Aneuploidies in Embryos and Spermatozoa From Patients With Y-chromosome Microdeletions

NCT02527954 | Terminated

• 1 other identifier: 1412-ALC-086-PH
• Study Type: observational
• Target: 5
• Locations: 1 country
• Sites: 3

Brief Summary

In this study, investigators assess, using Fluorescence in situ Hybridization (FISH) and Comparative Genomic Hybridization (CGH) arrays for Preimplantation Genetic Screening (PGS), the incidence of aneuploidies in spermatozoa and embryos from infertile men with and without microdeletions who undergo assisted reproduction in their clinics.

Conditions

Male Sterility Due to Y-chromosome Deletions

Keywords

Y-chromosome microdeletions; aneuploidy; embryos; spermatozoa

Outcome Measures

Primary Outcomes (1)

• % Embryos with aneuploidies

  The incidence of embryonic aneuploidies will be examined by CGH arrays analysis after biopsy in day 3 or day 5 of embryo development. This technology allows the analysis of all the chromosomes, so both aneuploidies in gonosomes and autosomes will be determined. To measure these percentages the images obtained after CGH array will be analyzed by BlueFuse Software (BlueGnome, Cambridge, UK), identifying normal euploid embryos, embryos with full or partial aneuploidy and chaotic embryos.

  three years

Secondary Outcomes (12)

• % Spermatozoa with aneuploidies

  Three years

• Fertilization rate (%)

  three years

• Day 3 embryos rate (%)

  Three years

• Blastocyst rate (%)

  Three years

• Cycle efficiency

  Four years

Study Arms (2)

Infertile with Y-chromosome deletions

No intervention will be performed. Couples whose infertile men has a Y-chromosome microdeletion (detected in blood cells by Polymerase chain reaction multiplex) and fulfill the criteria will be included in this group (group 1)

Infertile without Y-chromosome deletions

No intervention will be performed. Couples whose infertile men has not any Y-chromosome microdeletion (detected in blood cells by polymerase chain reaction multiplex) and fulfill the criteria will be included in this group (group 2)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Couples undergoing "In vitro" Fertilization (IVF) treatment whose man has non-obstructive azoospermia or severe oligozoospermia (≤ 5x1000000 spermatozoa/ml) and consent the genetic analysis of semen samples, as well as the embryo cohort generated by ICSI.

You may qualify if:

• Couples with male infertility whose man has non-obstructive azoospermia or severe oligozoospermia with ≤5x1000000 spermatozoa/ml.
• Assisted Reproductive Technology: ICSI with motile spermatozoa and PGS by CGH arrays.
• Women \<38 years if microinjection is carried out in their own eggs, or 38≤ age \<50 years if they receive donated eggs.
• Women with body mass index (BMI)\<30.
• Men\<50 years

You may not qualify if:

• Couples with abnormal karyotypes.
• Women with any uterine pathology or abnormality, hydrosalpinx, thrombophilia or systemic diseases at the time of embryo transfer that could prejudge the outcome of the cycle
• Couples with repeated miscarriages (≥2) or implantation failures (≥2).
• Couples whose men has obstructive azoospermia, genital tract infections (mumps, inflammation, varicocele), cryptorchidism, or if he receives any treatment that can reduce the sperm count.
• Seminal samples processed by Magnetic Activated Cell Sorting (MACS) technique.

Sponsors & Collaborators

• Instituto Valenciano de Infertilidad, IVI Alicante: lead
• IVI Murcia: collaborator
• Igenomix: collaborator

Study Sites (3)

IVI Alicante

Alicante, 03015, Spain

Location

IVI Murcia

Murcia, 03007, Spain

Location

Igenomix

Valencia, 41980, Spain

Location

Related Publications (27)

• Ferlin A, Arredi B, Speltra E, Cazzadore C, Selice R, Garolla A, Lenzi A, Foresta C. Molecular and clinical characterization of Y chromosome microdeletions in infertile men: a 10-year experience in Italy. J Clin Endocrinol Metab. 2007 Mar;92(3):762-70. doi: 10.1210/jc.2006-1981. Epub 2007 Jan 9.

  PMID: 17213277 BACKGROUND

• Foresta C, Moro E, Ferlin A. Y chromosome microdeletions and alterations of spermatogenesis. Endocr Rev. 2001 Apr;22(2):226-39. doi: 10.1210/edrv.22.2.0425.

  PMID: 11294825 BACKGROUND

• Foresta C, Moro E, Ferlin A. Prognostic value of Y deletion analysis. The role of current methods. Hum Reprod. 2001 Aug;16(8):1543-7. doi: 10.1093/humrep/16.8.1543.

  PMID: 11473940 BACKGROUND

• Li Z, Haines CJ, Han Y. "Micro-deletions" of the human Y chromosome and their relationship with male infertility. J Genet Genomics. 2008 Apr;35(4):193-9. doi: 10.1016/S1673-8527(08)60027-2.

