Hyaluronan-enriched Medium and Euploid Blastocyst Transfers

NCT06165367 | Recruiting

• 1 other identifier: ART FERTILITY CLINICS
• Study Type: interventional
• Target: 783
• Locations: 1 country
• Sites: 1

Brief Summary

It has been proposed that enriching transfer media with hyaluronan (EmbryoGlue medium) improves pregnancy outcomes compared with media containing lower concentrations of this molecule. However, none of previous studies included preimplantation genetic testing for aneuploidy (PGT-A) embryos. In order to investigate the impact of this hyaluronan-enriched on pregnancy outcomes, it is essential to evaluate its efficacy on euploid-only embryo transfers. The aim of the present study is to evaluate whether a short period of exposure of euploid blastocysts to EmbryoGlue prior to and during transfer positively impact on pregnancy outcomes of frozen embryo transfer (FET) cycles.

Conditions

Infertility; Implantation Rate; Clinical Pregnancy Rate; Live Birth Rate; Blastocysts; FET

Keywords

HRT; PGT-A; Next-generation sequencing (NGS); Miscarriage rate; single embryo transfer (SET); EmbryoGlue; BMI; Embryo quality; Hyaluronan-enriched medium; Transfer medium

Outcome Measures

Primary Outcomes (1)

• Live birth rate (LBR)

  Defined as the delivery if a live infant born after 24 completed weeks of gestation

  41 weeks

Secondary Outcomes (4)

• human chorionic gonadotropin (hCG) positiveness

  10-12 days after embryo transfer

• Clinical pregnancy rate

  6 weeks

• Clinical miscarriage rate

  24 weeks

• Ongoing pregnancy rate after 12 weeks

  13 weeks

Study Arms (2)

Blastocysts exposed to normal media (NEG)

NO INTERVENTION

Blastocysts exposed to routine-in use medium No intervention

Blastocysts exposed to EmbryoGlue (EG)

ACTIVE COMPARATOR

Blastocysts exposed to EmbryoGlue

Drug: EmbryoGlue Medium

Interventions

EmbryoGlue Medium DRUG

Embryos will be exposed to hyaluronic-enriched media (EmbryoGlue) before and during embryo transfer

Blastocysts exposed to EmbryoGlue (EG)

Eligibility Criteria

• Age: 18 Years - 46 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• All frozen embryo transfer (FET) cycles with euploid blastocysts biopsied and vitrified on Day 5 after PGT-A.
• Rank of randomization based on embryo quality.
• Only hormonal replacement theraphy (HRT) cycle regimen.
• Women aged 18 years to 46 years.
• Having at least 1 chromosomally normal vitrified blastocyst(s) on Day 5 available for transfer.
• All sperm samples.
• BMI between 18 and 35.

You may not qualify if:

• FET cycles with preimplantation genetic testing for monogenic disorders (PGT-M) and for structural rearrangements (PGT-SR).
• FET cycles with mosaic / aneuploid blastocysts.
• FET cycles with unknown outcome.
• FET cycles with Day 6 or Day 7 biopsied blastocysts.
• FET with patients' endometrium preparation with treatments other than HRT.
• FET where PGT-A was performed for gender selection.

Sponsors & Collaborators

• ART Fertility Clinics LLC: lead

Study Sites (1)

ART Fertility Clinics LLC

Abu Dhabi, Abu Dhabi Emirate, 60202, United Arab Emirates

RECRUITING

Related Publications (21)

• Gardner DK, Rodriegez-Martinez H, Lane M. Fetal development after transfer is increased by replacing protein with the glycosaminoglycan hyaluronan for mouse embryo culture and transfer. Hum Reprod. 1999 Oct;14(10):2575-80. doi: 10.1093/humrep/14.10.2575.

  PMID: 10527990 BACKGROUND

• Stojkovic M, Kolle S, Peinl S, Stojkovic P, Zakhartchenko V, Thompson JG, Wenigerkind H, Reichenbach HD, Sinowatz F, Wolf E. Effects of high concentrations of hyaluronan in culture medium on development and survival rates of fresh and frozen-thawed bovine embryos produced in vitro. Reproduction. 2002 Jul;124(1):141-53.

