Cost Considerations in the Management of Nonobstructive Azoospermia in the United States.

Kallman syndrome and central non-obstructive azoospermia

Introduction Non-obstructive azoospermia (NOA) is characterized by the absence of sperm in the ejaculate due to testicular failure. Testicular biopsy may play a crucial role in evaluating and managing NOA by providing valuable diagnostic information and guiding treatment decisions. Performing a testicular biopsy before microdissection testicular sperm extraction (mTESE) can determine the presence and degree of spermatogenesis, evaluate the feasibility of sperm retrieval, optimize the surgical approach, and contribute to patient counselling during a fertility workup. Minimal literature exists describing the utility of a testicular biopsy prior to an mTESE in the management of NOA. Objective The primary aim of this study is to evaluate the role of testicular biopsy in the assessment and management of NOA and to determine the necessity and willingness of patients to undergo further mTESE procedures based on the pathological findings. Methods This retrospective single-center study included adult males with NOA meeting criteria of two consecutive semen analyses demonstrating azoospermia, FSH levels >8 mIU/mL and normal karyotype/Y chromosome microdeletion (YCMD). Data was extracted from medical charts of patients seen by a single surgeon between September 2022 and June 2024. Demographic variables (age, BMI, FSH levels) and histopathology findings from testicular biopsies were collected ranging from Sertoli cell-only syndrome (SCO), hypospermatogenesis, and maturation arrest to normal testicular tissue. Linear regression analysis was performed to determine if histopathology types predicted patient decisions to undergo mTESE. Results This study examined the relationship between testicular histopathology and mTESE decisions in 19 patients (mean age 35.9 ± 5.5 years, BMI 26.9 ± 4.4 kg/m2, FSH 22.0 ± 15.8 mIU/mL). 68.4% had homogenous pathology, 26.3% had two pathologies, and 5.3% had three pathologies. Hypospermatogenesis was most common (46.2%), followed by SCO (38.5%) and maturation arrest (15.4%). Logistic regression analysis revealed that the odds of choosing mTESE increased by a factor of 5.33 (CI95%: 1.23-23.14) for each additional pathology observed. Patients with hypospermatogenesis were 3.08 times more likely to opt for mTESE compared to other pathologies (CI95%: 1.42-6.67). The probability of choosing mTESE increased from 42.86% for one pathology to 95.24% for three pathologies, with 30.77% of hypospermatogenesis, 19.23% of SCO, and 15.38% of maturation arrest patients opting for the procedure. Conclusions This single-center retrospective study underscores the pivotal role of testicular biopsy in the management of NOA. Histopathologic findings from testicular biopsies significantly influenced patients' decisions to proceed with a mTESE, with those diagnosed with hypospermatogenesis demonstrating a strong inclination towards pursuing mTESE. These findings highlight the clinical utility of histopathological assessment in guiding personalized treatment for NOA patients, optimizing the effectiveness of fertility interventions and enhancing patient counselling during fertility evaluations. Future prospective studies should further validate these findings across diverse patient populations to refine clinical algorithms for effective NOA management. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Dr. Premal Patel has been a consultant for Boston Scientific.

Varicocele Repair in Patients With Nonobstructive Azoospermia: A Meta-Analysis

Non-obstructive azoospermia (NOA) is a common cause of infertility in males, which is characterized by the absence of sperm in the ejaculate, resulting from impaired spermatogenesis. The primary therapeutic approaches for the management of NOA include testicular sperm extraction, varicocelectomy in case of clinical varicoceles, and hormonal manipulation. While traditional treatments are found to have a limited role in the management of NOA, recent studies have explored the potential of platelet-rich plasma (PRP) as a safer and promising therapeutic option. Autologous PRP preparations are derived from the patient's blood and comprise growth factors and cytokines, promoting tissue repair and regeneration. PRP has a wide range of applications in the medical field, including managing infertility in males and females. This literature review aimed to evaluate the existing evidence on the efficacy and safety of PRP in the management of NOA. After a thorough review of relevant data from observational and experimental studies, the findings of this study suggested that PRP may positively influence spermatogenesis, sperm quality, DNA integrity, and sperm retrieval during assisted reproductive procedures. Further research is needed to establish the optimal PRP preparation, administration method, and long-term benefits. The newer studies shall include a diverse patient population and employ long-term follow-up to assess the durability of any positive effects of PRP treatment. The growing body of evidence regarding the therapeutic potential for NOA in humans offers greater opportunities for men seeking fertility treatment, informing clinical practice, and optimizing the use of PRP.

