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Clinical Management of Male Infertility
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Clinical Management of Male Infertility

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Nephrology & Urology".

Deadline for manuscript submissions: closed (25 March 2023) | Viewed by 14565

Special Issue Editor

Dr. Luca Boeri

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Guest Editor
Department of Urology, Foundation IRCCS Ca' Granda - Maggiore Policlinico Hospital, University of Milan, Milan, Italy
Interests: infertility; hypogonadism; sexual dysfunction; urologic oncology; endourology

Special Issue Information

Dear Colleagues,

Male factor infertility is a rising issue worldwide with significant socioeconomic costs and negative psychological consequences for the couple. Several conditions have been associated with male infertility, such as abnormalities of the urogenital tract, malignancies, endocrine and genetic disorders, immune factors, and sexually transmitted infections; however, infertility is still idiopathic in nature in approximately 30%–40% of men.

To this aim, a focused diagnostic work-up of the male patient must always be undertaken by specialists in male reproduction, including a medical and reproductive history, a physical examination, hormonal testing, and a detailed semen analysis, with strict adherence to WHO reference values for human semen characteristics.

The clinical management of male infertility has evolved over the years. The arrival of new diagnostic tests, such as sperm DNA fragmentation and markers of oxidative stress, has changed our way of managing couples with idiopathic infertility. Moreover, hormonal treatment with gonadotropins has shown promising results for improving sperm quality and DNA defects. Lastly, surgical sperm retrieval has also been considered for non-azoospermic men, but reliable predictors of sperm recovery are not yet identified.

The aim of this Special Issue of the Journal of Clinical Medicine is to provide new insights into the clinical management of male infertility.

Dr. Luca Boeri
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • infertility
  • diagnosis
  • treatment
  • hormones
  • etiology
  • varicocele
  • surgery
  • semen analysis
  • genetic disorders
  • oxidative stress
 

Published Papers (8 papers)

