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选择患有隐睾症且不育风险高的婴儿进行选择性辅助激素治疗和生殖细胞冷冻保存:一项试点研究的经验。

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

作者信息

Thorup Jorgen, Clasen-Linde Erik, Dong Lihua, Hildorf Simone, Kristensen Stine Gry, Andersen Claus Yding, Cortes Dina

机构信息

The Department of Pediatric Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

Front Endocrinol (Lausanne). 2018 Jun 5;9:299. doi: 10.3389/fendo.2018.00299. eCollection 2018.

Abstract

INTRODUCTION

Orchiopexy 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 METHODS

We 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.

RESULTS

Two 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.

CONCLUSION

Based 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.

摘要

引言

对于先天性隐睾症,建议在6个月至1岁之间进行睾丸固定术,以保护睾丸生殖细胞成熟。在22%至36%的病例中,早期手术不足以保留生育能力。本研究的目的是制定一项方案,用于睾丸固定术后的选择性辅助激素治疗,以及对双侧隐睾症且不育风险高的婴儿进行睾丸活检后的冷冻保存。

材料与方法

我们纳入了17名双侧隐睾症男孩,他们的促卵泡生成素(FSH)正常,在睾丸固定术时睾丸活检的每个管状横切面的生殖细胞数量(G/T)受损,年龄在7个月至3岁半之间。术后,提供选择性辅助促性腺激素释放激素(LHRH,商品名kryptocur)0.2mg/0.1mL,每两天注射2次,共16周。根据父母选择的治疗方案和G/T,10名男孩符合年龄匹配条件。其中5名接受了kryptocur治疗,5名作为对照。在初次睾丸固定术12个月后,对所有男孩进行重复双侧睾丸活检评估和冷冻保存。对于冷冻保存,将组织块与冷冻保护剂一起孵育,并采用慢速程序冷冻。

结果

在接受kryptocur治疗的5名男孩中,有2名的平均G/T和成年暗型精原细胞(Ad-S)数量均恢复正常。另一名接受kryptocur治疗的男孩,初始G/T较低且无Ad-S,在冷冻保存时G/T增加且Ad-S数量达到正常。在对照组中,有2名患者的G/T和Ad-S数量仅达到正常较低范围。G/T低于平均0.2的男孩,无论是否接受kryptocur治疗,均未显著改善。

结论

基于文献和目前的结果,我们建议对手术时真正的促性腺激素刺激不足的隐睾症男孩进行辅助LHRH治疗,因为这些患者不育风险高。如果辅助LHRH治疗失败,冷冻保存应作为一种选择。然而,为避免重复活检手术,一些父母可能会在初次双侧睾丸固定术时选择进行活检以进行冷冻保存,前提是他们充分了解该手术可能仅在22%至36%的病例中真正适用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a97f/5996032/4ac0b69aef0d/fendo-09-00299-g001.jpg

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