Relationship Between Sperm Head Vacuoles and Sperm DNA Alterations in Infertile Men

NCT02006446 | Completed

• 1 other identifier: 2013/005/HP
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

Brief Summary

In men presenting sperm alterations, the selection of genetically undamaged spermatozoa need to be improved in order to increase the success of assisted reproduction treatments. The aim of this study is to determine whether the presence of sperm head vacuoles is associated with sperm DNA alterations.

Conditions

Male Infertility

Keywords

Male infertility; sperm head vacuoles; sperm morphology; aneuploidy; DNA fragmentation; abnormal chromatin condensation; telomere abnormalities

Outcome Measures

Primary Outcomes (1)

• Correlation coefficient between mean vacuole areas in sperm heads (measured by MSOME) and sperm aneuploidy rates for chromosomes X, Y and 18 (evaluated by FISH)

  up to 30 months

Secondary Outcomes (7)

• Total sperm count

  1 day

• Percentage of mobile spermatozoa

  1 day

• Percentage of morphologically abnormal spermatozoa

  1 day

• Mean vacuole area threshold (measured with Receiver Operating Characteristic curves)

  up to 30 months

• Correlation coefficient between vacuole areas and sperm DNA fragmentation (evaluated by TUNEL analysis)

  up to 30 months

Study Arms (1)

Altered spermograms

EXPERIMENTAL

Men with altered spermograms (isolated teratozoospermia or oligo-astheno-teratozoospermia)

Other: Sperm Samples

Interventions

Sperm Samples OTHER

The study will focus on sperm samples collected via masturbation for routine pre-IVF screening tests, taken from patients with isolated teratozoospermia or oligoasthenozoospermia. The various tests and analyses planned will be carried out on sperm not used for IVF or diagnostic purposes.

Altered spermograms

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• men
• years old or more
• affiliated to social security
• with isolated teratozoospermia or oligo-astheno-teratozoospermia according to the WHO guidelines (2010):
• sperm concentration \< 15 million per ml or sperm number \< 39 million per ejaculate
• progressive motility \< 35%
• morphologically normal forms \< 50% according to the modified David's classification (Auger et al., 2001
• mobile spermatozoa selected by density gradient centrifugation \> 1 million, in previous spermograms
• with normal constitutional karyotypes (46, XY)
• signed an informed consent

You may not qualify if:

• with abnormal constitutional karyotypes
• with a major alteration of sperm parameters, with mobile spermatozoa selected by density gradient centrifugation \< 1 million
• under tutorship or guardianship by court order

Sponsors & Collaborators

• University Hospital, Rouen: lead

Study Sites (2)

Laboratoire de spermiologie, Hôpital Calmette, CHRU de Lille

Lille, France

Location

Laboratoire de Biologie de la Reproduction - CECOS - EA 4308, CHU - Hôpitaux de Rouen

Rouen, 76031, France

Location

Related Publications (18)

• Antinori M, Licata E, Dani G, Cerusico F, Versaci C, d'Angelo D, Antinori S. Intracytoplasmic morphologically selected sperm injection: a prospective randomized trial. Reprod Biomed Online. 2008 Jun;16(6):835-41. doi: 10.1016/s1472-6483(10)60150-2.

  PMID: 18549694 BACKGROUND

• Auger J, Eustache F, Andersen AG, Irvine DS, Jorgensen N, Skakkebaek NE, Suominen J, Toppari J, Vierula M, Jouannet P. Sperm morphological defects related to environment, lifestyle and medical history of 1001 male partners of pregnant women from four European cities. Hum Reprod. 2001 Dec;16(12):2710-7. doi: 10.1093/humrep/16.12.2710.

  PMID: 11726600 BACKGROUND

• Bartoov B, Berkovitz A, Eltes F. Selection of spermatozoa with normal nuclei to improve the pregnancy rate with intracytoplasmic sperm injection. N Engl J Med. 2001 Oct 4;345(14):1067-8. doi: 10.1056/NEJM200110043451416. No abstract available.

  PMID: 11586970 BACKGROUND

• Bartoov B, Berkovitz A, Eltes F, Kogosovsky A, Yagoda A, Lederman H, Artzi S, Gross M, Barak Y. Pregnancy rates are higher with intracytoplasmic morphologically selected sperm injection than with conventional intracytoplasmic injection. Fertil Steril. 2003 Dec;80(6):1413-9. doi: 10.1016/j.fertnstert.2003.05.016.

  PMID: 14667877 BACKGROUND

• Boitrelle F, Ferfouri F, Petit JM, Segretain D, Tourain C, Bergere M, Bailly M, Vialard F, Albert M, Selva J. Large human sperm vacuoles observed in motile spermatozoa under high magnification: nuclear thumbprints linked to failure of chromatin condensation. Hum Reprod. 2011 Jul;26(7):1650-8. doi: 10.1093/humrep/der129. Epub 2011 May 2.

  PMID: 21536591 BACKGROUND

• Bonduelle M, Van Assche E, Joris H, Keymolen K, Devroey P, Van Steirteghem A, Liebaers I. Prenatal testing in ICSI pregnancies: incidence of chromosomal anomalies in 1586 karyotypes and relation to sperm parameters. Hum Reprod. 2002 Oct;17(10):2600-14. doi: 10.1093/humrep/17.10.2600.