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Research

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14 pages, 1439 KiB  
Article
Semen Cryopreservation for Men Banking for Oligozoospermia, Cancers, and Other Conditions: 24 Years’ Experience of an Italian Bank
by Sara Marchiani, Selene Degl’Innocenti, Sara Dabizzi, Lara Tamburrino, Maria Grazia Fino, Giulia Traini, Costanza Calamai, Mario Maggi, Linda Vignozzi, Elisabetta Baldi and Francesco Lotti
J. Clin. Med. 2023, 12(14), 4657; https://doi.org/10.3390/jcm12144657 - 13 Jul 2023
Cited by 2 | Viewed by 933
Abstract
Background: Sperm cryopreservation is recommended to preserve male fertility for cancer patients or other medical conditions at risk of sperm decline. Whether motility and viability recovery rates vary depending on the medical conditions requiring cryopreservation is poorly known. We report here on the [...] Read more.
Background: Sperm cryopreservation is recommended to preserve male fertility for cancer patients or other medical conditions at risk of sperm decline. Whether motility and viability recovery rates vary depending on the medical conditions requiring cryopreservation is poorly known. We report here on the 24-year experience of our semen bank. Methods: Motility and viability recovery rates were evaluated in 1973 collections from patients with various medical conditions and 67 collections from donors, and the results were related to basal semen quality. Results: Motility and viability recovery were highly related to basal semen quality and varied between cancer and non-cancer conditions, independently of the duration of cryopreservation and patient age. In samples with a sperm number below 2 × 106/mL, recovery rates approximated to zero. The highest recovery rates were found in donor collections. Cut-off values for the recovery of at least 1% motile spermatozoa were established based on initial semen quality. Conclusions: Our results indicate that the occurrence of any pathological or medical condition resulted in lower recovery rates with respect to donors, indicating that intrinsic sperm characteristics drive susceptibility to cryodamage. Established cut-off values for motility recovery can be useful for patient counseling as well as for ART laboratories to decide the type of procedure. Full article
(This article belongs to the Special Issue Clinical Management of Male Infertility)
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8 pages, 247 KiB  
Article
Radiation Exposure and Surgical Outcomes after Antegrade Sclerotherapy for the Treatment of Varicocele in the Paediatric Population: A Single Centre Experience
by Carolina Bebi, Marco Bilato, Dario Guido Minoli, Erika Adalgisa De Marco, Michele Gnech, Irene Paraboschi, Luca Boeri, Irene Fulgheri, Roberto Brambilla, Mauro Campoleoni, Giancarlo Albo, Emanuele Montanari, Gianantonio Manzoni and Alfredo Berrettini
J. Clin. Med. 2023, 12(3), 755; https://doi.org/10.3390/jcm12030755 - 18 Jan 2023
Cited by 2 | Viewed by 1641
Abstract
Introduction: Antegrade sclerotherapy (Tauber) effectively treats varicocele. However, fluoroscopy exposes young males to ionizing radiation. We aimed to evaluate radiation exposure and surgical outcomes after the Tauber procedure. Materials and methods: We retrospectively analysed data from 251 patients. Dose area product (DAP) and [...] Read more.
Introduction: Antegrade sclerotherapy (Tauber) effectively treats varicocele. However, fluoroscopy exposes young males to ionizing radiation. We aimed to evaluate radiation exposure and surgical outcomes after the Tauber procedure. Materials and methods: We retrospectively analysed data from 251 patients. Dose area product (DAP) and fluoroscopy time were recorded. The effective dose was calculated with the PCXMC software. Descriptive statistics and linear regression tested the association between clinical predictors and radiation exposure. Results: Median (IQR) age and body mass index (BMI) were 14 (13–16) years and 20.1 (17.9–21.6) kg/m². Five (2.1%) patients developed clinical recurrence and two (0.81%) developed complications. Median fluoroscopy time and DAP were 38.5 (27.7–54.0) s and 89.6 (62.5–143.9) cGy*cm2. The effective dose was 0.19 (0.14–0.31) mSv. Fluoroscopy time was higher in patients with collateral veins (41 (26–49) s vs. 36 (31–61) s, p = 0.02). The median amount of sclerosing agent (SA) used was 3 (3–4) ml. DAP was higher when SA > 3 mL was used (101.4 (65–183) cGy*cm2 vs. 80.5 (59–119) cGy*cm2; p < 0.01). At univariable linear regression, age, BMI, operative time and SA > 3 mL were associated with higher DAP (all p < 0.01). At multivariable linear regression, only BMI (beta 12.9, p < 0.001) and operative time (beta 1.9, p < 0.01) emerged as predictors of higher DAP, after accounting for age and SA > 3 mL. Conclusions: The Tauber procedure is safe and associated with low effective doses. Operative time and the patient’s BMI independently predict a higher radiation dose. Full article
(This article belongs to the Special Issue Clinical Management of Male Infertility)
9 pages, 268 KiB  
Article
Clinically Meaningful Improvements in Sperm DNA Fragmentation Severity in Infertile Men Treated with Superoxide Dismutase Supplementation: A Single-Center Experience
by Luca Boeri, Gianpaolo Lucignani, Letizia Maria Ippolita Jannello, Matteo Turetti, Irene Fulgheri, Carlo Silvani, Franco Gadda, Paola Viganò, Edgardo Somigliana and Emanuele Montanari
J. Clin. Med. 2022, 11(21), 6540; https://doi.org/10.3390/jcm11216540 - 4 Nov 2022
Cited by 4 | Viewed by 1408
Abstract
Background. Antioxidants are commonly used for the treatment of idiopathic male infertility. Previous studies have shown that antioxidants are able to improve sperm quality, but little is known about their impact on sperm DNA fragmentation (SDF). Preliminary findings showed that superoxide-dismutase (SOD)-based antioxidant [...] Read more.
Background. Antioxidants are commonly used for the treatment of idiopathic male infertility. Previous studies have shown that antioxidants are able to improve sperm quality, but little is known about their impact on sperm DNA fragmentation (SDF). Preliminary findings showed that superoxide-dismutase (SOD)-based antioxidant plus hydroxytyrosol and carnosol (FertiPlus® SOD) therapy was associated with SDF improvement in a small cohort of infertile men. Therefore, we aimed to assess rates of and predictors of semen parameters and SDF improvements in infertile men treated with FertiPlus® SOD therapy (SOD+) or with other antioxidants without SOD (SOD−) in the real-life setting. Methods. Data from 60 consecutive infertile men with baseline SDF ≥ 30% and treated with SOD+ or SOD− for at least three months were analyzed. Clinical parameters and serum hormones were collected. Sperm parameters and SDF were requested at baseline and after SOD+ or SOD− treatment. Clinically meaningful SDF change after treatment was defined as SDF improvement >20% compared to baseline. Propensity score matching was performed to adjust for baseline differences between groups. Descriptive statistics were used to compare clinical and hormonal characteristics between SOD+ and SOD− groups. Semen characteristics were compared before and after treatment. Logistic regression models investigated the association between clinical variables and SDF