Testicular Fine-Needle Aspiration for Sperm Retrieval in Azoospermia: A Small Step toward the Technical Standardization

Gianmartin Cito,Maria Elisabetta Coccia,Francesco Sessa,Andrea Cocci,Pierangelo Verrienti,Rita Picone,Rossella Fucci,Luciana Criscuoli,Sergio Serni,Marco Carini,Alessandro Natali 대한남성과학회 2019 The World Journal of Men's Health Vol.37 No.1

Purpose: The aim was to describe our preliminary experience performing testicular fine-needle aspiration (TEFNA) with a larger needle in infertile patients with obstructive azoospermia, and to provide a systematic literature review of the different testicular sperm aspiration techniques, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. Materials and Methods: We prospectively collected data between March 2017 and June 2018. All men underwent bilateral TEFNA under analgo-sedation, using a larger disposable 18-gauge butterfly needle with 60 mL Luer-Lock syringe attached to it. Results: Thirty consecutive patients were enrolled. Median operative time was 16 minutes (interquartile range [IQR]: 12–30 minutes). No intraoperative complications occurred. Two/thirty patients (6.7%) reported postoperative adverse events: 1 pa-tient had prolonged orchialgia, 1 patient presented scrotal hematoma. Successful sperm retrieval was found in 28/30 cases (93.3%). Median sperm concentration was 0.05 ×106/mL (IQR: 0.001–0.1 ×106/mL). Median total sperm motility was 10% (IQR: 0%–15%). In 20/30 men (66.7%) sperm retrieved was used for fresh intracytoplasmic sperm injection cycle, in 8/30 (26.7%) sperm cryopreservation was necessary, because on the day of sperm retrieval the female resulted not responder to ovarian stimulation. In this cases mean number of 3 (IQR: 1–4) bio system straws was cryopreserved. Conclusions: TEFNA with 18-gauge needle proved to be a feasible, safe and effective treatment, even if future prospective studies will be addressed to clarify what type of azoospermia benefits from this procedure, and if a larger needle permits to improve Assisted Reproductive Technologies (ART) outcomes.

Vitamin D and Male Fertility: An Updated Review

Gianmartin Cito,Andrea Cocci,Elisabetta Micelli,Alejandro Gabutti,Giorgio Ivan Russo,Maria Elisabetta Coccia,Giorgio Franco,Sergio Serni,Marco Carini,Alessandro Natali 대한남성과학회 2020 The World Journal of Men's Health Vol.38 No.2

To date, the key role of vitamin D in male reproductive system has been suggested, since the expression of vitamin D receptors and metabolizing enzymes was demonstrated in the testis and spermatozoa. Nevertheless, a general consensus about the role of vitamin D in male fertility is still debated. The aim of this review is to provide an updated systematic revision of the current available literature, discussing the experimental and clinical evidence on the role of vitamin D in the regulation of testis hormone production, seminal parameters and male fertility. The consequences of vitamin D deficiency on serum levels of testicular hormones have been analysed by several observational and interventional studies, with controversial results. Equally, the experimental researches not were able to state a certain relationship between vitamin D status and testis hormone production. Possible bias, including age, body mass index, and baseline vitamin D status justified the differences among studies. As well as concerning the effect of vitamin D on semen parameters, most of the studies agreed in the possibility that vitamin D might have a positive effect on human male fertility potential, particularly through better sperm motility. Regarding pregnancy outcomes, normal level of vitamin D seems to be related to better pregnancies. However, all the previous studies displayed a wide heterogeneity in study design, population, methodology, and cut off values used for the evaluation of vitamin D status. Future studies are needed to better clarify the exact role of vitamin D on hormonal and seminal panel in both fertile and infertile men.

Male Inflammatory Parameters Are not Useful to Predict the Outcomes of Intracytoplasmic Sperm Injection: Results from a Cross-Sectional Study

Gianmartin Cito,Maria Elisabetta Coccia,Rita Picone,Andrea Cocci,Giorgio Ivan Russo,Tommaso Cai,Giulia Bencini,Rossella Fucci,Elisabetta Micelli,Luciana Criscuoli,Francesco Bertocci,Elena Borrani,Serg 대한남성과학회 2019 The World Journal of Men's Health Vol.37 No.3

