Hormonal therapy for the subfertility of cryptorchidism.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Huff
D S
DS
Department of Pathology and the Division of Pediatric Urology, Childrens Hospital of Philadelphia, Philadelphia, PA, USA. huff@email.chop.edu
Snyder
H M
HM
Rusnack
S L
SL
Zderic
S A
SA
Carr
M C
MC
Canning
D A
DA
D002648:Child; D002675:Child, Preschool; D003456:Cryptorchidism / Q000150:complications*; D005298:Fertility / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives*; D006801:Humans; D007223:Infant; D007248:Infertility, Male / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D017274:Nafarelin / Q000627:therapeutic use*; D013076:Sperm Count; D016896:Treatment Outcome
D017274:Nafarelin; D007987:Gonadotropin-Releasing Hormone