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

SUMMARYMicrosurgical testicular sperm extraction (mTESE), combined with intracytoplasmic sperm injection (ICSI) represents a chance for azoospermic men with Klinefelter 0 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.

The Klinefelter syndrome: current management and research challenges

“…(ii) The experience of the surgeon and the biologist is important for the success of TESE. Micro-TESE performed by trained surgeons results on average in higher sperm retrieval rate than open biopsy; and (iii) The age range giving rise to higher chances of sperm retrieval is 15-30 years (Plotton et al, 2015;Rohayem et al, 2015). Conversely, some important issues remain to be investigated properly:…”

“…3 Identification of predictive markers of successful TESE would be helpful and should be developed. Sabine Kliesch emphasized that such multicenter trials would require standardization of the techniques used in the participating centers and a strong collaboration between the involved clinicians and biologists to reconcile currently controversial conclusions from different studies (Plotton et al, 2015;Rohayem et al, 2015).…”

Sperm retrieval rate and pregnancy rate in infertile couples undergoing in-vitro fertilisation and testicular sperm extraction for non-obstructive azoospermia in Hong Kong

“…Previous studies showed that sperms are more likely to be retrieved in younger men with Klinefelter syndrome. 26,27 In our study, the man with nonmosaic Klinefelter syndrome was 42 years old and might have passed the window of opportunity for successful sperm retrieval. The two patients with mosaic Klinefelter syndrome were 34 and 47 years old, respectively.…”

Klinefelter syndrome: fertility considerations and gaps in knowledge

“…Based on current literature, the recommended age range to consider sperm retrieval among individuals with KS is 15-30 years (3,9,10). Medical professionals who care for individuals with KS have a responsibility to become educated on this topic and offer referrals to fertility specialists to (I) provide comprehensive counseling about the current options along with acknowledging their experimental nature; and (II) consider potential ethical implications in each individual case (6,11).…”