A risk prediction model of sperm retrieval failure with fine needle aspiration in males with non-obstructive azoospermia

Abstract

STUDY QUESTION Can we predict the risk of sperm retrieval failure among men with non-obstructive azoospermia (NOA) before they undergo fine needle aspiration (FNA)? SUMMARY ANSWER Our model, which includes FSH level, age and testicular volume as variables, can predict the risk of sperm retrieval failure with FNA. WHAT IS KNOWN ALREADY Combined with ICSI, testicular sperm aspiration (TESA) can enable patients with NOA to have their own genetic offspring. Nearly all reproductive medicine centres in China have applied FNA, but approximately half of patients with NOA experience testicular sperm retrieval failure. Nevertheless, the models developed to predict the likelihood of obtaining spermatozoa with testicular sperm extraction (TESE) cannot accurately predict sperm retrieval, and few of these models have been sufficiently validated. STUDY DESIGN, SIZE, DURATION This study involved three cohorts including 597 men with NOA. From 1 January 2015 to 31 July 2017, a retrospective cohort of 317 males with NOA who underwent FNA procedures at a university affiliated hospital were included to build a risk prediction model of sperm retrieval failure with FNA. Then, from 25 October 2017 to 31 March 2018, two prospective cohorts of 61 and 219 males with NOA from the same hospital and one other reproductive specialist hospital respectively, were recruited to validate the risk prediction model. PARTICIPANTS/MATERIALS, SETTING, METHODS All men with NOA undergoing their first TESE procedure as part of a fertility treatment were included. The primary end-point was the presence of one or more spermatozoa (regardless of their motility) obtained with FNA. A binary multivariable logistic model was built to predict the risk of sperm retrieval failure after TESA using the dataset from the retrospective cohort. A cut-off value for risk was calculated with receiver operating characteristic (ROC) curve analysis. Two validation sets from the prospective cohort were used to validate the risk prediction model by measures including prediction accuracy and the true positive rate. MAIN RESULTS AND THE ROLE OF CHANCE A total of 327 (54.8%) males with NOA experienced sperm retrieval failure with FNA. FSH level, age and testicular volume were included in the prediction model for sperm retrieval failure risk. The model had an AUC of 82.3% (95% CI: 77.6-87.1%) and a cut-off value of 64.61% with a sensitivity of 0.677 and specificity of 0.863 for predicted risk. The predictive accuracies were 85.25 and 83.56% in the external validation sets from two centres. Specifically, 85.71 and 85.15% of NOA patients from two centres that experienced sperm retrieval failure were correctly identified using our model. LIMITATIONS, REASONS FOR CAUTION A small proportion of males with NOA in whom sperm were successfully retrieved with FNA were misclassified; therefore, TESA techniques with higher sperm retrieval rates may be attempted in patients with high predicted risks of sperm retrieval failure rather than terminating the efforts to produce a genetic offspring. In addition, the ability to achieve a live birth using sperm retrieved with FNA was not tested in this study. WIDER IMPLICATIONS OF THE FINDINGS We would recommend the use of micro-TESE for men with NOA and a high predicted risk of FNA failure. STUDY FUNDING/COMPETING INTEREST(S) This study was partly supported by National Key R&D Program of China (No. 2017YFC0907305), the National Natural Science Foundation of China (No.81803332), Sichuan Science & Technology Program (No. 2018SZ0144, 2016SZ0066, 2018SZ0284 and 2018FZ0043), Chengdu Science & Technology Bureau (No. 2018-YF05-01265-SN), Postdoctoral Research foundation of Sichuan University (No. 2018SCU12012) and West China Second University Hospital of Sichuan University (No. kx027). There are no competing interests related to this study. TRIAL REGISTRATION NUMBER Not applicable.