Vitrification Systems for Egg Freezing
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: Overture Life
Disqualifiers: Age, Bmi, Uterine pathologies, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This study will recruit 260 female recipients (and up to a maximum of 130 donors). This study is a sequel to the protocol CP-DV-000-GEN-003, entitled, "NON-INFERIORITY STUDY COMPARING OVERTURE SEMI-AUTOMATED VITRIFICATION SYSTEM ("DaVitri") TO STANDARD MANUAL PROCESS USING BLASTOCYST RATE AS THE PRIMARY END POINT".
Donors will provide informed consent and will be enrolled before egg retrieval. Once the oocytes are retrieved, they will undergo thorough denudation to remove corona cells and will be assessed for maturity. Subsequently, mature MII oocytes exhibiting good morphology, as per the Vienna Consensus, ranging between 12 and 30 in number, will be processed.
These oocytes will then be randomly divided into groups comprising 6 to 8 oocytes each. Therefore, from a single donor, 2 to 4 groups can be generated. An identifier will be assigned for each group. One of the groups will be randomly selected. This group will be randomly assigned to DaVitri or Control. The remaining groups will be randomly selected and assigned alternatively to Control and DaVitri groups:
Control oocytes will be manually vitrified and placed into cryogenic storage. Test oocytes will be prepared for vitrification using the DaVitri system. Following preparation with DaVitri, test oocytes will be loaded onto a cryogenic device that is placed into cryogenic storage.
The same preservation media (Kitazato) will be used to prepare all oocytes.
All oocytes will be warmed manually. Survival rate will be recorded following warming. After warming, the oocytes will be fertilized via Intracytoplasmic Sperm Injection (ICSI) with either donor or patient's partner sperm and resulting embryos cultured to blastocyst stage, keeping score of which embryos come from the Test or Control group. Fertilization rate will be recorded.
Embryos will be morphologically assessed (according to Gardner grading system) on day 5-6 to determine blastulation rates and embryo quality in both groups. All the embryos will be vitrified according to the clinic\'s routine process and stored for further recipients.
Recipients will provide informed consent and will be enrolled before the retrieval of donor eggs. Once the donor has been matched with the recipient according to the phenotypic, demographic characteristics (following the regular clinical process established in the clinic donation program), the group of oocytes assigned will be randomly selected from either the DaVitri processed group or the manually processed group. Recipients of donated eggs will receive a single embryo transfer (SET).
The primary endpoint is Clinical Pregnancy Rate. Clinical Pregnancy will be confirmed by the presence of sac in uterus and chemical confirmation at 6-7 weeks after embryo transference, via ultrasound. Only the first embryo transfers will be used to calculate the primary endpoint. Successive transfers of any embryo group will not be considered inside the study.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the treatment Oocyte Cryopreservation for egg freezing?
Research shows that improvements in vitrification (a fast freezing method) have significantly increased pregnancy rates over the past five years. Closed vitrification systems, which avoid direct contact with liquid nitrogen, have been validated for routine use in egg donation programs, with higher oocyte survival rates linked to increased chances of pregnancy.
12345Is egg freezing (oocyte vitrification) safe for humans?
Oocyte vitrification, a method used for egg freezing, appears to be safe for both the eggs and the resulting children in the short term, according to studies involving over 4,000 babies. However, more long-term data is needed to fully understand its safety.
678910How does the treatment Oocyte Cryopreservation differ from other treatments for egg freezing?
Oocyte Cryopreservation, or egg freezing, is unique because it uses a process called vitrification, which involves ultra-rapid cooling to prevent ice crystal formation that can damage the eggs. This method is distinct from traditional slow-freezing techniques and is designed to preserve the quality and viability of the eggs more effectively.
1112131415Eligibility Criteria
This trial is for up to 260 women receiving egg donations and a maximum of 130 donors. Donors must provide mature, good quality eggs, while recipients are matched based on phenotypic and demographic characteristics. Participants need to consent to the use of their eggs or embryos in the study.Inclusion Criteria
I am a healthy female aged 18-35 with an AMH level between 2-10 ng/ml.
I am a woman aged 18-45, using a donated egg for IVF, with a normal uterus, planning to transfer one embryo.
