MALE INFERTILITY1270

Male Infertility

Re: Are There Subtle Genome-Wide Epigenetic Alterations in Normal Offspring

Conceived by Assisted Reproductive Technologies?

A. Batcheller, E. Cardozo, M. Maguire, A. H. DeCherney and J. H. SegarsDepartment of Obstetrics and Gynecology, William Beaumont Hospital, Royal Oak, Michigan

Fertil Steril 2011; 96: 1306–1311.

Objective: To review recent data regarding subtle, but widespread, epigenetic alterations in pheno-typically normal offspring conceived by assisted reproductive technologies (ART) compared withoffspring conceived in vivo. Design: A PubMed computer search was performed to identify relevantarticles. Setting: Research institution. Patient(s): Not applicable. Intervention(s): None. Main Out-come Measure(s): Not applicable. Result(s): Studies in animals indicate that in vitro culture may beassociated with widespread alterations in imprinted genes compared with in vivo-conceived offspring.Recently, studies in humans have likewise demonstrated widespread changes in DNA methylation,including genes linked to adipocyte development, insulin signaling, and obesity in offspring conceivedby ART compared with in vivo-conceived children. Changes in multiple imprinted genes after ARTalso were noted in additional studies, which suggested that the diagnosis of infertility may explain thedifferences between in vivo-conceived and ART offspring. Conclusion(s): These data suggest that ARTis associated with widespread epigenetic modifications in phenotypically normal children, and thatthese modifications may increase the risk of adverse cardiometabolic outcomes. Further research isneeded to elucidate the possible relationship between ART, genome-wide alterations in imprintedgenes, and their potential relevance to subtle cardiometabolic consequences reported in ART off-spring.

Editorial Comment: Is in vitro fertilization (IVF) safe? This is a great question, as IVFtechniques have become so common that they account for an estimated 1% of all childrenborn in the United States. In this systematic review the authors describe a number ofstudies that indicate subtle epigenetic changes in children born from IVF. The scope ofthese studies is limited, and we owe it to our children to exhaustively investigate theeffects of IVF, especially genetic ones.

Craig Niederberger, M.D.

Re: Epigenetics of the Male Gamete

D. T. CarrellDepartment of Surgery (Urology), University of Utah School of Medicine, Salt Lake City, Utah

Fertil Steril 2012; 97: 267–274.

Objective: To review and summarize the current understanding of the epigenetic status of humansperm in regards to protamination, specific localization and modifications of retained histones, andDNA methylation. Design: Review of the relevant literature. Setting: University-based clinical andresearch laboratories. Patient(s): Fertile and infertile men. Intervention(s): None. Main OutcomeMeasure(s): Critical review of the literature. Result(s): Sperm from normospermic, fertile men haveepigenetic modifications consistent with gene “poising” at the promoters of genes involved in devel-opment, including the localization of retained histones with bivalent histone modifications andhypomethylation of DNA. These epigenetic marks are altered in some patients with abnormalspermatogenesis, and in some men who exhibit unexplained, altered embryogenesis during IVFtherapy. Conclusion(s): The sperm epigenome implies a poising of the paternal genome for embryo-genesis and a possible role in the establishment of totipotency of the embryo and may help inunderstanding some causes of reduced fertility and transmission of disease risk.