Outcome prediction of microdissection testicular sperm extraction based on extracellular vesicles piRNAs.

PURPOSE: Microdissection testicular sperm extraction (micro-TESE) could retrieve sperm from the testicles to help the non-obstructive azoospermia (NOA) patients to get their biological children, but also would cause damage to the testicles. Therefore, it is necessary to preoperatively predict the micro-TESE outcome in NOA patients. For this purpose, we aim to develop a model based on extracellular vesicles' (EVs) piRNAs (EV-piRNAs) in seminal plasma. METHODS: To identify EV-piRNAs that were associated with spermatogenic ability, small RNA-seq was performed between the NOA group (n = 8) and normal group (n = 8). Validation of EV-piRNA expression in seminal plasma EVs and testicles tissues was used to select EV-piRNAs for the model. Candidate EV-piRNAs were further selected by LASSO regression analysis. Binary logistic regression analysis was used for the models' calculation formula. ROC analysis and Hosmer-Lemeshow test was used to assess the models' performance in the training (n = 20) and validation (n = 25) cohorts. RESULTS: We identified 8 EV-piRNAs which were associated with spermatogenic ability. Two EV-piRNAs (pir-60351 and pir-61927) were selected by LASSO regression analysis. Finally, we developed a favorable model based on the expression of pir-61927 with good discrimination wherein the AUC was 0.82 (95% CI: 0.63~1.00, p = 0.016) in the training cohort and 0.83 (95% CI: 0.66~1.00, p = 0.005) in the validation cohort, as well as good calibration. CONCLUSIONS: A favorable model based on the expression of pir-61927 in seminal plasma EVs was established to predict the micro-TESE outcome in NOA patients.

Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline PART II.

PURPOSE: The summary presented herein represents Part II of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part II outlines the appropriate management of the male in an infertile couple. Medical therapies, surgical techniques, as well as use of intrauterine insemination (IUI)/in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) are covered to allow for optimal patient management. Please refer to Part I for discussion on evaluation of the infertile male and discussion of relevant health conditions that are associated with male infertility. MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January 2000 through May 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. RESULTS: This Guideline provides updated, evidence-based recommendations regarding management of male infertility. Such recommendations are summarized in the associated algorithm (figure[Figure: see text]). CONCLUSION: Male contributions to infertility are prevalent, and specific treatment as well as assisted reproductive techniques are effective at managing male infertility. This document will undergo additional literature reviews and updating as the knowledge regarding current treatments and future treatment options continues to expand.

Testicular sperm extraction and intracytoplasmic sperm injection outcome in cancer survivors with no available cryopreserved sperm.

OBJECTIVE: To assess rates of successful testicular sperm retrieval and intracytoplasmic sperm injection (ICSI) outcome in cancer survivors affected by non-obstructive azoospermia (NOA) or retrograde ejaculation (RE)/failure of emission (FOE). METHODS: A retrospective analysis of cancer survivors who did not cryopreserve sperm prior to treatment undergoing testicular sperm extraction (TESE). Non-cancer NOA patients and neurologic RE/FOE were the control group. RESULTS: A total of 97 cancer survivors were offered TESE and 88 (91%) accepted. Sperm was retrieved and cryopreserved in 34/67 patients with NOA (50.7%) and in 21/21 patients affected by RE/FOE (100%). Sperm retrieval rates were similar in the control group (44.9% in NOA and 100% in RE/FOE). The ICSI cumulative pregnancy rate (60%) and live birth rate (40%) per couple in 30 NOA men did not differ from controls (50.0 and 46.5%, respectively; p = 0.399/0.670). The cumulative pregnancy rate (66.7%) and live birth rate (55.6%) in 18 RE/FOE men did not differ from the control group (38.9 and 33.3%, respectively; p = 0.181/0.315). The cancer type and the resulting infertility disorder (NOA or RE/FOE) were not associated with ICSI outcomes. Female partner age was inversely related to the cumulative live birth rate, being fourfold lower (11.5%) in women ≥ 40 years and 48.8% in younger women (p = 0.0037). CONCLUSIONS: The rate of successful TESE and the ICSI outcome in cancer survivors with NOA and RE/FOE is the same as non-cancer azoospermic patients. Female partner age (older than 40 years) was associated with a significant reduction in live birth rates after TESE-ICSI procedures.

Failure modes and effects analysis for testicular sperm extraction management process.

