1.Impact of Varicocele Repair on Assisted Reproductive Technique Outcomes in Infertile Men: A Systematic Review and Meta-Analysis
Ayad PALANI ; Rossella CANNARELLA ; Ramadan SALEH ; Gianmaria SALVIO ; Ahmed M. HARRAZ ; Andrea CRAFA ; Fahmi BAHAR ; Kadir BOCU ; Naveen KUMAR ; Priyank KOTHARI ; Germar-Michael PINGGERA ; Selahittin CAYAN ; Giovanni M. COLPI ; Widi ATMOKO ; Rupin SHAH ; Ashok AGARWAL
The World Journal of Men's Health 2025;43(2):344-348
Purpose:
In this systematic review and meta-analysis, we investigated assisted reproductive technology (ART) success in infertile men with clinical varicocele and abnormal semen parameters who underwent varicocele repair (VR) before the ART procedure as compared to those who did not.
Materials and Methods:
A comprehensive search of the Scopus, PubMed, Embase, and Cochrane Library databases was conducted using a specific query string to identify studies examining the impact of VR on ART outcomes, including fertilization rate, clinical pregnancy, pregnancy loss, and live-birth rate, until October 2023. Outcomes were analyzed based on the type of ART. Studies on VR in infertile men with non-obstructive azoospermia and those who underwent ART only due to female factor infertility were excluded from the study.
Results:
Out of 1,554 articles reviewed, only 9 met the inclusion criteria for the study. All the included articles were observational studies. The variability in study quality in the included literature resulted in a moderate overall risk of bias. Data analysis showed that for intrauterine insemination, there was no difference in the clinical pregnancy rate (odds ratio [OR] 1.01, 95% confidence interval [CI]: 0.42, 2.45; p=0.97). However, for intracytoplasmic sperm injection (ICSI), men with VR showed a significant improvement in fertilization rate (mean difference 10.9, 95% CI: 5.94, 15.89; p<0.01), clinical pregnancy rate (OR 1.38, 95% CI: 1.07, 1.78; p=0.01) and live-birth rate (OR 2.07, 95% CI: 1.45, 2.97; p<0.01), compared to men who did not undergo VR.
Conclusions
The findings of this systematic review and meta-analysis suggest that VR has a positive impact on pregnancy and live birth rates after ICSI. However, biases like small sample sizes and heterogeneous populations highlight the need for larger, well-designed prospective studies to validate these findings.
3.Global Practice Patterns and Variations in the Medical and Surgical Management of NonObstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations
Amarnath RAMBHATLA ; Rupin SHAH ; Imad ZIOUZIOU ; Priyank KOTHARI ; Gianmaria SALVIO ; Murat GUL ; Taha HAMODA ; Parviz KAVOUSSI ; Widi ATMOKO ; Tuncay TOPRAK ; Ponco BIROWO ; Edmund KO ; Mohamed ARAFA ; Ramy Abou GHAYDA ; Vilvapathy Senguttuvan KARTHIKEYAN ; Giorgio Ivan RUSSO ; Germar-Michael PINGGERA ; Eric CHUNG ; Ashok AGARWAL ;
The World Journal of Men's Health 2025;43(1):92-122
Purpose:
Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA.
Materials and Methods:
A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process.
Results:
Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12–19 IU/mL by 22.5% of participants and 20–40 IU/mL by 27.8%, while 31.8% reported no upper limit.
Conclusions
This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.
4.Impact of Varicocele Repair on Assisted Reproductive Technique Outcomes in Infertile Men: A Systematic Review and Meta-Analysis
Ayad PALANI ; Rossella CANNARELLA ; Ramadan SALEH ; Gianmaria SALVIO ; Ahmed M. HARRAZ ; Andrea CRAFA ; Fahmi BAHAR ; Kadir BOCU ; Naveen KUMAR ; Priyank KOTHARI ; Germar-Michael PINGGERA ; Selahittin CAYAN ; Giovanni M. COLPI ; Widi ATMOKO ; Rupin SHAH ; Ashok AGARWAL
The World Journal of Men's Health 2025;43(2):344-348
Purpose:
In this systematic review and meta-analysis, we investigated assisted reproductive technology (ART) success in infertile men with clinical varicocele and abnormal semen parameters who underwent varicocele repair (VR) before the ART procedure as compared to those who did not.
