ICSI vs. IVF and the "iceberg effect"
1 Replies
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Dr. Smith,
I'm getting ready for an IVF consult and was wondering if you had any advice regarding the decision to do IVF vs ICSI.
Me: 31 yrs, all tests are normal except for 24% anti-sperm antibodies.
DH: 31 yrs, poor SCSA (DFI 47.3%, HDS 18%) and stress pattern in SA's until he had a bi-lateral varicocelectomy in June 2005. 3 months post-surgery his new SCSA was DFI 19.8% and HDS 20%. 6 months post-surgery his count was 150 mil with 60% motility.
My question:
Given the sig improvement in DFI just 3 months post-surgery, is it beneficial to do another SCSA 9 months post-surgery to find out if there has been even more improvement or should we move directly to IVF or ICSI?
Reason I'm asking is because if DFI improved even more, is IVF the better route since it has slightly higher success than ICSI?
Also, I came across a Feb 2006 article on SCSA and was interested in your thoughts on the question below
http://www.andrologyjournal.org
/cgi/rapidpdf/jandrol.05217v1.pdf
I'm
particularly interested in pg. 3 (pardon the long paragraph) and would like to know if the "iceberg effect" may explain why DH and I have never even had a positive pregnancy test during 14 months of TTC with 4 failed IUI's... isn't oxidative stress related to bi-lateral varicoceles (see below)?
"DNA fragmentation induced by apoptosis usually affects a fraction of the spermatozoa whereas DNA fragmentation induced by oxidative stress and radiation therapy leads to double-stranded DNA fragmentation and nucleotide damage of the 8-OH-2-deoxyguanosine (oxo8dG) type in most spermatozoa. DNA fragmentation induced by the hydroxyl radical results in the formation of oxo8dG in a first stage followed by double-stranded DNA fragmentation thereafter (Cui et al., 2000) [9]. While DNA damage of the first type could be repaired to some extent by the oocyte, doublestranded DNA damage is virtually irreversible and incompatible with the development of a viable pregnancy. Since DNA fragmentation values in ejaculated spermatozoa above 10%, as assessed by TUNEL (Benchaib et al., 1993) [10] or above 30%, as
assessed by the SCSA test (Evenson et al., 1999) [7], are associated with low pregnancy rates, one would think that the remaining 90% or 70% of the spermatozoa, respectively, could fertilize the egg and result in a viable pregnancy. However, in addition to double-stranded breaks, a significant proportion of these spermatozoa could have DNA nucleotide modifications of the oxo8dG type. Therefore, the probability that a spermatozoon with normal DNA would fertilize the egg would be much lower than that expected from a DNA fragmentation value of 10% or 30%, respectively. That is, in addition to the measurable 10% and 30% of spermatozoa with DNA fragmentation, the remaining 90% and 70% of spermatozoa would have some type of DNA damage that is not compatible with the development of a viable pregnancy. This concept has been designated as the 'iceberg effect' (Evenson et al. 1999) [7]."
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When using "strict" criteria, the vast majority of sperm in the ejaculate have an abnormal shape (morphology). Poor morphology is associated with high levels of DNA fragmentation. During "natural" fertilization (i.e. non-ICSI), the protein coat that surrounds the egg prevents any sperm with an abnormal shape from penetrating and fertilizing the egg. This is nature's way of keeping crappy sperm from fertilizing the egg and thereby maximizing the genetic potential on the embryo. So there is an "iceberg effect" operating all the time in all men, but nature has evolved a way to deal with it - namely make more sperm. Since the varicocelectomy, your husband is producing an adequate number of sperm to get the job done. It only takes one "normal" sperm for each egg.
In the conventional IVF versus ICSI argument, the success rate with conventional IVF may be slightly higher because the egg is doing the sperm choosing, not the embryologist. I don't think another SCSA test is necessary. The embryologist will have to choose whether or not to perform ICSI based on the sperm [i]du jour[/i] on the day of IVF. If it is good enough for conventional insemination (concentration, motility and morphology), then that should be the first choice. If the sperm doesn't measure up on that day, then ICSI is justified.
Remember, IVF is also a diagnostic test to determine the quality of your eggs. I know you've been focused on the sperm side of the equation, but (at this point) we don't know anything about the quality of your eggs. There may be a problem there too that is contributing to your difficulty in conceiving. I don't want to make you paranoid, but keep an open mind to possibility of other causes.
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