Bilateral cryptorchidism: should be systematically explored?

Anne Bergougnoux; Benoit Tessier; Laura Gaspari; Nadege Servant; Aurelie Cazals; Guibal Marie Pierre; Nicolas Kalfa; Françoise Paris

P2-264

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ESPE Abstracts (2024) 98 P2-264

ESPE2024 Poster Category 2 Sex Differentiation, Gonads and Gynaecology, and Sex Endocrinology (24 abstracts)

Bilateral cryptorchidism: should be systematically explored?

Anne Bergougnoux ^1,2 , Benoit Tessier ^3,2 , Laura Gaspari ^4,2 , Nadege Servant ^1,2 , Aurelie Cazals ² , Marie Pierre Guibal ^3,2 , Nicolas Kalfa ^3,2 & Françoise Paris ^4,2,5

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¹Montpellier University, Molecular Genetics, DevGen team, Montpellier, France. ²French Reference Center for abnormalities of Genital Development (DevGen), CHU Lapeyronie, Montpellier University, Montpellier France, Montpellier, France. ³Montpellier University, Department of pediatric urological surgery, Montpellier, France. ⁴Montpellier University, Department of Pediatric Endocrinology, Hospital Arnaud de Villeneuve, Montpellier, France. ⁵INSERM Unit 1203 DEFE, IRMB, Montpellier, France

Background: Currently, 1-4% of newborns have cryptorchidism and 30% of them have bilateral cryptorchidism (BC). BC should rule out 46, XX Disorder of Sexual Development (DSD). In 46, XY patients gonosomal abnormalities, alterations in genes involved in 46, XY DSD or hypogonadotropic hypogonadism may be the cause. Currently, patients with BC undergo early orchiopexy in the first 18 months of life. However, in these patients, BC etiology, pubertal development and fertility are not systematically monitored whereas it is well known that BC is associated with impaired fertility in 25% of cases, despite early orchiopexy.

Objective and hypothesis: At the Reference Center (RC) of genital development from fetal to adult age (DevGen) of Montpellier, our goal is to be more systematic in phenotyping BC patients to better describe the various subgroups of patients. We report on 95 of the 464 BC patients under 18 years of age followed in the Pediatric Endocrine Department whose explorations are complete to date.

Methods: Family history, clinical examination and pubertal status (for the older ones) were reported for all the patients. Hormonal evaluation including basal LH, FHS, T, AMH, Inhibine B, karyotype and genetic study by next generation sequencing (NGS) of genes implicated in DSD were performed for all patients.

Results: Vanishing testis (n = 4) without genetic abnormality, Klinefelter’s syndrome (n = 2), persistent Mullerian syndrome with mullerian ducts discovered during surgery (n = 1) have been identified (7.4%). The last 3 patients are reported in Table1. In addition 1 patient had AR gene variant of uncertain significance but probably responsible for splicing defect (minigene studies in progress) with a notion BC in the maternal family.


Age	Karyotype	Hormonal data				Gene	ACMG
	FSH/LH (IU/L)	T (ng/mL)	AMH (ng/ml)	Inhibine (ng/l)
6ys	48, XXYY	0.6/0.3	< 0.03	108 (N13-167)	119 (N 7-125)
5ys 10 m	47,XXY/46, XY	0.8/0.3	< 0.03	60 (N13-167)	118 (N 7-125)
3 ys	45, XY	0.6/0.1	< 0.03	25 (N 17-193)	15 (N 17-94)	AMHR2 NM_020547.3 Homozygous c.118G>A p.(Gly40Arg)	PS1,PM1, PM2,PP3,PP4 Pathogenic

Conclusion: This study underlines that BC may be due to a genetic defect in a significant number of cases and points out the usefulness of investigating affected children to identify a specific cause. Systematic clinical, hormonal and genetic investigations, combined with the essential pubertal monitoring of these patients (sometimes indicative of more or less complete hypogonadotropic hypogonadism), should enable us to offer them optimal care and improve their fertility in adulthood.