Exclusion Criteria
Age >35 years of age BMI <18.5 or >25 Infertility history Three previously failed IVF cycles, including abortions Abnormal ovulation cycle FSH >10 or AMH <2 Alcoholism, drug addiction Infectious diseases (such as HIV, hepatitis, sexually transmitted infections) Donors producing less than 12 mature oocytes of good quality (according to Vienna Consensus criteria) (donors)
Severe male factor Infertility (unless donated sperm is used) Alcoholism, drug addiction (sperm)
Age >45 years of age BMI <18.5 or >29 Patients using a surrogate Evidence of uterine pathologies Severe male factor Infertility (unless donated sperm is used) Alcoholism, drug addiction Infectious diseases (such as HIV, hepatitis, sexually transmitted infections) (recipients)
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Oocyte Retrieval and Vitrification
Donors provide oocytes which are then vitrified using either the DaVitri system or manually, and stored in cryogenic storage.
2 weeks
Fertilization and Embryo Culture
Oocytes are warmed, fertilized via ICSI, and cultured to the blastocyst stage. Embryos are assessed for quality and vitrified for future transfer.
2 weeks
Embryo Transfer and Initial Pregnancy Assessment
Recipients receive a single embryo transfer, and clinical pregnancy is confirmed by ultrasound and chemical tests at 6-7 weeks post-transfer.
6-7 weeks
Follow-up
Participants are monitored for ongoing pregnancy and delivery success, with assessments for congenital abnormalities and delivery outcomes.
9 months
Participant Groups
The study compares two methods of freezing eggs: DaVitri (a semi-automated system) versus manual vitrification. Eggs from each donor are split into groups and randomly assigned to either method before being fertilized and grown into embryos for transfer.
2Treatment groups
Experimental Treatment
Active Control
Group I: Test OocytesExperimental Treatment1 Intervention
Test oocytes will be prepared for vitrification using the DaVitri system. Following preparation with DaVitri, test oocytes will be loaded onto a cryogenic device that is placed into cryogenic storage.
Group II: Manually vitrified oocytesActive Control1 Intervention
Control oocytes will be manually vitrified and placed into cryogenic storage.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Lane Fertility InstituteNovato, CA
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Who Is Running the Clinical Trial?
Overture LifeLead Sponsor
References
Evolution of human oocyte cryopreservation: slow freezing versus vitrification. [2018]The purpose is to determine the efficiency and efficacy of oocyte cryopreservation by slow freezing versus vitrification, recent data collected from the Italian National Assisted Reproductive Technology Register during the period 2009-2014 will be presented and reviewed. The data on oocyte cryopreservation were also compared with the results obtained with embryo cryopreservation and relative IVF with fresh oocytes.
Closed vitrification system and egg donation: Predictive factors of oocyte survival and pregnancy. [2021]Although many studies have demonstrated the superiority of ultra-fast freezing compared with slow freezing, the debate is still ongoing concerning the best type of vitrification method: direct exposure to liquid nitrogen (i.e., open systems), or sterile system without contact with liquid nitrogen (i.e., closed systems). The aims of this study were to share our experience on closed vitrification systems in the framework of our egg donation programme with fully asynchronous cycles, and to identify predictive factors of successful outcome in this context. Logistic regression analysis indicated that the number of vitrified oocytes was the only factor predictive of the oocyte survival rate and of clinical pregnancy. The addition of one vitrified oocyte increased by 15 % the odds of oocyte survival. When the oocyte survival rate was considered as a continuous variable, the following results were obtained: 7 % of clinical pregnancy probability for 50 % survival rate, 15 % for 75 % survival rate, and 32 % for 100 % survival rate. The rates of oocyte survival and fertilization, embryo implantation, and clinical pregnancy were in agreement with the recommended values established by ALPHA Scientists in Reproductive Medicine in 2012. On the basis of these results, and according to the European directives on safety, we validate the routine use of closed oocyte vitrification systems for egg donation programmes. These results must be confirmed in larger samples before extrapolation to all patient types.
Oocyte cryopreservation: advances and drawbacks. [2012]The field of oocyte cryopreservation (OC) had advanced dramatically since the first reported birth from cryopreserved oocytes in 1986, with a significant increase in pregnancy rates described over the past 5 years due to improvements in vitrification technology, a cryopreservation method which virtually means to achieve a "glass-like" state through avoidance of ice formation. The potential clinical benefits of achieving efficient OC protocols have long been recognized. Specifically, OC can be offered to women who face fertility-threatening situations such as therapy for cancer or rheumatologic disease, premature ovarian insufficiency, or need for ovarian surgery as a measure to preserve fertility. Moreover, many women who plan to delay childbearing are interested in pursuing OC in order to protect against age-related fertility decline. For infertility practices, efficient OC technology stands to dramatically streamline donor egg programs, and is a helpful adjuvant in situations where sperm is unexpectedly unavailable at the time of egg retrieval and for couples who do not wish to cryopreserve supernumerary embryos created from in vitro fertilization for moral / ethical reasons. This review will describe the history of OC technology over the past three decades, discuss clinical circumstances for its implementation, and address areas where more research is needed. Given the remarkable improvements in pregnancy rates witnessed over the past five years, OC is certain to play a much larger role in reproductive medicine over the coming decades.
