Successful pregnancy and delivery following microdissection testicular sperm extraction and intracytoplasmic sperm injection for non-obstructive azoospermia after microsurgical varicocelectomy: A case report and review of the literature.

Although surgical varicocele treatment is generally considered to result in improved reproductive outcomes, we encountered a rare case of postoperative azoospermia in an infertile male patient who underwent microsurgical varicocelectomy for a palpable left-sided varicocele with concomitant cryptozoospermia. More than 1 year after varicocelectomy, the patient still had not recovered from azoospermia. Thereafter, he underwent microdissection testicular sperm extraction (micro-TESE), allowing him and his partner to obtain one good quality blastocyst via intracytoplasmic sperm injection following oocyte retrievals. Finally, the couple had a successful pregnancy following a frozen embryo transfer, and a live male infant was subsequently delivered to them at 39 weeks and 5 days. In cases of severe testicular dysfunction, varicocelectomy may worsen the postoperative semen parameters until azoospermia. Therefore, it is important to consider preoperative sperm cryopreservation and to explore the possibility of subsequent TESE.

Micromapping testicular sperm extraction: A new technique for microscopic testicular sperm extraction in nonobstructive azoospermia.

Purpose: In microscopic testicular sperm extraction (mTESE) for nonobstructive azoospermia (NOA), sperm can be recovered relatively easily in some cases, and mTESE may be retrospectively considered excessive. However, mTESE is routinely performed in the majority of NOA patients because of the difficulty in predicting tissue status. A minimally invasive and comprehensive sperm retrieval method that allows on-the-spot tissue assessment is needed. We have developed and evaluated a novel sperm retrieval technique for NOA called micromapping testicular sperm extraction (MMTSE). Methods: MMTSE involves dividing the testis into four sections and making multiple small needle holes in the tunica albuginea to extract seminiferous tubules and retrieve sperm. The sperm-positive group by MMTSE (Group I) underwent additional tissue collection (ATC) via a small incision, whereas the sperm-negative group by MMTSE (Group 0) underwent mTESE. Results: In total, 40 NOA participants underwent MMTSE. Group I included 15 patients and Group 0 included 25 patients. In Group 1, sperm were recovered from all patients by ATC. In Group 0, sperm were recovered in 4 of 25 cases using mTESE. Conclusions: MMTSE shows promise as a simple method that comprehensively searches testicular tissue and retrieves sperm using an appropriate method while minimizing patient burden.

Genetic profiling of azoospermic men to identify the etiology and predict reproductive potential.

PURPOSE: To identify germline mutations related to azoospermia etiology and reproductive potential of surgically retrieved spermatozoa, and to investigate the feasibility of predicting seminiferous tubule function of nonobstructive azoospermic men by transcriptomic profiling of ejaculates. MATERIALS AND METHODS: Sperm specimens were obtained from 30 men (38.4 ± 6 years) undergoing epididymal sperm aspiration for obstructive azoospermia (OA, n = 19) acquired by vasectomy, or testicular biopsy for nonobstructive azoospermia (NOA, n = 11). To evaluate for a correlation with azoospermia etiology, DNAseq was performed on surgically retrieved spermatozoa, and cell-free RNAseq on seminal fluid (n = 23) was performed to predict spermatogenesis in the seminiferous tubule. RESULTS: Overall, surgically retrieved sperm aneuploidy rates were 1.7% and 1.8% among OA and NOA cohorts, respectively. OA men carried housekeeping-related gene mutations, while NOA men displayed mutations on genes involved in crucial spermiogenic functions (AP1S2, AP1G2, APOE). We categorized couples within each cohort according to ICSI clinical outcomes to investigate genetic causes that may affect reproductive potential. All OA-fertile men (n = 9) carried mutations in ZNF749 (sperm production), whereas OA-infertile men (n = 10) harbored mutations in PRB1, which is essential for DNA replication. NOA-fertile men (n = 8) carried mutations in MPIG6B (stem cell lineage differentiation), whereas NOA-infertile individuals (n = 3) harbored mutations in genes involved in spermato/spermio-genesis (ADAM29, SPATA31E1, MAK, POLG, IFT43, ATG9B) and early embryonic development (MBD5, CCAR1, PMEPA1, POLK, REC8, REPIN1, MAPRE3, ARL4C). Transcriptomic assessment of cell-free RNAs in seminal fluid from NOA men allowed the prediction of residual spermatogenic foci. CONCLUSIONS: Sperm genome profiling provides invaluable information on azoospermia etiology and identifies gene-related mechanistic links to reproductive performance. Moreover, RNAseq assessment of seminal fluid from NOA men can help predict sperm retrieval during testicular biopsies.

Age, Sperm Retrieval, and Testicular Histology in Klinefelter Syndrome.

