Genetic Diagnosis in Infertile Men with Numerical and Constitutional Sperm Abnormalities

Abstract

Infertile men having numerical or structural sperm defects may carry several genetic abnormalities (karyotype abnormalities, Y chromosome microdeletions, cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations, androgen receptor gene mutations, and abnormalities seen in sperm cells) leading to this situation. First we aimed to investigate the relationship between the numerical and constitutional (morphological) sperm anomalies and the genetic disorders that can be seen in infertile males. Our other aim was to compare two different kinds of kits that we use for the detection of Y chromosome microdeletions. Sixty-three infertile males [44 nonobstructive azoospermic, 8 severe oligozoospermic, and 11 oligoasthenoteratozoospermic] were investigated in terms of somatic chromosomal constitutions and microdeletions of the Y chromosome. Sperm aneuploidy levels were analyzed by fluorescence in situ hybridization (FISH) in sperm cells obtained from the semen of six OAT patients. Microdeletion and sex chromosome aneuploidy (47,XXY) rates in somatic cells were found to be approximately 3.2% and 4.7%, respectively. Sperm aneuploidy rates were determined as 9%, 22%, and 47% in three patients out of six. Two of these three patients also had high rates of head anomalies in semen samples. High correlation was found between sperm aneuploidy rates and sperm head anomalies. Since the introduction of the assisted reproductive techniques for the treatment of severe male infertility, genetic tests and genetic counseling became very important due to the transmission of genetic abnormalities to the next generation. Thus in a very near future, for a comprehensive male infertility panel, it will be essential to include additional genetic tests, such as CFTR gene mutations, sperm mitochondrial DNA mutations, and androgen receptor gene mutations, besides the conventional chromosomal analyses, Y chromosome microdeletion detection, and sperm-FISH analyses.

Chromosomal and molecular abnormalities in a group of Brazilian infertile men with severe oligozoospermia or non-obstructive azoospermia attending an infertility service

“…It has to be considered, however, that testicular sperm retrieval procedures performed on men with severe male infertility of genetic origin might bear a potential risk of transmitting genetic abnormalities to the offspring (7,28,32). If a man with an AZFc microdeletion takes part in an ICSI procedure, he can pass the same deletion, or a larger one, on to his male offspring, since deletions can generate chromosomal instability and lead to deletions of the nearby regions, in further generations (33).…”

Y-chromosome microdeletion and male infertility: a systematic review

“…Studies have good methodological accuracy. The sample universe is quite heterogeneous, given the very design of the studies (22 case reports with 02 individuals up to 33 cross-sectional studies with 4, 441 individuals), age differences between individuals in the samples ranging from 17 years [10] to 66 years [21], as well as the origin of the patients who were: India [2,23,25,35], Brazil [3,31,34,36], China [4,10,17,18], Iran [1,7,19,21] Turkey [5,26,27] [20], Denmark [37], USA [22], england [38], Mexico [30], Serbia [28] and Venezuela [32]. Because of this situation, the data becomes divergent and the comparative analysis becomes troublesome.…”

“…al. [27] is that of the 63 patients Y-chromosome microdeletion were observed in two patients with azoospermia and normal karyotype (46, XY). In one study [37], the frequency of Y-chromosome microdeletions was higher in men with azoospermia (2%) compared with oligozoospermic men (0.6%).…”

Defining laboratory reference values and decision limits: populations, intervals, and interpretations

“…Examples of this include haptoglobin (in which concentrations progressively decrease across the Hp 1-1, Hp 2-1, and Hp 2-2 phenotypes) [16] and HDL cholesterol (in which concentrations are lower in individuals carrying the Apo A1Milano mutation) [17]. Several genetic markers are known to have a role in male infertility [18], and it is possible that as yet undefined genetic markers may influence observed reference intervals for tests of human semen or male fertility.…”