associated with a higher risk of ice crystal formation.

Both methods can reduce cell survival and embryo ability to develop, either by the high concentrations of cryoprotectants in case of vitrification, or by ice crystals formation in case of slow freezing. The advantages of vitrification in embryology may be considerable because embryos seem more sensitive to ice crystal formation than to cyroportectant concentration; consequently, the elimination of office crystal injury may increase their survival chances. Additionally in the case of vitrification, the time required for equilibration and cooling is considerably reduced as well as the need for expensive equipment such as programmable machine is eliminated.

At present, vitrification and slow freezing are used for the cryopreservation of oocytes and embryos at all stages of development. Encouraging results have been obtained with vitrification, but no study has randomly compared in one study, the two protocols and cryoprotectors. The purpose of this clinic randomised study is to compare three treatments: traditional slow freezing method currently employed (control group) and two different commercial vitrification methods (experimental groups) to assess the efficacy that this technique may involve.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 584
• Est. completion date: May 2011
• Est. primary completion date: October 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 43 Years

Eligibility

Inclusion Criteria:

• Infertility requiring IVF

Exclusion Criteria:

• Women's age > 43 years

• Patients positive for hepatitis B or C

• Patients positive for HIV

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Human Embryo Cryopreservation

Intervention

Other:
• Slow freezing
Embryos at different developmental stages will be frozen using a solution that contains propanediol and sucrose, individually placed in high security straws, cooled with a programmator and stored in liquid nitrogen.
• VIT-Irvine
Embryos at different developmental stages will be frozen using the vitrification solution according to the manufacturer's instructions, individually placed in high security vitrification devices and plunged directly in liquid nitrogen for storing.
• Vit-Vitrolife
Embryos at different developmental stages will be frozen using the vitrification solution according to the manufacturer's instructions, individually placed in high security vitrification devices and plunged directly in liquid nitrogen for storing.

Locations

Country	Name	City	State
Belgium	IVF laboratory, Hospital Erasme, Route de Lennik 808	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Erasme University Hospital

Country where clinical trial is conducted

Belgium, 

References & Publications (19)

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

Balaban B, Urman B, Ata B, Isiklar A, Larman MG, Hamilton R, Gardner DK. A randomized controlled study of human Day 3 embryo cryopreservation by slow freezing or vitrification: vitrification is associated with higher survival, metabolism and blastocyst formation. Hum Reprod. 2008 Sep;23(9):1976-82. doi: 10.1093/humrep/den222. Epub 2008 Jun 10. — 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

Escribá MJ, Zulategui JF, Galán A, Mercader A, Remohí J, de los Santos MJ. Vitrification of preimplantation genetically diagnosed human blastocysts and its contribution to the cumulative ongoing pregnancy rate per cycle by using a closed device. Fertil Steril. 2008 Apr;89(4):840-6. Epub 2007 Aug 6. — View Citation

Huang CC, Lee TH, Chen SU, Chen HH, Cheng TC, Liu CH, Yang YS, Lee MS. Successful pregnancy following blastocyst cryopreservation using super-cooling ultra-rapid vitrification. Hum Reprod. 2005 Jan;20(1):122-8. Epub 2004 Oct 7. — 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

Kattera S, Chen C. Cryopreservation of embryos by vitrification: current development. Int Surg. 2006 Sep-Oct;91(5 Suppl):S55-62. Review. — View Citation

Kuwayama M, Vajta G, Ieda S, Kato O. Comparison of open and closed methods for vitrification of human embryos and the elimination of potential contamination. Reprod Biomed Online. 2005 Nov;11(5):608-14. — View Citation

Kuwayama M. Highly efficient vitrification for cryopreservation of human oocytes and embryos: the Cryotop method. Theriogenology. 2007 Jan 1;67(1):73-80. Epub 2006 Oct 20. Review. — View Citation

Liebermann J, Dietl J, Vanderzwalmen P, Tucker MJ. Recent developments in human oocyte, embryo and blastocyst vitrification: where are we now? Reprod Biomed Online. 2003 Dec;7(6):623-33. Review. — View Citation

Liebermann J, Nawroth F, Isachenko V, Isachenko E, Rahimi G, Tucker MJ. Potential importance of vitrification in reproductive medicine. Biol Reprod. 2002 Dec;67(6):1671-80. 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

Loutradi KE, Kolibianakis EM, Venetis CA, Papanikolaou EG, Pados G, Bontis I, Tarlatzis BC. Cryopreservation of human embryos by vitrification or slow freezing: a systematic review and meta-analysis. Fertil Steril. 2008 Jul;90(1):186-93. Epub 2007 Nov 5. Review. — View Citation

Nawroth F, Rahimi G, Isachenko E, Isachenko V, Liebermann M, Tucker MJ, Liebermann J. Cryopreservation in assisted reproductive technology: new trends. Semin Reprod Med. 2005 Nov;23(4):325-35. Review. — 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

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

Vajta G, Nagy ZP. Are programmable freezers still needed in the embryo laboratory? Review on vitrification. Reprod Biomed Online. 2006 Jun;12(6):779-96. Review. — View Citation

Youssry M, Ozmen B, Zohni K, Diedrich K, Al-Hasani S. Current aspects of blastocyst cryopreservation. Reprod Biomed Online. 2008 Feb;16(2):311-20. Review. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival embryo rate		one year	Yes
Secondary	Delivery rate		one year	Yes