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From Androlog

In spite of the progress that in vitro technologies have generated in the management of severe male factor infertility, some clinical situations still pose challenging clinical dilemmas. One such circumstance is that of the male patient who is found to have sperm in the ejaculate but with 0% motility. Would testicular biopsy likely yield motile sperm in such a situation, and if not, would intracytoplasmic sperm injection (ICSI) be of use? Also, if ICSI is used, what is the best method for determining which sperm to inject? These questions were proposed to the members of Androlog. Let's see what advice was offered.

I submitted the following question regarding one of my patients:

Esteemed Colleagues: I am currently evaluating a 28-year-old gentleman whose semen analyses have shown excellent sperm counts on 2 occasions (99 and 102 million per mL, respectively) but 0% motility. He is completely normal on physical examination and has no correctable factors that I can identify. His past medical history is noncontributory. We have not, thus far, performed any additional tests to evaluate sperm viability. He and his wife are very interested in establishing a pregnancy and are willing to consider ICSI if this would be of help. I would be interested in the group's current thoughts on 2 questions: 1) How optimistic are you that hypo-osmotic swelling (HOS) (or other techniques) would reliably identify sperm suitable for ICSI in a case such as this? 2) Does anyone feel any optimism that testis biopsy might yield motile sperm, which could then be used in an ICSI procedure? Your thoughts on this would be much appreciated.

Randall B. Meacham, MD, Denver, Colorado

Dr Christopher De Jonge made the following excellent observations in response to Dr Meacham's questions about 100% nonmotile sperm:

1. How optimistic are you that HOS (or other techniques) would reliably identify sperm suitable for ICSI in a case such as this? I am very optimistic that if the plasma membrane is functional, then a coiled tail will result. Establishing baseline is important. I would also do the HOS on a specimen prior to onset of female stimulation for oocyte retrieval.
   
2. Does anyone feel any optimism that testis biopsy might yield motile sperm, which could then be used in an ICSI procedure?
   If the results from HOS indicate viable sperm, then my optimism for motile sperm in a biopsy would be increased. To establish if the patient's seminal plasma might contribute to sperm stasis, I would have him collect in media and also expose washed control sperm with the patient's seminal plasma.
   Good luck!
   Christopher De Jonge, PhD, HCLD
   

Dr Charles Muller provided additional useful insights:

Regarding Andy Meacham's question of how to proceed with a case exhibiting 100% nonmotile sperm, I would like to suggest some lines of investigation in addition to the proposed use of HOS to choose sperm for ICSI.

First, a viability test is essential. Alternatives to HOS are eosin Y or trypan blue staining or use of a fluorescent DNA-binding probe such as Hoechst 33258.

If all the sperm in semen are "dead," we would not suggest ICSI using them. In our practice (Dr Richard Berger), we determine whether there is an immediate possible cause of cell death such as high reactive oxygen species generation by leukocytes, which might be addressed. If not, a vas or testicular aspiration is considered. We have seen normal (for the site) motility from either vas or testis when semen sperm motility is poor.

Second, if some of the sperm are apparently live, we would attempt to stimulate motility using pentoxifylline. Surprisingly, this has worked in some cases of 0% motility. The induced motility may or may not be of sufficient quality and quantity to consider intrauterine insemination (IUI) or in vitro fertilization (IVF). But, even if there is only twitching motility, this may be sufficient to choose sperm for ICSI. The pentoxifylline is washed out of the sperm preparation before any of the insemination procedures. This also avoids having to use HOS to choose nonmotile sperm.

Third, if no sperm respond to pentoxifylline, medical, genetic, or electron microscopic evidence could be gathered to rule out an immotile cilia syndrome, followed by genetic counseling.

Good luck with this case!

Charles H. Muller, PhD, HCLD

Dr Marc Goldstein advocated a strictly surgical approach (as a surgeon, I have to admit a certain fondness for his point of view):

Do a testicular retrieval fresh at the time of IVF/ICSI. You will probably find motile (twitching) sperm. This is much more reliable than trying to identify viable sperm in a 0% motile ejaculate.

Sincerely, Marc Goldstein, MD, FACS

On the other hand, Dr Dawn Kelk argued the virtues of a laboratory-based strategy (Regarding Dr Meacham's question about 100% nonmotile sperm):

I have seen a couple of cases like this with 2 different causes. Do you know if this gentleman has Kartagener syndrome (I've also heard it called immotile cilia syndrome)? I would do an HOS test and an eosin-nigrosin stain. Both tests are quite simple. You can perform ICSI using the HOS test. It is technically difficult to pick up curled sperm that have been exposed to HOS solution. But you can pick up the sperm from culture media, transfer your needle into a drop of HOS solution, hold the sperm near the opening of the needle, and allow the HOS solution to diffuse into the needle, and you can watch the sperm start to curl inside the ICSI needle. As soon as you see the sperm tail curl, you can move to a polyvinylpyrrolidone drop, break the tail, and perform the ICSI. This particular couple had twins using this technique.

In the other case, the individual simply didn't follow proper collection technique and had been using Lubriderm lotion. As soon as he collected without the Lubriderm, his motility was in the normal range.

If you can be sure that you have live/viable sperm, I don't know of any reason to perform a biopsy, but I'd be interested in others' thoughts.

Dawn A. Kelk, PhD

Finally, Dr Arnold Belker weighed in with the voice of experience in the following response:

I agree with Marc Goldstein's response. Indeed, I reported (J Urol. 1998; 160:2058-2062), along with Dick Sherins and other members of his group, that testicular sperm obtained by testicular epidymal sperm aspiration from men with necrospermia would be useful for IVF/ICSI. The motility of testicular sperm from such men ranged from 0% to 10%, but the median viability using eosin Y dye exclusion ranged from 55% to 75%.

Arnold M. Belker, MD

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