Prediction of semen analysis parameters improvement after varicocelectomy using 1 H NMR-based metabonomics assays.

Varicocele is the most common correctable cause of male infertility, however, predicting varicocelectomy outcomes is difficult. "Omics" techniques have been increasingly used to develop new diagnostic and prognostics tools for several male infertility causes, and could be applied to study varicocele.

To create metabolomics models capable of segregating men who improved semen analysis (SA) parameters or achieved natural pregnancy after microsurgical varicocelectomy (MV) from those who did not, using Hydrogen-1 nuclear magnetic resonance (1 H NMR) spectra of seminal plasma of pre-operative samples.

We recruited 29 infertile men with palpable varicocele. 1 H NMR spectra of seminal plasma were obtained from pre-operative samples and used to create metabonomics models. Improvement was defined as an increase in the total motile progressive sperm count (TMC) of the post-operative SA when compared to the baseline, and pregnancy was assessed during 24 months after MV.

Using Linear Discriminant Analysis (LDA), we created a model that discriminated the men who improved SA from those who did not with accuracy of 93.1%. Another model segregated men who achieved natural pregnancy from men who did not. We identified 7 metabolites that were important for group segregation: caprylate, isoleucine, N-acetyltyrosine, carnitine, N-acetylcarnitine, creatine and threonine.

We described the use of metabonomics model to predict with high accuracy the outcomes of MV in infertile men with varicocele. The most important metabolites for groups segregation are involved in energy metabolism and oxidative stress response, highlighting the pivotal role of these mechanisms in the pathophysiology of varicocele.

1 H NMR spectroscopy of seminal plasma can be used in conjunction with multivariate statistical tools to create metabonomics models useful segregate men with varicocele based on the reproductive outcomes of MV. These models may help counseling infertile men with varicocele regarding their prognosis after surgery. This article is protected by copyright. All rights reserved.

Andrology. 2022 Aug 26 [Epub ahead of print]

Filipe Tenorio Lira Neto, Ronmilson Alves Marques, Alexandre de Freitas Cavalcanti Filho, João Eduardo Freire da Fonte, Salvador Vilar Correia Lima, Ricardo Oliveira Silva

Andros Recife, Recife, Brazil. Department of Urology, Instituto de Medicina Integral Prof. Fernando Figueira, Recife, Brazil. Departamento de Cirurgia, Universidade Federal de Pernambuco, Recife, Brazil., Department of Fundamental Chemistry, Universidade Federal de Pernambuco, Recife, Brazil., Instituto de Medicina Integral Prof. Fernando Figueira, Recife, Brazil., Department of Radiology, Real Hospital de Beneficiência Portuguesa, Recife, Brazil., Department of Surgery, Universidade Federal de Pernambuco, Recife, Brazil.