improvement. Results. Groups were similar in terms of clinical, serum hormones and semen parameters at baseline after matching. Compared to baseline, sperm progressive motility (17 (10–36)% vs. 27 (12–41)%) and normal morphology (2 (1–6)% vs. 4 (2–6)%) significantly improved after SOD+ treatment (all p < 0.01), but not after SOD−. SDF values significantly improved after treatment in both groups, compared to the baseline evaluation (all p < 0.01). However, SDF values were lower after SOD+ than SOD− treatment (30 (22–36)% vs. 37 (31–42)%, p = 0.01). Similarly, a clinically meaningful improvement in SDF at follow-up was more frequently found after SOD+ than SOD− treatment (76.7% vs. 20.0%, p = 0.001). Multivariable logistic regression analysis showed that SOD+ treatment (OR 5.4, p < 0.001) was an independent predictor of clinically meaningful SDF improvement, after accounting for age and baseline FSH values. Conclusions. This cross-sectional study showed that, in a cohort of primary infertile men with SDF ≥ 30%, SOD-based treatment was significantly effective in improving SDF compared to antioxidants without SOD. Approximately 80% of men treated with SOD+ achieved clinically meaningful improvement in SDF after three months of treatment. Sperm progressive motility and normal morphology also improved after SOD+ therapy but not after SOD−. These results suggest that SOD+ treatment could be considered an effective option for the management of idiopathic infertile men with elevated SDF. Full article
(This article belongs to the Special Issue Clinical Management of Male Infertility)
13 pages, 301 KiB  
Article
The Role and Place of Antioxidants in the Treatment of Male Infertility Caused by Varicocele
by Marek Szymański, Piotr Domaracki, Angelika Szymańska, Tomasz Wandtke, Robert Szyca, Łukasz Brycht, Karolina Wasilow and Wojciech Jan Skorupski
J. Clin. Med. 2022, 11(21), 6391; https://doi.org/10.3390/jcm11216391 - 28 Oct 2022
Cited by 4 | Viewed by 2521
Abstract
The inability to become pregnant for at least 1 year despite regular unprotected intercourse may indicate infertility of one or both partners. This problem affects approximately 10–20% of couples worldwide, regardless of race, with male infertility reported to account for 25–60% of cases. [...] Read more.
The inability to become pregnant for at least 1 year despite regular unprotected intercourse may indicate infertility of one or both partners. This problem affects approximately 10–20% of couples worldwide, regardless of race, with male infertility reported to account for 25–60% of cases. Among the most common pathological causes of male infertility is the presence of varicocele and chronic infections of the male reproductive system. This study was performed using data collected at the Genesis Infertility Treatment Clinic, Bydgoszcz, Poland, between 1 January 2015 and 30 June 2017. A total of 163 men meeting the inclusion criteria were selected and divided into the idiopathic infertility group (78 men) and varicocele-related infertility group (85 men). All patients received treatment with a male fertility supplement containing a combination of 1725 mg of L-carnitine fumarate, 500 mg of acetyl-L-carnitine, 90 mg of vitamin C, 20 mg of coenzyme Q10, 10 mg of zinc, 200 µg of folic acid, 50 µg of selenium, and 1.5 µg of vitamin B12 (Proxeed® Plus, Sigma-Tau, Italy) twice a day for a period of 6 months from the time of the diagnosis of infertility. The treatment resulted in significant improvements in general semen parameters, particularly sperm count, sperm concentration, total motility, and progressive motility. This antioxidant therapy produced a particularly marked therapeutic benefit in patients with Grade III varicocele, with a greater improvement in progressive motility than in men with less severe or no varicocele. The use of the antioxidant preparation examined here seems reasonable in men with idiopathic infertility and as an adjuvant in those with varicocele-related infertility in whom surgical treatment has resulted in no improvement. Its use should be considered particularly in patients with Grade III varicocele who do not wish to undergo surgical treatment or in whom such a treatment is not possible for various reasons. Full article
(This article belongs to the Special Issue Clinical Management of Male Infertility)
9 pages, 1264 KiB  
Article
Combined Trifocal and Microsurgical Testicular Sperm Extraction Enhances Sperm Retrieval Rate in Low-Chance Retrieval Non-Obstructive Azoospermia
by Marco Falcone, Luca Boeri, Massimiliano Timpano, Lorenzo Cirigliano, Mirko Preto, Giorgio I. Russo, Federica Peretti, Ilaria Ferro, Natalia Plamadeala and Paolo Gontero
J. Clin. Med. 2022, 11(14), 4058; https://doi.org/10.3390/jcm11144058 - 13 Jul 2022
Cited by 1 | Viewed by 2114
Abstract
Background: Low-chance retrieval non-obstructive azoospermic (NOA) patients are a subpopulation of NOA patients. The objective of this study is to compare the surgical outcome of microsurgical-assisted testicular sperm extraction (M-TeSE) and combined trifocal/M-TeSE in low-chance retrieval NOA patients. Material and Methods: A single-center [...] Read more.
Background: Low-chance retrieval non-obstructive azoospermic (NOA) patients are a subpopulation of NOA patients. The objective of this study is to compare the surgical outcome of microsurgical-assisted testicular sperm extraction (M-TeSE) and combined trifocal/M-TeSE in low-chance retrieval NOA patients. Material and Methods: A single-center retrospective analysis of NOA patients who underwent testicular sperm extraction was performed. Low-chance retrieval NOA (testicular volume < 10 cc and FSH > 12.4 UI/L) was set as the inclusion criteria. Re-do TeSE procedures were excluded from the current analysis. Data were extrapolated from clinical records and operative notes. We compared data from patients who underwent classic M-TeSE (group A) with that from patients submitted to combined trifocal/M-TeSE (group B). Sperm retrieval rate (SRr) was the primary outcome of the study. Surgical outcomes and postoperative complications were evaluated. A multivariate analysis was conducted to investigate predictive factors for positive SR. Results: Overall, 80 patients (60 patients in Group A and 20 patients in Group B) fulfilled the inclusion criteria. The average (SD) age was 35 (8.2) years. The average preoperative FSH was 27.5 (13) UI/L. The average testicular volume was 6.3 (3) cc on the left side and 6.8 (2.5) cc on the right. Groups were similar in terms of preoperative parameters. The overall SRr was 28%. Patients in group B had higher SRr than those in group A (29.4% vs. 26.9%, p < 0.03). We identified a significant association between testicular histopathology and positive SR (hypospermatogenesis 100%, spermatogenic arrest 32%, and Sertoli cell-only syndrome 22%). The histopathology report was the only significant predicting factor for SR in the multivariate analysis. Conclusion: The combined trifocal and M-TeSE approach is safe and may represent a valuable approach to enhance the SRr in low-chance retrieval NOA. The histopathology report is confirmed to be the only valuable predicting factor for a positive SR. Full article
(This article belongs to the Special Issue Clinical Management of Male Infertility)
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Review