Failure modes and effects analysis (FMEA) is a proactive risk evaluation to identify and reduce potential failures that may occur during a procedure within a quality management programme. One of the procedures performed in assisted reproduction technology centres is testicular sperm extraction (TESE) as treatment of azoospermic patients. To examine the risks associated with the 'TESE management' process, we applied the FMEA method, before and after implementation of corrective measures defined in a standard operative procedure (SOP). A multidisciplinary team was formed. Possible causes of failures and their potential effects were identified, and risk priority number (RPN) for each failure was calculated. The FMEA team identified 4 process activities, 19 process steps and 19 potential failure modes. The re-evaluation after the corrective measures disclosed a reduction in the number of phases with high/moderate risk (pre-SOP: n = 13; post-SOP: n = 3). Improvements in the traceability system removed 11 out of 13 (85%) steps with a low risk of occurrence. In our experience, FMEA is efficient in helping multidisciplinary groups to strengthen knowledge and awareness on routine processes, identifying critical steps and planning practical improvements for a better compliance with criteria of traceability and conformity of biological samples and patients.

Reference range and cutoff value of serum inhibin B to predict successful sperm retrieval: A cross-sectional study of 30 613 Chinese men.

BACKGROUND: The power of inhibin B to predict competent spermatogenesis is not fully understood. The aims of this study were to identify the reliable reference range of inhibin B among normozoospermic men in China and to evaluate the diagnostic accuracy of serum inhibin B level as a complementary predictor of successful sperm retrieval in patients with azoospermia. METHODS: This was a cross-sectional study. The male partners of 30 613 infertile couples who visited our hospital were investigated between March 2017 and March 2019. We analysed semen parameters, serum levels of reproductive hormones (inhibin B, FSH and testosterone) and sperm retrieval results from PESA/TESE in Chinese men. RESULTS: The normal reference range of inhibin B was 87.42-299.93 pg/mL among men with normozoospermia in China. Inhibin B levels were negatively correlated with age (r = -.111; P < .001) but positively correlated with total sperm counts in the overall population, reference group and case group (r = .311, r = .208 and r = .444, respectively; P < .001). Stepwise multiple regression analyses revealed that compared with the FSH and testosterone levels, the inhibin B level had the closest relationship with the total sperm count. The best cutoff value of inhibin B for predicting the retrieval outcome of testicular/epididymal sperm was >77.72 pg/mL (sensitivity = 59.14%, specificity = 92.00% and AUC = 0.801). The inhibin B:FSH ratio (cutoff value > 6.98, sensitivity = 56.99%, specificity = 96.00% and AUC = 0.814) performed better than either the inhibin B level or the FSH level alone. CONCLUSION: A new reference range for serum inhibin B was established in China. However, neither serum inhibin B, FSH nor their ratio is adequate for men to decide whether to undergo PESA/TESE to determine the adequacy of spermatogenesis.

Two Successful Sperm Aspirations in High-Risk Adolescent and Young Adult Lymphoma Patients Before Initiation of Emergent Therapy.

As survival rates for adolescent and young adult (AYA) cancer patients improve, fertility preservation has gained increased attention. Many AYAs report significant concerns about fertility potential after therapy. Preservation at diagnosis may be the only opportunity for future genetic parenthood for many patients. Time constraints, concerns about treatment delays, and difficulty accessing resources are reported as reasons for providers not providing counseling. In addition, some pubertal males are unable/unwilling to produce a sample through self-stimulation. Testicular sperm aspiration/extraction with sperm cryopreservation can be successfully performed in "high-risk" pubertal males with significant barriers to traditional collection before initiation of emergent chemotherapy.

Dual consent? Donors' and recipients' views about involvement in decision-making on the use of embryos created by gamete donation in research.

