Safety issues in assisted reproduction technology: Should ICSI patients have genetic testing before treatment? A practical proposition to help patient information

Abstract

ICSI is a highly efficient treatment of male factor infertility and therefore increasingly used to treat infertile men successfully. However, when used to treat patients with a genetic cause for their infertility, there may be an increased risk for the offspring. Chromosome aberrations, Y chromosome microdeletions and CFTR (cystic fibrosis transmembrane conductance regulator) mutations alone may explain up to 25% of azoospermia and severe oligozoospermia. These genetic defects could be identified before treatment, in which case informed decisions could be made by the couple to be treated concerning the treatment, prenatal testing or preimplantation genetic diagnosis. Therefore, we propose that men with very low sperm counts (<5 x 10(6)/ml) considering ICSI should always be informed of the possibility of genetic testing. The information should include a precise statement of the implications of the results for the patient, his family and his offspring, and reassurance that a decision to test or not to test, or the subsequent test results will not be used as a reason for withholding treatment. Testing should always remain voluntary, and the couples themselves should decide whether or not they choose to be tested. If an abnormality is identified, patients should be referred to specialist genetic counselling.

The interface between assisted reproductive technologies and genetics: technical, social, ethical and legal issues

“…36,40 Karyotype analysis and Y-chromosome microdeletion screening have been recommended to be performed in men with nonobstructive azoospermia, because as many as 10 -15% of these patients have an identifiable abnormality. 39,41,42 Aittomäki et al 22 suggest that these tests should also be carried out in men with oligozoospermia below 5 Â 10 6 /ml. Although it has been suggested that karyotype analysis should, before ART, be performed even in normozoospermic men, because some aberrations (such as 47,XYY) can be found, 36 this is not a general recommendation.…”

“…43 The deletions arise usually de novo, but are transmitted to all male offspring in ICSI. 22 New findings have shown that not every steroid sulphatase (STS) deletion in Y-chromosome causes male infertility. 37 The existence of a spermatogenesis-controlling factor(s), called azoospermia factor (AZF), in the long arm of the Y-chromosome was first based on identification of large deletions of this chromosomal area in azoospermic or oligozoospermic men.…”

“…47 -49 PGS may be useful for some of these couples in making the IVF treatment more successful by choosing the embryos with the best possible developmental potential. 22 In aneuploidy of the sex chromosomes or Klinefelter syndrome (KS), there are few, if any, spermatozoa in the ejaculate. Couples must either be treated following testicular sperm retrieval (if successful) combined with ICSI or use donor sperm to have children.…”

Outcomes for offspring of men having ICSI for male factor infertility

“…3 For those with oligozoospermia, the actual sperm concentration is indicative of the potential presence of a genetic disorder, specifically a Y-chromosome microdeletion in those with ,1310 6 sperm ml 21 . 4 Overall, there is variation in reports of the frequency of abnormal karyotypes in infertile men, most estimating between 8% and 10%. [5][6][7] This variation persists when specifically looking for the Yq deletions, but it appears that 5%-10% of men with NOA or SO may have such a deletion.…”

“…The third and most likely cause of adverse outcomes is the non-natural selection of a single sperm (ejaculated or non-ejaculated) which may lead to the passage of genetic defects that have caused the male infertility in the first place. 4,14 It has been interesting to see over the years that most studies comparing ICSI with in vitro fertilisation (IVF) generally report no increased risks associated with ICSI over and above those associated with IVF in any particular outcomes for the offspring. [15][16][17][18][19] There has been a recent study from Norway reporting that ICSI pregnancies have a lower risk of iatrogenic moderate preterm delivery, than IVF pregnancies.…”