Present knowledge on the impact of varicoceles on testicular function is largely based on studies of subfertile and infertile men, making it difficult to extrapolate the impact of varicocele on the general population.
Objective
To describe associations between varicocele and testicular function assessed by semen analysis and reproductive hormones in men from the general population.
Design, setting, and participants
A cross-sectional multicentre study of 7035 young men, median age 19 yr, from the general population in six European countries (Denmark, Finland, Germany, Estonia, Latvia, and Lithuania) were investigated from 1996 to 2010.
Outcome measurements and statistical analysis
We analysed results from physical examination, conventional semen variables, and serum reproductive hormones using multivariable regression analyses.
Results and limitations
A total of 1102 (15.7%) had grade 1–3 varicocele. Increasing varicocele grade was associated with poorer semen quality, even in grade 1 varicocele. In grade 3 varicocele, sperm concentration was less than half of that in men with no varicocele. Presence of varicocele was also associated with higher serum levels of follicle-stimulating hormone, lower inhibin B, and higher levels of luteinising hormone; testosterone and free testosterone were not significantly different between men with and without varicocele. This study cannot draw a conclusion on the progressiveness of varicocele or the effect of treatment.
Conclusions
We demonstrated an adverse effect of increasing grade of varicocele on testicular function in men not selected due to fertility status.
Patient summary
The presence and increasing grade of varicocele is adversely associated with semen quality and reproductive hormone levels in young men from the general population.
Introduction
Varicocele is the medical term for dilated, tortuous spermatic veins in the pampiniform plexus. In the adult general population, the prevalence is approximately 15% [1], [2], [3]. It is 35–44% in men with primary infertility and 45–81% in men with secondary infertility [4], [5]. The association between the presence of a varicocele and poorer semen quality is well documented in men presenting to fertility clinics [6] and in small-scale studies of patients not selected on fertility criteria [7], [8]. Several meta-analyses report improvements in semen quality following varicocelectomy in infertile men [9], [10]. However, far from all men with a varicocele are infertile [11].
Varicocele is most commonly observed on the left side, although some men are affected bilaterally. The isolated right-sided varicocele is rare [12]. The right testicular vein drains obliquely into the vena cava, whereas the left drains perpendicularly into the left renal vein, resulting in higher hydrostatic pressure on the left compared with the right side. Also believed to increase left-sided hydrostatic pressure is the so-called nutcracker effect with compression of the left renal vein between the aorta and the superior mesenteric artery [13], [14]. The exact pathophysiology behind the adverse effect of varicocele on semen quality remains uncertain. A number of proposed mechanisms have been examined including scrotal hyperthermia, altered testicular blood flow, increased venous pressure, hypoxia, testicular hormonal dysfunction, accumulation of toxic substances, and catecholamine reflux [13], [14].
Studies comparing reproductive hormones in infertile men with varicoceles with unaffected infertile men have reported conflicting results. Some reported higher follicle-stimulating hormone (FSH) among infertile men with varicoceles compared with controls but no difference in fertile men [15], whereas others detected no difference among infertile men with varicocele compared with controls [16]. Serum inhibin B was lower in men with varicocele compared with controls in some studies [16], [17] but not all [18]. Serum testosterone has been reported lower [16], unchanged [15], or higher in grade 3 varicocele patients compared with grade 1 [19].
Our present knowledge on the potential impact of varicoceles on semen quality and reproductive hormones is largely based on studies of subfertile and infertile men, as well as observations of increased prevalence in groups of men referred to fertility and urology clinics where the cause of infertility might not be limited to the varicocele. Even in cases where varicocele is the only discernible cause of infertility, preselection of infertile patients will include only the severely affected cases. The lack of large-scale population-based studies makes it difficult to extrapolate the impact of the varicocele on reproductive health to the general population. We therefore describe associations between varicocele and hormonal and semen variables in a large number of young men from general populations in Europe who were not selected due to fertility status, semen quality, or presence of varicocele to evaluate the potential impact of the varicocele on testicular function.