Alternate indications for varicocele repair: non-obstructive azoospermia, pain, androgen deficiency and progressive testicular dysfunction

68 - Management of non-obstructive azoospermia with extracorporeal shock wave therapy and platelet-rich plasma

Management of nonobstructive azoospermia: a committee opinion

The management of non-obstructive azoospermia (NOA) remains challenging because no predictive test for the presence of localized spermatogenesis exists. Previous work considered MRI techniques, such as spectroscopy (MRS) and diffusion weighted imaging (DWI), in this role. We report here data from a prospective study evaluating additional advanced MRI sequences for predicting spermatogenesis in patients with NOA. 9 fertile volunteers and 18 men with NOA were prospectively recruited. Each participant underwent a novel multi-parametric MRI consisting of T1 and T2 mapping as well as intravoxel incoherent motion (IVIM) and diffusion weighted imaging (DWI). A single radiologist drew representative regions of interest on the best quality images for each sequence and recorded the mean values. Sperm extraction procedure results were recorded. Two-end points were evaluated: NOA versus fertile controls and the presence of viable sperm within the NOA cohort. The data were analyzed per patient. Nonparametric and logistic regression statistical analysis were used. 9 fertile men (median 43years old, 2 children) and 18 men with NOA (median 37years old, 0 children) were studied. 11 of the 18 men with NOA had testicle sampling. 4 men with NOA had viable sperm. Follicle-stimulating hormone and testosterone levels were not significantly different among NOAmen with and without sperm (p-value = 0.58 and 0.25). Nonparametric analysis with the Wilcoxon rank sum test showed T2 relaxation time was lower among NOA patients (median 101 vs 135ms, p-value = 0.002), apparent diffusion coefficient (ADC) was higher among NOA patients (median 127.9 vs. 106.7 × 10-5 mm2/sec, p-value = 0.005). T1 relaxation time, alpha (Water diffusion heterogeneity index), D (IVIM-based apparent diffusion coefficient), DDC (Distributed diffusion coefficient) and D* (pseudodiffusion) were also significantly different. On logisticregression analysis, both T2 and ADC were associated with NOA; The odds of NOA decreased by 6% for each msec increase in T2 (p-value = 0.02) while the odds of NOA increased by 11% for each 10⁻5 mm2/sec increase in ADC, (p-value = 0.02). T2 yielded a larger area under the receiver operating characteristic curve than ADC (0.87 versus 0.84). Alpha, D, DDC and D* also predicted NOA. Amongst men with NOA who underwent testicle sampling, T2 was lower in testicles of patients with no sperm retrieved (median 73 vs 134. msec, p-value = 0.02). The remaining variables were not significantly different between the cohorts. In spite of the small sample size, particularly for men with NOA who underwent sperm extraction, these results suggest that several novel MRI parameters, such as T2 relaxation time and certain IVIM/DWI parameters, are able to distinguish between fertile men and men with NOAas well as potentially predict successful sperm extraction in men with NOA. Additional larger prospective studies of men with NOA undergoing sperm extraction are warranted.

Early Versus Late Maturation Arrest: Reproductive Outcomes of Testicular Failure

BackgroundVaricocele is an abnormal dilation and tortuosity of the internal spermatic veins within the pampiniform plexus of the spermatic cord. Varicocele is associated with progressive testicular damage and infertility. Azoospermia is associated with a varicocele in approximately 4–14% cases. For men with azoospermia or severe oligoasthenospermia, varicocele repair may result in modest improvement in semen quality which may have a significant advantage on couple’s fertility options. The aim of the study was to evaluate the role of microsurgical varicocelectomy in the men of non-obstructive azoospermia (NOA) with clinical varicocele.MethodsThis was a retrospective study conducted between August 2012 and January 2017, a backward review of 104 patients with the diagnosis of infertility and NOA with palpable varicocele that underwent microsurgical varicocelectomy at our institution was performed. In addition, microdissection testicular sperm extraction (MDTESE) results of these post-varicoceletomy patients were compared with the patients of NOA without varicocele.ResultsA total of 104 patients underwent varicocelectomy; out of these, 19 patients (18.26%) had sperm on sperm analysis post-operatively. Two of them had spontaneous pregnancy (10.5%), and 3 had children by intracytoplasmic sperm injection (15.78%). Out of the 85 patients who had MDTESE, 29 patients (34.11%) had sperms in their testis. The fertilization rate was 89.65%. Sperm retrieval rate (SRR) in NOA men with varicocele was 34.11% which was higher from those who had NOA without varicocele (24.03%). Live birth rate was 31.03% in NOA men who had varicocelectomy which was more in comparison to NOA men without varicocele (24%).ConclusionsIn NOA men with varicocele microsurgical varicocelectomy may have favourable effects which results in recovery of motile sperms in the post-operative ejaculate and also on spontaneous or assisted pregnancies, but it appears that this effect was more remarkable on MDTESE results when following successful intracytoplasmic sperm injection. Importantly, Sperm retrieval rate, pregnancy rate and subsequent live birth rate were higher in these patients in comparison to patients affected by NOA alone. In patients with NOA and coexisting varicocele, varicocelectomy can be considered to be essential to the overall reproductive outcome in these patients.

