Information about Sperm Aneuploidy for Clinicians

Chromosomal abnormalities may be somatic cell in origin, in which case they can be detected by a simple blood karyotype analysis. However, most sperm chromosome anomalies arise as a result of errors during meiosis, which cannot be detected by a blood karyotype analysis. These anomalies can only be detected by looking at the sperm chromosomes directly. 


Sperm Aneuploidy and Semen Parameters

Approximately 2 to 13% of all sperm are genetically abnormal in normally fertile men however this percentage may be 3 times higher in men who are infertile1-4. Aneuploidy rates in sperm of men with poor semen parameters are between 2 to 10 times higher that of fertile men4 although men with normal semen parameters may also display high levels of aneuploidy3,5. This may partly explain why there are conflicting results regarding direct correlations between individual semen parameters and sperm aneuploidy. There is general agreement that the frequency of sperm aneuploidy is particularly high in men with severe sperm defects1,2,6,7. High rates of aneuploidy are found in severe asthenozoospermia6, severe oligozoospermia1,3,7 and in testicular sperm from men with non-obstructive azoospermia8,9. In approximately 1% cases of male infertility, men are diagnosed with a predominant morphological defect in their sperm, namely globozoospermia (round headed sperm), macrozoospermia (sperm with enlarged heads and multiple tails) or dysplasia of the fibrous sheath (severe tail defects). Sperm from men with these defects show a significant increase in sperm aneuploidy2,4,10 and generally have a very poor prognosis for IVF/ICSI treatment11,12. Globozoospermia may have an increased frequency of aneuploidy 8 to 10 times13, sperm with dysplasia of the fibrous sheath 2 to 12 times12,14 and sperm with tapered heads 1.6 to 3.6 times15 that of normal sperm. Macrocephalic sperm are especially prone to aneuploidy showing aneuploidy frequencies between 10 and 30 times that of controls and between 20 and 90% of these sperm may be aneuploid11,13. The frequency of aneuploidy is greatest in sperm from men who have severe defects in all major semen parameters4,16,17. Indeed sperm from men with oligoasthenoteratozoospermia are up to 30 times more likely to be aneuploid4.


Influence of Sperm Aneuploidy on Embryo Development, Pregnancy and Miscarriage

A high rate of sperm aneuploidy leads to a significant increase in the occurrence of chromosome aneuploidy in embryos 18-21. The consequences of this are poor embryo development, a significantly reduced pregnancy rate, and an increased risk of abnormalities in newborns. Sperm aneuploidy influences ICSI treatment outcome and is associated with multiple assisted conception treatment failure22. The incidence of aneuploidy was found to be significantly higher in sperm of men who are unsuccessful with ICSI treatment compared to those who achieve pregnancies23,24. Furthermore, there are numerous studies that show a significant correlation between sperm aneuploidy and recurrent pregnancy loss 3,18,25-27irrespective of whether the semen parameters are normal 27.


Causes of Sperm Aneuploidy

Sperm aneuploidy occurs due to increased errors in meiotic pairing, synapsis and recombination during sperm development2,28 . In patients who have an abnormal blood chromosome karyotype, such as Klinefelter's, their sperm have an increased incidence of aneuploidy but the rates are not as high as expected2,28. It has been suggested that advancing male age may be linked to sperm aneuploidy29. Although there is only a slight increased risk of aneuploidy, there is a significantly higher risk of aneuploidy in embryos derived from sperm from men aged 50 or above44. The effects of specific lifestyle factors on aneuploidy frequencies are inconsistent, and this is likely due to the difficulty in controlling for other factors as well as variation between individuals. However most studies show a strong association between cigarette smoking and aneuploidy2,17,30-32 and there is some evidence relating sperm aneuploidy to alcohol consumption30, caffeine consumption32,33 and obesity33. High levels of sperm aneuploidy can also be caused by exposure to pesticides34,35 and occupational hazards36. It is well established that sperm from men who have been treated with chemotherapy and radiotherapy have a significant increase in aneuploidy37,38 which leads to an increased risk of impaired embryo development, miscarriage and congenital abnormalities in the children born38. This risk appears to be mitigated within 18 months to two years post treatment37.


