Optimum Time for Orchiopexy in Cryptorchidism Frank Hinman, Jr., M.D. THE RESULTS of orchiopexy are disappointing. Is it that the surgical procedure is faulty, or can the defect be in the patient or in the testis? Realization that cryptorchidism is a symptom and not a diagnosis or a disease entity helps us answer these questions. A study of biopsies from undescended testes made during the 8-year period, 1946--1954, was made in order to compare them histologically (as Cooper, and as Robinson & Engle have done) with normal testes from children of similar ages. Our experience has been weighted: our associates in Endocrinology have referred unusual material to us because of their interest in testicular cytologic changes in various endocrine disorders (Table 1). Extreme variation in direction and degree of development can be seen among sections from cryptorchid patients of the same age or even in the same patient. Our observations made us realize that we cannot talk of the effects of cryptorchidism or of orchiopexy without recognizing that the undescended testis may be just one manifestation of congenital malformation or of endocrine dyscrasia. Study of this material appears to lead inevitably to two conclusions. First, many testes are constitutionally so abnormal that they will not function no matter what sort of hormonal or operative therapy is applied. Second, if the testes are potentially normal, surgical placement must be done before they are irreversibly damaged by the high intra-abdominal temperature. From the Deparbnent of Surgery-Urology, University of California School of Medicine, San Francisco, California. Read before the Tenth Annual Meeting of the American Society for the Study of Sterility at San Francisco, California, June 18, 19, and 20, 1954. 206
Vol. 6. No.3. 1955 ORCHIOPEXY 207 CAUSES OF CRYPTORCHIDISM One of three basic factors prevents descent of the testis: 1. Physical Abnormalities of Gubernaculum and Canal Physical abnormalities of the gubernaculum and canal may obstruct descent. For example, the patient with unilateral cryptorchidism who is otherwise normal, in whom descent does not occur either with administered hormones or at puberty. Ectopy of the testis would be a variant type. With the testis otherwise normal, early orchiopexy would help this patient. TABLE 1. Cryptorchidism, with Associated Abnormalities (University of California Hospital) Unilateral without other abnormalities Bilateral without other abnormalities Associated abnormalities Obesity Intersexuality (hypospadias) Primary testicular hypogonadism Pituitary hypogonadism Maldevelopment of the testis TOTAL 2 5 3 3 3 11 2 16 29 In patients with abnormalities of the canal, including most cases with unilateral nondescent, orchiopexy is the only effective treatment, since the patient's own pituitary hormones have proved sufficient to bring down the opposite side. Operation is also necessary if the retained testis is associated with a clinically demonstrable hernia. 2. Abnormalities in Testis Abnormalities in the testis itself are not at all rare in our particular experience. The classic example is primary testicular hypogonadism. Here, the testis itself is inadequately developed, and in spite of adequate pituitary stimulation (as shown by the high circulating F.S.H. level) never produces enough androgens to promote testicular descent. At the University of California Medical Center, 5 of 17 patients (29 per cent) with primary testicular hypogonadism had undescended testes. Lesser degrees of the same basic testicular abnormality are present in many cases of cryptorchidism in which
208 HINMAN Fertility & Sterility the only evidence of testicular hypofunction is an increased level of F.S.H., with or without a decreased level of androgen.1i The high number of patients seen with seminomas with increased F.S.H. is of interest in this connection. Since cryptorchid testes are also frequently associated with increased F.S.H. and since cryptorchid testes are twenty times more likely to be involved by tumor (seminoma) than the normal testis,6 we can speculate that there may be some causal relationship between the endocrine and testicular abnormality, and the neoplasm. The fact that the contralateral, normally placed testis may also be ab- Fig. 1. A, Biopsy of "normal" cryptorchid testis in 3-year-old child. B, Abnormal testis on opposite side. (x 324) normal, 7 is additional support for the concept that either there is abnormal testicular formation or that this is a generalized disorder, in contrast to the idea that the testicular changes are necessarily secondary to the higher temperature in the abnormal position. Cryptorchid testes may be different in the same individual. Figure 1 shows a «normal" cryptorchid testis on one side contrasted with an abnormal testis on the other in a child 3 years of age. An extreme example is the finding of severe developmental defects in one testis, almost to the point of agenesis. In Fig. 2, the hypoplastic testis shows only rudimentary structures with a few Leydig cells. Orchiopexy, which probably will be attempted for many of these patients