PURPOSE: We sought to examine sperm retrieval and testicular histology in males of different ages with Klinefelter syndrome. MATERIALS AND METHODS: We identified all males with Klinefelter syndrome who underwent microdissection testicular sperm extraction at our institution from 1995 to 2020. Patients were divided into adolescent (<20 years) and adult (≥20 years) cohorts. Histology and sperm retrieval were compared using chi-square statistics. Multivariable logistic regression models were used to examine factors associated with successful sperm retrieval. RESULTS: We identified 217 males with Klinefelter syndrome, of whom 59 were adolescents and 158 were adults. Adults were stratified into 10-year groupings (20-29 years, n = 62; 30-39 years, n = 88; ≥40 years, n = 8). Approximately 17% of adolescents had testis histology containing germ cells compared with 15% of the 20 to 29-year cohort, 14% of the 30 to 39-year cohort, and 0% over 40 years. In comparison to adolescents (53%), the sperm retrieval rate was significantly higher in the 20 to 29-year cohort (71%, P = .04) and lower in the ≥40-year cohort (13%, P = .03). In multivariable analysis, the presence of hypospermatogenesis on testis biopsy (OR 5.8, P = .03) was associated with higher odds of successful sperm retrieval. CONCLUSIONS: Younger males more frequently had germ cell-containing testis histology, however this finding was not associated with a higher odds of sperm retrieval. Reproductive urologists should counsel azoospermic males with Klinefelter syndrome that sperm retrieval during adolescence for fertility preservation is not required and can be performed in young adulthood.

An examination of predictive markers for successful sperm extraction procedures: a linear model and systematic review / 亚洲男科学杂志(英文版)

The authors performed a comprehensive review of current literature to create a model comparing commonly evaluated variables in male factor infertility, for example, follicle-stimulating hormone (FSH), testicular volume (TV), and testosterone (T), to better predict sperm retrieval rate (SRR). Twenty-nine studies were included, 9 with data on conventional testicular sperm extraction (cTESE) for a total of 1227 patients and 20 studies including data on microdissection testicular sperm extraction (mTESE) for a total of 4760 patients. A weighted-means value of SRR, FSH, T, and TV was created, and a weighted linear regression was then used to describe associations among SRR, type of procedure, FSH, T, and TV. In this study, weighted-means values demonstrated mTESE to be superior to cTESE with an SRR of 51.9% vs 40.1%. Multiple weighted linear regressions were created to describe associations among SRR, procedure type, FSH, T, and TV. The models showed that for every 1.19 mIU ml-1 increase in FSH, there would be a significant decrease in SRR by 1.0%. Seeking to create a more clinically relevant model, FSH values were then divided into normal, moderate elevation, and significant elevation categories (FSH <10 mIU ml-1, 10-19 mIU ml-1, and >20 mIU ml-1, respectively). For an index patient undergoing cTESE, the retrieval rates would be 57.1%, 44.3%, and 31.2% for values normal, moderately elevated, and significantly elevated, respectively. In conclusion, in a large meta-analysis, mTESE was shown to be more successful than cTESE for sperm retrievals. FSH has an inverse relationship to SRR in retrieval techniques and can alone be predictive of cTESE SRR.

The timing of micro-TESE: what is the ideal age for male and female partner to bring a child to home?

SUMMARY OBJECTIVE: The aim of this study was to analyze the results of microsurgical testicular sperm extraction (micro-TESE) and investigate the potential factors that may affect the successful sperm retrieval and timing of micro-TESE. METHODS: A total of 56 patients with nonobstructive azoospermia (NOA) who underwent micro-TESE procedure between January 2017 and December 2019 were retrospectively analyzed. The patient age, marriage duration, infertility duration, smoking, chronic illness, varicocele status, previous scrotal surgeries, and the presence of genetic disease were noted by an urologist for all patients. RESULTS: The mean age of patients was 33.28±4.4 (22-44) years. Our total sperm-retrieval rate was 55.4% (n:31). Sixteen (28.6%) pregnancies were achieved and 15 (26.8%) healthy live births could be managed. Only the marriage duration (p=0.016) and infertility duration (p=0.015) were detected to be the significant factors to manage successful sperm retrieval. Men with NOA younger than 35.2 years and having a female partner younger than 36.9 years seemed to have the best chance to have a living healthy baby. CONCLUSIONS: The fertility decreased by both male and female age and for men with NOA. The early visit to doctor seemed to have positive effect.

