Study question: Is fertility preservation feasible after the onset of puberty in adolescents with Klinefelter syndrome (KS)?
Summary answer: Fertility preservation counseling should be an integral part of the care of XXY adolescents. Frozen ejaculated or testicular spermatozoa and even frozen immature germ cells can give them the potential to conceive their genetic progeny. However, no biological or clinical parameters were predictive of mature or immature germ cell retrieval.
What is known already: KS is the commonest sex chromosome disorder observed in azoospermic infertile males. Testicular sperm extraction success decreases with age and after testosterone therapy. Arguably, spermatozoa should be retrieved from KS males at the onset of puberty and before testosterone therapy to increase the chance of success.
Study design, size, duration: A retrospective study was performed in eight KS adolescents, aged between 15 and 17 years, who were referred for counseling about their future fertility to the center CECOS (Centre d'Etude et de Conservation des Oeufs et du Sperme humain) at Rouen University Hospital between October 2008 and December 2011.
Participants/materials, setting, methods: The patients were first seen with their parents and then separately. It was proposed to them that they should provide a semen sample, if this was azoospermic, two other semen samples spaced by 3 months were collected. If azoospermia was confirmed, a bilateral testicular biopsy was proposed for sperm retrieval and testicular tissue preservation. Each adolescent met the psychologist before undergoing testicular biopsy. Paraffin-embedded testicular tissue was evaluated after staining with hematoxylin-eosin and saffron and immunostaining using vimentin, anti-Müllerian hormone, androgen receptor and MAGE-A4 antibodies. Sertoli cell maturity, germ cell identification and lamina propria alteration were assessed on seminiferous tubules.
Main results and the role of chance: KS adolescents were not deeply concerned about their future fertility and only became involved in the process of fertility preservation after at least three medical consultations. The parents agreed immediately that fertility preservation should be attempted. Seven non-mosaic XXY adolescents presented with azoospermia and one XXY/XY adolescent had oligozoospermia. Increased plasma levels of FSH and LH as well as bilateral testicular hypotrophy were observed in all patients. The XXY/XY adolescent banked four semen samples before testosterone replacement therapy. Two patients refused testicular biopsy. Five patients accepted a bilateral testicular biopsy. Spermatozoa were retrieved in one patient, elongated spermatids and spermatocytes I in a second patient.
Limitations, reasons for caution: The number of patients enrolled in our study was low because the diagnosis of KS is only rarely made before or at the onset of puberty. Most XXY males are diagnosed in adulthood within the context of male infertility.
Wider implications of the findings: Spermatozoa can be retrieved in semen sample and in testicular tissue of adolescent Klinefelter patients. Furthermore, the testis may also harbor spermatogonia and incompletely differentiated germ cells. However, the physician should discuss with the patient and his parents over a period of several months before collecting a semen sample and performing bilateral testicular biopsy. Fertility preservation might best be proposed to adolescent Klinefelter patients just after the onset of puberty when it is possible to collect a semen sample and when the patient is able to consider alternative options to achieve fatherhood and also to accept the failure of spermatozoa or immature germ cell retrieval.
Keywords: adolescent; fertility preservation; klinefelter syndrome; testicular sperm extraction; testicular tissue preservation.