Telomere Length in Human Polar Body and Telomere Length in Cumulus Cells: A Clinical Validation Study

Telomere Length Clinical Trial

Official title:

Does the Telomere Length in First Human Polar Body Correlates With the Telomere Length in Cumulus Cells: A Clinical Validation Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04577560
• Other study ID #: 2006-ABU-007-AA
• Status: Recruiting
• Phase: N/A
• Start date: June 6, 2021
• Est. completion date: January 1, 2022

Study information

• Verified date: June 2021
• Source: ART Fertility Clinics LLC
• Contact: Ana Arnanz Poyatos, MSc
• Phone: +971563703889
• Email: ana.arnanz[@]artfertilityclinics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To investigate whether telomere length (TL) of the first Polar body (PB) correlates with TL in Cumulus cells (CC)

Description:

With the present study we want to analyze, as a primary objective, whether telomere length (TL) in the first Polar Body (PB) correlates with TL in the corresponding Cumulus cells (CC). As a secondary objective, a possible correlation between TL in PBs and blastocyst TL and ploidy will be evaluated.

To our best knowledge, there are no studies evaluating TL in CC and TL in PBs of the corresponding oocyte. With the present prospective study, we sought to investigate whether there is a correlation between CC-TL and PB-TL. If a correlation exists, CC-TL assessment would serve as a valuable non-invasive technique to gain information about oocyte competence.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: January 1, 2022
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 43 Years

Eligibility

Inclusion Criteria:

• BMI 18- 30kg/m2

• Expected normo/high responders

• Normal female/male karyotype

• Antagonist protocol with agonist trigger.

• PGT-A: NGS in blastocysts

• Fresh autologous ejaculates (=5 mill/ml)

• Primary and secondary infertility

• Only ICSI as insemination technique

Exclusion Criteria:

• PCOS patients according to International evidence-based guideline for the assessment and management of polycystic ovarian syndrome 2018.

Related Conditions & MeSH terms

• Telomere Length

Intervention

Genetic:
• First polar body biopsy in MII oocytes
Since PBs are by-products of the meiotic division of the oocyte and are not required for fertilization and subsequent embryo development, they can be removed to assess exclusively maternal chromosomal information without harming the embryo integrity. As previously described, PB biopsy does not impact the morphokinetic parameters of the embryo development and can be safely applied without the risk of impairing the reproductive potential of the embryo.
• PGT-A blastocyst
preimplantation genetic screening for aneuploidies

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
ART Fertility Clinics LLC

Country where clinical trial is conducted

United Arab Emirates, 

References & Publications (11)

Cheng EH, Chen SU, Lee TH, Pai YP, Huang LS, Huang CC, Lee MS. Evaluation of telomere length in cumulus cells as a potential biomarker of oocyte and embryo quality. Hum Reprod. 2013 Apr;28(4):929-36. doi: 10.1093/humrep/det004. Epub 2013 Feb 1. — View Citation

Keefe DL, Marquard K, Liu L. The telomere theory of reproductive senescence in women. Curr Opin Obstet Gynecol. 2006 Jun;18(3):280-5. Review. — View Citation

Kidder GM, Vanderhyden BC. Bidirectional communication between oocytes and follicle cells: ensuring oocyte developmental competence. Can J Physiol Pharmacol. 2010 Apr;88(4):399-413. doi: 10.1139/y10-009. Review. — View Citation

Kosebent EG, Uysal F, Ozturk S. Telomere length and telomerase activity during folliculogenesis in mammals. J Reprod Dev. 2018 Dec 14;64(6):477-484. doi: 10.1262/jrd.2018-076. Epub 2018 Sep 28. Review. — View Citation

Lara-Molina EE, Franasiak JM, Marin D, Tao X, Díaz-Gimeno P, Florensa M, Martin M, Seli E, Pellicer A. Cumulus cells have longer telomeres than leukocytes in reproductive-age women. Fertil Steril. 2020 Jan;113(1):217-223. doi: 10.1016/j.fertnstert.2019.08 — View Citation

Montag M, Köster M, Strowitzki T, Toth B. Polar body biopsy. Fertil Steril. 2013 Sep;100(3):603-7. doi: 10.1016/j.fertnstert.2013.05.053. Epub 2013 Jun 21. Review. — View Citation

Ozturk S. Telomerase activity and telomere length in male germ cells. Biol Reprod. 2015 Feb;92(2):53. doi: 10.1095/biolreprod.114.124008. Epub 2015 Jan 7. Review. — View Citation

Riethman H, Ambrosini A, Paul S. Human subtelomere structure and variation. Chromosome Res. 2005;13(5):505-15. Review. — View Citation

Schenk M, Groselj-Strele A, Eberhard K, Feldmeier E, Kastelic D, Cerk S, Weiss G. Impact of polar body biopsy on embryo morphokinetics-back to the roots in preimplantation genetic testing? J Assist Reprod Genet. 2018 Aug;35(8):1521-1528. doi: 10.1007/s108 — View Citation

Treff NR, Su J, Taylor D, Scott RT Jr. Telomere DNA deficiency is associated with development of human embryonic aneuploidy. PLoS Genet. 2011 Jun;7(6):e1002161. doi: 10.1371/journal.pgen.1002161. Epub 2011 Jun 30. — View Citation

Wang W, Chen H, Li R, Ouyang N, Chen J, Huang L, Mai M, Zhang N, Zhang Q, Yang D. Telomerase activity is more significant for predicting the outcome of IVF treatment than telomere length in granulosa cells. Reproduction. 2014 Apr 8;147(5):649-57. doi: 10. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	telomere length (TL) of the first Polar body (PB) and TL in Cumulus cells (CC)	Correlation between telomere length (TL) of the first Polar body (PB) and TL in Cumulus cells (CC)	8 weeks
Secondary	To correlate TL between both polar bodies	If the MII fertilize after performing ICSI, polar body biopsy for the second PB will be performed	8 weeks
Secondary	To correlate TL in male WBC and TL in sperm	TL will be assess in leukocytes (male´s blood sample) and in the sperm (fresh ejaculate)	8 weeks
Secondary	To correlate TL in female WBC and TL in CC	TL will be assess in leukocytes (female´s blood sample) and in the cumulus cells (CC) from the retrieved oocytes.	8 weeks
Secondary	To evaluate a possible correlation between TL-CC and TL-TE	Correlation between TL-CC and TL in trophectoderm biopsy performed in the developed blastocysts	8 weeks
Secondary	To evaluate a possible correlation between TL-CC and ploidy TE	Correlation between TL-CC and PGT-A results in trophectoderm biopsy performed in the developed blastocysts	8 weeks
Secondary	To evaluate telomerase activity (TA) in CC and a possible correlation with CC-TL	Telomerase is a ribonucleoprotein complex responsible for de novo telomere synthesis and addition of telomeric repeats to existing telomeres	8 weeks
Secondary	To evaluate FSH/LH gene expression in CC	During the follicular phase LH whose receptors (LHR) are expressed in granulosa cells under the influence of FSH, plays an important role in the regulation of ovarian function and is essential to promote the growth of the dominant follicle, final oocyte maturation as well as ovulation induction	8 weeks
Secondary	To evaluate a possible correlation between ploidy in PBs and ploidy in TE biopsy	PGT-A in PB and PGT-A in TE biopsy	8 weeks
Secondary	PB biopsy and embryo development	To validate that PB biopsy does not impair embryo development compared to their sibling embryos with no PB biopsied	8 weeks
Secondary	To evaluate TL in sperm + TL-PB and TL in TE	TL in sperm + TL-PB and TL in the resulting biopsied	8 weeks