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33 pages, 1002 KiB  
Review
A Narrative Review Discussing Vasectomy-Related Impact upon the Status of Oxidative Stress and Inflammation Biomarkers and Semen Microbiota
by Bogdan Doroftei, Ovidiu-Dumitru Ilie, Radu Maftei, Ioana-Sadyie Scripcariu, Theodora Armeanu, Irina-Liviana Stoian and Ciprian Ilea
J. Clin. Med. 2023, 12(7), 2671; https://doi.org/10.3390/jcm12072671 - 3 Apr 2023
Viewed by 1591
Abstract
Background: Male contraceptive approaches besides tubal sterilization involve vasectomy and represent the method of choice among midlife men in developing countries thanks to many advantages. However, the subsidiary consequences of this intervention are insufficiently explored since the involved mechanisms may offer insight into [...] Read more.
Background: Male contraceptive approaches besides tubal sterilization involve vasectomy and represent the method of choice among midlife men in developing countries thanks to many advantages. However, the subsidiary consequences of this intervention are insufficiently explored since the involved mechanisms may offer insight into a much more complex picture. Methods: Thus, in this manuscript, we aimed to reunite all available data by searching three separate academic database(s) (PubMed, Web of Knowledge, and Scopus) published in the past two decades by covering the interval 2000–2023 and using a predefined set of keywords and strings involving “oxidative stress” (OS), “inflammation”, and “semen microbiota” in combination with “humans”, “rats”, and “mice”. Results: By following all evidence that fits in the pre-, post-, and vasectomy reversal (VR) stages, we identified a total of n = 210 studies from which only n = 21 were finally included following two procedures of eligibility evaluation. Conclusions: The topic surrounding this intricate landscape has created debate since the current evidence is contradictory, limited, or does not exist. Starting from this consideration, we argue that further research is mandatory to decipher how a vasectomy might disturb homeostasis. Full article
(This article belongs to the Special Issue Clinical Management of Male Infertility)
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22 pages, 577 KiB  
Review
Microsurgical Management of Male Infertility: Compelling Evidence That Collaboration with Qualified Male Reproductive Urologists Enhances Assisted Reproductive Technology (ART) Outcomes
by Jessica Marinaro and Marc Goldstein
J. Clin. Med. 2022, 11(15), 4593; https://doi.org/10.3390/jcm11154593 - 6 Aug 2022
Cited by 7 | Viewed by 2197
Abstract
A male factor plays a significant role in a couple’s reproductive success. Today, advances in reproductive technology, such as intracytoplasmic sperm injection (ICSI), have allowed it to be possible for just a single sperm to fertilize an egg, thus, overcoming many of the [...] Read more.
A male factor plays a significant role in a couple’s reproductive success. Today, advances in reproductive technology, such as intracytoplasmic sperm injection (ICSI), have allowed it to be possible for just a single sperm to fertilize an egg, thus, overcoming many of the traditional barriers to male fertility, such as a low sperm count, impaired motility, and abnormal morphology. Given these advances in reproductive technology, it has been questioned whether a reproductive urologist is needed for the evaluation and treatment of infertile and subfertile men. In this review, we aim to provide compelling evidence that collaboration between reproductive endocrinologists and reproductive urologists is essential for optimizing a couple’s fertility outcomes, as well as for improving the health of infertile men and providing cost-effective care. Full article
(This article belongs to the Special Issue Clinical Management of Male Infertility)
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Other