  PMID: 12351536 BACKGROUND

• Figueira Rde C, Braga DP, Setti AS, Iaconelli A Jr, Borges E Jr. Morphological nuclear integrity of sperm cells is associated with preimplantation genetic aneuploidy screening cycle outcomes. Fertil Steril. 2011 Mar 1;95(3):990-3. doi: 10.1016/j.fertnstert.2010.11.018. Epub 2010 Dec 4.

  PMID: 21130987 BACKGROUND

• Foresta C, Garolla A, Bartoloni L, Bettella A, Ferlin A. Genetic abnormalities among severely oligospermic men who are candidates for intracytoplasmic sperm injection. J Clin Endocrinol Metab. 2005 Jan;90(1):152-6. doi: 10.1210/jc.2004-1469. Epub 2004 Oct 27.

  PMID: 15509635 BACKGROUND

• Franco JG Jr, Baruffi RL, Mauri AL, Petersen CG, Oliveira JB, Vagnini L. Significance of large nuclear vacuoles in human spermatozoa: implications for ICSI. Reprod Biomed Online. 2008 Jul;17(1):42-5. doi: 10.1016/s1472-6483(10)60291-x.

  PMID: 18616888 BACKGROUND

• Franco JG Jr, Mauri AL, Petersen CG, Massaro FC, Silva LF, Felipe V, Cavagna M, Pontes A, Baruffi RL, Oliveira JB, Vagnini LD. Large nuclear vacuoles are indicative of abnormal chromatin packaging in human spermatozoa. Int J Androl. 2012 Feb;35(1):46-51. doi: 10.1111/j.1365-2605.2011.01154.x. Epub 2011 Apr 28.

  PMID: 21535011 BACKGROUND

• Garolla A, Fortini D, Menegazzo M, De Toni L, Nicoletti V, Moretti A, Selice R, Engl B, Foresta C. High-power microscopy for selecting spermatozoa for ICSI by physiological status. Reprod Biomed Online. 2008 Nov;17(5):610-6. doi: 10.1016/s1472-6483(10)60307-0.

  PMID: 18983744 BACKGROUND

• Hazout A, Dumont-Hassan M, Junca AM, Cohen Bacrie P, Tesarik J. High-magnification ICSI overcomes paternal effect resistant to conventional ICSI. Reprod Biomed Online. 2006 Jan;12(1):19-25. doi: 10.1016/s1472-6483(10)60975-3.

  PMID: 16454928 BACKGROUND

• Oliveira JB, Massaro FC, Baruffi RL, Mauri AL, Petersen CG, Silva LF, Vagnini LD, Franco JG Jr. Correlation between semen analysis by motile sperm organelle morphology examination and sperm DNA damage. Fertil Steril. 2010 Oct;94(5):1937-40. doi: 10.1016/j.fertnstert.2010.01.042. Epub 2010 Mar 2.

  PMID: 20189558 BACKGROUND

• Perdrix A, Travers A, Chelli MH, Escalier D, Do Rego JL, Milazzo JP, Mousset-Simeon N, Mace B, Rives N. Assessment of acrosome and nuclear abnormalities in human spermatozoa with large vacuoles. Hum Reprod. 2011 Jan;26(1):47-58. doi: 10.1093/humrep/deq297. Epub 2010 Nov 18.

  PMID: 21088015 BACKGROUND

• Van Steirteghem A, Bonduelle M, Devroey P, Liebaers I. Follow-up of children born after ICSI. Hum Reprod Update. 2002 Mar-Apr;8(2):111-6. doi: 10.1093/humupd/8.2.111.

  PMID: 12099626 BACKGROUND

• Vanderzwalmen P, Hiemer A, Rubner P, Bach M, Neyer A, Stecher A, Uher P, Zintz M, Lejeune B, Vanderzwalmen S, Cassuto G, Zech NH. Blastocyst development after sperm selection at high magnification is associated with size and number of nuclear vacuoles. Reprod Biomed Online. 2008 Nov;17(5):617-27. doi: 10.1016/s1472-6483(10)60308-2.

  PMID: 18983745 BACKGROUND

• Watanabe S, Tanaka A, Fujii S, Mizunuma H, Fukui A, Fukuhara R, Nakamura R, Yamada K, Tanaka I, Awata S, Nagayoshi M. An investigation of the potential effect of vacuoles in human sperm on DNA damage using a chromosome assay and the TUNEL assay. Hum Reprod. 2011 May;26(5):978-86. doi: 10.1093/humrep/der047. Epub 2011 Feb 28.

  PMID: 21362682 BACKGROUND

• Wilding M, Coppola G, di Matteo L, Palagiano A, Fusco E, Dale B. Intracytoplasmic injection of morphologically selected spermatozoa (IMSI) improves outcome after assisted reproduction by deselecting physiologically poor quality spermatozoa. J Assist Reprod Genet. 2011 Mar;28(3):253-62. doi: 10.1007/s10815-010-9505-5. Epub 2010 Nov 12.

  PMID: 21072684 BACKGROUND

MeSH Terms

Conditions

Infertility, Male; Aneuploidy

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Infertility; Male Urogenital Diseases; Chromosome Aberrations; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Nathalie Rives, MD., PhD.

  Laboratoire de Biologie de la Reproduction - CECOS - EA 4308, CHU - Hôpitaux de Rouen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2013
• First Posted: December 10, 2013
• Study Start: December 1, 2013
• Primary Completion: December 1, 2016
• Study Completion: January 1, 2017
• Last Updated: June 10, 2026

Record last verified: 2017-01

Locations

FR (2)