Materials and Methods:
A comprehensive search of the Scopus, PubMed, Embase, and Cochrane Library databases was conducted using a specific query string to identify studies examining the impact of VR on ART outcomes, including fertilization rate, clinical pregnancy, pregnancy loss, and live-birth rate, until October 2023. Outcomes were analyzed based on the type of ART. Studies on VR in infertile men with non-obstructive azoospermia and those who underwent ART only due to female factor infertility were excluded from the study.
Results:
Out of 1,554 articles reviewed, only 9 met the inclusion criteria for the study. All the included articles were observational studies. The variability in study quality in the included literature resulted in a moderate overall risk of bias. Data analysis showed that for intrauterine insemination, there was no difference in the clinical pregnancy rate (odds ratio [OR] 1.01, 95% confidence interval [CI]: 0.42, 2.45; p=0.97). However, for intracytoplasmic sperm injection (ICSI), men with VR showed a significant improvement in fertilization rate (mean difference 10.9, 95% CI: 5.94, 15.89; p<0.01), clinical pregnancy rate (OR 1.38, 95% CI: 1.07, 1.78; p=0.01) and live-birth rate (OR 2.07, 95% CI: 1.45, 2.97; p<0.01), compared to men who did not undergo VR.
Conclusions
The findings of this systematic review and meta-analysis suggest that VR has a positive impact on pregnancy and live birth rates after ICSI. However, biases like small sample sizes and heterogeneous populations highlight the need for larger, well-designed prospective studies to validate these findings.
6.Global Practice Patterns and Variations in the Medical and Surgical Management of NonObstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations
Amarnath RAMBHATLA ; Rupin SHAH ; Imad ZIOUZIOU ; Priyank KOTHARI ; Gianmaria SALVIO ; Murat GUL ; Taha HAMODA ; Parviz KAVOUSSI ; Widi ATMOKO ; Tuncay TOPRAK ; Ponco BIROWO ; Edmund KO ; Mohamed ARAFA ; Ramy Abou GHAYDA ; Vilvapathy Senguttuvan KARTHIKEYAN ; Giorgio Ivan RUSSO ; Germar-Michael PINGGERA ; Eric CHUNG ; Ashok AGARWAL ;
The World Journal of Men's Health 2025;43(1):92-122
Purpose:
Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA.
Materials and Methods:
A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process.
Results:
Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12–19 IU/mL by 22.5% of participants and 20–40 IU/mL by 27.8%, while 31.8% reported no upper limit.
Conclusions
This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.
7.Technologies to improve sperm retrieval in men undergoing micro-TESE for NOA.
Parviz K KAVOUSSI ; Widi ATMOKO ; Germar-Michael PINGGERA
Asian Journal of Andrology 2025;27(3):375-382
Nonobstructive azoospermia (NOA) is considered the most challenging clinical scenario for infertile men and current treatments leave many men unsuccessful at being able to achieve a pregnancy with their partner using their own sperm. Microdissection testicular sperm extraction (micro-TESE) is the choice for men with NOA desiring to father children with their own gametes. Micro-TESE results in the highest numbers of sperm cells retrieved for use with in vitro fertilization/intracytoplasmic sperm injection. With suboptimal micro-TESE success rates of sperm retrieval and then pregnancy and live birth using the retrieved sperm with in vitro fertilization/intracytoplasmic sperm injection, advances to improve outcomes are necessary. This article comprehensively reviews the technologies investigated to date to improve the outcomes for men undergoing micro-TESE.
Humans
;
Male
;
Sperm Retrieval
;
Azoospermia/surgery*
;
Pregnancy
;
Female
;
Sperm Injections, Intracytoplasmic
;
Microdissection/methods*
;
Fertilization in Vitro
;
Testis/surgery*
8.Clinician's guide to the management of azoospermia induced by exogenous testosterone or anabolic-androgenic steroids.
