Genetics: Testicular sperm recovery in nine 47,XXY Klinefelter patients

Abstract

Klinefelter's syndrome is generally characterized by hypergonadotrophic hypogonadism and azoospermia. The clinical features, however, are variable, and occasionally severe oligozoospermia may be present. Usually in these cases a 46,XY/47,XXY mosaic karyotype is involved. However, focal spermatogenesis and severe oligozoospermia have been reported in 47,XXY individuals too. In the present study we investigated whether testicular spermatozoa can be recovered in 47,XXY patients with a view to intracytoplasmic sperm injection (ICSI). In four out of nine apparently non-mosaic 47,XXY patients, spermatozoa were recovered from the wet preparations of testicular tissue and ICSI was performed in three couples. In one patient in whom spermatozoa were successfully recovered and used for ICSI, no spermatozoa were retrieved at a second trial. Although these results show that in some 47,XXY individuals testicular spermatozoa can be successfully recovered and even used for ICSI, at present this approach should be considered experimental. There may indeed be some concern about the chromosomal normality of the embryos generated through this infertility treatment. Patients with Klinefelter's syndrome should therefore be counselled about the complexity of this treatment, which involves multiple testicular biopsies from hypogonadal testes, ICSI and preimplantation diagnosis by fluorescence-in-situ hybridization.

Male infertility: Pathogenesis and clinical diagnosis

“…However, Testicular Sperm Extraction (TESE) and especially microsurgical TESE (micro-TESE) followed by ICSI with an average of 30-50% of testicular sperm recovery rate may allow Klinefelter patients to generate their own genetic children. [43][44][45][46][47] Moreover spermatozoa can even be found in the ejaculate of mainly mosaic patients or in non mosaic but young patients, 43 indicating the potential importance of an early diagnosis which would allow a preventive cryopreservation of ejaculated spermatozoa to preserve fertility. The genetic integrity of gametes has been questioned by FISH studies (for review see Martin RH 48 and references therein) and a study based on ICSI combined with PGD reporting a significant fall in the rate of normal embryos for couples with Klinefelter syndrome in respect to controls (54% versus 77,2%).…”

Male factor infertility and ART

“…67 Lastly, in adult azoospermic 47,XXY Klinefelter patients, spermatozoa can be recovered for ICSI. 68,69 Apart from a multiple biopsy approach, the most important factor to improve sperm recovery from testicular specimens is the microscopic assessment of the wet preparation and the concomitant application of erythrocyte-lysing buffer and/or enzymatic digestion. 70,71 In men with NOA, including 47,XXY males, there is controversy on the timing of TESE relative to the cycle of ICSI.…”

Ejaculated spermatozoa in non‐mosaic Klinefelter’s syndrome

“…This couple desired ICSI using testicular spermatozoa for the next trial because a series of semen analyses showed complete azoospermia after the third trial. Testicular sperm extraction (TESE) from the left testis was performed as previously described 6 and many immotile and six motile spermatozoa were retrieved. Ovulation induction of the female partner was performed via the routine long protocol and 14 oocytes were collected.…”

“…However, several studies have reported patients with non-mosaic Klinefelter karyotype showing focal spermatogenesis and severe oligozoospermia 2,3 in whom fatherhood results following spontaneous pregnancies. 4,5 Recently, testicular spermatozoa have been recovered at high rates 6 and intracytoplasmic sperm injection (ICSI) has been used in such cases. A high fertilization and embryo transfer rate has been reported 7 but very few cases result in successful birth.…”