Imaging in Male Infertility.

Infertility is defined as inability to conceive despite regular unprotected sexual intercourse for greater than 1 year. Conditions involving the male partner accounts for the infertility in approximately 50% of cases. The goals of imaging in male infertility are to detect treatable/ reversible causes, imaging for sperm retrieval from testis or epididymis for assisted reproductive techniques like in vitro fertilization or intracytoplasmic sperm injection and to provide appropriate genetic counselling for prevention of occurrence of disease in future offspring. The purpose of this article is to describe imaging features in various causes of male infertility to acquaint radiologists with various imaging appearances of causes of male infertility to avoid missing these pathologies.

Intense venous reflux, quantified by a new software to analyze presurgical ultrasound, is associated with unfavorable outcomes of microsurgical varicocelectomy.

The hemodynamic characteristics of venous reflux are associated with infertility in patients with varicocele; however, an effective method for quantifying the structural distribution of the reflux is lacking. This study aimed to predict surgical outcomes using a new software for venous reflux quantification. This was a retrospective cohort study of a consecutive series of 105 patients (age range: 22-44 years) between July 2017 and September 2019. Venous reflux of the varicocele was obtained using the Valsalva maneuver during scrotal Doppler ultrasonography before microsurgical varicocelectomy. Using this software, the colored reflux signals were segmented, and the gray scale of the color pixels representing the reflux velocity was comprehensively quantified into the mean reflux velocity of the green layer (MRVG) and the reflux velocity standard deviation of the green layer (RVSDG). Spontaneous pregnancy and changes from baseline in the semen parameters were assessed during a 12-month follow-up period. Data were analyzed using logistic regression analysis. An association of the high MRVG group with impaired progressive motility (odds ratio [OR] = 2.868, 95% confidence interval [CI]: 1.133-7.265) and impaired sperm concentration (OR = 2.943, 95% CI: 1.196-7.239) was found during multivariate analysis. High MRVG (OR = 2.680, 95% CI: 1.086-6.614) and high RVSDG (OR = 2.508, 95% CI: 1.030-6.111) were found to be independent predictors of failure to achieve pregnancy following microsurgical repair. In summary, intense venous reflux is an independent predictor of impaired progressive motility, sperm concentration, and pregnancy outcomes after microsurgical varicocelectomy.

Dynamic contrast-enhanced MRI in the assessment of testicular perfusion in infertile men with clinical varicocele.

BACKGROUND: Varicocele represents the most common correctable cause of male infertility. The presence of non-invasive imaging parameters providing evidence as to which patients with varicocele are at risk for infertility would be important. PURPOSE: To explore the role of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) using semi-quantitative parameters in the assessment of testicular perfusion in infertile men with clinical varicocele. MATERIAL AND METHODS: The study cohort included 11 infertile men with clinical varicocele and six controls, with prior paternity. Subtraction DCE-MRI was performed after gadolinium administration, using a three-dimensional fast field-echo sequence. Time-signal intensity curves were created and semi-quantitative parameters were calculated. The independent samples t-test was used to compare basic T1 perfusion parameters between infertile testes with clinical varicocele and normal testes. Logistic regression analysis was performed to assess the most significant predictor of the diagnosis of clinical varicocele. RESULTS: Both testes with clinical varicocele and normal testes enhanced moderately and homogeneously, with a linear increase of enhancement throughout the examination. Higher mean values of maximum enhancement (P = 0.026), maximum relative enhancement (P = 0.024), and wash-in rate (P = 0.013) were detected in the testes of infertile men with clinical varicocele, compared to the normal population. The wash-in rate proved the most significant predictor of the diagnosis of clinical varicocele (P = 0.013). CONCLUSION: DCE-MRI may provide a valuable insight into the testicular perfusion of infertile men with clinical varicocele. The wash-in rate proved a strong and independent predictor of the diagnosis of clinical varicocele.

Doppler Ultrasonography - An Important Tool in Managing Patients With Varicocele and Secondary Infertility.

