*These authors contributed equally to this study.
Azoospermia owing to testicular disorders is the most severe manifestation of male infertility. The main concern for patients with nonobstructive azoospermia (NOA) is the probability of successful sperm retrieval following testicular sperm extraction (TESE). Therefore, the goal of this study was to determine predictive factors correlated with sperm retrieval.
We assessed the testicular histopathological patterns, the choice of TESE surgical procedure, hormone levels, and chromosomal abnormalities in patients with NOA (n=170). The histopathology specimens were analyzed based on the histopathological patterns of hypospermatogenesis, maturation arrest, and Sertoli cell-only syndrome.
The mean rate of sperm retrieval was 48.8%. The rate of sperm retrieval was significantly higher in the hypospermatogenesis group than in the other groups (
Some parameters, including testicular histopathology patterns, FSH levels, testicular volume, and method of TESE surgery, may be able to predict the chances of obtaining spermatozoa in patients with NOA. However, despite the efficiency of some predictive models, the hope of retrieving any functioning spermatozoa may be sufficient to disregard predictive factors of the success of intracytoplasmic sperm injection in these patients.
Azoospermia originating from testicular disorders, defined as the complete absence of spermatozoa in ejaculation, is the most severe manifestation of male infertility [
Sperm retrieval after testicular sperm extraction (TESE) for infertility treatment by intracytoplasmic sperm injection (ICSI) is the main challenge in patients with nonobstructive azoospermia (NOA). One of the effective parameters that should be considered in the management of patients with NOA undergoing ICSI treatment with TESE or micro-TESE procedures is the ability to predict the rate of spermatozoa recovery in these patients. Understanding these parameters is also important for counseling the patient and his partner [
The seminiferous tubules of patients with NOA display differing degrees of deficient spermatogenesis, including hypospermatogenesis, tubular sclerosis, Sertoli cell-only syndrome (SCOS), and maturation arrest (MA) [
Patients with NOA have an increased risk of chromosomal abnormalities [
In addition, other suggested predictors of a successful or unsuccessful TESE operation include the levels of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin, and testis size [
The present study aimed to identify valuable factors for predicting and managing TESE outcomes in patients with NOA. Based on our study, this information would be useful in counseling couples about the rate of successful sperm retrieval after an invasive surgical procedure such as TESE in azoospermic men, or even the chances of success for oocyte pick-up in their partners.
A retrospective cohort study was performed at the Shahid Beheshti Hospital in Isfahan, Iran. A total of 170 patients with NOA who were referred for fertility treatment from 2013 to 2016 were included in this study. Informed consent was obtained from all patients before inclusion in the study. All patients were confirmed to have NOA using at least two semen analyses according to World Health Organization guidelines [
For the hormonal assay, serum FSH, LH, testosterone, and prolactin concentrations were measured by an electrochemical luminescence assay in the morning. The reference ranges were considered to be 1.5 to 12.45 mIU/mL for FSH, 1.7 to 8.6 mIU/mL for LH, 2.84 to 8 ng/mL for testosterone, and 1.8 to 20.3 ng/mL for prolactin. Testicular volume was measured by physical examination using an orchidometer. A volume of <15 mL per testis was considered to indicate small testicular size. The mean body mass index of the patients was 25.2±3.9 kg/m2 (range, 16–42 kg/m2) and the couples had a median duration of infertility of 3.5 years.