  PMID: 18439975 BACKGROUND

• Sadeghi-Nejad H, Farrokhi F. Genetics of azoospermia: current knowledge, clinical implications, and future directions. Part II: Y chromosome microdeletions. Urol J. 2007 Fall;4(4):192-206.

  PMID: 18270942 BACKGROUND

• Silber SJ. The Y chromosome in the era of intracytoplasmic sperm injection: a personal review. Fertil Steril. 2011 Jun 30;95(8):2439-48.e1-5. doi: 10.1016/j.fertnstert.2011.05.070.

  PMID: 21704208 BACKGROUND

• Suganthi R, Vijesh VV, Vandana N, Fathima Ali Benazir J. Y choromosomal microdeletion screening in the workup of male infertility and its current status in India. Int J Fertil Steril. 2014 Jan;7(4):253-66. Epub 2013 Dec 22.

  PMID: 24520494 BACKGROUND

• Choi JM, Chung P, Veeck L, Mielnik A, Palermo GD, Schlegel PN. AZF microdeletions of the Y chromosome and in vitro fertilization outcome. Fertil Steril. 2004 Feb;81(2):337-41. doi: 10.1016/j.fertnstert.2003.06.030.

  PMID: 14967370 BACKGROUND

• Kihaile PE, Kisanga RE, Aoki K, Kumasako Y, Misumi J, Utsunomiya T. Embryo outcome in Y-chromosome microdeleted infertile males after ICSI. Mol Reprod Dev. 2004 Jun;68(2):176-81. doi: 10.1002/mrd.20074.

  PMID: 15095338 BACKGROUND

• Liu XH, Qiao J, Li R, Yan LY, Chen LX. Y chromosome AZFc microdeletion may not affect the outcomes of ICSI for infertile males with fresh ejaculated sperm. J Assist Reprod Genet. 2013 Jun;30(6):813-9. doi: 10.1007/s10815-013-0009-y. Epub 2013 May 30.

  PMID: 23715876 BACKGROUND

• Mulhall JP, Reijo R, Alagappan R, Brown L, Page D, Carson R, Oates RD. Azoospermic men with deletion of the DAZ gene cluster are capable of completing spermatogenesis: fertilization, normal embryonic development and pregnancy occur when retrieved testicular spermatozoa are used for intracytoplasmic sperm injection. Hum Reprod. 1997 Mar;12(3):503-8. doi: 10.1093/humrep/12.3.503.

  PMID: 9130751 BACKGROUND

• Oates RD, Silber S, Brown LG, Page DC. Clinical characterization of 42 oligospermic or azoospermic men with microdeletion of the AZFc region of the Y chromosome, and of 18 children conceived via ICSI. Hum Reprod. 2002 Nov;17(11):2813-24. doi: 10.1093/humrep/17.11.2813.

  PMID: 12407032 BACKGROUND

• Patrat C, Bienvenu T, Janny L, Faure AK, Fauque P, Aknin-Seifer I, Davy C, Thiounn N, Jouannet P, Levy R. Clinical data and parenthood of 63 infertile and Y-microdeleted men. Fertil Steril. 2010 Feb;93(3):822-32. doi: 10.1016/j.fertnstert.2008.10.033. Epub 2008 Dec 4.

  PMID: 19062004 BACKGROUND

• Stouffs K, Lissens W, Tournaye H, Van Steirteghem A, Liebaers I. The choice and outcome of the fertility treatment of 38 couples in whom the male partner has a Yq microdeletion. Hum Reprod. 2005 Jul;20(7):1887-96. doi: 10.1093/humrep/deh847. Epub 2005 Mar 24.

  PMID: 15790609 BACKGROUND

• van Golde RJ, Wetzels AM, de Graaf R, Tuerlings JH, Braat DD, Kremer JA. Decreased fertilization rate and embryo quality after ICSI in oligozoospermic men with microdeletions in the azoospermia factor c region of the Y chromosome. Hum Reprod. 2001 Feb;16(2):289-92. doi: 10.1093/humrep/16.2.289.

  PMID: 11157822 BACKGROUND

• Wu W, Zhou ZM, Lin M, Mao YD, Wang W, Yang XY, Liu JY. [Y-chromosome microdeletions do not affect the outcomes of ICSI for infertile males]. Zhonghua Nan Ke Xue. 2011 Sep;17(9):771-4. Chinese.

  PMID: 21961234 BACKGROUND

• Patsalis PC, Sismani C, Quintana-Murci L, Taleb-Bekkouche F, Krausz C, McElreavey K. Effects of transmission of Y chromosome AZFc deletions. Lancet. 2002 Oct 19;360(9341):1222-4. doi: 10.1016/s0140-6736(02)11248-7.