  PMID: 12090927 BACKGROUND

• Miyano T, Hiro-Oka RE, Kano K, Miyake M, Kusunoki H, Kato S. Effects of hyaluronic acid on the development of 1- and 2-cell porcine embryos to the blastocyst stage in vitro. Theriogenology. 1994;41(6):1299-305. doi: 10.1016/0093-691x(94)90488-5.

  PMID: 16727484 BACKGROUND

• Schoolcraft W, Lane M, Stevens J, Gardner D. Increased hyaluronannan concentration in the embryo transfer medium results in a signifcant increase in human embryo implantation rate. In American Society for Reproductive Medicine. 2002 Fertility and Sterility

  BACKGROUND

• Atkinson B, Woodland E. Embryo Glue: The Use of Hyaluronan in Embryo Transfer Media. Semin Reprod Med. 2021 Mar;39(1-02):24-26. doi: 10.1055/s-0041-1730415. Epub 2021 May 25.

  PMID: 34034352 BACKGROUND

• Valojerdi MR, Karimian L, Yazdi PE, Gilani MA, Madani T, Baghestani AR. Efficacy of a human embryo transfer medium: a prospective, randomized clinical trial study. J Assist Reprod Genet. 2006 May;23(5):207-12. doi: 10.1007/s10815-006-9031-7. Epub 2006 Jun 20.

  PMID: 16786421 BACKGROUND

• Urman B, Yakin K, Ata B, Isiklar A, Balaban B. Effect of hyaluronan-enriched transfer medium on implantation and pregnancy rates after day 3 and day 5 embryo transfers: a prospective randomized study. Fertil Steril. 2008 Sep;90(3):604-12. doi: 10.1016/j.fertnstert.2007.07.1294. Epub 2007 Oct 23.

  PMID: 17936283 BACKGROUND

• Hazlett WD, Meyer LR, Nasta TE, Mangan PA, Karande VC. Impact of EmbryoGlue as the embryo transfer medium. Fertil Steril. 2008 Jul;90(1):214-6. doi: 10.1016/j.fertnstert.2007.05.063. Epub 2007 Sep 4.

  PMID: 17765233 BACKGROUND

• Safari S, Razi MH, Safari S, Razi Y. Routine use of EmbryoGlue((R)) as embryo transfer medium does not improve the ART outcomes. Arch Gynecol Obstet. 2015 Feb;291(2):433-7. doi: 10.1007/s00404-014-3416-0. Epub 2014 Aug 24.

  PMID: 25151028 BACKGROUND

• Heymann D, Vidal L, Or Y, Shoham Z. Hyaluronic acid in embryo transfer media for assisted reproductive technologies. Cochrane Database Syst Rev. 2020 Sep 2;9(9):CD007421. doi: 10.1002/14651858.CD007421.pub4.

  PMID: 32876946 BACKGROUND

• Child et al. A rCT assessing effectiveness of embryoglue in IVF transfer cycles. ASRM abstract 2021.

  BACKGROUND

• Adeniyi T, Horne G, Ruane PT, Brison DR, Roberts SA. Clinical efficacy of hyaluronate-containing embryo transfer medium in IVF/ICSI treatment cycles: a cohort study. Hum Reprod Open. 2021 Mar 3;2021(1):hoab004. doi: 10.1093/hropen/hoab004. eCollection 2021.

  PMID: 33718621 BACKGROUND

• Good practice for recommendation for add-ons in reproductive medicine. ESHRE-working group, 2023.

  BACKGROUND

• Oron G, Son WY, Buckett W, Tulandi T, Holzer H. The association between embryo quality and perinatal outcome of singletons born after single embryo transfers: a pilot study. Hum Reprod. 2014 Jul;29(7):1444-51. doi: 10.1093/humrep/deu079. Epub 2014 May 8.

  PMID: 24812313 BACKGROUND

• Vinals Gonzalez X, Odia R, Naja R, Serhal P, Saab W, Seshadri S, Ben-Nagi J. Euploid blastocysts implant irrespective of their morphology after NGS-(PGT-A) testing in advanced maternal age patients. J Assist Reprod Genet. 2019 Aug;36(8):1623-1629. doi: 10.1007/s10815-019-01496-9. Epub 2019 Jun 4.