BACKGROUND: Reasonable disagreement about the role awarded to gamete donors in decision-making on the use of embryos created by gamete donation (EGDs) for research purposes emphasises the importance of considering the implementation of participatory, adaptive, and trustworthy policies and guidelines for consent procedures. However, the perspectives of gamete donors and recipients about decision-making regarding research with EGDs are still under-researched, which precludes the development of policies and guidelines informed by evidence. This study seeks to explore the views of donors and recipients about who should take part in consent processes for the use of EGDs in research. METHODS: From July 2017 to June 2018, 72 gamete donors and 175 recipients completed a self-report structured questionnaire at the Portuguese Public Bank of Gametes (response rate: 76%). Agreement with dual consent was defined as the belief that the use of EGDs in research should be consented by both donors and recipients. RESULTS: The majority of participants (74.6% of donors and 65.7% of recipients) were willing to donate embryos for research. Almost half of the donors (48.6%) and half of the recipients (46.9%) considered that a dual consent procedure is desirable. This view was more frequent among employed recipients (49.7%) than among non-employed (21.4%). Donors were less likely to believe that only recipients should be involved in giving consent for the use of EGDs in research (25.0% vs. 41.7% among recipients) and were more frequently favourable to the idea of exclusive donors' consent (26.4% vs. 11.4% among recipients). CONCLUSIONS: Divergent views on dual consent among donors and recipients indicate the need to develop evidence-based and ethically sustainable policies and guidelines to protect well-being, autonomy and reproductive rights of both stakeholder groups. More empirical research and further theoretical normative analyses are needed to inform people-centred policy and guidelines for shared decision-making concerning the use of EGDs for research.

Reproductive Urologist and Gynecologist Involvement in Postvasectomy Sperm Retrieval Procedures at American Fertility Clinics.

OBJECTIVE: To evaluate reproductive urologist and reproductive endocrinologist practice patterns for postvasectomy surgical sperm retrieval at American private practice fertility clinics. METHODS: Private practice American fertility clinics were contacted by telephone and administered a telephone survey. In states with multiple large cities, several clinics in different cities were surveyed. Our primary endpoint was to determine what specialty of physician (urologist or reproductive endocrinology gynecologist) performed sperm retrieval procedures. Secondarily, we inquired about the location that these procedures were performed (urology vs gynecology clinic), type of anesthesia used, and cash cost for the procedure. RESULTS: Two hundred and twenty-five infertility clinics were contacted (per state range 2-10). 90.2% (203/225) of clinics responded to our queries. Zero clinics had an on-site urologist. An on-staff gynecologist with reproductive endocrinology training performed postvasectomy sperm retrievals in 9.4% (19/203) of clinics. A urologist "partnered" with the infertility clinic performed sperm retrievals at the fertility clinic in 11.8% (24/203) of clinics. 18.7% (38/203) did not offer sperm retrieval on-site, but did have a referral pattern established with a local urologist. Among reproductive endocrinologist performing sperm retrievals, intravenous anesthesia was used in 76.9% (10/13) of clinics. The quoted costs for surgical sperm retrieval performed by a reproductive endocrinologist ranged from $1000 to 10,000. CONCLUSION: Surgical sperm retrieval postvasectomy performed by an on-site reproductive endocrinologist was offered by 9.4% of contacted fertility clinics. The majority (76.9%) of these cases were routinely performed under intravenous anesthesia. Costs for reproductive endocrinologist performed sperm retrievals varied considerably. The reasons for, and safety of reproductive endocrinologists performing these procedures remains to be determined.

Management of nonobstructive azoospermia: a committee opinion.

The management of nonobstructive azoospermia in the context of fertility treatment is discussed. This document replaces the ASRM document titled "Evaluation of azoospermia," last published in 2008.

Optimizing human semen cryopreservation by reducing test vial volume and repetitive test vial sampling.

OBJECTIVE: To investigate optimal test vial (TV) volume, utility and reliability of TVs, intermediate temperature exposure (-88°C to -93°C) before cryostorage, cryostorage in nitrogen vapor (VN2) and liquid nitrogen (LN2), and long-term stability of VN2 cryostorage of human semen. DESIGN: Prospective clinical laboratory study. SETTING: University assisted reproductive technology (ART) laboratory. PATIENT(S): A total of 594 patients undergoing semen analysis and cryopreservation. INTERVENTION(S): Semen analysis, cryopreservation with different intermediate steps and in different volumes (50-1,000 µL), and long-term storage in LN2 or VN2. MAIN OUTCOME MEASURE(S): Optimal TV volume, prediction of cryosurvival (CS) in ART procedure vials (ARTVs) with pre-freeze semen parameters and TV CS, post-thaw motility after two- or three-step semen cryopreservation and cryostorage in VN2 and LN2. RESULT(S): Test vial volume of 50 µL yielded lower CS than other volumes tested. Cryosurvival of 100 µL was similar to that of larger volumes tested. An intermediate temperature exposure (-88°C to -93°C for 20 minutes) during cryopreservation did not affect post-thaw motility. Cryosurvival of TVs and ARTVs from the same ejaculate were similar. Cryosurvival of the first TV in a series of cryopreserved ejaculates was similar to and correlated with that of TVs from different ejaculates within the same patient. Cryosurvival of the first TV was correlated with subsequent ARTVs. Long-term cryostorage in VN2 did not affect CS. CONCLUSION(S): This study provides experimental evidence for use of a single 100 µL TV per patient to predict CS when freezing multiple ejaculates over a short period of time (<10 days). Additionally, semen cryostorage in VN2 provides a stable and safe environment over time.

