Effects of Antioxidant Supplementation of Culture Media on IVF Embryos

NCT05919186 | Completed DMC

• 1 other identifier: CI-20-102
• Study Type: interventional
• Target: 293
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to investigate the impact of repeated antioxidant supplementation on blastocyst utilization and expansion rates in embryos under different oxygen concentrations. The study aims to answer the following main questions:

• Does adding antioxidants every 12 hours to embryo culture media improve usable and expanded blastocyst utilization rates on days 5 and 6?
• How are the O2 concentrations related to the effect of different methods of antioxidants supplementation on blastocysts utilization and expansion rates? Participants in this study are infertile couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles.
• Zygotes will be incubated at either 5% or 20% oxygen tension until the blastocyst stage.
• Sibling zygotes will be divided into four groups: Group 1A and 1B: Antioxidants every 12 hours at either 5% or 20% O2 tension, respectively. Group 2A and 2B: Antioxidants only once at the beginning of embryo culture at either 5% or 20% O2 tension, respectively. Researchers will compare the four groups to determine if the repeated antioxidant supplementation of the culture media leads to improved blastocyst utilization and expansion rates compared to the baseline group.

Conditions

Infertility, Female; Infertility, Male

Keywords

Blastocyst Rate; IVF; Embryo Culture; Antioxidants

Outcome Measures

Primary Outcomes (6)

• Rate of usable blastocysts on day 5

  Usable blastocysts were defined as vitrified, transferred, and/or biopsied blastocysts at day 5

  5 days

• Rate of expanded blastocysts on day 5

  Expanded blastocysts were defined as usable blastocysts with a 4 to 6 expansion grade at day 5

  5 days

• Rate of sable blastocysts on day 6

  Usable blastocysts were defined as vitrified, transferred, and/or biopsied blastocysts at day 6

  6 days

• Rate of expanded blastocysts on day 6

  Expanded blastocysts were defined as usable blastocysts with a 4 to 6 expansion grade at day 6

  6 days

• Rate of acumulative usable blastocysts

  Usable blastocysts were defined as vitrified, transferred, and/or biopsied blastocysts at days 5 and 6

  5 - 6 days

• Rate of acumulative expanded blastocysts.

  Expanded blastocysts were defined as usable blastocysts with a 4 to 6 expansion grade at days 5 and 6

  5 - 6 days

Study Arms (4)

EmrbyORP continued at high O2

EXPERIMENTAL

Antioxidants supplementation Every 12 hours (3.5 μL)

Drug: EmbryORP®; Device: O2 tension 20%

EmrbyORP at baseline with high O2

EXPERIMENTAL

Antioxidants supplementation At baseline only (6.5 μL)

Drug: EmbryORP®; Device: O2 tension 20%

EmrbyORP continued at low 02

EXPERIMENTAL

Antioxidants supplementation Every 12 hours (3.5 μL)

Drug: EmbryORP®; Device: O2 tension 5%

EmrbyORP at baseline with low o2

EXPERIMENTAL

Antioxidants supplementation At baseline only (6.5 μL)

Drug: EmbryORP®; Device: O2 tension 5%

Interventions

EmbryORP® DRUG

EmbryORP® is a novel antioxidant (Cystein 32.9 mM, Glutation 32.6 mM, Ascorbic Acid 22.7 mM)

Also known as: EmbryORP

EmrbyORP at baseline with high O2; EmrbyORP at baseline with low o2; EmrbyORP continued at high O2; EmrbyORP continued at low 02

O2 tension 20% DEVICE

After fertilization check, zygotes were placed in the incubator at 37°C, 8% CO2, and 95%

EmrbyORP at baseline with high O2; EmrbyORP continued at high O2

O2 tension 5% DEVICE

After fertilization check, zygotes were placed in the incubator at 37°C, 8% CO2 and 95%

EmrbyORP at baseline with low o2; EmrbyORP continued at low 02

Eligibility Criteria

• Age: 18 Years - 37 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Infertile women with from 18 to 37 years old at the moment of oocyte collection, tubal factor, polycystic ovary syndrome, uterine factor, or unexplained infertility.
• More than 2 oocytes by conventional in vitro fertilization (cIVF) and intracytoplasmic sperm injection (ICSI).