Section snippets
Materials and methods
The current study is based on a large cross-sectional investigation of semen quality in unselected young men from the general population, standardised and coordinated between six European countries. The local Science Ethics Committees approved the studies, and participants gave written informed consent before participation. Information about inclusion and assessment procedures were previously described in detail [20], [21]. We offer a very brief overview, with expanded details in Supplement 1.
Descriptions
Table 1 summarises the results from the physical examination and questionnaire. Most of the men were Danish. Age differed very slightly between the four varicocele subgroups, and BMI seemed lower with increasing grade of varicocele, most likely due to a slightly higher height across the varicocele groups. Median ejaculation abstinence was above the requested minimum of 48 h, but in all subgroups of men, some had shorter abstinence time (<11% in all groups; differences between groups were
Discussion
In this large-scale study of 7035 healthy young men from general European populations, the presence of varicocele was associated with poorer semen quality, even in men with the mildest form of varicocele (grade 1). In accordance, the concentrations of the spermatogenesis-related reproductive hormones FSH and inhibin B were associated with the presence of a varicocele. Men with varicocele also had a higher LH concentration, although testosterone and free testosterone levels did not significantly
Conclusions
Our large cross-sectional clinical study of men from the general population showed that semen quality was significantly impaired in men presenting with all grades of varicocele, even at the mildest stage, with the most severe impairment at higher grades.
Varicocele is a condition that seriously affects male fertility. It can cause pathological changes in the testicles and affect their spermatogenesis and endocrine function.
To formulate nomograms to predict sperm improvements after microscopic varicocelectomy.
A retrospective analysis was conducted on varicocele patients who met the research criteria and were enrolled from March 2020 to June 2022. They were divided into a development and a validation cohort in a 2:1 ratio.
Data on preoperative testicular atrophy index, bilateral testicular elastic modulus, testosterone, pre- and postoperative 6-mo total sperm count, sperm concentration, and sperm vitality were collected. An increase of ≥25% is considered a postoperative improvement in sperm parameters. Predictive nomograms were constructed through forward stepwise LR regression, based on independent risk factors filtered by univariate and multivariate logistic regression analyses. Receiver operating characteristic curve analysis, calibration curve, and decision curve analysis were employed to assess the performance of the models.
The areas under the curve of nomograms for predicting the postoperative improvement of total sperm count, sperm concentration, and sperm vitality were 0.915, 0.986, and 0.924 respectively. The nomogram models demonstrated good predictive performance. The single-center sample size was a limitation of this study.
In this study, we developed effective predictive nomogram models for anticipating postoperative improvements in sperm quality among varicocele patients. These models offer a significant value in providing accurate predictions of surgical outcomes. However, it is crucial to conduct further external validation.
In this study, a predictive nomogram model was constructed for assessing the improvement of sperm quality in varicocele patients after surgery. The model offered satisfactory results.
La varicocèle est la plus fréquente cause corrigible d’infertilité masculine. Elle a fait l’objet de recommandations récentes du Comité d’andrologie et de médecine sexuelle (CAMS) de l’Association française d’urologie (AFU). Depuis, la littérature a apporté des éléments supplémentaires. Cette revue réévaluera de manière exhaustive les indications actuelles du traitement des varicocèles, et reviendra sur les questions contemporaines au regard des avancées actuelles.
Réactualisation de la recherche bibliographique effectuée dans le cadre des recommandations du CAMS sur la période entre 2020 et 2023.