Clinical guidelines for sperm cryopreservation in cancer patients.

No clear clinical guidelines exist on how to counsel male cancer patients about fertility preservation. Detailed counseling is recommended before treatment when issues of collection and storage need to be highlighted. Concern about the quality of sperm collected before and/or after treatment in terms of assisted reproduction is needed, and the potential outcomes should be discussed early as part of cancer survivorship. The discussion should be sensitive and tailored to the ethical situation based on the age of the patient, the severity of the illness, the need to initiate treatment, and genetic risk. Cryopreservation should be attempted/achieved before cancer treatment is initiated. Cryopreservation should not be performed during treatment or for some time after treatment because of the chromosomal and structural damage to sperm from cancer treatment. Contraception should be instigated during this period.

A content analysis of posthumous sperm procurement protocols with considerations for developing an institutional policy.

OBJECTIVE: To identify and analyze existing posthumous sperm procurement (PSP) protocols in order to outline central themes for institutions to consider when developing future policies. DESIGN: Qualitative content analysis. SETTING: Large academic institutions across the United States. PATIENT(S) N/A INTERVENTION(S): We performed a literature search and contacted 40 institutions to obtain nine full PSP protocols. We then performed a content analysis on these policies to identify major themes and factors to consider when developing a PSP protocol. MAIN OUTCOME MEASURE(S): Presence of a PSP policy. RESULT(S): We identified six components of a thorough PSP protocol: Standard of Evidence, Terms of Eligibility, Sperm Designee, Restrictions on Use in Reproduction, Logistics, and Contraindications. We also identified two different approaches to policy structure. In the Limited Role approach, institutions have stricter consent requirements and limit their involvement to the time of procurement. In the Family-Centered approach, substituted judgment is permitted but a mandatory wait period is enforced before sperm use in reproduction. CONCLUSION(S): Institutions seeking to implement a PSP protocol will benefit from considering the six major building blocks of a thorough protocol and where they would like to fall on the spectrum from a Limited Role to a Family-Centered approach.

Evaluation of diagnostic testis biopsy and the repetition of testicular sperm extraction surgeries in infertility patients.

OBJECTIVE: To evaluate the use of a diagnostic testis biopsy and a repetition of testicular sperm extraction (TESE) surgeries in azoospermic patients and its impact on the outcome of TESE. DESIGN: Retrospective, case-control study. SETTING: University IVF center and hospital. PATIENT(S): A total of 552 azoospermic patients undergoing TESE for intracytoplasmic injection. INTERVENTION(S): At the time of the TESE, a piece of testicular tissue was prepared for histopathologic evaluation. MAIN OUTCOME MEASURE(S): Sperm retrieval rate. RESULT(S): Testicular sperm retrieval was successful in 100% of patients with obstructive azoospermia, 95.6% of patients with hypospermatogenesis, 47.9% of patients with maturation arrest, and 28.6% of patients with Sertoli cell-only syndrome in cases with no previous testicular surgery; in 100%, 91.4%, 32%, and 13.3%, respectively, in cases with a history of one testicular surgery; and in 100%, 10%, 0, and 0, respectively, in cases with a history of two testicular surgeries. CONCLUSION(S): Testicular sperm retrieval may be successful for some patients in each histopathologic category of azoospermia, with variable degrees of success for different histopathologic categories. The repetition of testicular surgeries decreases the chance of finding sperm in subsequent testicular sperm retrieval procedures.

Post-mortem sperm retrieval in Australasia.

Post-mortem Sperm Retrieval (PMSR) is seldom requested in Australasia. The retrieval of sperm is permitted only by prior written consent or by order of the court. Sperm should be retrieved within 24 h following death; however, collection within 36 h may still be successful. The clinical response to such a request must be mindful of complex ethical and legal considerations. Clear, accessible and consistent law in this area would benefit medical, legal and societal stakeholders.