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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Observational [Patient Registry]

Official Title: Impact of Y-chromosome Microdeletions From Infertile Men on the Chromosomal Constitution of Their Spermatozoa and Embryos. Combined IntraCytoplasmatic Sperm Injection (ICSI) and Preimplantation Geneti

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.

Detailed Summary:

Nowadays, Y-chromosome microdeletions are one of the most common causes of male infertility. With a frequency of 8-20% in non-obstructive azoospermic men and 3-14% in severe oligozoospermic men, is the most usual chromosome anomaly associated with failure in sperm production, although the frequency seems to change due to differences in the experimental designs, the ethnic differences, the genetic background, or even environmental influences.

The absence of some genes located on certain regions in the long arm of the human Y chromosome, known as the azoospermia factor region (AZF), causes spermatogenic failure, while spermatozoa has been found in either the ejaculate or the testicle of most patients. Detection of deletions is crucial for the medical treatment of these patients, since it has a prognostic value in predicting potential success of testicular sperm retrieval in azoospermic patients with certain microdeletions, and allows avoiding invasive techniques in oligozoospermic patients whose sperm production could result in progressive worsening.

The development of assisted reproduction techniques, such as intracytoplasmatic sperm injection (ICSI), together with testicular or epididymis sperm retrieval for azoospermic men has allowed these patients to become fathers using their own gametes. Although the effect of Y-chromosome microdeletions on ICSI outcome is controversial, the ability to vertically transmit that genetic defect, and so the infertility, to the offspring has been accepted. Until recently, no clinical consequences other than infertility were supposed in the ICSI-conceived sons of fathers with deletions. However, different studies in the last years, suggest other potentially risks transmitted to the offspring, such as the development of sexual dysfunction due to sex chromosome abnormalities (Turner or Klinef
Sponsor: Instituto Valenciano de Infertilidad, IVI Alicante

Current Primary Outcome: % Embryos with aneuploidies [ Time Frame: three years ]

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.



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • % Spermatozoa with aneuploidies [ Time Frame: Three years ]

    The incidence of aneuploidy (%) in sperm will be examined by FISH, analyzing chromosomes 13, 18, 21, X and Y.

    To measure these percentages two examiners will analyze 2000 spermatozoa in each sample.

  • Fertilization rate (%) [ Time Frame: three years ]
    nº fertilized oocytes/ nº metaphase II oocytes
  • Day 3 embryos rate (%) [ Time Frame: Three years ]
    nº embryos at day 3/ nº fertilized oocytes
  • Blastocyst rate (%) [ Time Frame: Three years ]
    nº blastocyst/ nº fertilized oocytes
  • Cycle efficiency [ Time Frame: Four years ]
    nº transferred embryos + vitrified embryos
  • Pregnancy rate (%) [ Time Frame: Four years ]
    nº pregnancies/ nº embryos transferred
  • Biochemical pregnancy rate (%) [ Time Frame: Four years ]
    % of positive pregnancy tests
  • Clinical pregnancy rate (%) [ Time Frame: Four years ]
    nº pregnancies (proven by the presence of at least 1 embryo with cardiac activity positive by ultrasound after 5-6 weeks of development)/ nº of transfer cycles
  • Implantation rate (%) [ Time Frame: Four years ]
    nº gestational sacs/ nº transferred embryos
  • Abortion rate (%) [ Time Frame: Four years ]
    nº miscarriages/ nº pregnancies.
  • Ongoing pregnancy rate (%) [ Time Frame: Four years ]
    % clinical pregnancies that do not finish in abortion or ectopic pregnancy
  • Live birth rate (%) [ Time Frame: Four years ]
    Proportion of live birth at home per embryo transferred.


Original Secondary Outcome: Same as current

Information By: Instituto Valenciano de Infertilidad, IVI Alicante

Dates:
Date Received: August 11, 2015
Date Started: September 2015
Date Completion: September 2019
Last Updated: August 30, 2016
Last Verified: February 2016