BACKGROUND/AIM: Doppler ultrasound was successfully implemented as part of the diagnostic plan of medical emergencies in scrotal pathology. This study aimed to investigate whether it could play an important role in managing not only varicocele, but patients with secondary infertility as well. PATIENTS AND METHODS: The current study included 135 patients with varicocele and infertility. Surgery was performed in 18 cases with painful varicocele, 15 cases with testicular hypotrophy, and 48 cases with infertility. RESULTS: Among cases with infertility who underwent surgery, aged between 19 and 36 years old, 80% showed a significant improvement in the spermogram after curing the varicocele. In patients over 36 years of age, only 42% had some improvement in the spermogram after surgery. In addition, after surgery, antispermatic antibodies showed a significant decrease in all patients. CONCLUSION: Varicocele and secondary infertility are a well-known pathology. While the role of Doppler ultrasonography is established in varicocele diagnosis, we found an important pool of patients with secondary infertility and asymptomatic varicocele that would not have been diagnosed in the absence of Doppler ultrasound investigations. Since the best results in fertility were observed in patients younger than 36 years of age, we reiterate the importance of Doppler ultrasonography in addressing infertility.

The European Academy of Andrology (EAA) ultrasound study on healthy, fertile men: An overview on male genital tract ultrasound reference ranges.

BACKGROUND: So far, male genital tract color-Doppler ultrasound (MGT-CDUS) was not standardized. Recently, the European Academy of Andrology (EAA) published the results of a multicenter study assessing the CDUS characteristics of healthy-fertile men (HFM) to obtain normative parameters. OBJECTIVES: To report the EAA US study (i) standard operating procedures (SOPs) for assessing MGT-CDUS, (ii) main MGT-CDUS normative parameters, and (iii) compare the EAA and previously published "normal" CDUS values. METHODS: A cohort of 248 HFM (35.3 ± 5.9 years) was studied, evaluating MGT-CDUS before and after ejaculation following SOPs. RESULTS: SOPs for MGT-CDUS assessment are summarized here. All subjects underwent scrotal CDUS and 188 men underwent transrectal ultrasound before and after ejaculation. The main CDUS reference ranges and characteristics of the HFM-MGT are reported here. The mean testicular volume was ∼17 mL. The lower limit for right and left testis was 12 and 11 mL, defining testicular hypotrophy. The upper limit for epididymal head, body, tail, and vas deferens was 11.5, 5, 6, and 4.5 mm, respectively. Testicular and epididymal arterial reference ranges are reported. The EAA varicocoele classification is reported. CDUS-varicocoele was detected in ∼37% of men. Prostate mean volume was ∼25 mL, while lower and upper limits were 15 and 35 mL, defining hypotrophy and enlargement, respectively. Prostate arterial reference ranges are reported. Prostate calcifications and inhomogeneity were frequent; midline prostatic cysts were rare and small. Ejaculatory duct abnormalities were absent. The upper limit for periprostatic venous plexus was 4.5 mm. Lower and upper limits of seminal vesicles (SV) anterior-posterior diameter were 6 and 16 mm, defining hypotrophy or dilation, respectively. Seminal vesicle volume and ejection fraction reference ranges are reported. SV-US abnormalities were rare. Deferential ampullas upper limit was 6 mm. A discussion on the EAA and previously published "normal" CDUS values is reported here. CONCLUSIONS: The EAA findings will help in reproductive and general male health management.

Is it important to measure the internal spermatic vein diameter after varicocelectomy? A self-controlled trial.

To analyse spermatic vein parameters and post-varicocelectomy diagnostic ultrasound methods by comparing pre- and post-operative ultrasound parameters and semen quality in patients undergoing varicocelectomy. Ultrasound and semen analyses were performed within 1 week before surgery and 3 months after surgery in 125 patients who underwent varicocelectomy for infertility. Patients were divided into three groups according to the post-operative internal diameter of the spermatic vein and reflux: recovery, dilatation, and reflux. Changes in semen quality before and after surgery were compared between groups. Sperm concentration, motility, and morphology were significantly improved (p < 0.05); however, semen volume did not improve (p > 0.05) in patients in the recovery and dilatation groups compared to those in patients before surgery. Sperm concentration, motility, and semen volume did not improve in patients in the reflux group compared with those in patients before surgery (p > 0.05). Logistic regression analysis revealed that the internal diameter of the spermatic vein and reflux duration were risk factors for post-operative spermatic vein dilatation without reflux. Ultrasonography after varicocelectomy should primarily be used to observe reflux, and should not be used as a diagnostic criterion for varicocele based on the internal diameter of the spermatic vein alone.