  PMID: 31165389 BACKGROUND

• Capalbo A, Rienzi L, Cimadomo D, Maggiulli R, Elliott T, Wright G, Nagy ZP, Ubaldi FM. Correlation between standard blastocyst morphology, euploidy and implantation: an observational study in two centers involving 956 screened blastocysts. Hum Reprod. 2014 Jun;29(6):1173-81. doi: 10.1093/humrep/deu033. Epub 2014 Feb 26.

  PMID: 24578475 BACKGROUND

• Irani M, Reichman D, Robles A, Melnick A, Davis O, Zaninovic N, Xu K, Rosenwaks Z. Morphologic grading of euploid blastocysts influences implantation and ongoing pregnancy rates. Fertil Steril. 2017 Mar;107(3):664-670. doi: 10.1016/j.fertnstert.2016.11.012. Epub 2017 Jan 6.

  PMID: 28069172 BACKGROUND

• Li N, Guan Y, Ren B, Zhang Y, Du Y, Kong H, Zhang Y, Lou H. Effect of Blastocyst Morphology and Developmental Rate on Euploidy and Live Birth Rates in Preimplantation Genetic Testing for Aneuploidy Cycles With Single-Embryo Transfer. Front Endocrinol (Lausanne). 2022 Apr 13;13:858042. doi: 10.3389/fendo.2022.858042. eCollection 2022.

  PMID: 35498424 BACKGROUND

• Xiao Y, Wang X, Gui T, Tao T, Xiong W. Transfer of a poor-quality along with a good-quality embryo on in vitro fertilization/intracytoplasmic sperm injection-embryo transfer clinical outcomes: a systematic review and meta-analysis. Fertil Steril. 2022 Dec;118(6):1066-1079. doi: 10.1016/j.fertnstert.2022.08.848. Epub 2022 Oct 14.

  PMID: 36244848 BACKGROUND

• Brosens JJ, Salker MS, Teklenburg G, Nautiyal J, Salter S, Lucas ES, Steel JH, Christian M, Chan YW, Boomsma CM, Moore JD, Hartshorne GM, Sucurovic S, Mulac-Jericevic B, Heijnen CJ, Quenby S, Koerkamp MJ, Holstege FC, Shmygol A, Macklon NS. Uterine selection of human embryos at implantation. Sci Rep. 2014 Feb 6;4:3894. doi: 10.1038/srep03894.

  PMID: 24503642 BACKGROUND

• C. Jennison and B. W. Turnbull, "Group Sequential Methods with Applications to Clinical Trials," Chapman & Hall/CRC, Boca Raton, 2000.

  BACKGROUND

MeSH Terms

Conditions

Infertility

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Central Study Contacts

Daniela Nogueira

CONTACT

+971504374961; daniela.nogueira@artfertilityclinics.com

Jonalyn DV Edades, Nursing

CONTACT

+97152640866; jonalyn.edades@artfertilityclinics.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: The study will be double-blinded (blinded to patient and doctor performing transfer).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Global Scientific Laboratory Director ART Fertility Clinics

Model Details: Randomization will be stratified according to the in-house embryo prognosis classification. Our internal data shows top quality embryos have 65% ongoing pregnancy rate and good quality embryos have 55% ongoing pregnancy rate. We assume a 20% relative increase over the baseline with the intervention which corresponds to 78% and 66% ongoing pregnancy rates for top and good quality euploid embryos, respectively. Total sample size requires in each group corresponds to 295 and 488 transfers of top and good quality embryos for a total of 783. Two interim analyses are planned when 35% (n=274) and 70% (n=548) of the target sample size is achieved to calculate conditional power. If conditional power is estimated to be lower than 15% at first interim analysis or lower than 30% in the second interim analysis, the trial will be stopped due to futility.

Study Record Dates

• First Submitted: November 22, 2023
• First Posted: December 11, 2023
• Study Start: January 15, 2024
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: March 12, 2025

Record last verified: 2025-01

Locations

AE (1)