Vol. 6, No.3, 1955 ORCHIOPEXY 209 with less extreme abnormality, cannot be expected to assure a normally functioning testis. In fact, it is in this group that the greatest number of failures occur. These failures are usually and erroneously assumed to be due to inadequacy in surgical technic. 3. Primary Endocrine Abnormalities Primary endocrine abnormalities as a cause of cryptorchidism do not need emphasis here. Three out of 15 patients (20 per cent) at the University of California Medical Center with pituitary hypogonadism had cryptorchid Fig. 2. Low- and high-power views of rudimentary retained testis, composed of Leydig cells in a loose stroma with malformed ducts. testes. It is conceivable that certain patients with cryptorchidism who respond to hormone administration or in whom the testes come down spontaneously only with the increased pituitary output at puberty, have a subclinical deficiency of pituitary hormonal secretion. Operation on this group is in itself not worthwhile, unless the endocrine abnormalities can be adequately corrected. EFFECTS OF CRYPTORCHIDISM ON THE TESTIS The primary effect is delay in maturation. Cooper 25 years ago showed that the retained testis is not necessarily imperfect, but is retarded along the path of normal development-since the earlier the organ is examined,
210 HINMAN Fertility & Sterility the more normal is its appearance. The secondary changes are increase in fibrous tissue, decrease in the relative number of tubules, the persistence of quiescent nuclei at puberty, and the later disappearance of the more Fig. 3. A, Normal testis, 3 years. B, Retained testis, 3 years. (X 324) Fig. 4. A, Normal testis, 9 years. B, Retained testis, 9 years. (X 324) central rows of tubular cells. We, as well as others,l 8 have noted similar delayed sequential changes. Up to the age of 6 years, few changes occur in the testis (Fig. 3). From 6 years to puberty, tubular growth occurs unless
Vol. 6, No.3, 1955 ORCHIOPEXY 211 the testis is retained. Sections from a boy 9 years old with cryptorchidism (Fig. 4), show small immature tubules in contrast to those from a normal boy of the same age. More striking still is the difference between the normal and cryptorchid testis at 12 years (Fig. 5). The disorganization and regression at puberty is usually great (Fig. 6). These testes are uniformly incapable of producing normal sperm, and so if both testes have been retained to that time within the body the patient is Fig. 5. A, Normal testis, 12 years. B, Retained testis, 12 years. (X 324) Fig. 6. A, Normal testis, 17 years. B, Retained testis, 17 years. (X 324)
212 HINMAN Fertility & Sterility sterile. Orchiopexy, of course, would not reverse the changes at this age. These changes are caused by increased temperature, which has been repeatedly shown experimentally to produce spermatogenic arrest. 5 Placement of the testis in the scrotum before puberty perhaps does not significantly improve spermatogenesis (Table 2), although we have no figures on those brought down by the age of 6. It is on the poor results of After Hansen.4 TABLE 2. Bilateral Untreated Orchiopexy Unilateral Untreated Orchiopexy Impairment of Fertility After Orchiopexy Impairment by semen analysis Severe to Slight to Complete moderate none 9 14 1 3 orchiopexy that the arguments focus. If the testis is fundamentally normal and if no gross endocrine abnormalities exist, then placement of the testis in the scrotum at an early enough age, before irreversible changes have taken place which prevent proper maturation, should afford fertility if the surgical procedure itself does not damage the blood supply to the testis. These are a lot of "ifs," and they point up the fact that patients with cryptorchidism and especially the figures on the results of orchiopexy, cannot be lumped together for statistical analysis. Rather, each case must be studied for the basic cause of the cryptorchidism to assess properly the value of operation which will be viewed in relation to the age at operation. The argument that because the results of orchiopexy at 6 years of age are not always good, we should operate earlier (at 3 years of age or at birth) is not logical. It does not take into account the fact that the testis and the patient may be fundamentally abnormal. PRACTICAL CONCLUSIONS 1. Make the decision early, for or against treatment-between the ages of 3 to 6 years, because after 6 years, irreversible damage may occur. For psychologic reasons also, early placement is desirable. 2. Determine if obstruction exists by giving anterior pituitary-like hor- o 6 10 8 o 5 24 25
