Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations.

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.

Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. MATERIALS AND METHODS: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. RESULTS: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. CONCLUSIONS: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

Comparison of Baseline and Post-Nitrate Exercise Testing in Patients with Angina but Non-Obstructed Coronary Arteries with Different Acetylcholine Test Results.

Background: Intracoronary acetylcholine testing may induce epicardial coronary artery spasm (CAS) or coronary microvascular spasm (CMVS) in patients with angina syndromes but non-obstructive coronary artery disease, but their causal role in individual patients is not always clear. In this prospective, observational single-center study, we aimed to assess whether (1) the induction of myocardial ischemia/angina by electrocardiogram (ECG) exercise stress test (EST) differs between patients showing different results in response to acetylcholine testing (i.e., CAS, CMVS, or no spasm); (2) the preventive administration of short-acting nitrates has any different effects on the EST of those patients who showed a positive basal EST. We expected that if exercise-induced angina and/or ischemic ECG changes are related to CAS, they should improve after nitrates administration, whereas they should not significantly improve if they are caused by CMVS. Methods: We enrolled 81 patients with angina syndromes and non-obstructive coronary artery disease, who were divided into three groups according to acetylcholine testing: 40 patients with CAS (CAS-group), 14 with CMVS (CMVS-groups), and 27 with a negative test (NEG-group). All patients underwent a basal EST (B-EST). Patients with a positive B-EST repeated the test 24-48 h later, 5 min after the administration of short-acting nitrates (N-EST). Results: There were no significant differences among the groups in terms of the B-EST results. B-EST was positive in eight (20%) patients in the CAS-group, seven (50%) in the CMVS-group, and six (22%) in the NEG-group (p = 0.076). N-EST, performed in eight, six, and five of these patients, also showed similar results in the three groups. Furthermore, the N-EST results also did not significantly differ compared to B-EST in any group, remaining positive in seven (87.5%), four (66.7%), and four (80%) patients in the CAS-group, CMVS-group, and NEG-group, respectively (p = 0.78). Conclusions: Our data show that patients with angina and non-obstructive coronary artery disease show largely comparable results of the ECG exercise stress test and similar poor effects of short-acting nitrates on abnormal ECG exercise stress test results. On the whole, our findings suggest caution in attributing to the results of Ach testing a definite causal role for the clinical syndrome in individual patients.

Reverse sheathing technique for iliocaval thrombectomy in the setting of IVC filters.

The Inari ClotTriever system (Inari Medical, Irvine, California) is safe and effective for the treatment of DVT. However, because it consists of a 31 cm coring device and collection bag that must be extended for use, application may be precluded by available intravascular "running room", such as in the presence of an IVC filter. Here we present a technique for bypassing IVC filters via retrograde deployment of the ClotTriever within a sheath, as illustrated in three cases. This technique extends the applicability of the ClotTriever to locations in which its length would otherwise preclude use.

Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. MATERIALS AND METHODS: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. RESULTS: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). CONCLUSIONS: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial.

Use of a funneled sheath for embolic protection during removal of thrombosed Simon Nitinol filters.

Inferior vena cava (IVC) filters should be removed when no longer needed, given their association with complications such as thrombosis of the IVC and lower extremities, fracture, migration, and growth into adjacent structures. While this is generally straightforward in the setting of retrievable filters, permanent filters present more of a challenge. In fact, many operators will not attempt to do so for fear of intraprocedural complications, among them, filter fracture and fragment embolization. Despite this, leaving the filters in situ places patients at risk of the complications described above. Here, the authors illustrate a novel technique for retrieving permanent filters using a funneled sheath to protect against embolization.

Six-Month Deep Vein Thrombosis Outcomes by Chronicity: Analysis of the Real-World ClotTriever Outcomes Registry.