You may not qualify if:

• Infertile woman in assisted reproduction treatment with less than 2 oocytes collected.
• Infertile woman in assisted reproduction treatment with less than 2 oocytes fertilized by conventional in vitro fertilization (cIVF) and intracytoplasmic sperm injection (ICSI)

Sponsors & Collaborators

• Liliana Berenice Ramírez Domínguez: lead

Study Sites (1)

CITMER

Mexico City, 11520, Mexico

Location

Related Publications (21)

• Khalied Kaskar, C. Optimizing embryo culture conditions and spent culture media analysis as predictors of em-bryo quality and pregnancy; PhD Thesis, University of the West Cape, Cape Town, South Africa, February 2021.

  BACKGROUND

• Swain JE. Optimizing the culture environment in the IVF laboratory: impact of pH and buffer capacity on gamete and embryo quality. Reprod Biomed Online. 2010 Jul;21(1):6-16. doi: 10.1016/j.rbmo.2010.03.012. Epub 2010 Mar 21.

  PMID: 20570214 BACKGROUND

• Lane M, Lyons EA, Bavister BD. Cryopreservation reduces the ability of hamster 2-cell embryos to regulate intracellular pH. Hum Reprod. 2000 Feb;15(2):389-94. doi: 10.1093/humrep/15.2.389.

  PMID: 10655311 BACKGROUND

• Nastri CO, Nobrega BN, Teixeira DM, Amorim J, Diniz LMM, Barbosa MWP, Giorgi VSI, Pileggi VN, Martins WP. Low versus atmospheric oxygen tension for embryo culture in assisted reproduction: a systematic review and meta-analysis. Fertil Steril. 2016 Jul;106(1):95-104.e17. doi: 10.1016/j.fertnstert.2016.02.037. Epub 2016 Mar 21.

  PMID: 27012651 BACKGROUND

• Edwards LJ, Williams DA, Gardner DK. Intracellular pH of the preimplantation mouse embryo: effects of extracellular pH and weak acids. Mol Reprod Dev. 1998 Aug;50(4):434-42. doi: 10.1002/(SICI)1098-2795(199808)50:43.0.CO;2-J.

  PMID: 9669527 BACKGROUND

• Hong KH, Lee H, Forman EJ, Upham KM, Scott RT Jr. Examining the temperature of embryo culture in in vitro fertilization: a randomized controlled trial comparing traditional core temperature (37 degrees C) to a more physiologic, cooler temperature (36 degrees C). Fertil Steril. 2014 Sep;102(3):767-73. doi: 10.1016/j.fertnstert.2014.06.009. Epub 2014 Jul 17.

  PMID: 25044079 BACKGROUND

• Chui, A.; Kalionis, B.; Brennecke, S.; Murthi, P. 201 Homeobox Gene DLX3 Regulates Forskolin Induced Tropho-blast Differentiation. Reprod Fertil Dev 2008, 20(9), 1-1

  BACKGROUND

• Agarwal A, Gupta S, Sharma RK. Role of oxidative stress in female reproduction. Reprod Biol Endocrinol. 2005 Jul 14;3:28. doi: 10.1186/1477-7827-3-28.

  PMID: 16018814 BACKGROUND

• Carocho M, Ferreira IC. A review on antioxidants, prooxidants and related controversy: natural and synthetic compounds, screening and analysis methodologies and future perspectives. Food Chem Toxicol. 2013 Jan;51:15-25. doi: 10.1016/j.fct.2012.09.021. Epub 2012 Sep 24.

  PMID: 23017782 BACKGROUND

• 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.

  PMID: 11284661 BACKGROUND

• Budani MC, Tiboni GM. Effects of Supplementation with Natural Antioxidants on Oocytes and Preimplantation Embryos. Antioxidants (Basel). 2020 Jul 12;9(7):612. doi: 10.3390/antiox9070612.