Preliminary study of virtual touch tissue imaging quantification in diffuse testicular diseases of male infertility.

Objective To explore the preliminary application method and diagnostic value of virtual touch tissue imaging quantification (VTIQ) in diffuse testicular diseases of male infertility. A total of 70 male examiners in our hospital from June 2019 to March 2020 were selected as the research objects. According to whether the subjects are sick (testicular microlithiasis, varicocele), all subjects are divided into three groups: normal group, testicular microlithiasis group, and varicocele group. Whether there is a difference between the groups, and analyze whether there is a correlation between the index reflecting the quality of the semen and the testicular shear wave velocity. The measurement of different positions in the testis will affect the magnitude of the shear wave velocity (P < 0.05). The shear wave velocities of the testes of different diseases are obviously different from the normal side. At the same time, postural changes will have a certain impact on the shear wave velocities of both testes (all P < 0.05). There is a certain correlation between the testicular shear wave velocity and the conventional semen quality index (total sperm motility (P < 0.05)) of the subjects. Acoustic palpation tissue imaging quantitative technology can be applied to the diagnosis of male testes and testicular-related diseases (especially diffuse testicular diseases), and is more suitable for male infertility, which can provide clinical diagnosis and treatment options certain imaging basis.

Sonography in male infertility: a useful yet underutilized diagnostic tool.

PURPOSE: To assess the utility of comprehensive sonographic examination including scrotal sonography, Testicular Doppler and Transrectal Ultrasound (TRUS) to evaluate the male reproductive system and differentiate between obstructive (OG) and non-obstructive (NOG) causes of azoospermia. METHODS: 30 infertile men with azoospermia and 30 control subjects with normospermia underwent sonographic evaluation. FNAC/biopsy findings were used for assigning a final diagnosis of obstructive or non-obstructive azoospermia. Qualitative and quantitative imaging parameters were retrospectively compared between the groups using Chi-square/Fisher's exact test and unpaired t-test, respectively. P < 0.05 was considered significant. RESULTS: Ectasia of rete testis/epididymal tubules, altered epididymal echogenicity, dilated terminal vas deferens were significantly more common in OG while inhomogeneous testicular echo-texture and reduced testicular vascularity were more common in NOG (P < 0.05). Testicular volume and epididymal head size were significantly higher in OG than in NOG and controls (18.2 ml/10 mm Vs 8.2 ml/7.2 mm and 13.4 ml/8.8 mm respectively; P < 0.05); while Resistive Index (RI) of intra-testicular vessels was higher in NOG as compared to OG and controls (0.65 vs 0.54 and 0.52 respectively; P < 0.05). On ROC curve analysis, cut-off values of testicular volume (AUC: 0.939; P < 0.001), epididymal head size (AUC: 0.772; P = 0.001) and testicular RI (AUC: 0.761; P = 0.001) to differentiate between the groups were 12.1 ml (sensitivity-94.4%; specificity-83.3%), 9 mm (sensitivity-66.7%; specificity-71%) and 0.62 (sensitivity-62%; specificity-100%) respectively. CONCLUSION: Comprehensive sonographic evaluation can be used to differentiate obstructive from non-obstructive infertility and should be routinely incorporated in the diagnostic workup of infertile men with azoospermia.

Thyroid disorders and pathospermia in the ART clinic patients.