Purpose: The relationship between male systemic inflammation and fertility seems intriguing, but no data about its impact on the assisted reproductive technology outcomes has been reported. Here, we aimed to evaluate the prognostic role of male systemic inflammatory parameters in intracytoplasmic sperm injection (ICSI) outcomes prediction, in couples undergoing an ovum donation program.Materials and Methods: From January 2016 to December 2017, one hundred-ten couples were considered for this cross-sectional study. Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-eosinophil ratio (MER), platelet-to-lymphocyte ratio (PLR), seminal parameters, fertilization rate (FR), cleavage rate (CR), pregnancy rate (PR) were evaluated. Male patients were divided into Group A with FR ≤70%, Group B with FR >70%.Results: Overall, FR was 74.5%, CR 90.9%, PR 41.8%. Group A included 43 patients, Group B 67 men. Group A showed a median NLR of 1.55, PLR of 106.09, MER of 2.33. Group B reported a median NLR of 1.64, PLR 109.0, MER 2.76. We found no statistically differences between two groups with respect to NLR, PLR, MER (p=0.90, p=0.70, p=0.96, respectively). The age-adjusted linear regression analysis demonstrated only a relationship between NLR and sperm motility count (r=-0.02; p<0.05). Using the univariate logistic regression analysis, we found no significant associations. Conclusions: We did not find any relationship between ICSI outcomes and male inflammation parameters.

Sperm retrieval by conventional testicular sperm extraction for assisted reproduction in patients with Zinner syndrome

Cito Gianmartin,Luca Gemma1,Claudia Giachini,Micelli Elisabetta,Cocci Andrea,Fucci Rossella,Picone Rita,Simone Sforza,Gabriella Nesi,Raffaella Santi,Minervini Andrea,Lorenzo Masier,Carini Marco,Coccia 대한생식의학회 2021 Clinical and Experimental Reproductive Medicine Vol.48 No.1

We present data from three Caucasian men with Zinner syndrome who attended our center for the treatment of primary couple’s infertility. Each patient was scheduled for multiple conventional testicular sperm extraction (cTESE) and cryopreservation. The mean duration of infertility was 243 months. Sperm analysis confirmed absolute azoospermia. In patient 1, imaging revealed right and left testis volumes of 24 mL and 23 mL, respectively; dilatation of the right caput epididymis, corpus, and cauda; left seminal vesicle agenesis; severe right seminal vesicle hypotrophy; right renal agenesis; and left nephroptosis. The patient’s levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone (TT) were 3.2 IU/L, 5.2 IU/L, and 22.3 nmol/L, respectively. Patient 2 exhibited right and left testis volumes of 18 mL and 16 mL, respectively; a left seminal vesicle cyst of 3228 mm; ipsilateral kidney absence; and right seminal vesicle agenesis. The patient’s levels of FSH, LH, and TT were 2.8 IU/L, 4.2 IU/L, and 14.3 nmol/L, respectively. In patient 3, ultrasound showed a testicular volume of 10 mL bilaterally, a 6546 mm left seminal vesicle cyst, right seminal vesicle enlargement, and left kidney agenesis. The patient’s levels of FSH, LH, and TT were 32.0 IU/L, 16.3 IU/L, and 9.0 nmol/L, respectively. Sperm retrieval via cTESE was successful in all patients. It may be advisable to perform cTESE to obtain fresh sperm on the day of oocyte retrieval. Sperm cryopreservation should be avoided, since thawing could further compromise the sperm quality.

Paternal Behaviors in the Era of COVID-19

Cito Gianmartin,Micelli Elisabetta,Cocci Andrea,Polloni Gaia,Coccia Maria Elisabetta,Carini Marco,Minervini Andrea,Natali Alessandro 대한남성과학회 2020 The World Journal of Men's Health Vol.38 No.3

Hepatitis B Surface Antigen Seropositive Men in Serodiscordant Couples: Effects on the Assisted Reproductive Outcomes

Cito Gianmartin,Coccia Maria Elisabetta,Fucci Rossella,Picone Rita,Cocci Andrea,Sessa Maurizio,Sessa Francesco,Rizzello Francesca,Micelli Elisabetta,Trotta Michele,Badolato Laura,Campi Riccardo,Criscu 대한남성과학회 2021 The World Journal of Men's Health Vol.39 No.1