  PMID: 12401251 BACKGROUND

• Patsalis PC, Skordis N, Sismani C, Kousoulidou L, Koumbaris G, Eftychi C, Stavrides G, Ioulianos A, Kitsiou-Tzeli S, Galla-Voumvouraki A, Kosmaidou Z, Hadjiathanasiou CG, McElreavey K. Identification of high frequency of Y chromosome deletions in patients with sex chromosome mosaicism and correlation with the clinical phenotype and Y-chromosome instability. Am J Med Genet A. 2005 Jun 1;135(2):145-9. doi: 10.1002/ajmg.a.30712.

  PMID: 15880425 BACKGROUND

• Siffroi JP, Le Bourhis C, Krausz C, Barbaux S, Quintana-Murci L, Kanafani S, Rouba H, Bujan L, Bourrouillou G, Seifer I, Boucher D, Fellous M, McElreavey K, Dadoune JP. Sex chromosome mosaicism in males carrying Y chromosome long arm deletions. Hum Reprod. 2000 Dec;15(12):2559-62. doi: 10.1093/humrep/15.12.2559.

  PMID: 11098026 BACKGROUND

• Dewan S, Puscheck EE, Coulam CB, Wilcox AJ, Jeyendran RS. Y-chromosome microdeletions and recurrent pregnancy loss. Fertil Steril. 2006 Feb;85(2):441-5. doi: 10.1016/j.fertnstert.2005.08.035.

  PMID: 16595224 BACKGROUND

• Jorgez CJ, Weedin JW, Sahin A, Tannour-Louet M, Han S, Bournat JC, Mielnik A, Cheung SW, Nangia AK, Schlegel PN, Lipshultz LI, Lamb DJ. Aberrations in pseudoautosomal regions (PARs) found in infertile men with Y-chromosome microdeletions. J Clin Endocrinol Metab. 2011 Apr;96(4):E674-9. doi: 10.1210/jc.2010-2018. Epub 2011 Jan 20.

  PMID: 21252244 BACKGROUND

• Mateu E, Rodrigo L, Martinez MC, Peinado V, Milan M, Gil-Salom M, Martinez-Jabaloyas JM, Remohi J, Pellicer A, Rubio C. Aneuploidies in embryos and spermatozoa from patients with Y chromosome microdeletions. Fertil Steril. 2010 Dec;94(7):2874-7. doi: 10.1016/j.fertnstert.2010.06.046. Epub 2010 Jul 24.

  PMID: 20655521 BACKGROUND

• Page DC, Silber S, Brown LG. Men with infertility caused by AZFc deletion can produce sons by intracytoplasmic sperm injection, but are likely to transmit the deletion and infertility. Hum Reprod. 1999 Jul;14(7):1722-6. doi: 10.1093/humrep/14.7.1722.

  PMID: 10402375 BACKGROUND

• Perrin A, Douet-Guilbert N, Laudier B, Couet ML, Guerif F, Royere D, Le Bris MJ, De Braekeleer M, Morel F. Meiotic segregation in spermatozoa of a 45,XY,-14,der(18)t(14;18)(q11;p11.3) translocation carrier: a case report. Hum Reprod. 2007 Mar;22(3):729-32. doi: 10.1093/humrep/del420. Epub 2006 Oct 24.

  PMID: 17062581 BACKGROUND

• Yogev L, Segal S, Zeharia E, Gamzu R, Maymon BB, Paz G, Botchan A, Hauser R, Yavetz H, Kleiman SE. Sex chromosome alignment at meiosis of azoospermic men with azoospermia factor microdeletion. J Androl. 2004 Jan-Feb;25(1):110-6. doi: 10.1002/j.1939-4640.2004.tb02765.x.

  PMID: 14662793 BACKGROUND

• Martinez MC, Bernabe MJ, Gomez E, Ballesteros A, Landeras J, Glover G, Gil-Salom M, Remohi J, Pellicer A. Screening for AZF deletion in a large series of severely impaired spermatogenesis patients. J Androl. 2000 Sep-Oct;21(5):651-5.

  PMID: 10975411 BACKGROUND

• Oliva R, Margarit E, Ballesca JL, Carrio A, Sanchez A, Mila M, Jimenez L, Alvarez-Vijande JR, Ballesta F. Prevalence of Y chromosome microdeletions in oligospermic and azoospermic candidates for intracytoplasmic sperm injection. Fertil Steril. 1998 Sep;70(3):506-10. doi: 10.1016/s0015-0282(98)00195-2.

  PMID: 9757880 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, ejaculated semen or testicular biopsy, blastomere

MeSH Terms

Conditions

Male sterility due to Y-chromosome deletions; Aneuploidy

Condition Hierarchy (Ancestors)

Chromosome Aberrations; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Purificación Hernández-Vargas, PhD

  Instituto Valenciano de Infertilidad, IVI Alicante

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Coordinator

Study Record Dates

• First Submitted: August 11, 2015
• First Posted: August 19, 2015
• Study Start: September 22, 2015
• Primary Completion: June 11, 2018
• Study Completion: June 11, 2018
• Last Updated: March 8, 2019

Record last verified: 2019-03

Locations

ES (3)