Long‐term follow‐up of ICSI‐conceived offspring compared with spontaneously conceived offspring: a systematic review of health outcomes beyond the neonatal period

Abstract

Background: A significant increase in the use of intracytoplasmic sperm injection (ICSI) since its introduction in 1992 has been observed worldwide, including beyond its original intended use for severe male factor infertility. Concerns regarding ICSI include the effects of poor quality spermatozoa on offspring health and future fertility, and of the technique itself. The health and development of ICSI-conceived children beyond early infancy have not been comprehensively assessed. Objective: A systematic review of health outcomes of ICSI-conceived offspring beyond the neonatal period compared to spontaneously conceived (SC) offspring. Design: PubMed, OVID Medline/Embase, InformIT, Web of Science, and ProQuest databases were searched for studies reporting on health outcomes in ICSI-conceived offspring beyond 28 days after birth. Main outcomes measure(s): Physical and psychosocial health. Results: The search strategy yielded 2826 articles. Of these, 2580 were not relevant or did not meet inclusion criteria and 138 were duplicates. One hundred and eight full-text papers were evaluated further, and 48 satisfied the inclusion criteria. Most studies reported on neurodevelopment during early infancy and childhood with reassuring results. Growth, vision, and hearing of ICSI and SC offspring also appear comparable, although important differences in general physical health, and particularly metabolic and reproductive health have been described, including recently poorer semen quality among ICSI-conceived young adult men compared to SC peers. Conclusion: Whilst neurodevelopment, growth, vision, and hearing appear similar between ICSI and SC children, evidence suggests differences in general physical health, and metabolic and reproductive endpoints. The clinical significance of many findings, however, remains unclear, and further prospective, large, and good quality studies with a focus on all these health outcomes in ICSIconceived young adults are required.

Male reproductive health and intergenerational metabolic responses from a small RNA perspective

“…More recent data, however, contradict these claims. Several meta-analyses now show that children produced by ICSI express greater risks for congenital abnormalities and complex diseases later in life, including metabolic problems [120][121][122][123][124][125]. It must be emphasized that methods such as ICSI and ROSI only have been relatively recently applied in clinical practice -ICSI being in regular use since the 1990s and ROSI only for the last decade.…”

The present crisis in male reproductive health: an urgent need for a political, social, and research roadmap

“…Alarmingly, there is an association between offspring conceived using IVF‐ICSI and imprinting disorders, such as Beckwith–Wiedemann and Angelman syndromes (Monk et al , ). While the aforementioned IVF‐ICSI‐associated imprinting disorder outcomes require additional confirming or refuting large data studies, results from a recent systematic review (Catford et al, ) of long‐term follow‐up of offspring conceived through IVF‐ICSI point in a similar direction for possibly both genomic and non‐genomic (epigenetic) impacts on neonatal well‐being, for example, metabolic disorders and general health morbidities. Highlighted in Catford et al () and in a previous systematic review by the same group (Catford et al, ) is the critical need for more comparable large datasets from high‐quality studies in order to draw strong‐evidence conclusions.…”

‘Serious’ factor—a relevant starting point for further debate: a response

“…Indeed, many ART techniques (such as in vitro fertilization and intracytoplasmic sperm injection) were introduced into clinical use without research on their longitudinal implications for the health and well-being of those conceived by them. For example, the impact of intracytoplasmic sperm injection (ICSI) on the health and development of children conceived using this technology was and still is unclear 10. Follow-up studies of ICSI-conceived children seem to indicate that there is indeed merit and a need for continuous, longitudinal monitoring by fertility centres, so as to build a solid evidence-base 10–12.…”

“…For example, the impact of intracytoplasmic sperm injection (ICSI) on the health and development of children conceived using this technology was and still is unclear 10. Follow-up studies of ICSI-conceived children seem to indicate that there is indeed merit and a need for continuous, longitudinal monitoring by fertility centres, so as to build a solid evidence-base 10–12. Moreover, it would be ethically even more unacceptable in the context of HGGM to not undertake such monitoring, because unlike ART, HGGM specifically involves heritable modifications to the human germline, which in turn can have irrevocable and unforeseen consequences for future generations.…”