Purpose: To evaluate the influence of hepatitis B virus (HBV) infection in men of serodiscordant couples on the reproductive outcomes. Materials and Methods: A total of 134 infertile couples were included in this retrospective single-center cohort study. Sixty-six couples had hepatitis B surface antigen (HBsAg)-seropositive men and seronegative partners, while 68 couples were controls with both seronegative men and women. Overall, 134 fresh in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments were performed. As the main outcome measures, on the day of the fresh IVF/ICSI cycle, we assessed seminal parameters Before and after sperm preparation techniques. Two-pronuclear (2PN) fertilization, 1-2-3PN fertilization, cleavage, miscarriage, pregnancy and live birth rates were collected. Results: No significant differences were found between groups in terms of oocytes retrieved, oocytes injected and embryos obtained (p=0.64, p=0.97, and p=0.40, respectively). The 2PN fertilization rate (FR) was comparable among groups (p=0.51). The 1-2-3PN FR was significantly lower in the HBsAg group than in the control group (66.6% vs. 69.7%, respectively). The clinical pregnancy per cycle, implantation, miscarriage and live birth rate were comparable between the HBsAg group and the control group. The median sperm concentration/ml and total sperm count, measured at baseline and after sperm preparation, was comparable between groups (p>0.05). There was a trend toward significant lower progressive motility (35.0% vs. 55.0%; p<0.05) in the HBsAg group at baseline and after sperm preparation (p<0.05). Conclusions: HBV infected men have the same chance to became father, compared to seronegative patients.

Novel method of histopathological analysis after testicular sperm extraction in patients with nonobstructive and obstructive azoospermia

Cito, Gianmartin,Coccia, Maria Elisabetta,Picone, Rita,Nesi, Gabriella,Cocci, Andrea,Dabizzi, Sara,Garaffa, Giulio,Fucci, Rossella,Falcone, Patrizia,Bertocci, Francesco,Santi, Raffaella,Criscuoli, Luc The Korean Society for Reproductive Medicine 2018 Clinical and Experimental Reproductive Medicine Vol.45 No.4

Objective: To assess whether the "testicular pool" could be used for histological analysis and whether it gave more accurate information than the standard testicular biopsy. Methods: Between January 2017 and March 2018, this single-center prospective study included 60 azoospermic men undergoing conventional bilateral testicular sperm extraction. Six samples were excised from each testicle and transferred to an embryologist. One additional biopsy was randomly taken from each testis for a histological analysis. After processing, the testicular pool was also sent for a histological analysis, which showed normal spermatogenesis (NS), hypospermatogenesis (HYPO), maturation arrest (MA), Sertoli cell-only syndrome (SCOS), and tubular atrophy (TA). Results: Twenty of the 60 patients (33.3%) had obstructive azoospermia (OA), while the remaining 40 (66.6%) had nonobstructive azoospermia. Their mean age was 40.5 years. All patients with OA had previously undergone unsuccessful testicular fine-needle aspiration. Successful sperm retrieval (SSR) occurred in 93.3% of patients. Histological analysis of the testicular biopsy revealed NS in 12 patients (20%), HYPO and TA in 28 patients (46.6%), MA in eight patients (13.3%), and SCOS in 12 patients (20%). The testicular pool analysis showed NS in 12 patients (20%), HYPO and TA in 44 patients (73.3%), MA in four patients (6.6%), and SCOS in no patients. In four patients with MA (6.6% of the total sample) and 12 patients with SCOS (20% of the total sample) according to the standard testicular biopsy, the embryologist found SSR with cryopreservation. Overall, in 44 patients (73.3%), the testicular pool analysis confirmed the histological findings of the standard testicular biopsy. In the 16 cases (26.6%) with a discrepancy between the single-biopsy histological findings and SSR, the testicular pool analysis confirmed the embryological data on SSR. Conclusion: The testicular pool proved to be easily analyzable, practical, manageable, and more accurate for predicting sperm retrieval than standard testicular biopsy.

The Natural History of Peyronie's Disease

Di Maida Fabrizio,Cito Gianmartin,Lambertini Luca,Valastro Francesca,Morelli Girolamo,Mari Andrea,Carini Marco,Minervini Andrea,Cocci Andrea 대한남성과학회 2021 The World Journal of Men's Health Vol.39 No.3

Peyronie’s disease (PD), a fibrotic disorder of the tunica albuginea fully described in 1793 by French physician Francois de la Peyronie, is characterized by pain, plaque formation, penile deformity, and ultimately sexual function decline. The epidemio-logical data on PD vary considerably across previous studies, with recent evidence reporting a prevalence of up to 9%. PD is generally divided into two different phases: active or acute and stable or chronic. Plaque formation generally occurs during the acute phase, while during chronic phase pain usually tends to complete resolution and penile deformity stabilizes. PD’s pathophysiology is still subject of great discussion. Tunical mechanical stress and microvascular trauma are major contribu-tory factors. However, better understanding of the molecular pathophysiology of this condition remains paramount towards an in-depth comprehension of the disorder and the development of newer and more effective disease-targeted interventions. In this review we provide a detailed overview of natural history of PD, specifically focusing on clinical manifestations and the underlying molecular regulation patterns.

