Plain English Summary
Background and study aims
Cryopreservation is the use of very low temperatures to preserve living cells and tissues. Sperm cryopreservation is an essential procedure of Assisted Reproduction Technologies (ART) to preserve male fertility and ensure that the specimen is available on the day of the egg retrieval regardless of the availability of the male partner. Currently, the most commonly used technique for sperm cryopreservation is slow freezing. Nevertheless, this technique has been shown to decrease sperm quality. During the last years, vitrification has been proposed as an alternative to conventional freezing. This technique is based on the ultra-rapid descent and rise of temperatures, avoiding ice crystal formation and its associated effects. Vitrification improves cell survival rates and reduces cell damage. This technique has been widely used for eggs and embryos but it has been hardly applied to human sperm. Recently, the development of EasySperm®, a new cryoprotectant-free vitrification method for human sperm, provided an improved and reliable alternative for sperm cryopreservation. This new method has been tested in normal sperm samples with better preservation of sperm quality compared to slow freezing. The aim of this study is to compare the effectiveness of the EasySperm® vitrification protocol with conventional slow freezing in ART cycles.
Who can participate?
Couples who are interested in ART with an egg donation program. The male patients should have normal sperm and be aged less than 45. The female patients should have no endometrial (womb lining) alterations and be aged less than 48.
What does the study involve?
Patients are randomly allocated to one of two groups: group 1: vitrification and group 2: slow freezing. In both groups sperm cryopreservation is performed using both the vitrification and slow freezing techniques. Half of the donated eggs are fertilised with vitrified/warmed sperm and the other half with frozen/thawed sperm. All embryos are grown to day 5 and single good quality embryos are transferred to the woman's womb. In group 1 the embryo is selected from the embryos produced by the vitrified/warmed sperm. In group 2 the embryo is selected from the embryos produced by the frozen/thawed sperm. Sperm fertilisation ability, embryo quality and developmental potential and clinical outcomes are assessed and compared between the groups.
What are the possible benefits and risks of participating?
The results will show which technique is the best to be used in daily practice. The cryopreservation protocol based on vitrification is expected to result in better embryo development and quality and improved clinical outcomes. There are no risks of participating.
Where is the study run from?
1. IVF Spain Alicante (Alicante, Spain)
2. IVF Donostia (San Sebastian, Spain)
When is the study starting and how long is it expected to run for?
May 2016 to August 2020
Who is funding the study?
IVF Spain Foundation (Spain)
Who is the main contact?
Ms Llanos Medrano López-Tello
Trial website
Contact information
Type
Scientific
Primary contact
Ms Llanos Medrano
ORCID ID
http://orcid.org/0000-0002-7053-7423
Contact details
Av. Ansaldo
Alicante
03540
Spain
+34 (0)965267890
mll.lopez@ivf-spain.com
Type
Scientific
Additional contact
Dr Maria Enciso
ORCID ID
http://orcid.org/0000-0002-3238-7065
Contact details
Carrer Britania
Alacant
03540
Spain
+34 (0)618 77 40 99
m.enciso@igls.net
Type
Scientific
Additional contact
Dr Yosu Franco
ORCID ID
Contact details
Begiristain Doktorea Pasealekua
Donostia
20014
Spain
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
2016ACE
Study information
Scientific title
Comparison of the efficacy of EasySperm® vitrification protocol vs conventional slow freezing in assisted reproduction treatments
Acronym
CEES
Study hypothesis
The cryopreservation protocol based on vitrification is expected to result in better embryo development and quality and improved clinical outcomes.
Ethics approval
Alacant General Hospital, 01/07/2016, ref: CEIC PI2016/18
Study design
Prospective randomised trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Specialty: human fertility / Disease: No specific disease
Intervention
The method of randomisation: the history number of the patients is used for the randomisation: odd number goes to group 1, even number to group 2.
Group 1: Sperm cryopreservation will be performed using both vitrification and slow freezing techniques. Half of the donated oocytes will be fertilised with vitrified spermatozoa and the other half with frozen spermatozoa. The best single good morphological quality blastocyst (BB quality at least) among the embryos produced by vitrified/warmed spermatozoa will be selected and transferred.
Group 2: Sperm cryopreservation will be performed using both vitrification and slow freezing techniques. Half of the donated oocytes will be fertilised with vitrified spermatozoa and the other half with frozen spermatozoa. The best single good morphological quality blastocyst (BB quality at least) among the embryos produced by frozen/thawed spermatozoa will be selected and transferred.
Sperm fertilisation ability, embryo quality and developmental potential and clinical outcomes will be assessed and compared between the groups. The duration of follow-up is around 4 years.
Intervention type
Procedure/Surgery
Phase
Drug names
Primary outcome measure
Pregnancy rates, measured using the hormone β-HCG for the positive beta, echography for the presence of sac, cardiac activity, all measured at one time (10 days after embryo transfer for the beta, in the 4th or 5th week after embryo transfer and 7th-9th week after embryo transfer, respectively). The results of the birth are obtained 10 months after embryo transfer.
Secondary outcome measures
1. Sperm quality parameters (sperm count, motility, morphology, vitality, apoptosis and DNA integrity measured by flow cytometry), measured on the day of egg retrieval (post cryopreservation)
2. Sperm competence in terms of fertilization rate and blastocyst formation rate. The fertilization rate is the number of zygotes with good fertilization vs number of eggs, recorded the day after egg retrieval (day 1 of development). The blastocyst formation rate is the number of blastocyst vs zygotes, recorded on day 5 and 6 of development.
3. Embryo quality measured using Gardner’s cataloging (Gardner DK, Schoolcraft WB, 2008) and the kinetics of the embryos measured using an incubator with time-lapse technology. The embryo quality is assessed on day 5 and 6 (once a day) and the time-lapse data are collected on day 5 of development (once a day)
4. Chromosome status evaluated by PGD-A (Preimplantation Genetic Diagnosis for aneuploidy) and the results are obtained 20 days after egg retrieval
Overall trial start date
01/05/2016
Overall trial end date
31/08/2020
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Couples who are interested in ART with an egg donation program
2. The male patients have to present a normozoospermic spermiogram and an age less than 45
3. The female patients have not to present endometrial alterations and an age less to 48
Participant type
Health professional
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 100
Participant exclusion criteria
1. Couples who are interested in ART with own eggs
2. Male patients with not normozoospermic spermiogram and an age greater than 45
3. Female patients with endometrial alterations and more than 48 years old
Recruitment start date
13/07/2016
Recruitment end date
31/08/2019
Locations
Countries of recruitment
Spain
Trial participating centre
IVF Spain
Av. Ansaldo
Alicante
03540
Spain
Sponsor information
Organisation
iGLS
Sponsor details
Carrer Britania
Alicante
03540
Spain
Sponsor type
Other
Website
Funders
Funder type
Hospital/treatment centre
Funder name
IVF Spain Alicante
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Academic outputs will include a minimum of two papers submitted to high-impact peer reviewed journals, and at least three conference presentations or workshops.
IPD sharing statement
The datasets generated during and/or analysed during the current study are/will be available upon request from Ms Llanos Medrano López-Tello.
Intention to publish date
30/12/2020
Participant level data
Available on request
Basic results (scientific)
Publication list