PURPOSE: To analyze the first 250 patients from the prospective, multicenter, industry-sponsored ClotTriever Outcomes (CLOUT) registry, assessing the safety and effectiveness of mechanical thrombectomy for acute, subacute, and chronic deep vein thrombosis (DVT). MATERIALS AND METHODS: Real-world patients with lower extremity DVT were treated with the ClotTriever System (Inari Medical, Irvine, California). Adjuvant venoplasty, stent placement, or both were performed at the physician's discretion. Thrombus chronicity was determined by visual inspection of removed thrombus, categorizing patients into acute, subacute, and chronic subgroups. Serious adverse events (SAEs) were assessed through 30 days. Clinical and quality-of-life (QoL) outcomes are reported through 6 months. RESULTS: Thrombus chronicity was designated for 244 of the 250 patients (acute, 32.8%; subacute, 34.8%; chronic, 32.4%) encompassing 254 treated limbs. Complete or near-complete (≥75%) thrombus removal was achieved in 90.8%, 81.9%, and 83.8% of the limbs with acute, subacute, and chronic thrombus, respectively. No fibrinolytics were administered, and 243 (99.6%) procedures were single sessions. One (0.4%) patient in the subacute group experienced a device-related SAE, a fatal pulmonary embolism. On comparing baseline and 6-month data, improvements were demonstrated in median Villalta scores (acute, from 10 to 1; subacute, from 9 to 1; chronic, from 10 to 3; for all, P < .0001) and mean EuroQol group 5-dimension (EQ-5D) self-report questionnaire scores (acute, 0.58 to 0.89; subacute, 0.65 to 0.87; chronic, 0.58 to 0.88; for all, P < .0001). There were no significant differences in outcomes across the subgroups. CONCLUSIONS: Mechanical thrombectomy using the ClotTriever System with adjunctive venoplasty and stent placement is safe and similarly effective for acute, subacute, and chronic DVT.

Emergency department initiated resuscitative endovascular balloon occlusion of the aorta (REBOA) for out-of-hospital cardiac arrest is feasible and associated with improvements in end-tidal carbon dioxide.

Objectives: Out-of-hospital cardiac arrest (OHCA) claims the lives of approximately 350,000 people in the United States each year. Resuscitative endovascular balloon occlusion of the aorta (REBOA) when used as an adjunct to advanced cardiac life support may improve cardio-cerebral perfusion. Our primary research objective was to determine the feasibility of emergency department (ED)-initiated REBOA for OHCA patients in an academic urban ED. Methods: This was a single-center, single-arm, early feasibility trial that used REBOA as an adjunct to advanced cardiac life support (ACLS) in OHCA. Subjects under 80 years with witnessed OHCA and who received cardiopulmonary rescuitation (CPR) within 6 minutes were eligible. Results: Five patients were enrolled between February 2020 and April 2021. The procedure was successful in all patients and 4 of 5 (80%) patients had transient return of spontaneous circulation (ROSC) after aortic occlusion. Unfortunately, all patients re-arrested soon after intra-aortic balloon deflation and none survived to hospital admission. At 30 seconds post-aortic occlusion, investigators noted a statistically significant increase in end tidal carbon dioxide of 26% (95% confidence interval, 10%, 44%). Conclusion: Initiating REBOA for OHCA patients in an academic urban ED setting is feasible. Aortic occlusion during chest compressions is temporally associated with improvements in end tidal carbon dioxide 30 seconds after aortic occlusion. Four of 5 patients achieved ROSC after aortic occlusion; however, deflation of the intra-aortic balloon quickly led to re-arrest and death in all patients. Future research should focus on the utilization of partial-REBOA to prevent re-arrest after ROSC, as well as the optimal way to incorporate this technique with other endovascular reperfusion strategies.

Algorithm-based individualization methodology of the starting gonadotropin dose in IVF/ICSI and the freeze-all strategy prevent OHSS equally in normal responders: a systematic review and network meta-analysis of the evidence.

PURPOSE: Ovarian hyperstimulation syndrome (OHSS) represents a rare but dangerous condition associated with controlled ovarian stimulation (COS) in IVF/ICSI. Over the last decades, many strategies have been introduced into clinical practice with the objective of preventing this potentially life-threatening condition. Among these, the freeze-all policy has gained great popularity, thanks to improvements in vitrification. Nevertheless, not all clinics have adequate skills in vitrification procedures and patients may be dissatisfied with a longer time to pregnancy. METHODS: This study is a systematic review and network meta-analysis of randomized controlled trials comparing different strategies of ovarian stimulation in IVF/ICSI cycles (freeze-all policy, algorithm-based individualization of the starting dose, experience-based individualization of the starting dose, standard dose) in terms of reduction of OHSS, in normal responders. RESULTS: The results indicate that only the algorithm-based individualization of the starting gonadotropin dose reduces OHSS similarly to the freeze-all strategy. CONCLUSION: Albeit in the era of the freeze-all policy, the personalization of the starting gonadotropin dose obtained by the use of algorithms should be pursued as a valid and safe option for IVF.

Cryoablation of Venous Malformations: A Systematic Review.