Obstetric and perinatal outcome of babies born from vitrified oocytes. [2022]To assess outcomes after oocyte vitrification on obstetric and perinatal outcomes compared with those achieved with fresh oocytes.
Use of cryo-banked oocytes in an ovum donation programme: a prospective, randomized, controlled, clinical trial. [2022]An efficient oocyte cryopreservation method is mandatory to establish a successful egg-banking programme. Although there are increasing reports showing good clinical outcomes after oocyte cryopreservation, there is still a lack of large controlled studies evaluating the effectiveness of oocyte cryo-banking. In this study, we aimed to compare the outcome of vitrified-banked oocytes with the gold standard procedure of employing fresh oocytes.
The Impact of Oocyte Vitrification on Offspring: a Systematic Review. [2022]Oocyte vitrification is a widespread and well-established assisted reproduction technique that has enabled some patient groups to obtain clinical results equivalent to those using fresh oocytes. However, as the number of babies born from vitrified oocytes has increased, so has the discussion regarding the method's safety for the offspring. Cryogenic oocyte damage caused by chemical, mechanical, and thermal stress has raised concern. In this systematic review, we asked the question of whether oocyte vitrification impacts offspring health. From 2007 to 2021, 13 studies were included in the analysis. All studies were observational and presented neonatal outcomes. A total of 4,159 babies were analyzed. Data from these studies were used to assess the following outcomes: multiple pregnancies, cesarean section, gestational age at delivery, the number of live births, birth weight, Apgar scores, congenital anomalies, and baby health. The most extended follow-ups evaluated children until 1, 2, and 6 years of age. According to the evidence appraised in this systematic review, vitrification seems to be a safe method for oocyte cryopreservation and child health, at least in the short term. Nevertheless, there is an urgent need for additional long-term data results from big databases and also for randomized controlled trials to improve the levels of evidence.
Oocyte and embryo cryopreservation before gonadotoxic treatments: Principles of safe ovarian stimulation, a systematic review. [2022]Review the safety of fertility preservation through ovarian stimulation with oocyte or embryo cryopreservation, including cycle and medication options.
Female fertility: is it safe to "freeze?". [2019]To evaluate the safety and risk of cryopreservation in female fertility preservation.
Human oocyte cryopreservation: evidence for practice. [2009]The aim of this article is to review the evidence regarding human oocyte cryopreservation by slow freezing and vitrification and to provide evidence-based clinical and laboratory guidelines on the effectiveness and safety of these technologies.
Risks associated with cryopreservation: a survey of assisted conception units in the UK and Ireland. [2016]A number of recent, high-profile incidents involving loss or damage to cryopreserved material held in IVF units or sperm storage centres have highlighted the need for centres to carefully review their cryostorage practice and take action. Critical disasters involving lost or damaged patient material, although high profile, are still thought to be rare, and there has been concern that we should ensure that any response is proportionate to risk. However, as no regulators, manufacturers or similar professional disciplines have collected information in the long term, our knowledge of the true incidence of such adverse events is extremely poor. Recognizing the need for some solid data, the UK Association of Clinical Embryologists (ACE) conducted a survey on the subject, at its joint meeting with the Association of Irish Clinical Embryologists (ICE) (January, 2006). Questions were asked in relation to the risk of: injury to personnel; and potential loss of and potential damage to stored material. The number of serious and not so serious adverse events/situations relating to both staff and sample safety are discussed in detail. The incidence of problems was certainly higher than we had imagined; the lack of general training and awareness amongst our staff is a serious cause for concern, and appears to leave the industry vulnerable. Moreover, the survey highlighted the need for a coordinated approach to the collection of more detailed information both prospectively and retrospectively. Regulators, manufacturers, allied professional bodies and, more importantly, centres should be encouraged to share both recent and historic data relating to adverse events, in order that accurate risk assessments can be made in future.
Preservation of human ovarian follicles within tissue frozen by vitrification in a xeno-free closed system using only ethylene glycol as a permeating cryoprotectant. [2013]To study the preservation of follicles within ovarian tissue vitrified using only one or a combination of three permeating cryoprotectants.
