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Perspectives and Editorials |
Tartagni M, Schonauer MM, Cicinelli E, Selman H, de
Ziegler D, Petruzzelli, F, D'Addario V. Usefulness of the hypo-osmotic
swelling test in predicting pregnancy rate and outcome in couples undergoing
intrauterine insemination. J Androl.2002
;23:498–502.
The authors state that standard semen parameters have not been successful in predicting men with subfertility. However, when HOST scores are <50%, it has been demonstrated as highly effective in predicting men who are subfertile. Even with conventional IVF, a subnormal HOST score was found to be far more predictive of a poor pregnancy rate when compared to either motile density or normal morphology using strict criteria (Kiefer et al, 1996).
Although HOST is inexpensive, simple to perform, and is stable over time once subnormality has been determined (Shanis et al, 1992), in contrast to other semen parameters, which seem to fluctuate, the test is rarely performed by most clinicians. Whereas the first in vivo study (in 1989) demonstrated no pregnancies despite normal semen parameters, the in vivo study by Tartagni et al is the first designed to corroborate or refute the 1989 study by Check et al quoted by the authors. Tartagni et al not only corroborated the previous study, but they did it in a different manner, demonstrating that superovulation and IUI do not overcome subnormal HOST scores.
Finding low pregnancy rates following IUI is not surprising, because even conventional IVF fails to overcome the HOST abnormality.
It is interesting that several IVF studies published in 1989 and 1990, including one by Barratt et al (1989), found that subnormal HOST scores did not produce low fertilization rates. At that time, and even now, the traditional concept is that the role of the sperm is to fertilize the egg, and that once fertilization has been achieved, the sperm poses no threat to the future implantation of the embryo. It is interesting to note that none of these studies of the effect of subnormal HOST scores on fertilization rates mentioned pregnancy rates at all. I suspect they were left out because the rates were embarrassingly low and would serve to confuse the authors' conclusions that subnormal HOST scores do not adversely affect fertilization rates.
Tartagni et al referred in their manuscript to our matched control study,
published in Human Reproduction, in 1995, in which we agreed that low
HOST scores did not lead to lower fertilization rates with IVF-ET, but
resulted in extremely poor implantation rates. These conclusions were
corroborated by another study using shared oocytes (ie, an infertile woman
needing IVF-ET shares equally the retrieved oocytes with a recipient in need
of donated oocytes). We evaluated the outcome of 22 donor-recipient pairs in
which one male partner had normal semen parameters and a normal HOST score,
and the other had normal semen parameters but a HOST score of <50%. The
fertilization rates, the number of embryos transferred, and embryo morphology
were the same. However, in this study, in which conventional fertilization
techniques were used rather than intracytoplasmic sperm injection (ICSI), the
clinical pregnancy rate was 50% for those women whose partners scored 
50%
in their HOST score, but it was zero for those with subnormal HOST scores
(Katsoff et al, 2000).
The demonstration of normal fertilization rates but poor implantation rates suggested that the male partner can contribute to a given couple's infertility by producing sperm that are associated with a toxic factor that permits normal fertilization but somehow inhibits implantation. This phenomenon may be related not to the one sperm fertilizing the oocyte, but to the supernumerary sperm that attach to the zona pellucida. If this provocative hypothesis is true, then it should follow that bypassing exposure of sperm to the zona pellucida by performing ICSI should improve pregnancy rates. Indeed, the authors referred to our study published in 2001 in the Journal of Andrology in which we demonstrated a 49% pregnancy rate with IVF-ET and ICSI within a series of infertile couples in which male partners had subnormal HOST scores.
How frustrating it is for couples having unexplained infertility, or those with a seemingly obvious problem of tubal factor infertility to repeatedly fail to achieve a pregnancy despite transfers of what appear to be perfectly normal embryos because HOST was not performed even though it is simple, reliable, and inexpensive. At least when failed fertilization is unexplained, only one IVF cycle is wasted before proceeding to ICSI. However, with the low HOST score scenario, the couple may have invested in many expensive, invasive IVF cycles without achieving their goal of pregnancy. I certainly hope that the manuscript of Tartagni et al will now increase the credence of the conclusions about the subnormal HOST that up to this time came from only one research center. Corroboration from another center was greatly needed.
This study by Tartagni et al should generate interest among andrologists to better define this toxic factor and to find alternate, less expensive methods than IVF with ICSI to overcome this abnormality. Some preliminary data suggest that the factor may be proteinaceous in nature. In one study of just 12 patients, 67% had improved HOST scores following treatment of sperm with the protein digestive enzyme chymotrypsin, resulting in good pregnancy rates following IUI in the eight couples in which improvement of the score to >50% was demonstrated (Katsoff et al, 1997). This concept of sperm toxicity leads to a provocative recommendation for infertile couples undergoing IUI after attempts to neutralize this toxic factor with chymotrypsin: to avoid unprotected intercourse before insemination. Furthermore, andrologists may be encouraged to look for toxic factors inhibiting embryo implantation not manifested by subnormal HOST scores.
References
Barratt CLR, Osborn JC, Harrison PE, Monless N, Dumphy BC, Lenton
EA, Codie ID. The hypoosmotic swelling test and the sperm mucus penetration
test in determining fertilization of the human oocyte. Hum
Reprod. 1989;4:430
-434.
Katsoff D, Check JH. Two methods of achieving pregnancies despite subnormal hypo-osmotic swelling test scores. Fertil Steril. 1997;68:549 -551.[Medline]
Katsoff D, Check ML, Check JH. Evidence that sperm with low hypoosmotic swelling scores cause embryo implantation defects. Arch Androl. 2000;44:227 -230.[Medline]
Kiefer D, Check JH, Katsoff D. The value of motile density, strict morphology, and the hypoosmotic swelling test in in vitro fertilization-embryo transfer. Arch Androl.1996; 37:57 -60.[Medline]
Shanis B, Check JH, Bollendorf A, Lurie D. Stability of the hypoosmotic swelling test over time. Arch Androl.1992; 29:263 -266.[Medline]
Tartagni M, Schonauer MM, Cicinelli E, Selman H, de Ziegler D, Petruzzelli F, D'Addario V. Usefulness of the hypo-osmotic swelling test in predicting pregnancy rate and outcome in couples undergoing intrauterine insemination. J Androl.2002 ;23:498–502.
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