Measuring Sperm Aneuploidy 

Assessment of sperm aneuploidy involves fluorescent in situ hybridisation (FISH) to label individual chromosomes with specific probes39. One to two thousand sperm can be assessed from one ejaculate. The assay has been standardised and validated and is CE marked. There are limitations to the test as it will only determine numerical chromosome anomalies and cannot provide any information about structural abnormalities or single gene defects. Only 5 probes are currently used routinely for analysis (three of the 22 autosomes: chromosomes 13, 18 and 21, and the sex chromosomes, X and Y) as these chromosomes are the most susceptible to non-disjunction during meiosis2,18,39. They are also most important from a clinical perspective as they may be non-lethal and are compatible with survival40. Probes for other chromosomes are available upon specific request. The results are reported showing incidence of disomy or nullisomy for each of the autosomes and for both sex chromosomes compared to a reference range determined from fertile controls. A sex chromosome ratio and diploidy rate is also reported. The turnaround time for the results is between 10 and 14 days.


Exogenous Factors Influencing Sperm Aneuploidy

  • cigarette smoking
  • caffeine
  • alcohol
  • obesity
  • chemotherapy and radiotherapy treatment within the last 2 years
  • exposure to environmental and occupational pollutants
  • exposure to ionising radiation
  • advanced age

Indications for Male Patients Who May Benefit from a Sperm Aneuploidy Test

  • unexplained infertility
  • multiple failed IVF/ICSI treatment
  • recurrent miscarriage in partner
  • raised FSH
  • oligoasthenoteratozoospermia 
  • severe teratozoospermia (macrocepahly, globozoospermia, dysplasia of the fibrous sheath)
  • exposure to harmful substances
  • age 50 or above

Which Patients Would Benefit from Sperm Aneuploidy Testing?

The clinical implementation of sperm chromosome aneuploidy testing may be recommended for men with severe male factor infertility, especially when this has resulted in multiple failed ICSI treatment cycles or recurrent pregnancy loss2,4,40. Sperm aneuploidy testing should be performed in cases of severe defects in sperm morphology such as macrocephaly, globozoospermia and dysplasia of the fibrous sheath. The test is also recommended for men with normal semen parameters who experience unexplained assisted conception treatment failure or recurrent miscarriage in their partners3,40 and men over 50 years of age attempting to achieve a pregnancy44.


Treatment and Management of Sperm Aneuploidy

A reduction in exposure to harmful substances and a change in diet and lifestyle may help to reduce high frequencies of aneuploidy in sperm. One study demonstrated that diet supplementation with high folate may maintain lower aneuploidy rates41. However, some abnormalities may be irreversible. Particular types of severe sperm morphological abnormalities are themselves associated with gene defects which cannot be treated11. An alternative management strategy would be to implement sperm selection methods to identify sperm more likely to be chromosomally normal. A recent randomised controlled trial has shown very promising results using hyaluronan to select genetically healthy sperm for ICSI treatment42. Selecting sperm using this method has shown a significant reduction in miscarriage rates43. When there is a substantial risk of transmitting chromosomal defects to the offspring, preimplantation genetic screening of embryos following ICSI may be offered40.


Advantages of the Sperm Aneuploidy Test

Sperm aneuploidy testing may provide valuable information to assist in the diagnosis and management of male infertility, not only as a predictor of success, but for future genetic counselling for the couple. In cases of multiple IVF or ICSI treatment failure as well as for unexplained recurrent miscarriage18, identification of chromosome abnormalities in the sperm may guide the clinician as to whether sperm donation may be appropriate. Sperm aneuploidy testing may help couples to make an informed choice regarding their subsequent course of treatment. Couples who may be at an increased risk of recurrent pregnancy loss or passing on chromosomal abnormalities to their children may opt for sperm selection using hyaluronon or preimplantation genetic screening of their embryos thus increasing their chances of a healthy live birth.



Additional information downloads:

Sperm DNA Fragmentation, Aneuploidy & Epigenetics Test Request & GDPR Consent Form





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