Clinical trial NCT06261671: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Infertility
In Vitro Fertilization
Keywords: Intracytoplasmic sperm injection
Pre - implanttaion genetic diagnosis for aneuploidy
Antioxydante
Culture media
Embryo development
Euploidy
Lead sponsor: ART Fertility Clinics LLC
Sponsor class: OTHER
First posted: 2024-02-15
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 43
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomization list (indicating Gx Media Vitrolife or GT Coopersurgical) will be used to verify to which group the first half of oocytes will be allocated to. In case an odd number of oocytes is present, one extra oocyte is allocated to the group as indicated by the randomization list.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Primary outcomes:
measure: 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
timeFrame: 1 year
Secondary outcomes:
measure: 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)
timeFrame: 1 year
Other outcomes:
Locations:
city: Abu Dhabi
country: United Arab Emirates
facility: ART Fertility Clinics LLC
Study officials:
affiliation: ART Fertility Clinics LLC
name: Barbara Lawrenz
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Agarwal A, Said TM. Role of sperm chromatin abnormalities and DNA damage in male infertility. Hum Reprod Update. 2003 Jul-Aug;9(4):331-45. doi: 10.1093/humupd/dmg027.
citation: Lian HY, Gao Y, Jiao GZ, Sun MJ, Wu XF, Wang TY, Li H, Tan JH. Antioxidant supplementation overcomes the deleterious effects of maternal restraint stress-induced oxidative stress on mouse oocytes. Reproduction. 2013 Oct 21;146(6):559-68. doi: 10.1530/REP-13-0268. Print 2013 Dec.
citation: Kiani-Esfahani A, Bahrami S, Tavalaee M, Deemeh MR, Mahjour AA, Nasr-Esfahani MH. Cytosolic and mitochondrial ROS: which one is associated with poor chromatin remodeling? Syst Biol Reprod Med. 2013 Dec;59(6):352-9. doi: 10.3109/19396368.2013.829536. Epub 2013 Aug 22.
citation: Lu J, Wang Z, Cao J, Chen Y, Dong Y. A novel and compact review on the role of oxidative stress in female reproduction. Reprod Biol Endocrinol. 2018 Aug 20;16(1):80. doi: 10.1186/s12958-018-0391-5.
citation: Agarwal A, Rana M, Qiu E, AlBunni H, Bui AD, Henkel R. Role of oxidative stress, infection and inflammation in male infertility. Andrologia. 2018 Dec;50(11):e13126. doi: 10.1111/and.13126.
citation: Guerin P, El Mouatassim S, Menezo Y. Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum Reprod Update. 2001 Mar-Apr;7(2):175-89. doi: 10.1093/humupd/7.2.175.
citation: Hardy MLM, Day ML, Morris MB. Redox Regulation and Oxidative Stress in Mammalian Oocytes and Embryos Developed In Vivo and In Vitro. Int J Environ Res Public Health. 2021 Oct 29;18(21):11374. doi: 10.3390/ijerph182111374.
citation: Carbone MC, Tatone C, Delle Monache S, Marci R, Caserta D, Colonna R, Amicarelli F. Antioxidant enzymatic defences in human follicular fluid: characterization and age-dependent changes. Mol Hum Reprod. 2003 Nov;9(11):639-43. doi: 10.1093/molehr/gag090.
citation: Mauchart P, Vass RA, Nagy B, Sulyok E, Bodis J, Kovacs K. Oxidative Stress in Assisted Reproductive Techniques, with a Focus on an Underestimated Risk Factor. Curr Issues Mol Biol. 2023 Feb 3;45(2):1272-1286. doi: 10.3390/cimb45020083.
citation: Pigeolet E, Corbisier P, Houbion A, Lambert D, Michiels C, Raes M, Zachary MD, Remacle J. Glutathione peroxidase, superoxide dismutase, and catalase inactivation by peroxides and oxygen derived free radicals. Mech Ageing Dev. 1990 Feb 15;51(3):283-97. doi: 10.1016/0047-6374(90)90078-t.
citation: Van Montfoort APA, Arts EGJM, Wijnandts L, Sluijmer A, Pelinck MJ, Land JA, Van Echten-Arends J. Reduced oxygen concentration during human IVF culture improves embryo utilization and cumulative pregnancy rates per cycle. Hum Reprod Open. 2020 Jan 22;2020(1):hoz036. doi: 10.1093/hropen/hoz036. eCollection 2020.
citation: Truong T, Gardner DK. Antioxidants improve IVF outcome and subsequent embryo development in the mouse. Hum Reprod. 2017 Dec 1;32(12):2404-2413. doi: 10.1093/humrep/dex330.
citation: Bedaiwy M, Agarwal A, Said TM, Goldberg JM, Sharma RK, Worley S, Falcone T. Role of total antioxidant capacity in the differential growth of human embryos in vitro. Fertil Steril. 2006 Aug;86(2):304-9. doi: 10.1016/j.fertnstert.2006.01.025. Epub 2006 Jun 12.
citation: Gardner DK, Kuramoto T, Tanaka M, Mitzumoto S, Montag M, Yoshida A. Prospective randomized multicentre comparison on sibling oocytes comparing G-Series media system with antioxidants versus standard G-Series media system. Reprod Biomed Online. 2020 May;40(5):637-644. doi: 10.1016/j.rbmo.2020.01.026. Epub 2020 Feb 5.
citation: Lan KC, Lin YC, Chang YC, Lin HJ, Tsai YR, Kang HY. Limited relationships between reactive oxygen species levels in culture media and zygote and embryo development. J Assist Reprod Genet. 2019 Feb;36(2):325-334. doi: 10.1007/s10815-018-1363-6. Epub 2018 Nov 10.