To the Editor:
A recent publication by Frattarelli et al., found that sperm from males age 50 or over resulted in a lower percentage of live deliveries, even when using a donor oocyte model to negate the adverse effect of maternal oocyte age (1). These data reached a different conclusion compared to an earlier publication by another group using the donor oocyte model (2) (the group studied by Frattarelli et al. was twice as large as the study by Paulson et al.). Furthermore, the differences seen in the Frattarelli et al. study were not sufficient to demonstrate a statistically different clinical pregnancy rate per transfer only but a statistically lower pregnancy rate for older males in the live delivery rate. Thus one conclusion might be that advanced male age does matter (but not nearly so much as female age) and if one has a large enough sample, a statistically lower pregnancy rate will be found in the female partners of males with advanced reproductive age (1,2).
If the reason for the observation of reduced pregnancy rates using sperm from older males in a donor oocyte model is related to a greater risk of meiosis errors in the sperm, then practically nothing can be done about it and one should still be content that a reasonable live delivery rate can still be achieved. However, if there is some age-related factor partly responsible for the observed decline in fertility potential that is remediable, it would be important to identify this factor so that corrective measures can be taken.
A male infertility factor has been identified that allows normal fertilization of the oocyte, normal cleavage to day 3 and normal embryo morphology, but causes a severe implantation defect such that the transfer of these embryos rarely achieves a live or even clinical pregnancy (3,4). This infertility factor is known as the hypoosmotic swelling (HOS) test defect (3,4). For some reason, despite convincing, unrefuted data showing that sperm with subnormal HOS tests cause embryo implantation defects, this simple inexpensive test is rarely even evaluated by most infertility specialist. Indeed the HOS test was not performed by Frattarelli et al in their study.
There is evidence that the embryo implantation defect caused by sperm with low HOS test scores is by transferring a toxic factor from the sperm to the zona pellucida by the supernumerary sperm that attach and that the problem can be overcome by performing intracytoplasmic sperm injection (ICSI) (5).
At the April 2009 meeting of the American Society of Andrology, we presented data showing that whereas an abnormal HOS test score was only found in about 5% of younger males, it was found in about 25% of males age 50 or greater (poster #55). Thus it seems reasonable that the decline in male fertility potential detected by Frattarelli et al could be accounted for by the increase in frequency of HOS abnormalities with advanced age (1). They only performed ICSI for severe oligoasthenozoospermia or teratozoospermia, so it is safe to assume that the main oocyte fertilization method with sperm from older males was conventional rather than ICSI. In fact, at that same meeting we found absolutely no differences in clinical or live delivered pregnancy rates in 769 donor oocyte recipient cycles when using sperm from males age 50 or greater. However, we did perform ICSI with low HOS scores irrespective of male age (Poster # 52).
Thus I do not disagree with the conclusions made by Frattarelli that sperm from males of an older reproductive age may have less fertility potential than sperm from younger males. However, my point is that if one adjusts for low HOS tests that are more frequent in this population of older males and uses ICSI for fertilization when a low HOS score exists, these sperm from older males have the same fertility potential as sperm from younger males.
Jerome H. Check, M.D., Ph.D.
Division of Reproductive Endocrinology & Infertility
Department of Obstetrics and Gynecology
Cooper Hospital/University Medical Center
The University of Medicine and Dentistry of New Jersey
Robert Wood Johnson Medical School at Camden
Camden, New Jersey
1. Frattarelli JL, Miller KA, Miller BT, Elkind-Hirsch K, Schott RT. Male age negatively impacts embryo development and reproductive outcome in donor oocyte assisted reproductive technology cycles. Fertil Steril 2008;90:97.
2. Paulson RJ, Milligan RC, Sokol RZ. The lack of influence of age on male fertility. Am J Obstet Gynecol 2001;15:1703-8.
3. Check JH, Stumpo L, Lurie D, Benfer K, Callan C. A comparative prospective study using matched samples to determine the influence of subnormal hypo-osmotic test scores of spermatozoa on subsequent fertilization and pregnancy rates following in-vitro fertilization. Hum Reprod 1995;10:1197-200.
4. Katsoff D, Check ML, Check JH. Evidence that sperm with low hypoosmotic swelling scores cause embryo implantation defects. Arch Adnrol 2000;44:227-30.
5. Check JH, Katsoff D, Check ML, Choe JK, Swenson K. In vitro fertilization with intracytoplasmic sperm injection is an effective therapy for male factor infertility related to subnormal hypo-osmotic swelling test scores. J Androl 2001;22:261-5.
Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2009.05.051