Paired Non-inferiority Study Comparing Overture Semi-automated Vitrification System ("DaVitri") to Standard Manual Process for Clinical Pregnancy Outcomes

Overview

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.

Interventions

• Device Oocyte Cryopreservation
  The DaVitri System is intended to semi-automate vitrification preparation of human oocytes. The Overture Semi-Automated Vitrification System ("DaVitri") is a medical device that uses semi-automated oocyte vitrification. The system comprises the DaVitri Station, and the DaVitri Dish. The DaVitri Station is a piece of capital equipment with touch screen control that manages the vitrification preparation. The DaVitri Dish is a cartridge-like device onto which oocytes and vitrification reagents ar

Primary outcome measures

• Clinical Pregnancy Rate [Time frame: From enrollment to 6-7 weeks]

Secondary outcome measures (8)

• Warming survival rates of oocytes [Time frame: From enrollment to 2 weeks]
• Fertilization Rates [Time frame: From enrollment to 2 weeks]
• Gardner Score [Time frame: From enrollment to 2 weeks]
• Blastocyst Formation [Time frame: From enrollment to 2 weeks]
• Implantation rate [Time frame: From enrollment to 3 weeks]
• On-going pregnancy rate [Time frame: From enrollment to 12 weeks]
• Congenital abnormality rate [Time frame: From enrollment to 9 months]
• Delivery success rate [Time frame: From enrollment to 9 months]

Eligibility criteria

Inclusion criteria

\- Inclusion Criteria (donors) Ages 18-35 AMH range (2-10) ng/ml Healthy females (no pre-existing medical conditions)

Inclusion Criteria (recipient) Undergoing an in-vitro fertilization (IVF) cycle with egg donation Premenopausal female, 18-45 years of age Normal uterine cavity Single embryo transfer

Exclusion criteria

\- Exclusion Criteria (donors) 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)

Sperm Exclusion Criteria Severe male factor Infertility (unless donated sperm is used) Alcoholism, drug addiction

Exclusion Criteria (recipients) 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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Other

Study locations

United States · 1 center

• Lane Fertility Institute — Novato

Identifiers

NCT: NCT06853418 · CP-DV-000-GEN-004

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