Successful onco-testicular sperm extraction from a testicular cancer patient with a single testis and azoospermia / 대한생식의학회지

Onco-testicular sperm extraction is used to preserve fertility in patients with bilateral testicular tumors and azoospermia. We report the case of a testicular tumor in the solitary testis of a patient who had previously undergone successful contralateral orchiectomy and whose sperm was preserved by onco-testicular sperm extraction. A 35-year-old patient presented with swelling of his right scrotum that had lasted for 1 month. His medical history included a contralateral orchiectomy during childhood. Ultrasonography revealed a mosaic echoic area in his scrotum, suggesting a testicular tumor. The lesion was palpated within the normal testicular tissue along its edge and semen analysis showed azoospermia. Radical inguinal orchiectomy and onco-testicular sperm extraction were performed simultaneously. Motile spermatozoa were extracted from normal seminiferous tubules under microscopy and were frozen. Eventual intracytoplasmic sperm injection using the frozen spermatozoa is planned. Onco-testicular sperm extraction is an important fertility preservation method in patients with bilateral testicular tumors or a history of a previous contralateral orchiectomy.

Impacts of different procedures of testicular sperm retrieval on testicular function and antisperm antibodies in azoospermia patients / 中华男科学杂志

Objective@#To investigate the influence of different procedures of testicular sperm retrieval on the levels of serum inhibin B (INHB), antisperm antibodies (AsAb), follicle-stimulating hormone (FSH), and testosterone (T) in patients with azoospermia.@*METHODS@#We randomly assigned 210 azoospermia patients to receive testicular sperm extraction (TESE, n = 50), testicular sperm aspiration (TESA, n = 56), testicular fine needle aspiration (TEFNA, n = 64), or microscopic TESE (micro-TESE, n = 40). We measured the levels of serum INHB, FSH, and T and the positive rate of AsAb before and at 1 and 3 months after surgery.@*RESULTS@#Compared with the baseline, the levels of serum FSH at 1 and 3 months after surgery showed no statistically significant differences in the TESE (［8.51 ± 4.34］ vs ［8.76 ± 3.07］ and ［7.24 ± 3.32］ IU/L, P >0.05), TESA (［7.70 ± 2.72］ vs ［7.90 ± 4.57］ and ［8.04 ± 3.65］ IU/L, P >0.05), TEFNA (［6.04 ± 3.17］ vs ［6.08 ± 2.70］ and ［6.10 ± 3.32］ IU/L, P >0.05), or micro-TESE group (［6.59 ± 2.74］ vs ［6.89 ± 1.78］ and ［6.75 ± 2.57］ IU/L, P >0.05); the positive rate of AsAb (IgM) was significantly increased at 1 month in the TESE (0.00 vs 14.00%, P 0.05).@*CONCLUSIONS@#Different procedures of testicular sperm retrieval have different impacts on the testicular function and AsAb in patients with azoospermia.

Prognostic factors for sperm retrieval in non-obstructive azoospermia

Testicular sperm retrieval techniques associated with intracytoplasmic sperm injection have changed the field of male infertility treatment and given many azoospermic men the chance to become biological fathers. Despite the current use of testicular sperm extraction, reliable clinical and laboratory prognostic factors of sperm recovery are still absent. The objective of this article was to review the prognostic factors and clinical use of sperm retrieval for men with non-obstructive azoospermia. The PubMed database was searched for the Medical Subject Headings (MeSH) terms azoospermia, sperm retrieval, and prognosis. Papers on obstructive azoospermia were excluded. The authors selected articles that reported successful sperm retrieval techniques involving clinical, laboratory, or parenchyma processing methods. The selected papers were reviewed, and the prognostic factors were discussed. No reliable positive prognostic factors guarantee sperm recovery for patients with non-obstructive azoospermia. The only negative prognostic factor is the presence of AZFa and AZFb microdeletions.

Cryopreservation of testicular and epididymal sperm: techniques and clinical outcomes of assisted conception

The introduction of the technique of intracytoplasmic sperm injection to achieve fertilization, especially using surgically retrieved testicular or epididymal sperm from men with obstructive or non-obstructive azoospermia, has revolutionized the field of assisted reproduction. The techniques for the retrieval of spermatozoa vary from relatively simple percutaneous sperm aspiration to open excision (testicular biopsy) and the more invasive Micro-TESE. The probability of retrieving spermatozoa can be as high as 100% in men with obstructive azoospermia (congenital bilateral absence of the vas deferens, status post-vasectomy). However, in nonobstructive azoospermia, successful sperm retrieval has been reported in 10-100% of cases by various investigators. The surgical retrieval and cryopreservation of sperm, especially in men with non-obstructive azoospermia, to some extent ensures the availability of sperm at the time of intracytoplasmic sperm injection. In addition, this strategy can avoid unnecessary ovarian stimulation in those patients intending to undergo in vitro fertilization-intracytoplasmic sperm injection with freshly retrieved testicular sperm when an absolute absence of sperm in the testis is identified. Several different methods for the cryopreservation of testicular and epididymal sperm are available. The choice of the container or carrier may be an important consideration and should take into account the number or concentration of the sperm in the final preparation. When the number of sperm in a testicular biopsy sample is extremely low (e.g., 1-20 total sperm available), the use of an evacuated zona pellucida to store the cryopreserved sperm has been shown to be an effective approach.