Human Embryo CryopreservationNCT00910390
Comparison Between Three Freezing Protocols to Preserve Human Embryos
A study testing Slow freezing, VIT-Irvine and Vit-Vitrolife in people with Human Embryo Cryopreservation, run by Erasme University Hospital at 1 site in Belgium.
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. Read more about this study
- Who is it for?
- Ages 18 to 43 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Human Embryo Cryopreservation
- What is being tested?
- Slow freezing, VIT-Irvine and Vit-Vitrolife
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 584 participants
- Where
- 1 siteBelgium
- Study dates
- Apr 2009to May 2011
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 43 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Infertility requiring IVF
Who cannot join
- Women's age > 43 years
- Patients positive for hepatitis B or C
- Patients positive for HIV
Trial locations and contacts
1 site in 1 country.
Belgium1 site
IVF laboratory, Hospital Erasme, Route de Lennik 808
Brussels, 1070
About this study
Official title: Randomized Comparison to Freeze Human Embryos by Either Vitrification or Slow Freezing Protocols
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.
Read the detailed 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.
- Conditions
- Human Embryo Cryopreservation
- Being tested
- Slow freezing, VIT-Irvine, Vit-Vitrolife
- Keywords
- IVF, embryo cryopreservation, vitrification, Human Embryo, Embryonic development, Pregnancy rate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Slow freezingOther
Also called Home-made solutions, propanediol
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-IrvineOther
Also called IRVINE, California, ethylene glycol, DMSO
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-VitrolifeOther
Also called VITROLIFE, Sweden, ethylene glycol, propanediol
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.
| Study group | Role | What they receive |
|---|---|---|
| Slow Freezing | Placebo comparator | Standard freezing protocol (slow freezing) of preimplantation embryos Receives: Other: Slow freezing |
| VIT-Irvine | Experimental | Vitrification with Irvine solution (rapid freezing) of preimplantation embryos Receives: Other: VIT-Irvine |
| VIT-Vitrolife | Experimental | Vitrification (rapid freezing) with Vitrolife solution Receives: Other: Vit-Vitrolife |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival embryo rate
Measured: one year
Secondary outcomes (1)
Delivery rate
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2009 (estimated)
- Study startApr 2009
- Primary completionOct 2009
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Human Embryo CryopreservationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 584 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasme University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fasano Giovanna, Erasme University Hospital
- Investigators
- Anne Delbaere, Ph.D., Study director, Fertility Clinic, Hospital Erasme
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00910390
- Sponsor's protocol ID
- VITR-1-EMBRYOS
- Status last verified
- Jul 2016
- First submitted
- 28 May 2009
- Last updated
- 26 Jul 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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. doi: 10.1016/s1472-6483(10)60869-3.
PubMed 17359578Balaban 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.
PubMed 18544577Desai 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. doi: 10.1016/s1472-6483(10)60789-4.
PubMed 17298725Escriba MJ, Zulategui JF, Galan A, Mercader A, Remohi 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. doi: 10.1016/j.fertnstert.2007.04.035. Epub 2007 Aug 6.
PubMed 17681342Huang 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. doi: 10.1093/humrep/deh540. Epub 2004 Oct 7.
PubMed 15471932Kasai M, Mukaida T. Cryopreservation of animal and human embryos by vitrification. Reprod Biomed Online. 2004 Aug;9(2):164-70. doi: 10.1016/s1472-6483(10)62125-6.
PubMed 15333245Kattera S, Chen C. Cryopreservation of embryos by vitrification: current development. Int Surg. 2006 Sep-Oct;91(5 Suppl):S55-62.
PubMed 17436605Kuwayama 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. doi: 10.1016/s1472-6483(10)61169-8.
PubMed 16409712Kuwayama M. Highly efficient vitrification for cryopreservation of human oocytes and embryos: the Cryotop method. Theriogenology. 2007 Jan 1;67(1):73-80. doi: 10.1016/j.theriogenology.2006.09.014. Epub 2006 Oct 20.
PubMed 17055564Liebermann 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. doi: 10.1095/biolreprod.102.006833.
PubMed 12444040Liebermann 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. doi: 10.1016/s1472-6483(10)62084-6.
PubMed 14748959Liebermann 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. doi: 10.1016/j.fertnstert.2006.01.029. Epub 2006 Jun 8.
