Huff D S, Snyder H M, Rusnack S L, Zderic S A, Carr M C, Canning D A
Department of Pathology and the Division of Pediatric Urology, Childrens Hospital of Philadelphia, Philadelphia, PA, USA.
Horm Res. 2001;55(1):38-40. doi: 10.1159/000049962.
The subfertility of cryptorchidism correlates with severely reduced total germ cell counts in prepubertal testicular biopsies of undescended testes. Reduced total germ cell counts are associated with defects in the two prepubertal steps in maturation and proliferation in germ cells: first, the transformation of the fetal stem cell pool (gonocytes) into the adult stem cell pool (adult dark spermatogonia) at two to three months of age and, second, the transformation of adult dark spermatogonia into primary spermatocytes (meiosis) at 4-5 years. The defects in maturation are associated with blunting of the normal surges in gonadotropins and testosterone. Prepubertal treatment with gonadotropin-releasing hormones would theoretically trigger normal germ cell maturation and proliferation and thereby improve total germ cell counts and improve fertility. Prepubertal treatment of cryptorchidism with the GnRH analogue Buserelin has resulted in improved total germ cell counts and improved spermiograms. The purpose of this report is to describe the results of treatment of cryptorchidism with the GnRH analogue Naferelin.
Twelve boys with cryptorchidism, 6 unilateral and 6 bilateral, and severely reduced germ cell counts in testicular biopsies were treated with Naferelin following successful orchidopexy and bilateral testicular biopsies. Response of the total germ cell counts was assessed in follow-up bilateral biopsies within 5 months of completing the hormonal therapy.
Eight of the 12 boys (5 of the 6 with unilateral and 3 of the 6 with bilateral cryptorchidism) showed improvement in the total germ cell counts in one or both testes. All 8 had a poor prognosis for fertility pretreatment and a good prognosis for fertility posttreatment. Of the 5 with unilateral cryptorchidism who improved, 2 showed improvement in both testes; and 3, only in the contralateral descended testes. All 3 of the boys with bilateral cryptorchidism who improved showed improvement in both testes. Testes with absence of germ cells and older patients tended to show no improvement. Of the 6 contralateral descended, 5 (83%) improved, and of the 18 undescended testes, 8 (44%) improved.
In this preliminary study, Naferelin therapy appears to induce improvement in the total germ cell counts and the prognosis for future fertility in 75% of patients.
隐睾症导致的生育力低下与青春期前未降睾丸活检中生殖细胞总数严重减少相关。生殖细胞总数减少与生殖细胞成熟和增殖过程中青春期前两个阶段的缺陷有关：第一，在2至3个月大时，胎儿干细胞池（生殖母细胞）向成体干细胞池（成体暗型精原细胞）的转变；第二，在4至5岁时，成体暗型精原细胞向初级精母细胞的转变（减数分裂）。成熟缺陷与促性腺激素和睾酮的正常激增减弱有关。理论上，青春期前使用促性腺激素释放激素治疗可触发正常的生殖细胞成熟和增殖，从而提高生殖细胞总数并改善生育能力。用促性腺激素释放激素类似物布舍瑞林对隐睾症进行青春期前治疗已使生殖细胞总数增加，精子图得到改善。本报告的目的是描述用促性腺激素释放激素类似物那法瑞林治疗隐睾症的结果。
12名患有隐睾症的男孩，6名单侧隐睾，6名双侧隐睾，睾丸活检显示生殖细胞计数严重减少，在成功进行睾丸固定术和双侧睾丸活检后，用那法瑞林进行治疗。在完成激素治疗后5个月内进行的随访双侧活检中评估生殖细胞总数的反应。
12名男孩中的8名（6名单侧隐睾中的5名和6名双侧隐睾中的3名）在一个或两个睾丸中的生殖细胞总数有所改善。所有8名患者治疗前生育预后不良，治疗后生育预后良好。在改善的5名单侧隐睾患者中，2名双侧睾丸均有改善；3名仅对侧下降的睾丸有改善。在改善的3名双侧隐睾男孩中，双侧睾丸均有改善。无生殖细胞的睾丸和年龄较大的患者往往没有改善。在6个对侧下降的睾丸中，5个（83%）有改善，在18个未下降的睾丸中，8个（44%）有改善。
在这项初步研究中，那法瑞林治疗似乎能使75%的患者生殖细胞总数增加，未来生育预后改善。
