title: Age and markers of Leydig cell function, but not of Sertoli cell function predict the success of sperm retrieval in adolescents and adults with Klinefelter's syndrome.
abstract: Microsurgical testicular sperm extraction (mTESE), combined with intracytoplasmic sperm injection (ICSI) represents a chance for azoospermic men with Klinefelter's syndrome (KS) to father children. The objective of this study was to identify predictive factors for the success of mTESE from adolescents and adults with KS. The clinical data of 50 late pubertal adolescents (13-19 years) and 85 adult patients (20-61 years) with non-mosaic KS, who underwent mTESE, were analysed with respect to factors, potentially predictive of active spermatogenesis; specifically a history of cryptorchidism, age, testicular volumes, serum levels of LH, FSH, testosterone (T) and estradiol at the time of surgery. Inhibin B, AMH and INSL3 were additionally analysed in the adolescents. A younger age and a near-compensated Leydig cell function were associated with higher success of sperm retrieval via mTESE: In adolescents ≥15-19 years, spermatozoa were retrieved in 45%, compared to 31% in adults; in adolescents aged 13-14 years, spermatozoa were collected in only 10%. Adolescents with an LH ≤17.5 U/L, along with a T level ≥7.5 nmol/L had the best success rate (54%), which fell to 44% with higher LH, whereas those with low T (<7.5 nmol/L), irrespective of LH had no sperm retrieval. In adults with T levels above and LH below these thresholds, the success rate was 51%, falling to 19%, if LH was higher. When T was lower than threshold, the rate was 17%. No association between testicular volumes, serum levels of FSH, Inhibin B, AMH, estradiol and mTESE success was found. A history of cryptorchidism was associated with lower retrieval rates. A window of opportunity for an approximate 50% chance to retrieve spermatozoa via mTESE exists for young, late pubertal KS patients between age 15 and young adulthood, when Leydig cell function is at its best. In these cases, referral to a centre of expertise should be considered.
authors.affiliation: Department of Clinical Andrology, Center of Reproductive Medicine and Andrology, University of Muenster, Muenster, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Rohayem
authors.affiliation: Department of Clinical Andrology, Center of Reproductive Medicine and Andrology, University of Muenster, Muenster, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Fricke
authors.affiliation: Department of Clinical Andrology, Center of Reproductive Medicine and Andrology, University of Muenster, Muenster, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Czeloth
authors.affiliation: Center of Reproductive Medicine and Andrology, Institute of Reproductive and Regenerative Biology, University of Muenster, Muenster, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Mallidis
authors.affiliation: Center of Reproductive Medicine and Andrology, Institute of Reproductive and Regenerative Biology, University of Muenster, Muenster, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Wistuba
authors.affiliation: Department of Clinical Andrology, Center of Reproductive Medicine and Andrology, University of Muenster, Muenster, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Krallmann
authors.affiliation: Department of Clinical Andrology, Center of Reproductive Medicine and Andrology, University of Muenster, Muenster, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Zitzmann
authors.affiliation: Department of Clinical Andrology, Center of Reproductive Medicine and Andrology, University of Muenster, Muenster, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Kliesch
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D054304:Anti-Mullerian Hormone / Q000097:blood; D053713:Azoospermia / Q000473:pathology*; D015415:Biomarkers / Q000097:blood; D003456:Cryptorchidism / Q000473:pathology; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007265:Inhibins / Q000097:blood; D007328:Insulin / Q000097:blood; D007713:Klinefelter Syndrome / Q000473:pathology*; D007985:Leydig Cells / Q000502:physiology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D011506:Proteins; D012708:Sertoli Cells / Q000502:physiology*; D020554:Sperm Injections, Intracytoplasmic; D053625:Sperm Retrieval; D013091:Spermatogenesis / Q000502:physiology; D013094:Spermatozoa / Q000502:physiology; D013739:Testosterone / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins; C422364:inhibin B; D013739:Testosterone; D004958:Estradiol; D007265:Inhibins; D054304:Anti-Mullerian Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
keywords: Klinefelter's syndrome; adolescents; azoospermia; fertility; microsurgical testicular sperm extraction