To the Editor:
I have read your article “Intracytoplasmic sperm injection outcome of ejaculated versus extracted testicular spermatozoa in cryptozoospermic men” (1) with great interest. The subject is a matter of current debate in the treatment of male factor infertility, and the results of this study should therefore be considered with attention.
In this retrospectively designed study, you have assessed 17 patients with cryptozoospermia who underwent a total of 116 ICSI cycles with either ejaculated (n=68; 58.6%) or testicular sperm (n=48; 41.4%, 31 fresh and 17 frozen cycles) between January 2010 and December 2011 in your IVF unit. These patients initially underwent a mean of 4.1±2.4 ICSI cycles using ejaculated sperm that were followed by ICSI cycles using either fresh (1.4±1.1 cycles) or frozen (1.7±0.6 cycles) testicular sperm cycles.
You found that there were no significant differences in fertilization rates between the two subgroups. A comparison between testicular sperm extraction (TESE) versus ejaculated sperm cycles revealed a significantly higher implantation rate (20.7% vs. 5.7%), higher PR (42.5% vs. 15.1%), and a higher take-home baby rate (27.5% vs. 9.4%). You also showed that there was a trend of higher mean number of day 2 embryos per cycle in the TESE cycles compared with the ejaculated sperm cycles (5.2±5.6 vs. 3.2±3.4; P=0.058), and the cleavage rate of day 2 embryos was significantly lower when ejaculated sperm cells were used compared with TESE cycles (3.5±1.1 vs. 3.9±0.7; P=0.026). Similarly, the cleavage rate of day 3 embryos was significantly lower after ICSI using ejaculated sperm cells compared with TESE cycles (5.3±1.4 vs. 6.7±1.5; P=0.028). As a result, a significantly higher mean number of embryos were transferred to the uterus in the TESE cycles compared with the ejaculated sperm cycles (2.5±1.5 vs. 1.8±1.2; P=0.011). However, there were no statistically significant differences between the two subgroups in the mean morphology scores of day 2 and 3 embryos, as well as the mean number of cryopreserved embryos.
I think that while your study is of great importance by offering TESE to cryptozoospermic men instead of utilizing semen to improve clinical outcomes, your experience related to treatment and assessment of these cases could be of further aid in approach to these patients, yet such details have not been given in the paper.
First, your assessment of the data has been carried out on cycle instead of patient basis. In Table 3, you showed that from a total of 68 cycles with ejaculated sperm, only eight pregnancies occurred of which two resulted in missed abortion. Yet, 17 pregnancies with 6 missed abortions in 48 cycles where testicular material has been utilized resulted in a significantly higher take-home baby rate as compared with the former strategy. It may be of benefit to the readers of this study to know how many of these 17 patients delivered a healthy baby after utilizing testicular versus ejaculated material. It is also of interest to show whether a difference in missed abortion rates exists between these strategies on patient basis.
The second issue regards your experience in the treatment duration and related strategies. As I tried to summarize above, it appears that within a period of 2 years, you treated each of these 17 couples on average more than 6 times. A rough estimation of these six cycles is four initial treatments utilizing ejaculate and the following two with testicular material (one with fresh and the other with frozen). I think that this is a great achievement not only from the perspective of being able to keep the faith of these patients to the clinic during this period, but from a medical side, the value of the data brought to the community since it has to include application of a wide range of various protocols and strategies. Again, I believe these could be shared on patient basis to evaluate potential differences among them.
I find this study of great importance and interest not only because (as you also stated in your paper) it is the largest group of selected cases in the literature, but also because it includes a profound experience among such couples, which I believe should be shared more extensively with the scientific community.
H. Nadir Ciray, M.D., Ph.D.
Associate Professor, Certified Clinical Embryologist (ESHRE 2008)
Bahceci Health Group, Istanbul, Turkey
1. Ben-Ami I, Raziel A, Strassburger D, Komarovsky D, Ron-El R, and Friedler S. Intracytoplasmic sperm injection outcome of ejaculated versus extracted testicular spermatozoa in cryptozoospermic men. Fertil Steril 2013, in press.
Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2012.04.004
The authors respond:
We appreciate your interest in our article “Intracytoplasmic sperm injection outcome of ejaculated versus extracted testicular spermatozoa in cryptozoospermic men” (1) and your insightful remarks. Your first comment relates to data, regarding miscarriages and deliveries achieved per patient. Analyzing our data per patient, we may state that out of 17 patients, 5 patients achieved one pregnancy and delivery; 4 patients achieved two pregnancies each, and two pregnancies ended by early spontaneous abortion (ESA); and 4 patients achieved three pregnancies each, six ending with ESA.
Using sperm from extended sperm preparation (ESP) in these 17 patients, 6 patients achieved a singleton pregnancy and delivery; 2 patients had an ESA. In total, six out of the eight patients who achieved pregnancy using sperm from ESP, delivered.
Using sperm from testicular sperm extraction (TESE) in these 17 patients, 4 patients achieved a singleton pregnancy; 3 delivered, and one pregnancy ended in ESA; 1 patient had two singleton pregnancies ending with ESA; 3 patients had two singleton pregnancies and one ended in ESA; 4 patients had twin pregnancies and deliveries; 1 patient had three singleton pregnancies, and one ended in ESA. In total, 10 out of the 12 patients who achieved pregnancy using sperm from TESE, delivered.
Seven patients achieved a pregnancy after using both sperm sources.
Four patients achieved no pregnancy at all after using both sperm sources.
As the number of patients is rather small, analysis of the data by patient is without power for meaningful statistics.
Regarding the second remark, indeed our patients keep faith in our clinic. An average of six treatment cycles over 2 years is not uncommon in Israeli IVF units, as all treatments are covered by the mandatory health insurance for Israeli citizens. Actually our routine is to allow patients to undergo full IVF treatments every other cycle, if they wish.
Ido Ben-Ami, M.D., Ph.D.
Shevach Friedler, M.D.
IVF and Infertility Unit, Assaf Harofeh Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
1. Ben-Ami I, Raziel A, Strassburger D, Komarovsky D, Ron-El R, Friedler S. Intracytoplasmic sperm injection outcome of ejaculated versus extracted testicular spermatozoa in cryptozoospermic men. Fertil Steril. 2013 Mar 8. doi:pii: S0015-0282(13)00297-5. 10.1016/j.fertnstert.2013.02.025. [Epub ahead of print]
Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2012.04.006