Manaf Al HASHIMI ; Germar-Michael PINGGERA ; Rupin SHAH ; Ashok AGARWAL
Asian Journal of Andrology 2025;27(3):330-341
Azoospermia, defined as the absence of sperm in the ejaculate, is a well-documented consequence of exogenous testosterone (ET) and anabolic-androgenic steroid (AAS) use. These agents suppress the hypothalamic-pituitary-gonadal (HPG) axis, leading to reduced intratesticular testosterone levels and impaired spermatogenesis. This review examines the pathophysiological mechanisms underlying azoospermia and outlines therapeutic strategies for recovery. Azoospermia is categorized into pretesticular, testicular, and post-testicular types, with a focus on personalized treatment approaches based on the degree of HPG axis suppression and baseline testicular function. Key strategies include discontinuing ET and monitoring for spontaneous recovery, particularly in patients with shorter durations of ET use. For cases of persistent azoospermia, gonadotropins (human chorionic gonadotropin [hCG] and follicle-stimulating hormone [FSH]) and selective estrogen receptor modulators (SERMs), such as clomiphene citrate, are recommended, either alone or in combination. The global increase in exogenous testosterone use, including testosterone replacement therapy and AAS, underscores the need for improved management of associated azoospermia, which can be temporary or permanent depending on individual factors and the type of testosterone used. Additionally, the manuscript discusses preventive strategies, such as transitioning to short-acting testosterone formulations or incorporating low-dose hCG to preserve fertility during ET therapy. While guidelines for managing testosterone-related azoospermia remain limited, emerging research indicates the potential efficacy of hormonal stimulation therapies. However, there is a notable lack of well-structured, controlled, and long-term studies addressing the management of azoospermia related to exogenous testosterone use, highlighting the need for such studies to inform evidence-based recommendations.
Humans
;
Azoospermia/therapy*
;
Male
;
Testosterone/therapeutic use*
;
Anabolic Agents/adverse effects*
;
Clomiphene/therapeutic use*
;
Chorionic Gonadotropin/therapeutic use*
;
Follicle Stimulating Hormone/therapeutic use*
;
Spermatogenesis/drug effects*
;
Androgens/adverse effects*
9.Impact of Varicocele Repair on Assisted Reproductive Technique Outcomes in Infertile Men: A Systematic Review and Meta-Analysis
Ayad PALANI ; Rossella CANNARELLA ; Ramadan SALEH ; Gianmaria SALVIO ; Ahmed M. HARRAZ ; Andrea CRAFA ; Fahmi BAHAR ; Kadir BOCU ; Naveen KUMAR ; Priyank KOTHARI ; Germar-Michael PINGGERA ; Selahittin CAYAN ; Giovanni M. COLPI ; Widi ATMOKO ; Rupin SHAH ; Ashok AGARWAL
The World Journal of Men's Health 2025;43(2):344-348
Purpose:
In this systematic review and meta-analysis, we investigated assisted reproductive technology (ART) success in infertile men with clinical varicocele and abnormal semen parameters who underwent varicocele repair (VR) before the ART procedure as compared to those who did not.
Materials and Methods:
A comprehensive search of the Scopus, PubMed, Embase, and Cochrane Library databases was conducted using a specific query string to identify studies examining the impact of VR on ART outcomes, including fertilization rate, clinical pregnancy, pregnancy loss, and live-birth rate, until October 2023. Outcomes were analyzed based on the type of ART. Studies on VR in infertile men with non-obstructive azoospermia and those who underwent ART only due to female factor infertility were excluded from the study.
Results:
Out of 1,554 articles reviewed, only 9 met the inclusion criteria for the study. All the included articles were observational studies. The variability in study quality in the included literature resulted in a moderate overall risk of bias. Data analysis showed that for intrauterine insemination, there was no difference in the clinical pregnancy rate (odds ratio [OR] 1.01, 95% confidence interval [CI]: 0.42, 2.45; p=0.97). However, for intracytoplasmic sperm injection (ICSI), men with VR showed a significant improvement in fertilization rate (mean difference 10.9, 95% CI: 5.94, 15.89; p<0.01), clinical pregnancy rate (OR 1.38, 95% CI: 1.07, 1.78; p=0.01) and live-birth rate (OR 2.07, 95% CI: 1.45, 2.97; p<0.01), compared to men who did not undergo VR.
Conclusions
The findings of this systematic review and meta-analysis suggest that VR has a positive impact on pregnancy and live birth rates after ICSI. However, biases like small sample sizes and heterogeneous populations highlight the need for larger, well-designed prospective studies to validate these findings.

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