PubMed 16762345Loutradi 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. doi: 10.1016/j.fertnstert.2007.06.010. Epub 2007 Nov 5.
PubMed 17980870Nawroth 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. doi: 10.1055/s-2005-923390.
PubMed 16317621Rama 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. doi: 10.1016/s1472-6483(10)61135-2.
PubMed 16274602
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Comparison to Freeze Human Embryos by Either Vitrification or Slow Freezing Protocols
- ClinicalTrials.gov ID
- NCT00910390
- Acronym / sponsor ID
- VITR-1-EMBRYOS
- Conditions
- Human Embryo Cryopreservation
- Keywords
- IVF, embryo cryopreservation, vitrification, Human Embryo, Embryonic development, Pregnancy rate
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 584 participants (actual)
- Lead sponsor
- Erasme University HospitalUniversity, hospital or other
- Study start
- Apr 2009
- Primary completion
- Oct 2009 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 29 May 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Slow Freezing | Placebo comparator | Other: Slow freezingStandard freezing protocol (slow freezing) of preimplantation embryos |
| VIT-Irvine | Experimental | Other: VIT-IrvineVitrification with Irvine solution (rapid freezing) of preimplantation embryos |
| VIT-Vitrolife | Experimental | Other: Vit-VitrolifeVitrification (rapid freezing) with Vitrolife solution |
Who may qualify
- Ages
- 18 to 43 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Infertility requiring IVF
Key exclusion criteria (3 listed)
- Women's age > 43 years
- Patients positive for hepatitis B or C
- Patients positive for HIV
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Slow freezingAlso: Home-made solutions, propanediolEmbryos 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. | Other | Slow Freezing |
| VIT-IrvineAlso: IRVINE, California, ethylene glycol, DMSOEmbryos 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. | Other | VIT-Irvine |
| Vit-VitrolifeAlso: VITROLIFE, Sweden, ethylene glycol, propanediolEmbryos 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. | Other | VIT-Vitrolife |
Primary outcome
Survival embryo rate
Time frame: one year
1 secondary outcome
Delivery rate
Time frame: one year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2016.
- Background: PubMed 17359578Al-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. doi: 10.1016/s1472-6483(10)60869-3.
- Background: PubMed 18544577Balaban 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.
- Background: PubMed 17298725Desai 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. doi: 10.1016/s1472-6483(10)60789-4.
- Background: PubMed 17681342Escriba MJ, Zulategui JF, Galan A, Mercader A, Remohi 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. doi: 10.1016/j.fertnstert.2007.04.035. Epub 2007 Aug 6.
- Background: PubMed 15471932Huang 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. doi: 10.1093/humrep/deh540. Epub 2004 Oct 7.
- Background: PubMed 15333245Kasai M, Mukaida T. Cryopreservation of animal and human embryos by vitrification. Reprod Biomed Online. 2004 Aug;9(2):164-70. doi: 10.1016/s1472-6483(10)62125-6.
- Background: PubMed 17436605Kattera S, Chen C. Cryopreservation of embryos by vitrification: current development. Int Surg. 2006 Sep-Oct;91(5 Suppl):S55-62.
- Background: PubMed 16409712Kuwayama 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. doi: 10.1016/s1472-6483(10)61169-8.
- Background: PubMed 17055564Kuwayama M. Highly efficient vitrification for cryopreservation of human oocytes and embryos: the Cryotop method. Theriogenology. 2007 Jan 1;67(1):73-80. doi: 10.1016/j.theriogenology.2006.09.014. Epub 2006 Oct 20.
- Background: PubMed 12444040Liebermann 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. doi: 10.1095/biolreprod.102.006833.
- Background: PubMed 14748959Liebermann 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. doi: 10.1016/s1472-6483(10)62084-6.
- Background: PubMed 16762345Liebermann 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. doi: 10.1016/j.fertnstert.2006.01.029. Epub 2006 Jun 8.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne Delbaere, Ph.D. study director
Fertility Clinic, Hospital Erasme
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Slow freezing, VIT-Irvine and Vit-Vitrolife in people with Human Embryo Cryopreservation, run by Erasme University Hospital at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival embryo rate (time frame: one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00910390, which also lists 19 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2016; AzTrials last refreshed its copy on 30 Oct 2026.