Somatic chromosomal abnormalities in infertile men and women

Abstract

Infertility – the inability to achieve conception or sustain a pregnancy through to live birth – is very common and affects about 15% of couples. While chromosomal or genetic abnormalities associated with azoospermia, severe oligozoospermia or primary ovarian failure were of no importance for reproduction prior to the era of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), advances in assisted reproductive techniques (ART) now enable many infertile couples to have children. These developments have raised the question of the genetic consequences of ICSI: concerns of the potential harm of the invasive procedure and concerns about the genetic risk. The infertile male and female definitely have an increased risk to carry a chromosomal abnormality. Detection of such an abnormality is of fundamental importance for the diagnosis of infertility, the following treatment, the evaluation of the risk for the future child and the appropriate management of the pregnancy to be obtained. Therefore, cytogenetic screening of both partners is mandatory prior to any type of ART. The present review is based on several surveys on male and female infertility and analyzes the types and frequencies of the different reported chromosome abnormalities according to the type of impairment of spermatogenesis and the type of treatment planned or performed. With regard to assisted reproductive techniques (especially ICSI) the main types of chromosomal abnormalities are discussed and their potential risks for ICSI. If available, reported cases of performed ICSI and its outcome are presented. The detection of an abnormal karyotype should lead to comprehensive genetic counselling, which should include all well-known information about the individual type of anomaly, its clinical relevance, its possible inheritance, the genetic risk of unbalanced offspring, and the possibilities of prenatal diagnosis. Only this proceeding allows at-risk couples to make an informed decision regarding whether or not to proceed with ART. These decisions can be made only when both partners have clearly understood the genetic risks and possible consequences when ART is used.

Male Infertility; Evidences, Risk Factors, Causes, Diagnosis and Management in Human

“…Genetic causes must be sought by systematic evaluation of infertile men and affected couples informed about the implications of such diagnoses for assisted reproductive technology outcome and their potential offspring. An association between human male infertility and chromosomal anomalies has been known for a long time [56,57]. The incidence of karyotype abnormalities among patients with infertility has been reported to range between 2% to 21%, being low among azoospermic men [58][59][60].…”

“…The possible association between chromosomal abnormalities and male infertility became evident following the result of the first large karyotype survey involving subfertile males [56,61]. The Y chromosome in mammals carries the gene that switches the development of the indifferent gonad from the default female pathway to the male pathway and results in the development of the testis [62].…”

Thirty-two new cases with small supernumerary marker chromosomes detected in connection with fertility problems: Detailed molecular cytogenetic characterization and review of the literature

“…(ii) It has also been suggested that any kind of chromosomal aberration can reduce the ability of correct chromosomal pairing during meiosis I (1), which can cause fertility problems especially in males (17). (iii) There are indications that OAT/oligozoospermia is significantly correlated with sSMC presence (7%), while azoospermia and sSMC are correlated in <1% of the corresponding cases (18 Fig. 3); in these cases uniparental disomy (UPD) of the sister chromosomes might be a possible explanation, even though such UPD was up to now only proven for de novo sSMC cases.…”

Sequential FISH allows the determination of the segregation outcome and the presence of numerical anomalies in spermatozoa from a t(1;8;2)(q42;p21;p15) carrier

“…Based on this last classification criterion, CCR can be divided into three-way rearrangements (when three chromosomes suffer one break each and interchange the distal segments), exceptional CCR (when more than one breakpoint per chromosome is present), and double two-way translocations (involving two or three independent translocations in the same carrier). Despite the lack of surveys referring to a concrete incidence in the general population, the frequency among infertile individuals has been estimated around 0.1 % [14].…”