The impact of COVID-19 on the male genital tract: A qualitative literature review of sexual transmission and fertility implications

Verrienti, Pierangelo,Cito, Gianmartin,Maida, Fabrizio Di,Tellini, Riccardo,Cocci, Andrea,Minervini, Andrea,Natali, Alessandro The Korean Society for Reproductive Medicine 2022 Clinical and Experimental Reproductive Medicine Vol.49 No.1

The angiotensin-converting enzyme 2 receptor (ACE2) appears to be widely expressed in cells in the testes, predominantly in spermatogonia, Sertoli cells, and Leydig cells, and its co-expression with transmembrane protease serine 2 (TMPRSS2) is essential for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For this reason, the male reproductive system could be considered a potential target for SARS-CoV-2, as well as a possible reservoir of infection. However, to date, there is very little evidence about the presence of SARS-CoV-2 in semen and testicular samples. The aim of this paper was to review the current evidence regarding the impact of SARS-CoV-2 on male fertility and sexual health, with a particular focus on reproductive hormones, the presence of the virus in seminal fluid and testis, and its impact on fertility parameters. We found very limited evidence reporting the presence of SARS-CoV-2 in semen and testicular samples, and the impact of SARS-CoV-2 on reproductive hormones and fertility parameters is unclear. The quality of the examined studies was poor due to the small sample size and several selection biases, precluding definitive conclusions. Hence, future well-designed prospective studies are needed to assess the real impact of SARS-CoV-2 on male reproductive function.

Comparison of Intralesional Hyaluronic Acid vs. Verapamil for the Treatment of Acute Phase Peyronie's Disease: A Prospective, Open-Label Non-Randomized Clinical Study

Cocci Andrea,Di Maida Fabrizio,Cito Gianmartin,Verrienti Pierangelo,Laruccia Nicola,Campi Riccardo,Mari Andrea,Di Mauro Marina,Falcone Marco,Cacciamani Giovanni E.,Garaffa Giulio,Minervini Andrea,Russ 대한남성과학회 2021 The World Journal of Men's Health Vol.39 No.2

Purpose: To compare the efficacy and safety of intralesional hyaluronic acid (HA) as compared with verapamil injection in patients with Peyronie’s disease (PD). Materials and Methods: Between January 2015 and December 2018, men in PD acute phase were prospectively recruited. This open-label, prospective study included 2 different protocols. Group A: 8-week cycle of weekly intraplaque injections with HA; Group B: 8-week cycle of weekly intraplaque injections with verapamil. Penile curvature, plaque size, International Index of Erectile Function (IIEF)-15 score and visual analogue scale (VAS) were assessed at baseline and after 3 months. Results: Two-hundred forty-four patients were enrolled. Of these, 125 received intralesional HA (Group A), 119 received intralesional verapamil (Group B). At enrollment, median age was 56.0 years (interquartile range [IQR]=47.0–63.0 years), median curvature 35.0° (IQR=25.0°–45.0°), median IIEF-15 score 19.0 (IQR=16.0–23.0), median VAS 4.0 (IQR=4.0–5.0). Median difference for IIEF-15 was 1.0 (95% confidence interval [CI]=1.12–1.94) in Group A and 0.0 (95% CI=-0.04–0.14) in Group B (p<0.05) and median difference for VAS score was -4.0 (95% CI=-4.11–-3.65) in Group A and -1.0 (95% CI=-0.50–2.01) in Group B (p<0.05). Plaque size decreased by -1.50 mm (IQR=1.60–2.10 mm) in Group A and -1.20 in Group B (p=0.10), while penile curvature decreased by -9.50° (IQR=4.50°–13.00°) in group A and -4.50 (IQR=2.50–7.50) in Group B (p<0.01). Conclusions: Intralesional HA injections could represent a reliable treatment option for the conservative management of patients with acute phase of PD.