Clinical trial NCT04969575: A Benchtop Incubator Prospective Study
Official title: Exploring Single Step Culture Medium Refreshment Effect on Embryo Ploidy Rate: A Benchtop Incubator Prospective Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Infertility
Keywords: IVF
incubator
aneuploidy
embryoscope
embryo
ICSI
Lead sponsor: ART Fertility Clinics LLC
Sponsor class: OTHER
First posted: 2021-07-20
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study is eligible to all patients, meeting the inclusion criteria, undergoing a fertility treatment with PGT-A analysis at the blastocyst stage

Brief summary: The use of extended embryo culture to the blastocyst stage and preimplantation genetic testing for aneuploidy (PGT-A) has enabled identification and selection of embryos with the best developmental potential and improved in vitro fertilization (IVF) clinical outcomes. While numerous types of commercially available human embryo culture media exist for culture to the blastocyst stage, the impact of culture conditions on blastocyst development and aneuploidy formation is not well understood.

Culture conditions are very important for the success of the IVF cycle, many of the factors involved in the process have been extensively studied, including the use of sequential culture medium vs single step culture medium, humidified incubators vs dry incubators and refreshing the medium on day 3 vs uninterrupted culture till day 5. However, none of the studies investigated the effect on euploid rate in a sibling oocyte design with PGT-A, which requires culture till day 7.

Detailed description: It is considered a routine practice to grade the embryos on day 3 of development, which will require disturbing the culture conditions by annotating the embryos using inverted microscopes. Extended culture to day 7 is required in order to perform trophectoderm biopsy required for PGT-A. There are several culture factors that can affect embryo development, such as the pH, which is controlled through the concentration of CO2, and also the osmolality, which is the concentration of solute per liter of solution. Evaporation of the solution due to the exposure to high temperature (37°C) can change the concentrations and hence compromise embryo development.

To reduce the rate of evaporation, culture droplets are covered with a layer of mineral oil. Humidified incubators can also reduce the rate of evaporation. However, in the case of dry incubators, such as benchtop incubators, replenishing the culture medium at least once -by moving the embryos to a new culture dish- during these 7 days of culture might be the solution.

Since single-step medium is designed to sustain embryo development for 5 continuous culture days, while some laboratories culture embryos for 7 days, refreshing the culture medium is inevitable either on day 3 or day 5 of development.

There is no concrete evidence on which of these practices will provide a better environment for embryo development. Moreover, none of the studies investigated the effect of single-step culture medium changeover on day 3 or day 5, on the chromosomal errors (aneuploidy/mosaicism). Investigators aim in this prospective sibling oocyte study, to explore which day of culture medium refreshment (day 3 or day 5) provides a higher rate of euploid blastocysts.

Eligibility criteria: Inclusion Criteria:

* Patients with a minimum of 8 - 10 follicles during ovarian stimulation
* Patients with a minimum of 8 mature oocytes
* PGT-A
* ICSI
* BMI\<35
* Age 18- 40
* Fresh or frozen ejaculated sperm \>10,000 motile sperm
* Any ovarian stimulation
* Embryos cultured in benchtop incubator

Exclusion Criteria:

* PGT-M or PGT-SR
* Previous history of embryo arrest
* Endometriosis
* History of previous treatment which may impact the ovarian reserve (adnexal surgery, chemotherapy, radiation...)

Primary outcomes:
measure: Blastocyst ploidy
timeFrame: 3 days
Secondary outcomes:
measure: Cycle ploidy rate
timeFrame: 1 day
measure: Mosaicism Frequency
timeFrame: 1 day
measure: Blastocyst quality at time of biopsy
timeFrame: 1 day
measure: Blastulation rate
timeFrame: 5 days
Other outcomes:
Locations:
city: Abu Dhabi
country: United Arab Emirates
facility: ART Fertility Clinics LLC
Study officials:
affiliation: ART Fertility Clinics LLC
name: IBRAHIM ELKHATIB
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bavister BD, Poole KA. Duration and temperature of culture medium equilibration affect frequency of blastocyst development. Reprod Biomed Online. 2005 Jan;10(1):124-9. doi: 10.1016/s1472-6483(10)60813-9.
citation: Costa-Borges N, Belles M, Meseguer M, Galliano D, Ballesteros A, Calderon G. Blastocyst development in single medium with or without renewal on day 3: a prospective cohort study on sibling donor oocytes in a time-lapse incubator. Fertil Steril. 2016 Mar;105(3):707-713. doi: 10.1016/j.fertnstert.2015.11.038. Epub 2015 Dec 12.
citation: Pena F, Davalos R, Rechkemmer A, Ascenzo A, Gonzales M. Embryo development until blastocyst stage with and without renewal of single medium on day 3. JBRA Assist Reprod. 2018 Mar 1;22(1):49-51. doi: 10.5935/1518-0557.20180012.
citation: Krasnopolskaya KV, Beketova AN, Sesina NI, capital ES, Cyrillichinchenko NK, Badalyan GV, Sudarikova NM, Bocharova TV, Zakharchenko EO. The effect of short-term disturbance of day 3 embryo culture on the development and implantation. Gynecol Endocrinol. 2019;35(sup1):1-4. doi: 10.1080/09513590.2019.1632083.