Strategies for infertility treatment in men with azoospermia

Abstract: Introduction: Historically, treatment of severe male infertility has been restricted. With the introduction of intracytoplasmic sperm injection (ICSI), infertile men have been given new hope of achieving genetic fatherhood. Objective: The aim of this study was to investigate the probability of successful sperm recovery, frequency of chromosomal aberrations in azoospermic men and analyze possible predictive factors for successful sperm recovery in men with Klinefelter's syndrome. In addition, the physiological consequences of testicular sperm aspiration (TESA) and recovery of spermatozoa were investigated, as were fertilization/pregnancy rates following TESA in repeated ICSI cycles. Finally, the outcome of resulting pregnancies from ICSI was evaluated, with special regard to sperm origin and quality.Methods: The relationship between sperm recovery following percutaneous epididymal sperm aspiration (PESA), TESA and testicular sperm extraction (TESE), as related to testicular volumes, serum levels of FSH and chromosome analysis was analyzed retrospectively in men with obstructive and non-obstructive azoospermia (NOA). Predictive factors for sperm recovery were investigated utilizing ultrasonography and Doppler flow imaging, by which intratesticular echogenicity and blood flow resistance were evaluated. Additionally, fluorescence in situ hybridization (FISH) of lymphocytes and buccal cells was used to detect possible 47,XXY/46,XY mosaicism in 19 men with non-mosaic Klinefelter's syndrome. Sperm recovery and fertilization/pregnancy rates were analyzed retrospectively in 56 men with obstructive azoospermia and NOA after 3-6 repeated TESA procedures. Physiological consequences were investigated prospectively in 35 azoospermic men following TESA. Serum levels of FSH, testosterone and antisperm antibodies (ASA) were analyzed preoperatively, as well as 3 and 6 months post TESA. Intratesticular texture was compared before and 3 months after TESA. The outcome of the 1293 resulting pregnancies was investigated in 6 subgroups divided according to sperm origin, sperm quality and the use of cryopreservation of pre-embryos.Results: In all men with obstructive azoospermia and 39% of men with NOA, sperm retrieval was successful following the completed diagnostic sperm recovery work-up. An increased frequency of chromosomal aberrations (8%) was seen in patients with NOA. Histopathology seemed to be the best predictor of successful sperm recovery in men with NOA, including men with Klinefelter's syndrome. TESA can be repeated several times in azoospermic men, with the recovery of mature spermatozoa resulting in pregnancies. The time interval between procedures seems to be of little importance. Postoperative hematomas occurred in 6.6% of testes and 11.4% of patients following TESA, with no tendency toward persistence. Hormone profiles were not effected and formation of ASA was not observed subsequent to TESA. Neither sperm origin nor sperm quality had any influence on obstetric outcome after ICSI. Conclusions: Diagnostic sperm recovery and histopathology seem to be the best predictors of successful sperm recovery in subsequent ICSI cycles in patients with azoospermia. No azoospermic men should be denied an infertility work-up based on clinical or laboratory findings. Karyotyping of all men with NOA is recommended before ICSI treatment. TESA seems to be a safe method of sperm retrieval, resulting in minimal physiological consequences. Neither sperm origin nor sperm quality seem to influence the obstetric outcome following ICSI. Multiple births are still the main concern.