Hyaluronan-enriched Medium and Euploid Blastocyst Transfers

Infertility Clinical Trial

— GluePloid  

Official title:

Impact of Hyaluronan-enriched Medium on Pregnancy Outcomes Following Euploid Blastocyst Transfers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06165367
• Other study ID #: ART FERTILITY CLINICS
• Status: Recruiting
• Phase: N/A
• Start date: January 15, 2024
• Est. completion date: December 31, 2025

Study information

• Verified date: January 2024
• Source: ART Fertility Clinics LLC
• Contact: Daniela Nogueira
• Phone: +971504374961
• Email: daniela.nogueira[@]artfertilityclinics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The study period will be determined by the completion of the predetermined sample size, with two interim analyses 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. The study will be performed in Abu Dhabi-Fertility clinic. During the period of this prospective study, euploid blastocysts of enough quality that have been biopsied only on Day-5 for PGT-A, will be warmed for single blastocyst transfer. The patient´s endometrial preparation protocol for FET will be restricted to HRT only. The study will be double-blinded (blinded to patient and doctor performing transfer).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 783
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 46 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Clinical Pregnancy Rate
• Implantation Rate
• Infertility
• Live Birth Rate

Intervention

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

Locations

Country	Name	City	State
United Arab Emirates	ART Fertility Clinics LLC	Abu Dhabi

Sponsors (1)

Lead Sponsor	Collaborator
ART Fertility Clinics LLC

Country where clinical trial is conducted

United Arab Emirates, 

References & Publications (21)

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Live birth rate (LBR)	Defined as the delivery if a live infant born after 24 completed weeks of gestation	41 weeks
Secondary	human chorionic gonadotropin (hCG) positiveness	hCG pregnancy test checks human chorionic gonadotropin (HCG) levels in the blood.	10-12 days after embryo transfer
Secondary	Clinical pregnancy rate	ultrasonographic sac visible at 5 gestational weeks	6 weeks
Secondary	Clinical miscarriage rate	spontaneous loss of a clinical pregnancy before 24 weeks of gestation	24 weeks
Secondary	Ongoing pregnancy rate after 12 weeks	viable pregnancy with gestational age more than 12 weeks	13 weeks