A new, simple, automatic vitrification device: preliminary results with murine and bovine oocytes and embryos. [2019]This paper reports the use of a novel automatic vitrification device (Sarah, Fertilesafe, Israel) for cryopreservation of oocytes and embryos.
New methods for cooling and storing oocytes and embryos in a clean environment of -196°C. [2017]It is well documented that oocyte vitrification using open systems provides better results than closed systems. However, its use is limited owing to risks of contamination posed by direct exposure to liquid nitrogen and cross-contamination when stored in liquid nitrogen tanks. A device that produces clean liquid air (CLAir) having similar a temperature as liquid nitrogen and a sterile storage canister device (Esther) that keeps samples sealed in their own compartment while in regular liquid nitrogen tanks were developed. The following experiments were performed: temperature measurements, bioburden tests, vitrification and storage experiments with mice embryos and human oocytes. Results showed similar cooling rates for liquid nitrogen and liquid air. Bioburden tests of CLAir and Esther showed no contamination, while massive contamination was found in "commercial" liquid nitrogen and storage canisters. Mice blastocysts had a survival rate of over 90%, with 80% hatching rate after vitirification in CLAir and 1 week storage in Esther, similar to the fresh (control) results. Human oocytes vitrified in CLAir and in liquid nitrogen for three consecutive vitrification/warming cycles showed 100% survival, seen as re-expansion in both groups. These new systems represent a breakthrough for safe vitrification using open systems and a safe storage process generally.
A chronologic review of mature oocyte vitrification research in cattle, pigs, and sheep. [2012]Vitrification as a means of cryopreservation has become a standard approach for oocytes from livestock. This paradigm shift occurred primarily as a result of the demonstration in 1996 that bovine oocytes are extremely susceptible to chilling injury. Since that early work, numerous devices have been used as supports for oocytes during so-called "ultra-rapid cooling", and occasionally, trials involving the deposition of small volumes of media containing oocytes directly into liquid nitrogen to facilitate cooling have been reported. Results reporting blastocyst development exceeding 10% are common, but variability remains high, and a standard method for bovine oocytes remains to be established. Oocytes from pigs are particularly difficult to cryopreserve, even with the use of ultrarapid cooling approaches. Few reports have demonstrated blastocyst development exceeding 5%. The application of hydrostatic pressure before vitrification appears to impart stress tolerance to porcine oocytes, as the results of some treatments have shown development to blastocysts at proportions >10%. Work on sheep oocyte vitrification is relatively new, and a few articles have reported blastocyst development at 10% or more. Messenger RNA levels are reportedly altered in sheep oocytes as a result of vitrification, and damage to the cytoskeleton is common across species.
Theoretical and experimental basis of oocyte vitrification. [2011]In the last decades significant advances have been made in successful cryopreservation of mammalian oocytes. Human oocyte cryopreservation has practical application in preserving fertility for individuals at risk of compromised egg quality due to cancer treatments or advanced maternal age. While oocyte cryopreservation success has increased over time, there is still room for improvement. Oocytes are susceptible to cryodamage; which collectively entails cellular damage caused by mechanical, chemical or thermal forces during the vitrification and warming process. This review will delineate many of the oocyte intracellular and extracellular structures that are/may be stressed and/or compromised during cryopreservation. This will be followed by a discussion of the theoretical basis of oocyte vitrification and warming, and a non-exhaustive review of current experimental data and clinical expectations of oocyte vitrification will be presented. Finally, a forward-thinking vision of a potential means of modifying and improving vitrification and warming procedures and success will be proposed. This review addresses theoretical and experimental evidence accumulated over the last two decades supporting the application of vitrification and warming to oocyte cryopreservation. Issues ranging from clinical needs for oocyte cryopreservation, cryopreservation-induced stresses and normal oocyte function, practical application of vitrification-warming of oocytes, and potential future directions will be discussed. In addition, we debate commonly discussed technical methods of oocyte vitrification-warming that may not necessarily be grounded in scientific knowledge. Instead these methodologies are many times theoretical, potentially empirical and commonly lack significant testing and scientific rigor. Questions include: (i) what is the best cryoprotectant? (ii) are some cryoprotectants more toxic compared with others? (iii) how should cryosolutions be mixed with cells? (iv) is there a best container for vitrification? (v) is there a threshold cooling-warming rate or is a faster rate always better? and finally (vi) should oocytes be vitrified with or without adjacent cells? With this said, it is recognized that important advancements have been made in the past decade in oocyte cryopreservation, many times through empirical findings. Finally, we propose some new areas of research that may influence future success of oocyte vitrification and warming, fully recognizing that these theories require mechanical and biological experimental testing.