OBJECTIVE: Over the past decade, a decrease in the semen quality in men of reproductive age, along with an increase in the incidence of thyroid diseases among young patients have been clearly noticed. The study was designed to determine various forms of pathospermia in the ART clinic patients with thyroid disorders. MATERIALS AND METHODS: 168 men of reproductive age in infertile marriage were examined. Men with male infertility factor associated with erectile dysfunction and normospermia (9 patients, 5.3%) were excluded. The study included 159 men and the patients were divided into three groups: the 1st study group consisted of men with non-obstructive azoospermia - 11 men (6.9%); the 2nd study group included men with other forms of pathospermia - 38 men (23.9%) and the control group consisted of men in infertile marriage with normospermia - 110 men (69.2%). All patients had anthropometric measurements, laboratory tests, thyroid and testicular ultrasonography. Spermogram was analyzed in accordance with the WHO classification, 5th revision, 2010. RESULTS: Among all examined men with pathospermia (n = 49 patients), 51.02% had various thyroid disorders, while it was firstly verified in 34.7% men. In 45.5% patients with non-obstructive azoospermia, previously undiagnosed nodular goiter with normal values of thyroid-stimulating hormone and free thyroxine were found, and a significant correlation between nodular goiter and the presence of azoospermia was revealed: r = 0.610, p = .01. CONCLUSION.: Men with various forms of pathospermia and patients of the ART clinic had higher risks of thyroid disorders than in general population that could possibly affect fertility. Patients of the ART clinic with non-obstructive azoospermia are at risk for nodular thyroid disorders, even with normal values of thyroid function tests, and require thyroid ultrasonography.

Peak retrograde flow a potential objective management tool to identify young adults with varicocele 'at risk' for a high sperm DNA fragmentation.

INTRODUCTION: Determining which patients are negatively affected by varicocele would enable clinicians to better select those men who would benefit most from surgery. Since conventional semen parameters, have been limited in their ability to evaluate the negative effects of varicocele on fertility, specialized laboratory tests have emerged. OBJECTIVE: To identify clinical and ultrasound parameters (including PRF) which would negatively influence standard and functional semen variables in young adults with a varicocele. DESIGN: Prospective, cross-sectional observational study. SETTING: Antwerp University Hospital, Belgium. PATIENT(S): Young volunteers between 16 and 26 years, Tanner 5, were recruited. INTERVENTION(S): Every participant had a scrotal ultrasound to calculate testicular volumes. If a varicocele was present, the grade, vein diameter, peak retrograde flow (PRF) in supine position and spontaneous reflux in standing position were measured. All participants provided a semen sample. Standard semen parameters were analyzed and sperm DNA fragmentation. MAIN OUTCOME MEASURE(S): Of all clinical and ultrasound parameters tested, PRF was an objective tool identifying young adults with a varicocele. PRF was highlighted by the prevalence of SDF, both in the total and vital fractions of the spermatozoa, providing opportunities to manage such 'at-risk' adolescents/young adults. RESULT(S): Total SDF was significantly increased in grade 3 varicocele compared to grade 1 and 2 but no significant difference with vital SDF or standard descriptive semen parameters was seen. Total and vital SDF on the other hand were significantly increased when PRF was above 38.4 cm/s. Standard semen analysis showed no difference with PRF as an independent predictor. Testicular atrophy index, varicocele vein diameter and spontaneous reflux revealed no significant differences in both the descriptive and functional semen variables. DISCUSSION: Descriptive semen parameters showed no significant difference between the non-varicocele controls and the varicocele group with low and high PRF. Increased PRF negatively influenced sperm quality via increased DNA fragmentation both in the total as in the vital fractions of the semen. CONCLUSION(S): Of all clinical and ultrasound parameters tested, PRF was an objective non-invasive tool to identify varicocele patients at risk for a high SDF.

Multistage Optimization Using a Modified Gaussian Mixture Model in Sperm Motility Tracking.

Infertility is a condition whereby pregnancy does not occur despite having unprotected sexual intercourse for at least one year. The main reason could originate from either the male or the female, and sometimes, both contribute to the fertility disorder. For the male, sperm disorder was found to be the most common reason for infertility. In this paper, we proposed male infertility analysis based on automated sperm motility tracking. The proposed method worked in multistages, where the first stage focused on the sperm detection process using an improved Gaussian Mixture Model. A new optimization protocol was proposed to accurately detect the motile sperms prior to the sperm tracking process. Since the optimization protocol was imposed in the proposed system, the sperm tracking and velocity estimation processes are improved. The proposed method attained the highest average accuracy, sensitivity, and specificity of 92.3%, 96.3%, and 72.4%, respectively, when tested on 10 different samples. Our proposed method depicted better sperm detection quality when qualitatively observed as compared to other state-of-the-art techniques.

