Fish Carrell

Andrology Lab Corner* The Clinical Implementation of Sperm Chromosome Aneuploidy Testing: Pitfalls and Promises DOUGLAS T. CARRELL From the Andrology and IVF Laboratories, Departments of Surgery (Urology), Obstetrics and Gynecology, and Physiology, University of Utah School of Medicine, Salt Lake City, Utah. ABSTRACT: Severe mal e inf ert ili ty has been sho wn to be associated with improper meiotic recombination and elevated sperm chromosome aneuploidy. Elevated sperm aneuploidy increases the risk of embr yo leth ality or feta l anomalies . Alth ough difficu ltie s in interpreting aneuploidy data still exist, advances in fluorescent in situ hybridization (FISH) technology have facilitated the study of sperm from pati ents with seve re sper mato gen esis defe cts, whic h has demons trated the prudence of evaluating sperm chr omosome ane upl oid y in men wit h severe male fac tor inf ert ili ty, suc h as nonobstructive azoospermia or severe ultrastructure defects, espe- cially in cases of previous repeated in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) failure. Testing is also advisable in men with chro mosome translocations and unex plai ned recurren t pregnancy loss, and it may be beneficial in patients with unexplained, repea ted IVF failure. Automat ed FISH imaging and anal ysis technology is now available and is beneficial in reducing technician time anal yzin g sper m aneu ploid y. Eme rgin g tech nolo gies , such comp arat ive geno mic hybr idiza tion , may be bene fici al in furt her improving the quality of data derived from aneuploidy analysis and reducing the cost of the assay. Key words: FISH, meiotic r ecombinatio n, chroma tin. J Androl 2008;29:124–133 T he genetic and epigenetic contribution of sperm to early embryogenes is is an exc iti ng and promisin g area of research with profound clinical implication s. We are beginning to understand that the contributions of sperm to normal fer tili zat ion and embr yoge nesi s are extensive and include the centrosome, oocyte-a ctivati on factors, remodeled chromatin, epigenetic gene modifi- cations, and pos si bly RNA reg ulation mecha nis ms (Eme ry and Car rel l, 2006; Haaf, 200 6; Boer ke et al, 200 7; Car rel l et al, 2007; Chatzi mele tiou et al, 2007) . Howeve r, transmission of a haploid chromosome compl eme nt is the mos t fun damental and ess ent ial contribution, since embryonic aneuploidy is universally assoc iated wi th letha li ty or anoma li es in the fetus (Carrell, 2000; Egozcue et al, 2000; Martin, 2007). Intracytoplasmic sperm injection (ICSI) has facilitated fertilization in cases of extreme spermatogenesis defects, which is both benefic ial to infertility patients and the cause of heightened concern about the possibility of increased genetic risk, including the potential of an elevated risk of emb ryo aneupl oidies (Verp oest and Tourn aye, 2006 ; Tesarik and Mendoza, 2007). Indeed, it does appear that there is an increased risk—as much as threefold—of sex chromosome aneuploidies in the offspring of men with severe male factor infertility treated by ICSI (Rimm et al, 2004; Hansen et al, 2005; Ludwig, 2005). Therefore, it is important to understand whether certain sperm patholo- gies may be associated with an increased risk of sperm chr omo some aneup loi dy, if the increased risk can be ascertained prospectively, and if such information can be used to better assess the risks and potential of success of IVF for patients (Petit et al, 2005; Faure et al, 2007). Fluorescent in situ hybridization (FISH) technology has gr ea tl y ex panded our abilit y to study sperm chromos omes. However, technologic limitations, costs, and limits in our ability to translate the results of sperm aneu ploidy to actual risk to offs pri ng have allcontrib ute d to a decr eas ed cli nic al uti lit y of sper m chr omos ome aneupl oidy testing. This revie w briefl y traces the histor y of sperm aneuplo idy testin g, highlig hts recent techno logic advances, discusses our current understanding of sperm chr omosome ane uplo idy, and cons iders the futu re cli nica l use of sperm chromosome aneuploi dy testin g. Technological Advances in Sperm Chromosome Aneuploidy Testing Sperm/Oocyte Fusion Technique— In 1978, Rudak et al published the first account of the evaluation of sperm Corr espo ndence to: Dr Doug las T. Carr ell, Androlog y and IVF Laboratories, 675 S. Arapeen Dr, Suite 205, Salt Lake City, UT 84108 (e-mail: douglas.carre [email protected]. edu). Recei ved for publ icati on July 18, 2007 ; accep ted for publ icat ion September 5, 2007. *Andr olog y Lab Corner welc omes the submissio n of unso licit ed manu scrip ts, requ ested reviews , and arti cles in a deba te format. Manuscripts will be revi ewed and edit ed by the Section Editor. All submissio ns shou ld be sent to the Jour nal of Andro logy Editorial Office. Letters to the editor in response to articles as well as suggested topics for future issues are encouraged. DOI: 10.2164/jan drol.107.003 699 Journal of Andrology, Vol. 29, No. 2, March/April 2008 Copyright E American Society of Andrology 124

Fish Carrell

Documents

Transcript of Fish Carrell