Non-obstructive azoospermia (NOA), defined as the absence of sperm in the ejaculate due to testicular failure, is observed in 5% to 15% of infertile men and accounts for two-thirds of azoospermia cases. The management of NOA is marked by significant controversy and global variation in diagnostic and therapeutic approaches, highlighting the crucial need for well-designed and standardized clinical practice guidelines. We present comprehensive graded clinical practice recommendations and statements for diagnosing and treating NOA, aiming to establish standardized strategies that can globally help guide practitioners in their practice. A comprehensive literature review was conducted to gather evidence on the epidemiological, diagnostic, and therapeutic aspects of NOA. The Global Andrology Forum (GAF) recommendations were developed through the collaboration of a global panel of experts using the Delphi method and surveys to achieve consensus. Statements were graded according to the Oxford Centre for Evidence-Based Medicine "GRADE" classification as either "Strong" or "Weak." Statements receiving at least 80% expert consensus were graded as "Strong," while others were categorized as "Weak." The GAF has formulated a total of 49 recommendations and statements on the diagnosis and treatment of NOA, including 21 for diagnosis and 28 for treatment. The recommendations and statements were evaluated and graded by a panel of 48 GAF experts from 25 countries worldwide. The majority of experts (60.5%) had more than 10 years of clinical experience in managing NOA. The GAF guidelines address discrepancies in NOA management across diverse clinical settings and provide comprehensive graded recommendations to guide clinicians in its diagnosis and treatment. Developed and graded by a large worldwide panel of experts, the current guidelines present simplified, high-standard strategies that can be seamlessly integrated into the daily global practice, offering practitioners a clear framework for managing NOA.

The role of varicocele treatment in the management of non-obstructive azoospermia

Introduction TFNA mapping is a diagnostic procedure that enables the urologist to get a diagnostic overview of possible locations that sperm may be present and can serve as a guide for both urologist and patient as to what is the next appropriate step in the management of that particular patient’s NOA. Objective To model the potential cost savings and procedural triage benefits of using testicular fine needle aspiration (TFNA) mapping as a diagnostic step prior to microdissection testicular sperm extraction (mTESE) in men with non-obstructive azoospermia (NOA). Methods A theoretical cost model was developed using a cohort of 100 men with NOA. All patients underwent initial TFNA mapping ($1,000). Based on mapping results, 10 patients with abundant sperm underwent testicular sperm aspiration (TESA, $500), 20 with scattered sperm underwent targeted TESE ($2,500), and 20 with rare sperm were managed via shared decision-making-5 opting for TESE and 5 for mTESE ($10,000). Among the 50 patients with no sperm found on mapping, 40 proceeded to mTESE, while 10 declined further intervention. Total system costs were compared with a model in which all 100 patients underwent mTESE as the first-line approach. Results The TFNA-first strategy yielded a total cost of $617,500, compared to $1,000,000 in the mTESE-for-all model-a cost reduction of 38%. Mapping altered clinical decision-making in 45% of patients, either enabling less invasive procedures or averting unnecessary surgery. Additionally, mapping provided critical prognostic and counseling value, particularly for patients with no sperm detected, allowing for more informed consent and emotionally grounded decision-making prior to mTESE. Conclusions TFNA mapping may reduce costs, procedural morbidity, and decisional uncertainty in the management of NOA. Even when mapping does not preclude mTESE, it adds diagnostic clarity and facilitates more patient-centered care. This theoretical model supports the integration of TFNA mapping as a rational, cost-effective step in modern reproductive urology. Prospective validation is warranted. Disclosure No

Surgical testicular sperm retrieval for intra-cytoplasmic sperm injection purposes is the only possibility of biological fathering in case of non-obstructive azoospermia (NOA). Successful retrieval only correlates with histology, not with FSH values or testicular volume. Testicular sperm extraction (TESE) (mean of successful retrievals in the literature: 52.7%) is the technique of choice: we had successful retrievals in 100% of cases of hypospermatogenesis with >5 spermatids/tubule (spd/tub), 81.8% of cases of hypospermatogenesis with <4 spd/tub, 50% of cases of maturation arrest, and 25% of cases of histologically pure Sertoli cell only syndrome. Microsurgical TESE (MicroTESE) has been reported to increase successful retrievals: from 16.7 to 45% for standard TESE to 42.9–63.6% for MicroTESE, depending on the distribution of testicular histology in the various case studies. TeFNA does not appear to be indicated in NOA, both because of its low success rates—which, in practice, are only positive in hypospermatogenesis, and because it is unable to detect any carcinomas in situ. Previous surgery of left varicocele in NOA could increase the chances of subsequent recovery.

A general consensus on the role of testicular biopsy in non-obstructive azoospermia (NOA) is needed. This paper reviews and updates technical aspects and clinical performance of the percutaneous testicular biopsy techniques, in particular large-needle aspiration biopsy (LNAB), and proposes a flow chart for the management of NOA.The English literature and original data were reviewed or analyzed. Large-needle biopsy (LNB) includes large-needle cutting biopsy (LNCB) and large-needle aspiration biopsy (LNAB). LNCB usually requires scrotal incision for the insertion of relatively large needles. Fine-needle aspiration biopsy (FNAB) does not require surgical equipment or expertise, employs the smallest needles (23- to 20-gauge), and permits sperm cytologic detection. LNAB also does not require surgical equipment or expertise, employs needles of size from 20- to 18-gauge, is safe, and can be used for testicular histology and sperm recovery.An operative flow chart is proposed for the management of NOA in which FNAB, LNAB and open surgical biopsy are used for the optimal management of NOA.