Intracytoplasmic Sperm Injection (ICSI) of Sub-Optimal Sperm Increases The Risk of Sex-Chromosome, But Not Autosomal Aneuploidy among Embryos Evaluated with Comprehensive Chromosome Screening (CCS)

Intracytoplasmic Sperm Injection (ICSI) of Sub-Optimal Sperm Increases The Risk of... Background</h5> Prior studies suggest that ICSI results in an increased risk of transmitting aneuploidy to future offspring, however the underlying mechanisms remain unclear. Suggested mechanisms are based on the potential selection of sub-optimal sperm more likely to carry a chromosomal error versus an impairment in chromosome segregation within the egg/cleaving embryo resulting from the invasive nature of the procedure itself.</P>Objective</h5> To evaluate the rate of aneuploidy among embryos assessed by comprehensive chromosome screening (CCS) in four groups of patients undergoing assisted reproduction: standard in vitro fertilization (IVF), ICSI with normal semen analysis parameters, ICSI with mild male factor (6-15 x 10 6 /ml motile sperm with normal appearance) and ICSI with severe male factor (<6 x 10 6 /ml motile sperm with normal appearance or surgically retrieved sperm) to determine if a difference in aneuploidy rate exists while controlling for maternal age.</P>Materials and Methods</h5> 3306 embryos were evaluated from 575 couples who completed an IVF cycle, using ICSI or standard IVF between August 2010 and August 2014 at Oregon Reproductive Medicine (Portland, Oregon, USA). Trophectoderm biopsy was performed on day 5 or 6 followed by CCS using array comparative genomic hybridization (aCGH) to test for aneuploidy. Patients were sub-divided into 4 maternal age groups: Donor egg, < 35 y/o, 35-39 y/o and 40-42 y/o. Patients were further divided into the 4 groups described above. The aneuploidy rate stratified by age of the oocyte and % of sex chromosome abnormalities in each of the 4 treatment groups was calculated. Significant treatment differences were determined using One Way ANOVA on Ranks, followed by multiple-comparison tests if appropriate.</P>Results</h5> There was no significant difference in the rate of aneuploidy between the 4 treatment groups when controlling for age of the oocyte (Figure 1, p>0.05 for all groups). As expected, there was a significant increase in aneuploidy rate with advancing age of the oocyte. A significant increase in the rate of sex chromosome abnormalities was observed among patients utilizing ICSI for severe male factor infertility (Figure 2, p=0.049). Figure 1 Figure 2 </P>Conclusions</h5> These data suggest an increased risk of transmission of sex-chromosome, but not autosomal aneuploidy to offspring when using sperm from men with severe male factor infertility. The effect is greater than that associated with advancing maternal age. CCS should be considered for these patients to allow for the selective transfer of euploid embryos. ICSI appears to be safe and does not increase the risk of aneuploidy in developing embryos.</P>References</h5> 1. Hansen M, Kurinczuk JJ, Bower C, Webb S. The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N Engl J Med 2002;346(10):725-30.</P>2. Mehdi M, Gmidene A, Brahem S, Guerin JF, Elghezal H, Saad A. Aneuploidy rate in spermatozoa of selected men with severe teratozoospermia. Andrologia 2012;44 Suppl 1:139-43.</P>3. Lathi RB, Milki AA. Rate of aneuploidy in miscarriages following in vitro fertilization and intracytoplasmic sperm injection. Fertil Steril 2004;81(5):1270-2.</P>4. Lie RT, Lyngstadaas A, Orstavik KH, Bakketeig LS, Jacobsen G, Tanbo T. Birth defects in children conceived by ICSI compared with children conceived by other IVF-methods; a meta-analysis. Int Epidemiol 2005;34(3):696-701.</P> http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Fertility and Sterility Elsevier

Intracytoplasmic Sperm Injection (ICSI) of Sub-Optimal Sperm Increases The Risk of Sex-Chromosome, But Not Autosomal Aneuploidy among Embryos Evaluated with Comprehensive Chromosome Screening (CCS)

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Publisher
Elsevier
Copyright
Copyright © 2015 Elsevier Ltd
ISSN
0015-0282
D.O.I.
10.1016/j.fertnstert.2014.12.086
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Abstract

Background</h5> Prior studies suggest that ICSI results in an increased risk of transmitting aneuploidy to future offspring, however the underlying mechanisms remain unclear. Suggested mechanisms are based on the potential selection of sub-optimal sperm more likely to carry a chromosomal error versus an impairment in chromosome segregation within the egg/cleaving embryo resulting from the invasive nature of the procedure itself.</P>Objective</h5> To evaluate the rate of aneuploidy among embryos assessed by comprehensive chromosome screening (CCS) in four groups of patients undergoing assisted reproduction: standard in vitro fertilization (IVF), ICSI with normal semen analysis parameters, ICSI with mild male factor (6-15 x 10 6 /ml motile sperm with normal appearance) and ICSI with severe male factor (<6 x 10 6 /ml motile sperm with normal appearance or surgically retrieved sperm) to determine if a difference in aneuploidy rate exists while controlling for maternal age.</P>Materials and Methods</h5> 3306 embryos were evaluated from 575 couples who completed an IVF cycle, using ICSI or standard IVF between August 2010 and August 2014 at Oregon Reproductive Medicine (Portland, Oregon, USA). Trophectoderm biopsy was performed on day 5 or 6 followed by CCS using array comparative genomic hybridization (aCGH) to test for aneuploidy. Patients were sub-divided into 4 maternal age groups: Donor egg, < 35 y/o, 35-39 y/o and 40-42 y/o. Patients were further divided into the 4 groups described above. The aneuploidy rate stratified by age of the oocyte and % of sex chromosome abnormalities in each of the 4 treatment groups was calculated. Significant treatment differences were determined using One Way ANOVA on Ranks, followed by multiple-comparison tests if appropriate.</P>Results</h5> There was no significant difference in the rate of aneuploidy between the 4 treatment groups when controlling for age of the oocyte (Figure 1, p>0.05 for all groups). As expected, there was a significant increase in aneuploidy rate with advancing age of the oocyte. A significant increase in the rate of sex chromosome abnormalities was observed among patients utilizing ICSI for severe male factor infertility (Figure 2, p=0.049). Figure 1 Figure 2 </P>Conclusions</h5> These data suggest an increased risk of transmission of sex-chromosome, but not autosomal aneuploidy to offspring when using sperm from men with severe male factor infertility. The effect is greater than that associated with advancing maternal age. CCS should be considered for these patients to allow for the selective transfer of euploid embryos. ICSI appears to be safe and does not increase the risk of aneuploidy in developing embryos.</P>References</h5> 1. Hansen M, Kurinczuk JJ, Bower C, Webb S. The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N Engl J Med 2002;346(10):725-30.</P>2. Mehdi M, Gmidene A, Brahem S, Guerin JF, Elghezal H, Saad A. Aneuploidy rate in spermatozoa of selected men with severe teratozoospermia. Andrologia 2012;44 Suppl 1:139-43.</P>3. Lathi RB, Milki AA. Rate of aneuploidy in miscarriages following in vitro fertilization and intracytoplasmic sperm injection. Fertil Steril 2004;81(5):1270-2.</P>4. Lie RT, Lyngstadaas A, Orstavik KH, Bakketeig LS, Jacobsen G, Tanbo T. Birth defects in children conceived by ICSI compared with children conceived by other IVF-methods; a meta-analysis. Int Epidemiol 2005;34(3):696-701.</P>

Journal

Fertility and SterilityElsevier

Published: Feb 1, 2015

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