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      Infertility in Cryptorchidism Is Linked to the Stage of Germ Cell Development at Orchidopexy

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          Abstract

          Background: Cryptorchidism represents the most common endocrine disease in boys, with infertility frequently observed in unilateral as well as bilateral forms. In this study, we examined the role of Ad (dark) spermatogonia for fertility in cryptorchid boys. The hypothesis to be proven was that boys lacking Ad spermatogonia will develop infertility despite a successful orchidopexy at an early age. Methods: To estimate total sperm count, one of the most predictive parameters of male fertility, we analyzed the ejaculatein 218 cryptorchid men and correlated it with the developmental stage of their germ cells at the time of successful surgery. Results: Abnormal sperm concentration (<40 × 10<sup>6</sup>/ejaculate) was found in half of the patients under the study. 47.5% of unilateral and 78% of bilateral cryptorchid males had their sperm concentration in the infertility range according to the WHO standards. If transformation into Ad spermatogonia had occured, age-related differences in the fertility outcome was observed. The younger the unilateral cryptorchid boys were at surgery, the higher their sperm count. Age-related difference was not found in the group of cryptorchid men having had no A dark spermatogonia at time of surgery, indicating that in this group a successful orchidopexy is insufficient to prevent infertility development and, in particular, the development of azoospermia. Conclusion: The presence of Ad spermatogonia at surgery is an excellent prognostic parameter for future fertility. Cryptorchid boys lacking these cells will develop infertility despite successful orchidopexy at an early age.

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          Most cited references 14

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          The importance of mini-puberty for fertility in cryptorchidism.

          Mini-puberty is the hormonal surge of gonadotropins and testosterone which occurs in early infancy. It induces the development and transformation of gonocytes into Ad spermatogonia, which is impaired in many cryptorchid testes. We examine the role of testosterone in the transformation and development of Ad spermatogonia. A total of 32 patients 1 to 7 years old were treated with human chorionic gonadotropin (HCG) to achieve epididymo-testicular descent before orchiopexy (group 1), and 33 patients underwent orchiopexy without previous hormonal treatment (group 2). A testicular biopsy was obtained during surgery from all the patients. The number of Ad spermatogonia per tubular cross section (Ad/tbx) was assessed and compared between the 2 groups. The number of Ad spermatogonia per tubular cross section in group 1 was also correlated with the post-stimulatory testosterone plasma values. In group 1, 17 patients had greater than 0.1 Ad/tbx, and the remaining patients had 0.1 or less Ad/tbx. In group 2, 6 patients had greater than 0.1 Ad/tbx. Of the boys with cryptorchidism 35% responded inadequately to HCG stimulation, while 10% did not respond. Those patients with suboptimal Leydig cell capacity (and an inadequate response to HCG stimulation) had a defective Ad spermatogonia differentiation of 0.1 or less. Boys with cryptorchidism with an insufficient testosterone surge after HCG risk infertility despite early and successful surgery. The testicular biopsy assists in identifying those who might benefit from hormonal treatment following successful orchiopexy.
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            Treatment with a luteinizing hormone-releasing hormone analogue after successful orchiopexy markedly improves the chance of fertility later in life.

            Infertility has been considered a principal complication associated with cryptorchidism. A particularly high incidence of cryptorchid boys lack the priming effect during the first 3 months of life due to low concentrations of gonadotropins and testosterone (inadequate perinatal stimulation of the testes, which causes infertility). This condition causes impaired transformation of gonocytes into fetal spermatogonia. More pronounced hypogonadotropic hypogonadism results in fewer germ cells. Most importantly, cryptorchid boys with fewer than 0.2 cells per tubular cross section have a high probability of being infertile in adulthood, regardless of whether the condition is unilateral or bilateral and despite apparently successful orchiopexy. To counteract the paucity of priming hormones, cryptorchid patients with unilateral or bilateral cryptorchidism and a severe paucity of germ cells were treated with a low dose of the luteinizing hormone-releasing hormone analogue buserelin after successful orchiopexy. We analyzed the spermiograms of these patients, who are now young adults, and compared them to those of 23 other men who also had cryptorchidism with a comparable severe paucity of germ cells but who had not received hormonal treatment after successful orchiopexy. Patients who received hormonal therapy after orchiopexy had significantly improved spermiograms compared to those in the control group. Treatment with buserelin increased the number of spermatozoa, improved motility and increased the number of normal forms of spermatozoa. The luteinizing hormone-releasing hormone analogue buserelin, administered as a nasal spray every other day for 6 months following successful orchiopexy, appears to have a long lasting, positive effect on germ cells. Consequently, the prognosis of fertility has been greatly enhanced in patients treated with buserelin.
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              Early treatment of cryptorchidism, semen quality and testicular endocrinology.

              We evaluated the effect of patient age at treatment of cryptorchidism in relation to subsequent semen quality. Semen analyses and hormonal evaluations were performed in 51 men who were treated for cryptorchidism at ages 10 months to 12 years. Sperm concentration was normal in 90% of the patients with unilateral and 50% with bilateral cryptorchidism. No patient treated before age 4 years had severe sperm defects. Elevated follicle-stimulating hormone levels indicated severe testicular damage. Fertility is better in patients with bilateral cryptorchidism if treated before age 4 years. Age at treatment did not have a significant effect on semen quality in patients with unilateral cryptorchidism.
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                Author and article information

                Journal
                HRE
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                1663-2818
                1663-2826
                2007
                June 2007
                14 March 2007
                : 68
                : 1
                : 46-52
                Affiliations
                aKindertagesklinik Liestal, Liestal, bInstitut für Statistik Dr. M. Buser, Riehen, Switzerland; cKinderchirurgische Universitäts-Klinik Würzburg, Würzburg, Germany
                Article
                100874 Horm Res 2007;68:46–52
                10.1159/000100874
                17356291
                © 2007 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 5, References: 23, Pages: 7
                Categories
                Original Paper

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