  PMID: 32664650 BACKGROUND

• Coria-Gomez CR, Torres-Rodriguez P, Villar-Munoz LG, Jimenez-Medina I, Agarwal A, Henkel R, Maldonado-Rosas I, L Trevino C. Comparative study of fertility parameters in vitrified human spermatozoa in the presence or absence of EmbryORP(R) : A novel antioxidant. Andrologia. 2021 May;53(4):e13886. doi: 10.1111/and.13886. Epub 2021 Feb 7.

  PMID: 33550605 BACKGROUND

• David Gardner; William Schoolcraft. In Vitro Culture of Human Blastocysts. In Towards Reproductive Certainity: Fertility and Genetics Beyond 1999: The Plenary Proceedings of the 11th World Congress on In Vitro Fertilization & Hu-man Reproductive Genetics; Jansen, R., Mortimer, D., Eds.; Parthenon Publishing Group: London, 1999; Vol. 1, pp. 378-388.

  BACKGROUND

• Sallam, N.; Hegab, M.; Mohamed, F.; El-Kaffash, D. Effect of Oxidative Stress in Semen, Follicular Fluid and Em-bryo Culture Medium on the Outcome of Assisted Reproduction. Al-Azhar Internat Med J 2021, 2(7), 59-65, doi:10.21608/aimj.2021.79536.1495

  BACKGROUND

• 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.

  PMID: 29136144 BACKGROUND

• Bedaiwy MA, Falcone T, Mohamed MS, Aleem AA, Sharma RK, Worley SE, Thornton J, Agarwal A. Differential growth of human embryos in vitro: role of reactive oxygen species. Fertil Steril. 2004 Sep;82(3):593-600. doi: 10.1016/j.fertnstert.2004.02.121.

  PMID: 15374701 BACKGROUND

• 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.

  PMID: 16769062 BACKGROUND

• 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.

  PMID: 32299733 BACKGROUND

• Majumdar G, Majumdar A, Verma IC, Upadhyaya KC. Relationship Between Morphology, Euploidy and Implantation Potential of Cleavage and Blastocyst Stage Embryos. J Hum Reprod Sci. 2017 Jan-Mar;10(1):49-57. doi: 10.4103/0974-1208.204013.

  PMID: 28479756 BACKGROUND

• Swain JE. Media composition: pH and buffers. Methods Mol Biol. 2012;912:161-75. doi: 10.1007/978-1-61779-971-6_10.

  PMID: 22829374 BACKGROUND

• Agarwal A, Majzoub A. Role of Antioxidants in Assisted Reproductive Techniques. World J Mens Health. 2017 Aug;35(2):77-93. doi: 10.5534/wjmh.2017.35.2.77. Epub 2017 Apr 30.

  PMID: 28497913 BACKGROUND

MeSH Terms

Conditions

Infertility, Female; Infertility, Male

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility; Genital Diseases, Male; Male Urogenital Diseases

Study Officials

• Ashok Agarwal, PhD

  Global Andrology Forum

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Scientific Coordinator

Model Details: The data registry utilized internal and external measures to ensure accuracy. SOPs were developed for registry operations and data analysis. Data were recorded in clinical records and clinic-specific databases. Regular backups and monthly audits were conducted to safeguard data and verify accuracy. External audits occurred every 6 months. Access controls protected privacy. Appropriate statistical techniques and sample size assessment were used for data analysis. A study on embryo development analyzed 3603 zygotes, assessing blastocyst outcomes and detailing procedures for ovarian stimulation, retrieval, sperm preparation, and assisted reproduction techniques. These measures ensured accurate and reliable results.

Study Record Dates

• First Submitted: May 12, 2023
• First Posted: June 26, 2023
• Study Start: October 12, 2021
• Primary Completion: April 12, 2022
• Study Completion: May 10, 2022
• Last Updated: June 26, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)