Central role of ultrasound in the evaluation of testicular function and genital tract obstruction in infertile males.

BACKGROUND: Scrotal color Doppler ultrasonography and transrectal ultrasonography provide crucial information about the clinical status of testes and male accessory glands. OBJECTIVE: To analyze the impact of ultrasound in the evaluation of infertile males. MATERIALS AND METHODS: A total of 1120 records from infertile men were retrospectively evaluated (from January 2016 up to June 2020). Data on physical examination, semen analysis, sperm culture, scrotal color Doppler ultrasonography and transrectal ultrasonography, as well as sex hormones were analyzed. Among them, 238 reports from oligozoospermic/azoospermic infertile patients (P) fulfilling the inclusion criteria were considered for data analysis. Patients were subdivided into two groups according to follicle-stimulating hormone (FSH) values (Pa with FSH < 8 U/L and Pb with FSH ≥ 8 U/L). Sixty-three fertile volunteers (mean ± SD years) were enrolled as controls (C). RESULTS: A higher prevalence of ultrasound abnormalities was recorded in P compared to C. Pb group had significantly lower bitesticular volume compared to Pa and C. Pa had a higher prevalence of transrectal ultrasonography abnormalities than Pb (69.9% vs. 38.4%), whereas Pb had a higher prevalence of abnormalities at scrotal color Doppler ultrasonography (60.0% vs. 28.3%, both p < 0.01). Bitesticular volume was inversely proportional to the number of altered seminal parameters and able to predict gonadotropin levels. A bitesticular volume <17 cc was associated with a higher risk of azoospermia (odds ratio = 1.799). Intratesticular vascularization was inversely correlated with gonadotropin levels and directly correlated with sperm count. A higher prevalence of prostate and seminal vesicle alterations was detected in patients and in Pa group, when compared with Pb group. DISCUSSION AND CONCLUSION: Ultrasound abnormalities are correlated with seminal parameters and may guide the clinician in the diagnostic workflow of male infertility, suggesting spermatogenesis impairment or genital tract obstructions.

Varicocoele. Classification and pitfalls.

BACKGROUND: Varicocoeles have been considered for a long time potentially correctable causes for male infertility, even though the correlation of this condition with infertility and sperm damage is still debated. OBJECTIVE: To present a summary of the evidence evaluation for imaging varicocoeles, to underline the need for a standardized examination technique and for a unique classification, and to focus on pitfalls in image interpretation. METHODS: Based on the evidence of the literature, the current role of ultrasound (US) imaging for varicocoeles has been reported and illustrated, with emphasis on examination technique, classification, and pitfalls. RESULTS: US is the imaging modality of choice. It is widely used in Europe, while in other countries clinical classification of varicocoeles is considered sufficient to manage the patient. A number of US classifications exist for varicocoeles, in which the examinnation is performed in different ways. DISCUSSION: An effort toward standardization is mandatory, since lack of standardization contributes to the confusion of the available literature, and has a negative impact on the understanding of the role itself of imaging in patients with varicocoeles. CONCLUSION: Use of the Sarteschi/Liguori classification for varicocoeles is recommended, since it is the most complete and widely used US scoring system available today. Tubular extratesticular structures resembling varicocoeles, either at palpation or at US, should be identified and correctly characterized.

Ultrasound evaluation of patients with male accessory gland inflammation: a pictorial review.

Male accessory gland infection/inflammation (MAGI) is a major cause of male infertility. The importance of ultrasound evaluation in these patients is highly controversial, although evidence of its relevance has increased in recent years. Ultrasound criteria are an important element for confirming the clinical diagnosis. Furthermore, they help to localize the anatomical site or sites of the inflammatory process and in assessing its extension which, in turn, have different consequences on the seminological and symptomatic aspects. This article summarizes the clinical interpretations related to ultrasound aspects in patients with MAGI and the possible effects on the seminological, microbiological, endocrinologic, urological, sexological, and internist aspects.

Correlation between the DNA fragmentation index (DFI) and sperm morphology of infertile patients.

