Selecting Infants With Cryptorchidism and High Risk of Infertility for Optional Adjuvant Hormonal Therapy and Cryopreservation of Germ Cells: Experience From a Pilot Study

Abstract

IntroductionOrchiopexy for congenital cryptorchid testes is recommended between ½ and 1 year of age to preserve testicular germ cell maturation. Early operation is not enough to preserve fertility in 22 and 36% of cases. Aim of this study was to set up a protocol for optional adjuvant hormonal therapy after orchiopexy and thereafter cryopreservation of testicular biopsies from infants with bilateral cryptorchidism and high infertility risk.Materials and methodsWe included 17 boys with bilateral cryptorchidism, normal FSH, and impaired germ cell number per tubular transverse section (G/T) in testicular biopsies at orchiopexy, 7 months to 3½ years old. Postoperatively, optional adjuvant LHRH (kryptocur®) 0.2 mg/0.1 mL 2× every second day in 16 weeks were offered. Ten boys were applicable for age matching according to parent’s choice of treatment regime and G/T. Five of them had kryptocur®, and five were controls. Repeat bilateral testicular biopsy evaluation and cryopreservation were offered to all boys 12 months after primary orchiopexy. For cryopreservation, tissue pieces were incubated with a cryoprotectant with a slow program freezing.ResultsTwo out of five kryptorcur®-treated boys normalized both the average G/T and the number of adult dark spermatogonia (Ad-S). Another kryptocur®-treated boy with initial low G/T and no Ad-S increased the G/T and achieved normal number of Ad-S at time of cryopreservation. In the control group, two patients reached only normal lower range regarding the G/T and the number of Ad-S. None of boys with less than average 0.2 G/T improved significantly, whether they were kryptocur®-treated or not.ConclusionBased on literature and the present results, we recommend adjuvant LHRH treatment to boys with cryptorchidism and insufficient genuine gonadotropin stimulation at time of surgery, as these patients have high infertility risk. Cryopreservation should be an option in case of treatment failure of adjuvant LHRH. However, to avoid repeat surgery with biopsy, some parents may choose biopsy for cryopreservation at time of the initial bilateral orchiopexy, well informed that the procedure may only be truly indicated in 22 and 36% of the cases.

Hypogonadism and Cryptorchidism

“…The number of A dark spermatogonia from testicular biopsy at the time of orchiopexy was reported to predict the risk of infertility in adulthood (221,232). Some studies of GnRH administration, before (in most studies) or after orchiopexy or orchiolysis, showed increased fertility indices, as assessed by the number of germ cells or spermatogonia per tubular cross-section or percentage of normal histology from testicular biopsy in childhood, or semen quality (16,231,233,234). To date, there is only one study that reported a long-term effect of hormonal treatment on semen quality in adulthood (235), therefore the combined or sequential surgical and hormonal treatment cannot be recommended as routine practice at this time.…”

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, 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, to avoid repeated surgery with biopsy, some parents may choose biopsy for cryopreservation at the time of the initial bilateral orchidopexy, well informed that the procedure may only be truly indicated in around a third of the cases.…”

FERTILITY PRESERVATION: Testicular transplantation for fertility preservation: clinical potential and current challenges

“…Cryptorchidism is a common condition resulting in impaired testicular growth, reduction in spermatogonial numbers and impaired germ cell differentiation (Kollin et al 2012), resulting in an increased risk of infertility (Cortes et al 1996). Whilst testicular biopsy for cryopreservation at the time of orchidopexy has been advocated in patients with cryptorchidism (Thorup et al 2018), pre-existing impairment of germ cell development may affect the potential for generating sperm following transplantation. Furthermore, pre-existing impairment to the testicular somatic environment of the recipient testis may prevent further germ cell development.…”