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Cancer and Male Factor Infertility

Cancer and Male Factor Infertility

Dr. Costabile and Ms. Spevak provide a comprehensive and timely review of cancer-related male infertility issues. As the incidence of malignant diagnoses increases and advances in therapy allow for long-term survival, we face a growing population of reproductive-age men who are infertile. While cancer cure and management of acute toxicities from therapy remain the paramount goals for both the physician and patient, the authors correctly point out that future fertility is a major concern for young patients. It is vital that physicians be sensitive to the tremendous impact that infertility can have on a patient’s quality of life. They must remain abreast of the newest data on fertility impairment resulting from the various cancers and their therapies in order to adequately counsel the patient.

The authors provide a salient overview of the factors that impair fertility in cancer patients. These include baseline suboptimal semen parameters and gonadotoxic effects from the physical and chemical treatments of cancer, as well as more difficult to substantiate factors, such as malnutrition and emotional stress.

Interventions to Optimize Fertility in the Cancer Patient
Strategies that optimize fertility can be employed before cancer treatment begins, during therapy, and after treatment has been received. Prior to treatment, the issue of potential infertility should be discussed with the patient and a baseline semen analysis obtained. The article strongly supports sperm cryopreservation in patients prior to therapy, even in a setting of severe oligospermia (counts less than l million sperm/mL). Artificial insemination using cryopreserved sperm from men with testicular cancer or Hodgkin’s disease resulted in a pregnancy rate of 45% within 6 months.[1] More advanced assisted reproduction techniques, such as in vitro fertilization and intracytoplasmic sperm injection, permit the use of much lower sperm counts with higher success rates, albeit with more expense. Recent controversies regarding postmortem sperm retrieval and the use of cryopreserved semen after a male patient has expired suggest that this issue be addressed in written form prior to sperm banking.[2]

The authors stress available alternatives to chemotherapy, surgery, and radiation treatments that preserve fertility. The gonadotoxic effects of chemotherapy are related to the duration of therapy and the specific agent utilized. Alkylating agents, such as cyclophosphamide (Cytoxan, Neosar), cause far more gonadal damage than nonalkylators do.

In an effort to minimize the gonadal toxicity and improve therapeutic success for Hodgkin’s disease, several studies have compared ABVID regimens (Adriamycin, bleomycin, vinblastine, and dacarbazine) with standard MOPP (mechlorethamine, Oncovin, procarbazine, and prednisone) and MOPP/ABVD hybrid programs.[3,4] While comparable in therapeutic efficacy, ABVD resulted in recovery of spermatogenesis in up to 100% of patients with a mean recovery time of 10 months. In contrast, recovery of spermatogenesis occurred in only 22% of MOPP-treated patients with a mean recovery time of 36 months. These reports clearly show the variability in the gonadotoxic effects of antineoplastic agents and suggest the need for ongoing prospective trials that assess future fertility as part of all cancer treatment protocols in reproductive-age men.

Efforts to minimize the effects of other types of cancer treatment on gonadal function have shown mixed results. Elegant anatomic studies of the retroperitoneum by Donohue and others (authors' reference 47) have led to the preservation of sympathetic innervation during retroperitoneal lymph node dissection for testis cancer, thus avoiding the previous complications of failure of emission and retrograde ejaculation. In contrast, radiotherapy for Hodgkin’s disease or germ cell tumors may profoundly affect semen quality. Despite gonadal shielding techniques and alterations in the radiation portal, the majority of patients treated with radiation therapy below the diaphragm can expect to experience long-term azoospermia.[5,6]

Potential for Recovery
The authors provide an excellent discussion of the potential for recovery of spermatogenesis after radiation and chemotherapy. After a patient receives cancer treatment, the physician should reassess the patient’s fertility with serial semen analyses every 6 months to 1 year. Return of gonadal function is variable and will usually take 2 years but may take as long as 10 years. In a patient with severe gonadal depression after treatment, the recommended course of action depends on a number of factors, including age of the spouse, the couple’s attitude toward assisted reproduction techniques, their financial ability to pay for these techniques, and their patience with waiting for the potential spontaneous return of fertility.

If couples are unwilling to wait several years for possible recovery of spermatogenesis, assisted reproduction with either artificial insemination or in vitro fertilization/intracytoplasmic sperm injection is indicated. If a patient is azoospermic and did not bank sperm prior to therapy, new techniques, such as testicular sperm extraction, allow for the removal of small numbers of sperm directly from the testis for use with intracytoplasmic sperm injection. Recent studies using this technique in azoospermic men with severely depressed spermatogenesis have resulted in clinical pregnancy rates of between 28% and 31%.[7,8] The authors give a complete summary of available data on pregnancy outcomes in cancer patients. While initial results suggest no increased incidence of fetal anomalies, the newest techniques, such as testicular sperm extraction, have not undergone adequate long-term study to reach safety conclusions.

Summary
Advances in medicine have allowed our focus as physicians to extend beyond the immediate survival of cancer patients and toward optimizing the “post-cancer” quality of life. The article by Costabile and Spevak provides an excellent review of the causes of cancer-related male infertility, as well as options available to preserve fertility.

References

1. Scammell GE, White N, Stedronska J, et al: Cryopreservation of semen in men with testicular tumour or Hodgkin’s disease: Results of artificial insemination of their partners. Lancet 2:31-32, 1985.

2. Ohl DA, Park J, Cohen C, et al: Procreation after death or mental incompetence: Medical advance or technology gone awry? Fertil Steril 66(6):889-895, 1996.

3. Viviani S, Santoro A, Ragni, et al: Gonadal toxicity after combination chemotherapy for Hodgkin’s disease: Comparative results of MOPP vs ABVD. Eur J Clin Oncol 21:601-605, 1985.

4. Ragni G, Perotti L, Viviani S, et al: Fertility outcome in men with Hodgkin’s disease after four different combination chemotherapy regimens (abstract 0-094). Meeting of the American Society of Reproductive Medicine, 1996.

5. Jackson HL, Hass AC, Sooby D, et al: The gonadal exposure of boys and young men treated with inverted “Y” fields: Its reduction and genetic significance. Radiology 96:181-186, 1970.

6. Fossa SD, Klepp O, Aakvaag A: Serum hormone levels in patients with malignant testicular germ cell tumors without clinical and/or radiological signs of tumors. Br J Urol 52:151-157, 1980.

7. Tournaye H, Camus M, Goossens A, et al: Recent concepts in the management of infertility because of non-obstructive azoospermia. Hum Reprod 10(1):115-119, 1995.

8. Devroey P, Nagy P, Tournaye H, et al: Outcome of intracytoplasmic sperm injection with testicular spermatozoa in obstructive and non-obstructive azoospermia. Hum Reprod 11(5):1015-1018, 1996.

 
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