Quantifying Heterogeneity of Testicular Histopathology in Men with Nonobstructive Azoospermia

Abstract

Purpose:We sought to determine if testicular histopathological heterogeneity is associated with sperm retrieval rates (SRRs) in men with nonobstructive azoospermia (NOA) who are undergoing microdissection testicular sperm extraction (mTESE).Materials and Methods:All patients undergoing mTESE by a single, high-volume surgeon at a tertiary infertility referral center between 2010 and 2020 were evaluated. Pathology reports from testis biopsy at the time of mTESE reported by fellowship-trained genitourinary pathologists were reviewed. Testicular heterogeneity was correlated to absolute SRRs. Logistic regression was used to determine if heterogeneity was associated with sperm retrieval.Results:A total of 918 men with mTESE were included. Of these, 391 men (43%) had 1 pathology, 388 men (42%) had 2, 108 (12%) had 3, and 31 (3.4%) had 4. Overall, the most common histopathology was Sertoli-cell only, followed by maturation arrest. The overall SRR was 42% with a clinical intrauterine gestation rate of 30%. Increasing histopathological variety was associated with higher SRRs (p <0.01); a SRR of 33% was observed when one histopathological subtype was present vs 94% with 4 subtypes. Furthermore, men with any foci of spermatogenesis had higher SRRs.Conclusions:In men with NOA, increasing testicular histopathological heterogeneity is correlated with higher SRRs driven by the identification of focal areas of spermatogenesis. This is an important, although predictable, observation. While diagnostic biopsy is not routinely required, these findings emphasize the value of having histology to perhaps predict the chance of sperm retrieval for future mTESE procedures.

A complete dissection of the whole testicular parenchyma is required in most patients with nonobstructive azoospermia to obtain enough good quality testicular spermatozoa for ICSI

“…On the other hand, the probability of retrieving spermatozoa from the testis surface in patients with HS was lower compared to the probability of SSR in patients with HS undergoing cTESE in previous studies (45.6% vs. 73%). Such a finding may be explained due to the high number of patients undergoing bilateral mTESE: among these, most patients showing HS in one testis had discordant histological findings in the contralateral testis (usually SCO or LMA), in agreement with what has been observed in a larger cohort of patients with NOA, in whom up to four distinct histopathological reports were found in the same patient 9 . Since testis histology is not available during surgery, the larger testis is operated first, but testis volume is seldom predictive of spermatogenesis: when no spermatozoa are found in the first testis, the second testis is opened, and in most cases an extensive testicular dissection is performed despite the eventual finding of spermatozoa in the testis surface, to ensure that an adequate number of good quality spermatozoa is available for ICSI and for eventual cryopreservation.…”

“…The probability of retrieving spermatozoa from the testis surface in our patients with SCO was comparable to the SRR commonly found in whom up to four distinct histopathological reports were found in the same patient. 9 Since testis histology is not available during surgery, the larger testis is operated first, but testis volume is seldom predictive of spermatogenesis: when no spermatozoa are found in the first testis, the second testis is opened, and in most cases an extensive testicular dissection is performed despite the eventual finding of spermatozoa in the testis surface, to ensure that an adequate number of good quality spermatozoa is available for ICSI and for eventual cryopreservation. Relevant to this point, it has been brilliantly argued that since that more than a ICSI cycle is often required to obtain a clinical pregnancy in patients with NOA, the number of spermatozoa retrieved should be enough to guarantee the feasibility of more ICSI cycles with cryopreserved spermatozoa.…”

Modern surgical treatment of azoospermia

“…Since men with nonobstructive azoospermia have an overall abnormal pattern of sperm production, it is not surprising that heterogeneity of histology is a favorable finding. In a cohort of 918 men who underwent microTESE at our institution and had testis biopsy performed at the time of surgery, greater heterogeneity of histologic patterns was associated with a higher likelihood of sperm retrieval [21 ▪ ]. Only 33% of men with one histologic pattern had sperm retrieved, compared to 41% of men with two patterns, 64% of men with three patterns, and 94% of men with four patterns.…”

Recombinant gonadotropin therapy to improve spermatogenesis in nonobstructive azoospermic patients – A proof of concept study

“…Hypospermatogenesis and maturation arrest are typical findings in NOA males. In a 2021 study including 918 patients with NOA, testis biopsy specimens taken during micro-TESE showed hypospermatogenesis (either pure or mixed) in 16.6% and maturation arrest (either pure or mixed) in 30.6% of individuals (40).…”