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Androlog Summary |
From the * Department of Urology, Northwestern
University, Feinberg School of Medicine, Chicago, Illinois; and the
Department of Urology, Medical College of
Wisconsin, Milwaukee, Wisconsin.
| Correspondence to: Dr Robert E. Brannigan, Northwestern University, Feinberg School of Medicine, Urology Department, Galter Pavilion, Suite 20-150, 675 North St. Clair St, Chicago, IL 60611 (e-mail: r-brannigan{at}northwestern.edu). |
| Received for publication December 11, 2007; accepted for publication December 14, 2007. |
Despite the initiatives calling for early attention to fertility preservation procedures, urologists are still faced with clinical scenarios where patients are sent for sperm cryopreservation after having received gonadotoxic chemotherapy or radiation therapy. The below string of Androlog entries highlights approaches to this challenging clinical problem.
The first posting came from Dr Diane Kelly (United States), who encountered the following dilemma:
Recently, an oncologist requested semen cryopreservation for a young patient in medical crisis. He was willing to withhold chemotherapy treatment for a few hours so that a specimen could be collected and cryopreserved. Unfortunately, the young man was too ill to collect a specimen prior to the start of chemotherapy.Has anyone cryopreserved semen after chemotherapy? How long after treatment is it advisable to wait prior to evaluating a semen specimen for cryopreservation? Is the best option to advise the patient that if fertility is permanently impaired after chemo, the patient may need to undergo TESE?
In response, Dr Ole Schou (Denmark) noted:
We have done that many times. Even more ejaculates from the same patient with several days of abstinence in between. You can normally find motile sperm in the ejaculate up to about 70 days after chemotherapy and radiation. There is no documentation that the DNA will be affected.
Dr Marvin Meistrich (United States) offered a differing opinion, calling for patients to wait at least 6 months after the last cycle of chemotherapy before cyropreserving sperm due to concerns over increased sperm aneuploidy:
We believe that patients should wait 6 months after the end of the last chemotherapy cycle to cryopreserve sperm (if they are present). We have observed the presence of aneuploid sperm in semen collected at shorter times (Frias et al, 2003). The risk of known genetic damage arising from sperm collected during chemotherapy is significantly elevated above background, but is still relatively low in absolute magnitude, so the use of semen collected during chemotherapy should be avoided, if feasible. The duration of azoo- or oligospermia after the end of chemo depends on the agents used and the doses (Meistrich et al, 2005).
Dr David Handelsman (Australia) noted that while at his center, every effort is made to cryopreserve sperm prior to initiation of chemotherapy, sometimes this preferred approach is simply not possible. In such circumstances, his group does offer affected patients sperm cryopreservation:
Although we usually cryostore sperm before chemo or radiotherapy, sometimes it is just not possible. We have always routinely cryostored sperm after chemotherapy starts if it was not possible to collect before. Of course, some chemotherapy makes this difficult too, but we do not refrain from cryostorage just because chemotherapy has started. Am quite familiar with the theoretical arguments why it is not ideal to cryostore sperm after chemo exposure, but these concerns are based on theoretical and biochemical arguments and not any evidence of actual harm. Most cryostorage is a form of fertility insurance preparing for the patient's future survival. Even if <10% is ever used, such positive preparation is good for positive psychology when the patient is anxious. And if sperm is unlikely to be available afterwards, this may be the last chance for his own sperm storage. It is therefore better and kinder medical practice (in my view) to allow cryostorage in such an emergency. He can then consider the use of such sperm much later, if ever, in an elective situation where the entirely theoretical risks can be weighed up in a calm and deliberate atmosphere. Personally, I'd advise them not to be too concerned about using such sperm anyway, weighing up all the hypothetical and theoretical concerns, but then TESE would be an alternative, if more expensive and invasive, option. It lacks humanity, not to say common sense, to refuse cryostorage in this situation in principle.
Dr Dan Williams (United States) commented on the use of electroejaculation and TESE in patients unable to collect due to their illness:
When young men are too ill to collect a sample prior to chemo, there are 2 options to obtain sperm. One option is to perform an electroejaculation, which requires having access to the device as well as a general anesthetic. The second is to perform a TESE prior to chemo, also of course under an anesthetic.After chemo, the return of sperm to the ejaculate depends on a lot of different factors, including how much sperm was present before (which we wouldn't know in this case), as well as what type of chemo regimen was used.
There is no consensus on how long to wait after chemo or radiation, but many centers recommend waiting 1–2 years before trying.
Lastly, yes, if the patient is azoospermic after chemo, then TESE would be indicated to see if sperm may be found for IVF/ICSI.
Finally, Dr Ahmed Mahmoud (Belgium) urged clinicians to also consider use of vibratory stimulation and phosphodiesterase 5 (PDE5) inhibitors in patients unable to collect due to their illness. He urged clinicians to err on the side of caution and cryopreserve sperm up to a few days after starting chemotherapy if the need arises. He points out that it is probably impossible to define genetic risk associated with use of these spermatozoa in assisted reproductive techniques and that more investigation into this topic should be undertaken.
Dr Daniel Williams suggests that "When young men are too ill to collect a sample prior to chemo, there are 2 options to obtain sperm. One option is to perform an electroejaculation, which requires having access to the device as well as a general anesthetic. The second is to perform a TESE prior to chemo, also of course under an anesthetic."There are other, frequently forgotten, less invasive options. These include the use of a penile vibrator and PDE5 inhibitors. I agree with the view of Dr David Handelsman. We also freeze semen samples "up to a few days" after starting chemotherapy if necessary. Based on the information currently available, the medical profession is probably unable to quantify the genetic risk of using spermatozoa collected in the first few days after starting chemotherapy. Clearly, more research is needed.
In summary, the best approach for optimizing fertility preservation in men with cancer is semen collection prior to the initiation of chemotherapy. Unfortunately, male cancer patients may sometimes be too ill to collect a semen sample. As our contributors noted, consideration can be given to use of PDE5 inhibitors, penile vibratory stimulation, electroejaculation, and TESE to facilitate sperm collection for cryopreservation prior to initiating potentially sterilizing chemotherapy. For some patients, these methods may also be unfeasible. In such instances, the majority of the above Androlog contributors do offer sperm cryopreservation after initiation of chemotherapy, although with some reservation over the unknown impact such therapy ultimately has on the genetic integrity of a given sperm.
Footnotes
Note: Postings to Androlog have been lightly edited before publication.
References
Frias S, Van Hummelen P, Meistrich ML, Lowe XR, Hagemeister FB,
Shelby MD, Bishop JB, Wyrobek AJ. NOVP chemotherapy for Hodgkin's disease
transiently induces sperm aneuploidies associated with the major clinical
aneuploidy syndromes involving chromosomes X, Y, 18, and 21 Cancer
Res. 2003; 63(1): 44
–51.
Lee SJ, Schover LR, Partridge AH, Patrizio P, Wallace WH, Hagerty
K, Beck LN, Brennan LV, Oktay K. American Society of Clinical Oncology
Recommendations on Fertility Preservation in Cancer Patients. J
Clin Oncol. 2006;24: 2917
–2931.
Meistrich ML. Gonadal dysfunction. In: DeVita VT, Hellman S, Rosenberg SA, eds. Principles and Practice of Oncology. New York: Lippincott, Williams & Wilkins; 2005 : 2560–2574.
Reuben SH. President's Cancer Panel 2003–2004 Annual Report. Bethesda, MD: National Cancer Institute, National Institutes of Health, US Dept of Health and Human Services; 2004 .
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