Assisted Reproduction and Infertility
Do Not Forget the Man—Clinical Use, Interpretation and Medical Counsel Guidelines for the Sperm Chromatin Structure Assay (SCSA®
)
Sperm DNA Integrity Test Donald P Evenson, PhD, HCLD
President and Director, SCSA Diagnostics, Inc., Emeritus Distinguished Professor, South Dakota State University, Adjunct Professor, Department of Obstetrics and Gynecology, Sanford Medical School, University of South Dakota
Abstract
Male factor is now considered to be the cause of nearly half of cases of couple infertility. The classical semen parameters of sperm count, morphology, and motility significantly vary over time and are considered to be poor predictors of pregnancy outcome. In sharp contrast, the sperm chromatin structure assay (SCSA®
), which measures sperm DNA fragmentation, has negligible variation over time. A clinically significant threshold
of 25 % DNA fragmentation index of sperm in an ejaculate with damaged DNA has been established, with odds ratios of 8–10 for natural conception and a near loss of conception for intrauterine insemination. Such couples are referred for in vitro fertilization or intracyctoplasmic sperm injection for best results. The SCSA provides a highly cost-effective means for clinical management of couples with idiopathic infertility.
Keywords
Male factor infertility, sperm chromatin structure assay (SCSA®), sperm DNA fragmentation, technician friendly, flow cytometry precision, clinical thresholds, utility of SCSA for clinical management
Disclosure: Donald P Evenson is the inventor of the SCSA and President of SCSA Diagnostics, Inc. Received: September 9, 2011 Accepted: October 24, 2011 Citation: US Obstetrics & Gynecology, 2011;6(2):89–92 Correspondence: Donald P Evenson, PhD, HCLD, PO Box 107, 219 Kasan Ave., Volga, SD 57071. E:
don@scsatest.com
Support: The publication of this article was funded by SCSA Diagnostics, Inc.
Rationale for Testing of Sperm DNA Integrity Medical diagnosis and prognosis for couple infertility has dramatically changed from “Female factors are the vast primary cause of couple infertility,” to “Male factor causes nearly half of couple infertility.”
Light microscope analysis of semen samples for sperm count, morphology, and motility, as carried out for the past 50 years, is a very poor predictor of fertility, and to a significant degree has given way to “What the light microscope cannot see,” e.g., the state of sperm DNA integrity, the most vital male factor for a successful pregnancy. “The integrity of the paternal genome is of paramount importance in the initiation and maintenance of a viable pregnancy both in a natural conception and in assisted reproduction.”1
Since the introduction of the sperm chromatin structure assay (SCSA®) by our laboratory three decades ago,2
over 100,000 animal
and human samples have been assessed. The SCSA has very clearly and unequivocally shown that, when >25 % of sperm in a semen sample has measureable sperm DNA fragmentation (DNA fragmentation index [DFI]), the statistical odds of a pregnancy by natural conception or use of intrauterine insemination (IUI) are dramatically reduced by up to 10-fold or more.3–5
© TOUCH BRIEFINGS 2011
Bungum et al.5,6
showed that when DFI >30 %, the delivery rate was
25.8 % and 42.4 % for in vitro fertilization (IVF) and intracyctoplasmic sperm injection (ICSI) fertilization, respectively. Of interest for IUI, the delivery rate was 1.5 % when DFI >30 % but 19 % when DFI <30 %.
When couples attend an infertility clinic, nearly half of the men have DFI >15–20 %, which, with ever-increasing values, concomitantly decreases the odds for a pregnancy. It is recommended that couples with DFI >25 % try routine IVF, or preferably ICSI, which is around 1.5 times more successful than IVF.6
When DFI >50 %, it will likely inhibit the success of ICSI. Potential retrieval of sperm from the testis (testicular sperm extraction [TESE] procedure) combined with ICSI may be the final best option.7,8
What is the Sperm Chromatin Structure Assay? The SCSA uses acridine orange (AO) dye to differentially stain normal and damaged sperm DNA in an extremely precise and quantitative manner.9,10
Normal double-stranded DNA is fluorescent green. The 30-second low-pH treatment opens up the double-stranded DNA at sites of single- or double-strand breaks and the resulting single-stranded DNA interacts with AO to form a crystal. When exposed to a blue laser
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