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Cryptorchidism, Fertility, and Cancer

From the Department of Urology, University of Illinois at Chicago, Chicago, Illinois

While the relationship between cryptorchidism and sub-fertility in men is well established, as is the relationship between cryptorchidism and testicular carcinoma, the ability in the modern era for very few sperm to lead to reproductive success with IVF/ICSI blurs once dogmatic lines in clinical algorithms. To illustrate, Jon Pryor writes:

I request some advice on a 28-year-old man who presented to me with azoospermia. Although the young man recounts a negative past medical history, on examination his scrotal contents were empty. I could not feel his testes in the inguinal region. A repeat semen analysis shows azoospermia, and he has a slightly low testosterone at 235 (nl 300-1200) and a markedly elevated FSH at 35.8 (nl 1-8). I obtained a karyotype, which returned normal, and a microdeletion of the Y chromosome, which also returned normal. An inguinal ultrasound could not locate the testes so I obtained a pelvic computed tomography scan, which found them at the iliac bifurcations. The question is, what should I do? I am not excited about removing the testes because it is more difficult to perform than if they were in the inguinal area, he is happy with his libido, and he could, although doubtful, produce sperm. Although he may have sperm in his testes, I doubt there is enough to survive a freeze-and-thaw procedure, and therefore sperm would have to be obtained fresh if IVF and ICSI were to be performed. Do I encourage the couple to adopt a child or undergo donor in utero insemination, remove the testes, and check for sperm before IVF/ICSI...?"

Hector Chemes notes the risk of neoplasia in his reply:

I am afraid that because the man's testes are in the pelvis and not available for clinical examination, he may face the risk of unnoticed tumor development. He is in the age range in which germ cell cancer affects men, and cryptorchidism is a recognized risk factor. I agree that removal may be an extreme decision, but at least a bilateral biopsy could be obtained. If carcinoma in situ-intratubular germ cell neoplasia is present, then it will probably be OK to leave the testes where they have been. Chances are that no sperm will be present in the seminiferous tubules with such a long history of cryptorchidism.

Lawrence Ross describes the outpatient laparoscopic approach to orchiectomy, and concurs that the probability of finding mature sperm suitable for artificial reproductive techniques is low:

The patient must be apprised of the increased risk of developing germ cell tumors in the abdominal testis (Bongiovani reported a 40-fold increase in risk). We recommend removal for that reason unless the patient is willing to have a yearly abdominal computed tomography or magnetic resonance imaging scan. The testes can be removed laparoscopically as an outpatient procedure. Our experience has been that such testes will exhibit complete atrophy of the germinal epithelium, making it highly unlikely that sperm will be found. Of course the patient will need testosterone replacement therapy for maintenance of libido, muscle mass, and so on.

Sidney Glina agrees:

I would perform an orchiectomy through laparoscopy because of the risk of testicular cancer. I would examine the testis for sperm and freeze whatever sperm may be found. If sperm are not present the couple can be encouraged to adopt or proceed with IAD, and the patient should receive testosterone replacement therapy.

Teoman Cem Kadioglu also agrees that the chance of finding sperm is markedly low, but offers an alternative approach to orchiectomy by observation:

One may decide to screen a 28-year-old patient with tumor markers and perform biannual computed tomography scans for the next several years for tumor growth. The screening can be performed once a year from then on. I think the patient's chance of having sperm at exploration is close to zero and would not advise external androgen supplementation until he suffers from a decrease in libido. Thus for the time being, I advise no treatment at all.

Eugene Fuchs provides another alternative approach to orchiectomy by testicular autotransplantation, and reports a recent case:

Although there is no question that the risk of testis cancer in the patient is many times greater than in the general population, it is, nevertheless a relatively low risk. I would offer the patient autotransplantion of the gonad into his scrotum by attaching the gonadal vessels to the inferior epigastric artery and vein. This is a relatively easy operation to perform for any urologist with microsurgical skills. It is especially easy to perform in adults. Autotransplantation would preserve testosterone production and allow easy self-examination of the testicles or examination by a professional, thus avoiding periodic scanning. I would not hesitate to perform both procedures, but as two separate operative procedures. Restoration of spermatogenesis is unlikely but possible in low numbers. My most recent experience was with an 18-year-old man with a solitary, high undescended testicle. His scrotum was somewhat under-developed but the gonad fit into it nicely. His serum testosterone 6 weeks after surgery was greater than 300. I will look forward to other's thoughts.

Finally, Hector Chemes intrigues surgical andrologists by noting the utility of testicular biopsy in this instance:

I am amazed at the reluctance of andrologists to use testicular biopsy as a diagnostic method to screen for testicular cancer. It has been shown that if the patient does not have carcinoma in situ-intratubular germ cell neoplasia, his chances of developing a germ cell tumor of the testis are very low. The biopsy can be performed via laparoscopy and would solve the question of what to do on an objective basis more than in what we think it will happen. As a pathologist I may be biased toward biopsies, but if there is an indication for it, this is it.

This discussion demonstrates that while such dogmas as cryptorchidism leading to infertility and cancer are well founded, the march of science and technology continues to mold our clinical behavior in new and interesting ways.

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