17th International Congress of the Iranian Association for Fertility and Reproductive Medicine
Tehran– March 2011
ROLE OF SPERM INDEXES IN EMBRYO QUALITY: WHAT TO DO?
Sandro C. Esteves, MD, PhD
Spermatozoa are highly specializedcells with the purpose of not onlydelivering competent paternal DNA to the oocyte but also to provide a robust epigenetic contribution to embryogenesis. The identification of sperm fertility markers and the ability to selecthealthy spermatozoa for ART have a dual objective of choosing the best treatment strategy and optimizing ART outcomes. Currently, sperm indexes determination in the clinical setting is generally based on cell morphology and DNA content. Both sperm morphology and DNA integrity results, obtained from raw semen samples, have been shown to be of prognostic value for unassisted and assisted conception and useful in the selection of the best assisted conception modality.
These assays, however,provide an assessment of the distribution of cells in a given ejaculatethat may not be representative of the sperm population used in the ART treatment cycle. In fact, severe teratozoospermia,using Kruger’s strict criteria on pre-ART semen analysis, does notcorrelate to fertilization and embryo formation (including blastocyst development) in ICSI cycles. Nonetheless, if a more holistic approach to sperm morphology is taken, two prognostic groups can still be identified in cases of severeteratozoospermia (<4% normal) because certain morphology patterns and sperm abnormalities are known to affect ICSI outcomes. The first group includes mostly genetically determined sperm pattern defects, such asglobozoospermia, short tail syndrome and small-headed spermatozoa (in most cases combined with very small acrosomes). All of these types represent untreatable conditions that have been associated with abnormal sperm function andpoor ART outcomes. The second group includes unspecifiedor non-genetically determined sperm defects or patternscaused by environmental factors, medication, infection and related infertility conditions, including varicocele. Treatment of these conditions has been shown to optimize sperm morphology indexes with a positive impact on ART outcomes. Although the technician microscopically selects morphologically normal individual sperm during ICSI, form normalcy does not necessarily imply normal DNA content. As such, sperm DNA testing has been advocated to be an independent and reliable marker of fertility potential since sperm chromatin andDNA integrity is essential to ensure that the fertilizing sperm cansupport normal embryonic development of the zygote.At present, conflicting reports exist on the role of sperm DNA fragmentation index for embryo development, and it is apparent that DNA fragmentation does not significantly impair zygote and cleaving embryo morphology because major activation of the embryonic genome only beginafter the 4-cell stage. These observations do no underscore the importance of finding ways to increase sperm DNA integrity, since it has been suggested that DNA fragmentation is associated with late paternal effects that may lead to early miscarriages or diseases in the offspring. The etiology of sperm DNA damage is multi-factorial and may be due to primary (ageing, cryptorchidism, genetic defects, idiopathic) and or secondary (drugs, environmental, tobacco smoking, genital tract inflammation, infection,testicular hyperthermia and varicoceles) factors. Specific or non-specific treatments, including antioxidant supplements, are generally associated with reduced levels of sperm DNA damage and/or improved fertility potential.
Taken in conjunction, it is apparent that there is no unique sperm factor able to predict embryo development, but several candidate biomarkers are involved in this complex process.As a result, a wide variety of techniques have been proposed, including externalization of phosphotidylserine (magnetic-activated cell sorting),cell