Effect of Antioxydant-enriched Media on Blastocyst Euploidy Rates.

Official title

Antioxidants-enriched Single-step vs Global Total Single-step Embryo Culture Media: Effect on Blastocyst Euploidy Rates.

Overview

One of the most sensible factors in IVF culture conditions is the susceptibility of gametes and embryos to an induced increase in reactive oxidative species (ROS) caused by the artificial environment. This study aims to evaluate the impact of using antioxidant-supplemented media during culture to evaluate embryo ploidy rates in a prospective randomized trial using sibling oocytes.

Detailed description

Improvements in culture conditions is an ongoing process in IVF due to, on one hand, the still lack of knowledge on human embryonic development, and, on the other hand, the frequent need for repeated IVF cycles to achieve an 'implantable' embryo. The main factor for optimizing conditions of an embryo to develop is its microenvironment, mainly the culture media used. One of the most sensible factors in IVF culture conditions is the susceptibility of gametes and embryos to an induced increase in reactive oxidative species (ROS) caused by the artificial environment, as it has been extensively shown in animal models and to a certain extent in humans.

A primordial step for improvement is to alleviate an increase in ROS during embryo development. This can be manipulated by means of utilizing a culture media with supplements that can serve as scavengers, leading to an equilibrium between oxidation and reduction of ROS during the culture period. So far, the produced culture media contain low concentrations of limited additives involved in anti-oxidative stress. Recently, a culture medium containing an implementation in higher doses of distinctive elements known to clearly serve as cellular scavengers has been formulated. However, very few human IVF studies have been performed up to date. Our research intends to investigate the incorporation of antioxidant-rich culture media into IVF practices with the primary objective of analyzing its impact on embryo euploidy, as well as the previous culture steps including fertilization and blastocyst developmental rates. This study aims to evaluate the impact of using antioxidant-supplemented media during culture to evaluate embryo ploidy rates in a prospective randomized trial using sibling oocytes.

Interventions

• Drug antioxidants-enriched culture medium (Gx)
  Blastocyst will be in continuous culture conditions (parallel antioxidants-enriched culture medium (Gx) and Global total one step media (GT) without refreshment on day 3. A refreshment of the media will be done on D5 in both groups.

Primary outcome measures

• Blastocyst ploidy is determined after a biopsy of trophectoderm cells, taken from the blastocyst on day 5, 6 or 7 from development. The following outcomes are possible: • Normal • Abnormal • No result/Inconclusive • Low or high Mosaic [Time frame: 1 year]

Secondary outcome measures (1)

• Cycle ploidy rate: the number of euploid embryos in the group Blastocyst quality at the time of biopsy based on modified Gardner's criteria. Usable blastocyst rate per group and per day of biopsy (day 5, 6, 7) [Time frame: 1 year]

Eligibility criteria

Inclusion criteria

• Patients undergoing assisted reproductive technology cycles when ICSI is indicated.
• Patients when Iin vitto fertilization (IVF) is also performed will be included as far as there are enough oocytes for ICSI randomization. However, IVF oocytes will not be used for the study.
• Maternal age 18-43 years old.
• PGT-A cycles with only trophectoderm biopsies on day 5/6/7.
• Patients with more than 6 COCs expected for ICSI.
• Body mass index <35.
• Fresh and frozen ejaculated sperm.

Exclusion criteria

• PGT-M cycles
• Fresh and frozen testicular sperm.

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

Open label

Primary purpose

Treatment

Study locations

United Arab Emirates · 1 center

• ART Fertility Clinics LLC — Abu Dhabi

Publications

• Meldrum DR, Casper RF, Diez-Juan A, Simon C, Domar AD, Frydman R. Aging and the environment affect gamete and embryo potential: can we intervene? Fertil Steril. 2016 Mar;105(3):548-559. doi: 10.1016/j.fertnstert.2016.01.013. Epub 2016 Jan 23. PMID 26812244
• von Mengden L, Klamt F, Smitz J. Redox Biology of Human Cumulus Cells: Basic Concepts, Impact on Oocyte Quality, and Potential Clinical Use. Antioxid Redox Signal. 2020 Mar 10;32(8):522-535. doi: 10.1089/ars.2019.7984. PMID 31861967
• Ruder EH, Hartman TJ, Blumberg J, Goldman MB. Oxidative stress and antioxidants: exposure and impact on female fertility. Hum Reprod Update. 2008 Jul-Aug;14(4):345-57. doi: 10.1093/humupd/dmn011. Epub 2008 Jun 4. PMID 18535004
• Chambers GM, Dyer S, Zegers-Hochschild F, de Mouzon J, Ishihara O, Banker M, Mansour R, Kupka MS, Adamson GD. International Committee for Monitoring Assisted Reproductive Technologies world report: assisted reproductive technology, 2014dagger. Hum Reprod. 2021 Oct 18;36(11):2921-2934. doi: 10.1093/humrep/deab198. PMID 34601605
• Halliwell B, Aruoma OI. DNA damage by oxygen-derived species. Its mechanism and measurement in mammalian systems. FEBS Lett. 1991 Apr 9;281(1-2):9-19. doi: 10.1016/0014-5793(91)80347-6. PMID 1849843
• Kehrer JP, Lund LG. Cellular reducing equivalents and oxidative stress. Free Radic Biol Med. 1994 Jul;17(1):65-75. doi: 10.1016/0891-5849(94)90008-6. PMID 7959167
• Aitken RJ. Impact of oxidative stress on male and female germ cells: implications for fertility. Reproduction. 2020 Apr;159(4):R189-R201. doi: 10.1530/REP-19-0452. PMID 31846434
• Ruder EH, Hartman TJ, Goldman MB. Impact of oxidative stress on female fertility. Curr Opin Obstet Gynecol. 2009 Jun;21(3):219-22. doi: 10.1097/gco.0b013e32832924ba. PMID 19469044

Identifiers

NCT: NCT06261671 · 2312-ABU-028-VF

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