Impact of male factor infertility on offspring health and development

Abstract

Monitoring the safety of intracytoplasmic sperm injection (ICSI) has been impeded by uncertainties regarding the extent to which offspring health is influenced by paternal characteristics linked to male infertility or the processes that ICSI treatment entails. Few studies examining long-term health and developmental outcomes in children conceived with ICSI have considered the influence of paternal infertility adequately. In the available literature, large population-based studies suggest underlying male factors, and the severity of male factor infertility, increase the risk of mental retardation and autism in offspring, as does the ICSI procedure itself, but these findings have not been replicated consistently. Robust evidence of the influence of male factors on other health outcomes is lacking, with many studies limited by sample size. Nevertheless, emerging evidence suggests children conceived with ICSI have increased adiposity, particularly girls. Further, young men conceived with ICSI may have impaired spermatogenesis; the mechanisms underlying this remain unclear, with inconclusive evidence of inheritance of Y chromosome microdeletions. The current inconsistent and often sparse literature concerning the long-term health of children conceived with ICSI, and the specific influence of male infertility factors, underscore the need for concerted monitoring of children conceived with this technique across the lifespan. With the rapid expansion of use of ICSI for non-male factors, sufficiently large studies that compare outcomes between groups conceived with this technique for male factors versus non-male factors will provide critical evidence to elucidate the intergenerational impact of male infertility.

Sperm DNA Methylation Epimutation Biomarkers for Male Infertility and FSH Therapeutic Responsiveness

“…The current estimated infertility range is approximately 15–20% of the human male population 2 . A common strategy for medically assisted reproduction when male factor infertility is identified involves in vitro fertilization and intracytoplasmic sperm injection (ICSI), which are invasive and expensive procedures 22 . In addition to low sperm counts associated with infertility, there is also an increase in idiopathic infertility, which can have normal sperm cohorts and motility 2,22 .…”

“…A common strategy for medically assisted reproduction when male factor infertility is identified involves in vitro fertilization and intracytoplasmic sperm injection (ICSI), which are invasive and expensive procedures 22 . In addition to low sperm counts associated with infertility, there is also an increase in idiopathic infertility, which can have normal sperm cohorts and motility 2,22 . While seminal parameters are commonly used to screen for male factor infertility, the sperm number, motility and shape cannot fully explain the infertility 2,22 .…”

“…In addition to low sperm counts associated with infertility, there is also an increase in idiopathic infertility, which can have normal sperm cohorts and motility 2,22 . While seminal parameters are commonly used to screen for male factor infertility, the sperm number, motility and shape cannot fully explain the infertility 2,22 . The development of a clinical diagnostic analysis based on molecular alterations in the sperm would help address this clinical problem.…”

Identification of male infertility-related long non-coding RNAs and their functions based on a competing endogenous RNA network

“… 1 , 3 , 4 However, because the exact pathogenesis is unknown, there are a lack of clear treatment targets and effective treatment measures. 5 , 6 Therefore, there is an urgent need for basic research into the molecular mechanism of male infertility to identify new biomarkers and therapeutic targets.…”

Is Intracytoplasmic Sperm Injection the Solution for all in Unexplained Infertility?

“…In most studies, children conceived spontaneously are used as the control group, but whether this is the correct group is debatable, since parental factors such as infertility per se might influence the health of the offsprings. 112 It is worth noting that the long-term developmental outcomes of children, especially intelligence and cognitive function, are closely associated with parents' level of education and socioeconomic status. 113 Last, existing studies are also subject to bias as a result of incomplete follow-up arising from attrition.…”