This study aimed to review systematically the efficacy, safety, and technical aspects of cryoablation in the treatment of venous malformations (VMs) and to provide the groundwork for future studies. A literature search for clinical studies utilizing percutaneous cryoablation of VMs was performed. All clinical studies related to primary or secondary treatment of VMs with percutaneous cryoablation were included in this review. These selected studies were evaluated for patient characteristics, cryoablation technique, technical success, lesion size and pain scores before and after cryoablation, and adverse outcomes. Random effects analysis of postprocedural changes in lesion volume and pain scores was performed. There were 54 patients with 55 cases of cryoablation of VMs. Of these cases, 27 recorded changes in lesion volume and 31 recorded changes in pain scores. The weighted mean postprocedural decrease in lesion size was 92.0% (raw average, 71.7%). The weighted mean reduction in pain score was 77% (raw average, 78.2%). Considering all treated cases (55), complete resolution of symptoms was seen in 35 cases (63.6%) and overall (complete or partial) improvement in 52 cases (94.5%). Common postprocedural symptoms included pain, bruising, swelling and numbness lasting less than 2 weeks. There were two major adverse events (3.7%), with both cases due to persistent dysesthesia. Patients with a history of prior sclerotherapy demonstrated lower preprocedural and postprocedural pain scores (4.7 and 1.3) than patients without prior treatments (5.8 and 2.8). Cryoablation of VMs appears to be potentially safe and effective on limited short-interval follow-up.

The Gender Gap in the Diagnostic-Therapeutic Journey of the Infertile Couple.

Medical procreation impairs both the biological and psychological lives of couples. However, male and female attitudes to infertility are different and require a different approach during the IVF journey. Thus, the gender impact assessment (GIA) method was used to analyse original studies present in the literature. We found some gender-related differences and, subsequently, possible outcomes of intervention to improve healthy reproduction management and prevent infertility. In particular, it became apparent that there was the need for an in-depth male infertility assessment and a gender-specific follow-up.

Mechanical thrombectomy for pulmonary embolism in patients with patent foramen Ovale.

BACKGROUND: The current level of evidence for mechanical thrombectomy (MT) of pulmonary embolism (PE) in patients with patent foramen ovale (PFO) is limited. RESULTS: This was a retrospective analysis of 9 patients with PFO and acute high-risk or intermediate-high-risk PE, 6 with intermediate-high risk and 3 with high-risk PE. All underwent MT using the Inari FlowTriever System from Dec 2018 to November 2019. Six of these patients had confirmed deep venous thrombosis. The technical and clinical success rate for MT in all patients was 100% and 77.8%, respectively. Right-heart strain improved in 6/8 patients on follow-up echocardiography. Mean main pulmonary artery (MPA) pressure significantly decreased after MT (p < 0.012). One patient presented with altered mental status (somnolence and disorientation) prior to coronary artery angiogram and thrombectomy, developed a middle cerebral artery embolic stroke 1 day after MT, and recovered with minor sequalae and later was discharged. There was no in-hospital mortality. CONCLUSIONS: MT using FlowTriever was feasible and safe, successfully improving MPA pressure in patients presenting with concurrent PFO and PE.

Use of follicle-stimulating hormone for the male partner of idiopathic infertile couples in Italy: Results from a multicentre, observational, clinical practice survey.

BACKGROUND: The management of male idiopathic infertility is heterogeneous. Although meta-analyses reported the effectiveness on pregnancy rate, the real clinical impact of follicle-stimulating hormone (FSH) was not evaluated so far. In Italy, FSH is approved by the National Medicines Agency (AIFA) for idiopathic infertile patients with FSH < 8 IU/L, independently of semen parameters. AIM: Primary endpoint was to record the therapeutic approach to the male partner of infertile couples. Secondary aim was to assess changes of semen parameters during FSH treatment. METHODS: A multicentre, prospective, observational, clinical practice survey was carried out, enrolling the male partner of infertile couples attending ten Italian participating centres. Inclusion criteria were as follows: couple infertility, age >18 years and FSH serum levels <8 IU/L. Thus, all men in which AIFA allowed the FSH prescription were enrolled. Primary endpoint was the number of infertile patients treated with FSH. Secondary outcomes were semen parameters. The treating physician decided whether to offer FSH therapy and whether to re-evaluate the male partner. RESULTS: A total of 718 infertile couples were enrolled, and 241 patients were re-evaluated (median follow-up: 4.5 months). In 64.9% (466 patients), a treatment was prescribed. FSH was prescribed in 397 patients (85.2% of treated men). Sperm concentration (P = .002) and normal form percentage (P < .001) significantly improved during FSH administration. No correlation was found between these parameters and FSH duration (P = .545 and P = .627, respectively) or dosage (P = .455 and P = .533, respectively). Among patients treated with FSH, the incidence of oligozoospermia decreased from 73.0% to 56.0% (P < .001) and teratozoospermia from 43.6% to 27.7% (P < .001). DISCUSSION: This first nation-wide survey reveals a FSH prescription rate of 55% in patients qualifying for treatment according to AIFA. Although the study was not designed to highlight FSH efficacy in male infertility, a slight increase in semen parameters was demonstrated in about half of the treated men without adverse events.