La varicocélectomie microchirurgicale sub-inguinale demeure le traitement chirurgical de référence pour les hommes infertiles présentant une varicocèle clinique et des paramètres spermatiques anormaux. Elle offre des taux de récidive inférieurs à 4 %. Elle améliore significativement les taux de naissances vivantes et de grossesse à la fois naturellement et par fécondation in vitro, ainsi que la numération, la mobilité totale et progressive, la morphologie et le taux de fragmentation de l’ADN des spermatozoïdes. Au total, elle modifie la stratégie en aide médicale à la procréation (AMP) dans environ un cas sur deux. Le grade et la bilatéralité de la varicocèle sont prédictifs de l’amélioration des paramètres spermatiques et du taux de grossesse. Il n’est pas recommandé de traiter les varicocèles infracliniques. Les complications sont rares, notamment les hydrocèles (0,5 %), les atrophies testiculaires unilatérales par atteinte artérielle (1/1000), les hématomes, retards de cicatrisation, et douleurs postopératoires. L’embolisation rétrograde est une alternative à la chirurgie.
L’urologue doit chaque fois que possible présenter et discuter avec l’équipe d’AMP et le patient les possibilités de traitement d’une varicocèle dans une approche personnalisée.
Varicocele is the most common correctable cause of male infertility. It was the subject of recent Association française d’urologie (AFU) Comité d’andrologie et de médecine sexuelle (CAMS) recommendations. Since then, the literature has provided additional information. This review will comprehensively reassess current indications for the treatment of varicocele, and revisit contemporary issues in the light of current advances.
Update of the literature search carried out as part of the CAMS recommendations for the period between 2020 and 2023.
Microsurgical sub-inguinal varicocelectomy remains the surgical treatment of choice for infertile men with clinical varicocele and abnormal sperm parameters. It offers recurrence rates of less than 4%. It significantly improves both natural and in vitro fertilization live birth and pregnancy rates, as well as sperm count, total and progressive motility, morphology and DNA fragmentation rates. All in all, it modifies the MPA strategy in around one in two cases. Varicocele grade and bilaterality are predictive of improved sperm parameters and pregnancy rate. Treatment of subclinical varicocele is not recommended. Complications are rare, notably hydroceles (0.5%), unilateral testicular atrophy due to arterial damage (1/1000), hematomas, delayed healing and postoperative pain. Retrograde embolization is an alternative to surgery.
Whenever possible, the urologist should present and discuss treatment options for varicocele with the MPA team and the patient, taking a personalized approach.
The bioactive peptide hormone hepcidin-25 regulates iron levels by inhibiting iron transport to plasma via ferroportin. Hepcidin-25 is synthesized in the liver where the 84 amino acids pro-hepcidin is cleaved into the bioactive hepcidin-25. A patient admitted to the hospital presented with infertility and fatigue.
Genomic DNA was purified from whole blood using the Maxwell 16 system (Promega). MLPA analysis was performed to detect large genomic rearrangements using the SALSA MLPA kit # P347, Hemochromatosis (MRC Holland, Holland). Plasma hepcidin measurements were performed using liquid chromatography/tandem mass spectrometry (LC-MS/MS).
A novel HAMP mutation (homozygous one base deletion in c.215delG, p.Cys72Serfs*?) was detected. The deletion in nucleotide 215 causes a frameshift altering the predicted protein sequence from cysteine13 in mature peptide. Whether this leads to nonsense mediated decay of the mRNA or synthesis of an aberrant peptide in unknown, but bioactive hepcidin-25 was undetectable in plasma.
The patient had massive iron overload with ferritin up to 8360 µg/L. He was anaemic with a Hb at 7.0 mmol/L (11.3 g/dL) and suffered from hypogonadotropic hypogonadism with a total testosterone of 1.2 nmol/l. Continued treatment with venesection and gonadotropins led to reduced fatigue, reduction in iron overload, a normalized Hb and improvement of semen quality.
A novel hepcidin mutation was detected in a patient with massive iron overload, fatigue and hypogonadotropic hypogonadism.
2023, International Journal of Surgery Case Reports
Varicocele is a common condition affecting males of reproductive age and accounting for the most frequent cause of secondary infertility in males.
A young male presented with second infertility and bilateral varicoceles and underwent antegrade angioembolization. He developed testicular ischemia and testicular failure with new onset hypogonadism and cryptozoospermia.
Antegrade embolization is a valid option in patients with varicoceles but has its own unique risks of complications.