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8 pages, 228 KiB  
Brief Report
Semen Analysis in “Urology-Naïve” Patients: A Chance of Uroandrological Screening in Young Males
by Stefano Puliatti, Stefano Toso, Marco Ticonosco, Salvatore Rabito, Maria Chiara Sighinolfi, Riccardo Ferrari, Vincenzo Rochira, Daniele Santi, Tommaso Trenti, Michele Navarra, Stefania Ferretti, Luigi Montano and Salvatore Micali
J. Clin. Med. 2023, 12(11), 3803; https://doi.org/10.3390/jcm12113803 - 1 Jun 2023
Viewed by 1120
Abstract
(1) Background: While females start their gynecological examinations during puberty, only few men decide to be visited by urologists in their youth. Given the participation in the EcoFoodFertility research project, our department had the opportunity to screen young males that were supposedly healthy. [...] Read more.
(1) Background: While females start their gynecological examinations during puberty, only few men decide to be visited by urologists in their youth. Given the participation in the EcoFoodFertility research project, our department had the opportunity to screen young males that were supposedly healthy. (2) Results: from January 2019 to July 2020, we evaluated 157 patients with sperm, blood analysis, and uroandrological examinations. The inclusion criteria were age 18–40 and absence of previous urological disease (urology-naïve). The primary endpoint of the study was to record uroandrological diseases that are occasionally discovered during examination in asymptomatic young men. The average age was 26.9 years (range 18–40); average testicular volume was 15.7 mL (range 12–22 mL); and 45.2% reported abnormal semen analysis: 62 cases of teratozoospermia, 27 asthenozoospermia, 18 oligozoospermia, and 2 azoospermia were discovered respectively; 4/157 patients were diagnosed with hypogonadism; 2 cases with suspicious testicular mass resulted in testicular cancer; and 31 suspected varicoceles and 8 patients with mild sexual dysfunctions were managed. (3) Conclusions: an uroandrological evaluation of young asymptomatic males allowed for the prompt diagnosis of different urological conditions, including cancerous ones, in our series. Despite being debatable, combining urological counselling with physical examination, semen analysis, and a laboratory profile could be useful and cost-effective in order to ameliorate male health. Full article
(This article belongs to the Special Issue Clinical Management of Male Infertility)
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