PURPOSE: To evaluate the correlation between the DNA Fragmentation Index (DFI) and sperm morphology in patients undergoing ICSI, as a predictive parameter in reproductive outcomes. METHODS: A retrospective study was conducted on 125 infertile patients enrolled in a fertility clinic. Seminal characteristics were measured following the WHO guidelines (2010) for the examination of the seminal fluid. After collecting motile sperm population by pellet swim up, DFI was calculated and simultaneously associated with sperm morphology using in situ TUNEL assay and an image analyzer software in at least 250 spermatozoa for each patient. RESULTS: All subjects were divided into two groups according to a cutoff established, by choice, of the sperm DFI (15%): group A (< 15%) consisting of 65 patients and group B (≥ 15%) of 60 patients. Data were analyzed using non-parametric statistical methods. The results demonstrate that there is no statistical difference between the two groups in seminal characteristics. The collective data show a high significant correlation, suggesting that spermatozoa with abnormal morphology are the best candidates to contain DNA damage (p < 0.001). Also, when group A is compared with group B, an increased percentage of morphologically normal spermatozoa with fragmented DNA was observed in patients, with DFI values ≥ 15% (p < 0.001). CONCLUSION: These results are aimed at providing an exact value of DFI in morphologically normal spermatozoa, which will be helpful to the embryologist in evaluating the risk of transferring, during the ICSI procedure, a spermatozoon whit normal morphology but fragmented DNA.

[Varicocelectomy: a critical analysis of predictors for male reproductive function recovery].

Varicocele is one of the most common correctable cause of male subfertility. According to recent meta-analyzes of RCTs varicocelectomy, in general, leads to significant improvement in semen quality and thereby male fertility. However, varicocelectomy success rate is 55-70%, it means that 30-40% of infertile men does not experience fertility improvement after varicocelectomy. The aim of our review was to search and analyze literature data on clinical-anamnestic and laboratory-instrumental predictors that positively or negatively affect varicocelectomy efficacy. As a result of analysis, we systematized the studied predictors based on the total points calculated on the basis of number and quality of studies that confirm or reject the studied predictor as a significant, into three levels of evidence: predictors of high, moderate and low evidence levels. Predictors of high level of evidence included: initial semen parameters, sperm DNA fragmentation index, and Doppler ultrasound imaging of testicular vessels. The initial serum level of FSH and testicular volume were included in the group of predictors of moderate evidence level. At the same time, such factors as the male age and his female partner age, varicocele grade and infertility duration entered the group of predictors of low evidence level. In this way, we performed "gradation" of predictors of varicocelectomy efficacy in subfertile men based on the analysis of the evidence level of each predictor.

Experience of using shear wave elastography in evaluation of testicular stiffness in cases of male infertility.

PURPOSE: The purpose of this study was to determine quantitative testicular tissue stiffness values in normal and infertile men using shear wave elastography (SWE), and to evaluate the relationship between infertility and testicular stiffness value. METHODS: In total, 100 testes of 50 infertile patients with abnormal semen parameters were classified as group A, and 100 testes of 50 control subjects were classified as group B. These two groups were compared in terms of age, testicular volume, and SWE values. The group B testes were randomly chosen from patients who had applied for ultrasonography for any reason, and who had no testis disease and no history of infertility. RESULTS: The mean age of the patients was 27.83 years, and no significant difference in age was found between the groups (P = 0.133). No significant difference in testicular volume was found between the groups (P = 0.672). The SWE values were significantly higher in group A than in group B (P = 0.000 for both m/s and kPa values). SWE values had a negative correlation with mean testicular volume in group A (for m/s values: P = 0.043; for kPa values: P = 0.024). CONCLUSION: SWE can be a useful technique for assessing testicular stiffness in infertile patients to predict parenchymal damage in testicular tissue that leads to an abnormality in sperm quantity. In addition, decreased testicular volume, together with increased SWE values, can reflect the degree of parenchymal damage.

Ultrasound evaluation of varicoceles: guidelines and recommendations of the European Society of Urogenital Radiology Scrotal and Penile Imaging Working Group (ESUR-SPIWG) for detection, classification, and grading.