From telescope to binoculars. Dyadic outcome resulting from psychological counselling for infertile couples undergoing ART.

OBJECTIVE: This longitudinal study aims to evaluate the effect of psychological counselling on quality of life, marital satisfaction and need for parenthood in couples undergoing fertility treatments (ART). BACKGROUND: Recent guidelines on the ART suggest that psychological counselling should target both members of the infertile couple in order to improve their conjoint management of the infertility-related stress. However, studies on the dyadic outcome of couples are scarce. METHODS: 262 patients were originally considered in the study and completed questionnaires on quality of life, need for parenthood and marital satisfaction, before treatment (T1) and at the day of intrauterine insemination/embryo transfer (T2). For the purposes of this study, 34 counselled couples were then matched to 34 non-counselled couples by propensity scores. The Common Fate Model (CFM) was used to examine dyadic changes. RESULTS: Couples receiving counselling had higher dyadic quality of life and lower dyadic stress due to the need for parenthood at T2 compared to non-counselled couples. No differences were found on marital satisfaction. CONCLUSION: The findings provide support for the effectiveness of counselling on interpersonal outcome. The CFM allows researchers to examine how the dyad as a whole responds to counselling, highlighting the change in the couple's relational dynamics.

A randomized controlled trial investigating the use of a predictive nomogram for the selection of the FSH starting dose in IVF/ICSI cycles.

The number of oocytes retrieved is a relevant intermediate outcome in women undergoing IVF/intracytoplasmic sperm injection (ICSI). This trial compared the efficiency of the selection of the FSH starting dose according to a nomogram based on multiple biomarkers (age, day 3 FSH, anti-Müllerian hormone) versus an age-based strategy. The primary outcome measure was the proportion of women with an optimal number of retrieved oocytes defined as 8-14. At their first IVF/ICSI cycle, 191 patients underwent a long gonadotrophin-releasing hormone agonist protocol and were randomized to receive a starting dose of recombinant (human) FSH, based on their age (150 IU if ≤35 years, 225 IU if >35 years) or based on the nomogram. Optimal response was observed in 58/92 patients (63%) in the nomogram group and in 42/99 (42%) in the control group (+21%, 95% CI = 0.07 to 0.35, P = 0.0037). No significant differences were found in the clinical pregnancy rate or the number of embryos cryopreserved per patient. The study showed that the FSH starting dose selected according to ovarian reserve is associated with an increase in the proportion of patients with an optimal response: large trials are recommended to investigate any possible effect on the live-birth rate.

The carriers of the A/G-G/G allelic combination of the c.2039 A>G and c.-29 G>A FSH receptor polymorphisms retrieve the highest number of oocytes in IVF/ICSI cycles.

PURPOSE: The objective of this study was the elucidation of the possible role of the single-nucleotide polymorphisms (SNP) at position -29 and 2039 of the FSH receptor gene (FSHR) as independent predictive markers of ovarian response. Indeed, the tailoring of reproductive treatments is crucial for both maximizing the success of IVF patients and obtaining a reduction in hypo- or hyper-response rates. METHODS: This prospective, observational study analyzed the association of -29 and 2039 FSHR polymorphisms with the number of retrieved oocytes in 140 patients attending an IVF/ICSI cycle for severe male factors (≤5,000,000 spermatozoa/mL) or tubal factors at the ANDROS Day Surgery Clinic, Palermo, Italy. RESULTS: The results of this study demonstrate that the genetic combination of A/G for polymorphism c.2039 A>G with G/G for polymorphism c.-29 G>A is significantly associated with the highest number of collected oocytes (p = 0.03). This association was significant even after controlling for the effect of other clinical variables. CONCLUSIONS: The A/G-G/G allelic variant, identified as an independent variable, if confirmed in a larger number of patients, could be considered as a new genetic biomarker, which could increase the efficacy of prediction models for ovarian stimulation.