Vol. 6, No.3, 1955 ORCHIOPEXY 213 mone, or more directly, by giving methyl testosterone linguets. This will show what effect puberty will have, without the need for waiting while irreversible changes take place. In unilateral cases, nondescent usually means obstruction, so hormones will seldom be effective. An associated hernia also indicates operation. 3. Operate if hormonal stimulation fails, since puberty also will fail to bring about descent. Hormones have made orchiopexy easier by enlarging the testis and its adjacent structures, and have not been shown to harm the testis. 3 4. The decision between orchiopexy and orchiectomy will usually be made at the operating table, by consideration of the appearance of the testis and the technical difficulties in bringing it completely within the scrotum. Consideration of four factors will help in the decision: 8 a. Cosmetic aspects; a nylon prosthesis is an excellent substitute. b. Hormonal aspects; testosterone (now as the long-acting cyclopentyl proprionate) adequately compensates for loss of Leydig function. c. Fertility aspects; there is little chance for spermatogenesis unless the testis is reasonably normal in development, has not been too damaged by staying overlong in the abdomen, and can be brought completely within the scrotum. d. Neoplastic aspects; tumor of the testis is twenty times more frequent in patients with cryptorchidism, so we have an additional argument for either bringing the testis to a site where it can be followed by palpation, or removing it if it appears too maldeveloped to produce an effective number of sperm anyway. In summary, since the retained testis may be irreversibly damaged well before puberty, hormonal stimulation should be tried before the age of 6 years. If it fails, orchiopexy should be done at once. Many failures can be explained by congenitally defective testes or general endocrine abnormality, and are not necessarily the result of the surgical procedure. REFERENCES 1. CHARNY, C. W., CONSTON, A. S., and MERANZE, D. R. Testicular developmental histology. Ann. N. Y. Acad. Sc. 55:597, 1952. 2. COOPER, EUGENIA R. A. The histology of the retained testis in the human subject at different ages, and its comparison with the scrotal testis. ]. Anat. 64:5, 1929. 3. ENGBERG, H. Investigations on the endocrine function of the testicle in cryptorchidism. Proc. Roy. Soc. Med. 42:652, 1949.
214 HINMAN Fertility & Sterility 4. HANSEN, T. S. Fertility in operatively treated and untreated cryptorchism. Acta chir. Scandinav. 94:117, 1946. 5. MOORE, C. R. The behavior of the testis in transplantation, experimental cryptorchidism, vasectomy, scrotal insulation, and heat application. Endocrinology 8: 493,1924. 6. MOOSLIN, K. E. The incidence of malignancy in cryptorchid testes. Read at Urology Conference, Veterans Admin. Hosp., San Francisco, 1950. 7. NELSON, W. O. Some problems of testicular function. ]. Ural. 69:325, 1953. 8. ROBINSON, J. N., and ENGLE, E. T. Some observations on cryptorchid testis. J. Ural. 71 :726, 1954. The International Fertility Association announces The Second World Congress on Fertility and Sterility Naples, Italy, May 18-26, 1956 I. II. III. IV. V. VI. VII. VIII. IX. X. XI. XII. Major Subjects To Be Discussed Endocrine and metabolic factors in fertility and sterility. Occupational and toxic factors in relation to fertility. New methods of diagnosis and treatment of male sterility. New methods and diagnosis and treatment of female sterility. Diagnostics of ovulation and its disorders. Diagnostics of spermatogenesis and its disorders. Treatment of disorders of ovulation. Treatment of disorders of spermatogenesis. Surgery in male sterility. Surgery in female sterility. Experimental investigations in fertility and sterility. Problems in animal reproduction (veterinary). For information and registration blanks, write to: PROF. C. TESAURO Chairman, Committee on Arrangements Via S. Andrea Della Dama 19 Napoli, Italy