Varicoceles are relatively common particularly in asymptomatic men and are even more prevalent in subfertile men, representing the most common potentially correctable cause of male infertility. Ultrasound (US) is the imaging modality of choice for varicocele evaluation, but there is no widely accepted consensus on examination technique, diagnostic criteria, or classification. In view of this uncertainty, the guideline writing group (WG) of the European Society of Urogenital Radiology (ESUR) Scrotal and Penile Imaging Working Group (ESUR-SPIWG) undertook a literature review and assessment of the quality of relevant evidence. The group then produced evidence-based recommendations for varicocele US examination, interpretation, and classification by consensus agreement. The results are presented in the form of 15 clinical questions with a brief summary of the relevant evidence and the authorised recommendations from the SPIWG. This paper provides a short summary of the evidence evaluation and the complete recommendations.Key Points• Varicocele is a common clinical problem; it is highly prevalent amongst subfertile men and the most common potentially correctable cause of male infertility. • Ultrasound is the imaging modality of choice for varicocele assessment, but there is no generally agreed consensus on the US examination technique or the criteria that should be used for diagnosis, grading, and classification. • This paper summarises the recommendations of the ESUR-SPIWG for standardising the US assessment of varicoceles. This includes examination technique, image interpretation, classification, and reporting.

Testosterone levels after treatment with urofollitropin in infertile patients with idiopathic mild reduction of testicular volume.

INTRODUCTION: A reduction of testicular volume (TV) represents an important clinical sign, which may hide sperm abnormalities and predispose to hypogonadism. AIM: The primary purpose of this study was to evaluate the serum levels of total testosterone after treatment with urofollitropin in selected patients with male infertility and idiopathic mild reduction of testicular volume. METHODS: In this 1-year-long prospective design, patients with abnormal sperm parameters, mild reduction in TV (8-12 mL) and normal gonadotropin, and total testosterone (TT) serum levels were recruited in this study. Patients treated for 4 months with urofollitropin were included in group A, those treated with intracytoplasmatic sperm injection due to a female-factor infertility were included in group B. Hormone values, sperm parameters, and TV were detected at baseline (T0), after 4 (T1) and 12 months (T2) in group A and at T0 and T2 in group B. RESULTS: Group A (n = 80) showed increased follicle-stimulating hormone (FSH) at T1 and sperm morphology at T1 and T2 compared to T0 (all p < 0.05). Group B (n = 50) had lower TT and higher FSH levels at T2 compared to T0 (all p < 0.05). At T2, TT, VT, total sperm count, progressive motility, total motility, and sperm morphology were higher in group A compared to group B (all p < 0.05). CONCLUSION: Reduced TV may predispose to infertility and hypogonadism. FSH treatment may improve Sertoli and Leydig cell function and prevent the development of hypogonadism.

Loss-of-function mutations in SPEF2 cause multiple morphological abnormalities of the sperm flagella (MMAF).

BACKGROUND: Multiple morphological abnormalities of the sperm flagella (MMAF) is a kind of severe teratozoospermia. Patients with the MMAF phenotype are infertile and present aberrant spermatozoa with absent, short, coiled, bent and/or irregular flagella. Mutations in several genes can explain approximately 30%-50% of MMAF cases and more genetic pathogenies need to be explored. SPEF2 was previously demonstrated to play an essential role in sperm tail development in mice and pig. Dysfunctional mutations in SPEF2 impair sperm motility and cause a short-tail phenotype in both animal models. OBJECTIVE: Based on 42 patients with severe infertility and MMAF phenotype, we explored the new genetic cause of human MMAF phenotype. METHODS AND RESULTS: By screening gene variants in 42 patients with MMAF using whole exome sequencing, we identified the c. 12delC, c. 1745-2A > G, c. 4102 G > T and c. 4323dupA mutations in the SPEF2 gene from two patients. Both of these mutations are rare and potentially deleterious. Transmission electron microscope (TEM) analysis showed a disrupted axonemal structure with mitochondrial sheath defects in the patients' spermatozoa. The SPEF2 protein level was significantly decreased in the spermatozoa of the patients revealed by Western blot (WB) and immunofluorescence (IF) analyses. CONCLUSION: Our experimental findings indicate that loss-of-function mutations in the SPEF2 gene can cause the MMAF phenotype in human.