On the descent of the epididymo-testicular unit, cryptorchidism, and prevention of infertility

Abstract

This comprehensive review provides in-depth coverage of progress made in understanding the molecular mechanisms underlying cryptorchidism, a frequent pathology first described in about 1786 by John Hunter. The first part focuses on the physiology, embryology, and histology of epididymo-testicular descent. In the last 20 years epididymo-testicular descent has become the victim of schematic drawings with an unjustified rejection of valid histological data. This part also includes discussion on the roles of gonadotropin-releasing hormone, fibroblast growth factors, Müllerian inhibiting substance, androgens, inhibin B, and insulin-like 3 in epididymo-testicular descent. The second part addresses the etiology and histology of cryptorchidism as well as the importance of mini-puberty for normal fertility development. A critical view is presented on current clinical guidelines that recommend early orchidopexy alone as the best possible treatment. Finally, by combining classical physiological information and the output of cutting-edge genomics data into a complete picture the importance of hormonal treatment in preventing cryptorchidism-induced infertility is underscored.

Is Hormonal Treatment of Congenital Undescended Testes Justified A Debate

“…Interestingly, lower signals of long noncoding RNAs (lncRNAs) participating in epigenetic processes, including AIRN , FENDRR , XIST , and HOTAIR , were found in the HIR group. These data are consistent with the hypothesis that hypogonadotropic hypogonadism in boys with altered mini-puberty is the consequence of a profoundly altered gene expression program involving protein-coding genes and lncRNAs [Hadziselimovic et al, 2017].…”

Paternity in 5α-Reductase-2 Deficiency: Report of Two Brothers with Spontaneous or Assisted Fertility and Literature Review

“…It may have induced the maturation of the germinal line, since the younger brother with a similar history and genetic status needed assisted fertilization. In boys with iso- lated cryptorchidism, hormonal treatment has been advocated to improve fertility in adulthood [Hadziselimovic, 2017], because Gn-RH or hCG administration before or after orchidopexy has been shown to improve the fertility index on testicular biopsies [Schwentner et al, 2005;Thorup and Cortes, in press]. Indeed, consensus on this issue is still unreached [Niedzielski et al, 2016] and hormonal therapy alone to induce testicular descent is not supported [Tekgül et al, 2018].…”

Surgical Management of Undescended Testis - Timetable and Outcome: A Debate

“…To diagnose these high risks patients, a testicular biopsy at the time of orchidopexy is needed as a supplement to the hormonal profile of serum gonadotropins and inhibin-B [Faure et al, 2016]. This is important, because there is good evidence that patients will benefit from adjuvant LH-RH treatment [Hadziselimovic et al, 2017;Thorup et al, 2018b]. These recommendations have not been adopted in the aforementioned guidelines.…”

“…Some patients with syndromic cryptorchidism, as for example patients with Down syndrome or 45,X/46,XY males, will of course remain infertile. However, in cases with genuine gonadotropin insufficiency, early surgical correction is not enough and adjuvant LH-RH treatment should be implemented to improve the fertility potential [Hadziselimovic, 2017;Thorup et al, 2018b]. Cryopreservation may be an option in case of treatment failure of adjuvant LH-RH [Thorup et al, 2018b].…”

“…However, if there is an underlying endocrinopathy causing a low number of germ cells and inadequate maturation of the testis, merely putting the testis into the scrotum by early surgery will not correct that endocrinopathy. Genuine insufficient gonadotropin stimulation in mini-puberty will cause impaired germ cell maturation and a high risk of infertility in about 40-70% of bilateral and 10-30% of unilateral cases even though early surgery is performed [Schindler et al, 1987;Hadziselimovic et al, 2005;Thorup et al, 2013Thorup et al, , 2015Hadziselimovic, 2017]. To diagnose these high risks patients, a testicular biopsy at the time of orchidopexy is needed as a supplement to the hormonal profile of serum gonadotropins and inhibin-B [Faure et al, 2016].…”