Gonadotropin-Releasing Hormone Agonist Corrects Defective Mini-Puberty in Boys with Cryptorchidism: A Prospective Randomized Study

Vincel, Beata; Verkauskas, Gilvydas; Bilius, Vytautas; Dasevičius, Darius; Malcius, Dalius; Jones, Birute; Hadžiselimović, Faruk

doi:10.1155/2018/4651218

Cited by 24 publications

(25 citation statements)

References 25 publications

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“…The mean number of germ cells per tubule in the group treated with GnRH before surgery was significantly greater (0.88 ± 0.31) than in the group without hormonal stimulation (0.49 ± 0.52; p = 0.02). Zivkovic et al ( 28 ) also found that hormonal therapy (Buserelin ® ) improved the histopathology of the abnormal contralateral descended testis in unilateral cryptorchidism without harming the germ cells.” Vincel et al ( 29 ) presented recently a randomized study of 10 boys 8 months to 5 years old. Boys with high infertility risk (no Ad-S in the testicular biopsy) were randomly divided into two groups.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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“…The first study included 15 biopsies of 15 patients (7 unilateral and 8 bilateral undescended testes), which were selected prior to randomization and based on histological results. Seven patients were grouped into the High Infertility Risk group lacking Ad spermatogonia (HIR/Ad−), and 8 patients were grouped into the Low Infertility Risk group presenting Ad spermatogonia (LIR/Ad+) [ 9 , 28 , 29 ]. From randomized study, in which Ad-bilateral cryptorchid boys were treated with GnRHa (Buserelin) after the first orchidopexy (surgery), data was retrieved from 4 patients.…”

Section: Methodsmentioning

confidence: 99%

“…From randomized study, in which Ad-bilateral cryptorchid boys were treated with GnRHa (Buserelin) after the first orchidopexy (surgery), data was retrieved from 4 patients. Initial biopsies of these four patients revealed no Ad spermatogonia, indicating defective mini-puberty (Ad-group) [ 29 ]. The second testis was managed by orchidopexy and biopsied 6 months after the initial surgery and GnRHa treatment [ 28 , 29 ].…”

Section: Methodsmentioning

confidence: 99%

PRDM Histone Methyltransferase mRNA Levels Increase in Response to Curative Hormone Treatment for Cryptorchidism-Dependent Male Infertility

Hadžiselimović¹,

Cathomas

Verkauskas

et al. 2018

Genes

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There is a correlation between cryptorchidism and an increased risk of testicular cancer and infertility. During orchidopexy, testicular biopsies are performed to confirm the presence of type A dark (Ad) spermatogonia, which are a marker for low infertility risk (LIR). The Ad spermatogonia are absent in high infertility risk (HIR) patients, who are treated with a gonadotropin-releasing hormone agonist (GnRHa) to significantly lower the risk of infertility. Despite its prevalence, little is known about the molecular events involved in cryptorchidism. Previously, we compared the transcriptomes of LIR versus HIR patients treated with and without hormones. Here, we interpreted data regarding members of the positive regulatory domain-containing (PRDM) family; some of which encoded histone methyltransferases that are important for reproduction. We found there were lower levels of PRDM1, PRDM6, PRDM9, PRDM13, and PRDM14 mRNA in the testes of HIR patients compared with LIR patients, and that PRDM7, PRDM9, PRDM12, and PRDM16 were significantly induced after GnRHa treatment. Furthermore, we observed PRDM9 protein staining in the cytoplasm of germ cells in the testes from LIR and HIR patients, indicating that the mRNA and protein levels corresponded. This result indicated that the curative hormonal therapy for cryptorchidism involved conserved chromatin modification enzymes.

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“…On the other hand, in a small study of 10 boys, GnRH agonist therapy with orchiopexy improved impaired minipuberty and spermatogonia in patients with bilateral undescended testes. 46) According to international guidelines, routine hormonal therapy with hCG or GnRH/LHRH for undescended testes. is not recom mended due to the lack of evidence as previously described (Table 4).…”

Section: Hormonal Therapymentioning

confidence: 99%

Comparison of diagnostic and treatment guidelines for undescended testis

Shin

Jeon

2020

Clin Exp Pediatr

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Cryptorchidism or undescended testis is the single most com mon genitourinary disease in male neonates. In most cases, the testes will descend spontaneously by 3 months of age. If the testes do not descend by 6 months of age, the probability of spontaneous descent thereafter is low. About 1%-2% of boys older than 6 months have undescended testes after their early postnatal descent. In some cases, a testis vanishes in the abdomen or reascends after birth which was present in the scrotum at birth. An inguinal undescended testis is sometimes mistaken for an inguinal hernia. A surgical specialist referral is recommended if descent does not occur by 6 months, unde scended testis is newly diagnosed after 6 months of age, or testicular torsion is suspected. International guidelines do not recommend ultrasonography or other diagnostic imaging because they cannot add diagnostic accuracy or change treat ment. Routine hormonal therapy is not recommended for undescended testis due to a lack of evidence. Orchiopexy is recommended between 6 and 18 months at the latest to pro tect the fertility potential and decrease the risk of malignant changes. Patients with unilateral undescended testis have an infertility rate of up to 10%. This rate is even higher in patients with bilateral undescended testes, with intraabdominal un de scended testis, or who underwent delayed orchiopexy. Pa tients with undescended testis have a threefold increased risk of testicular cancer later in life compared to the general pop ulation. Selfexamination after puberty is recommended to facilitate early cancer detection. A timely referral to a surgical specialist and timely surgical correction are the most important factors for decreasing infertility and testicular cancer rates.

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Gonadotropin-Releasing Hormone Agonist Corrects Defective Mini-Puberty in Boys with Cryptorchidism: A Prospective Randomized Study

Cited by 24 publications

References 25 publications

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

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

PRDM Histone Methyltransferase mRNA Levels Increase in Response to Curative Hormone Treatment for Cryptorchidism-Dependent Male Infertility

Comparison of diagnostic and treatment guidelines for undescended testis

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