Background
Klinefelter syndrome (KS) is the most common sex chromosomal disorder in males. Although present from birth, diagnosis is usually in adulthood when men present with infertility (if KS is diagnosed at all).
Males with KS are infertile due to severe spermatogenesis impairment leading to azoospermia in about 90% of males with 47XXY karyotype and about 75% of mosaic 47XXY/46XY males.
However, testicular sperm extraction, combined with ICSI, allows some men with KS to father children.
Germ cell depletion occurs throughout life in males with KS and it would seem that fertility preservation at the onset of puberty or just after, and before testosterone replacement begins, could maximise the chance of sperm retrieval from ejaculate or from testicular sperm extraction.
Aim
To determine if fertility preservation after the onset of puberty is feasible and acceptable in adolescents with Klinefelter syndrome.
Methods
The study included eight KS adolescents, aged between 15 and 17 years (7 with 47XXY karyotype and 1 with 47 XXY(12)/46XY(6) karyotype), who were referred for counselling about their future fertility to the Centre d’Etude et de Conservation des Oeufs et du Sperme humain at Rouen University Hospital, France, between October 2008 and December 2011.
The patients were first seen with their parents and then separately and asked about their attitudes to fertility preservation after having the possible options explained to them. They were asked to provide a semen sample.
If this was azoospermic, two other semen samples were requested, 3 months apart. If azoospermia was confirmed, a bilateral testicular biopsy was proposed for sperm retrieval and testicular tissue preservation.
Each adolescent met with a 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.
Seminiferous tubules were examined for Sertoli cell maturity, identification of germ cells and lamina propria alteration.
Results
Adolescents with KS 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 and elongated spermatids and spermatocytes I in a second patient.
No biological or hormonal factors were predictive of mature or immature germ cell retrieval.
Conclusion
Spermatozoa can be retrieved in semen samples and in testicular tissue of adolescents with Klinefelter syndrome. However the adolescents need to be involved in the whole process, fully informed of the procedures and possible unsuccessful outcome and the alternatives to fertility preservation for becoming a father.