The TESE and micro-TESE procedures were performed according to the standard protocols described by Schlegel for micro-TESE [
Karyotyping was performed according to standard methods on phytohemagglutinin-stimulated peripheral lymphocyte cultures [
Summary measures for the factors, according to sperm retrieval and pathology, are presented in
All analyses were carried out with SPSS ver. 16.0 (SPSS Inc., Chicago, IL, USA) and the significance level was considered to be
The mean age of all patients was 32.56±5.53 years. Based on the histopathological findings, the 170 patients were classified into three groups: 74 (43.5%) cases of SCOS, 46 (27.1%) cases of MA, and 50 (29.4%) cases of hypospermatogenesis. The levels of FSH were significantly in excess of the normal ranges in the SCOS and MA groups when compared to the hypospermatogenesis group (MA: OR, 1.146,
Our results showed that the overall mean rate of sperm retrieval was 48.8%. These rates were 21.6% in the SCOS group, 43.5% in the MA group, and 94% in the hypospermatogenesis group. Based on the multinomial logistic regression model, the rates of unsuccessful sperm retrieval were significantly higher in the MA and SCOS groups than in the hypospermatogenesis group (
In this study, we assessed the effects of the histopathological pattern, age, the choice of TESE surgical procedure (conventional TESE or micro-TESE), hormones, testis volume, and karyotyping on sperm retrieval in patients with NOA.
In infertility consultations for patients with NOA, it is essential to provide information on the chances of sperm being retrieved. A failed TESE procedure on ovum pick-up day can have irreparable emotional effects and financial implications for both members of the couple [
Consistent with previous studies, in our study, SCOS was the most common histopathological pattern diagnosed (43.5% of patients with NOA) [
An elevated level of FSH was observed in all three histopathological groups. This increase in the observed concentrations of the hormone was related to the spermatogenetic defect and decrease in total number of testicular germ cells in patients with NOA. In accordance with the finding of Aydin et al. [
In our study, the mean rate of sperm retrieval was 48.8%, and this rate was significantly higher in the hypospermatogenesis group than in the SCOS and MA groups (94% vs. 21.6% and 43.5%, respectively). In accordance with earlier studies [
Based on our findings, high levels of FSH and small testicular volume were significantly associated with lower chances of successful sperm retrieval. These factors appear to be useful for predicting the success of TESE. These findings may be in part consistent with the study of Cissen et al. [
Our results showed better outcomes (higher rates of sperm retrieval) from the micro-TESE procedure than from conventional TESE. Currently, there is a trend toward using micro-TESE procedures due to the low complication rates, better approach to the problem of focal spermatogenesis observed in patients with NOA, and higher chance of sperm retrieval, particularly for patients with the histological pattern of SCOS [
Although no association was observed between chromosomal abnormalities and the histopathological pattern or sperm retrieval, it seems that the detection of chromosome abnormalities aided the assessment of the potential rate of sperm retrieval in patients with NOA. However, in this research, evaluation of chromosomal abnormalities was performed by karyotype analysis, which detects large-scale genetic changes and does not detect submicroscopic alterations in the DNA sequence. Therefore, following the detection of a normal karyotype, it would be wise to perform complementary genetic tests in order to assess the critical genes involved in the process of spermatogenesis. The other reason for our observations may be related to the small number of patients.
Thus far, three studies have assessed the predictive factors of achieving pregnancy after TESE [
In conclusion, valuable factors for predicting successful sperm retrieval during TESE, including testicular histopathology patterns, FSH levels, testicular volume, and the use of micro-TESE, were examined in our study, allowing an estimation of the chances of obtaining spermatozoa in patients with NOA. Accordingly, the combination and simultaneous interpretation of the factors studied here, such as histopathological patterns, hormone levels, and karyotyping, help provide an accurate diagnosis of testicular failure and subsequently help the clinician to pursue the appropriate methods of treatment for these patients. In addition, it should be considered that the hope of retrieving any spermatozoa at all might be a sufficient cause for attempting ICSI in these patients, regardless of the predictive factors.
The study was supported by Shahid Beheshti Infertility Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Values are presented as mean±standard deviation or number (%).
MA, maturation arrest; SCOS, Sertoli cell-only syndrome; FSH, follicle-stimulating hormone; LH, luteinizing hormone.
SE, standard error; OR, odds ratio; CI, confidence interval; MA, maturation arrest; FSH, follicle-stimulating hormone; LH, luteinizing hormone; SCOS, Sertoli cell-only syndrome.
a)The reference category was hypospermatogenesis.
Significant at *
SE, standard error; OR, odds ratio; CI, confidence interval; FSH, follicle-stimulating hormone; LH, luteinizing hormone; TESE, testicular sperm extraction.
Significant at **