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Nonobstructive azoospermia (NOA) is a disease with complex etiology, genetic heterogeneity and phenotypic heterogeneity caused by multiple factors, including chromosome abnormalities, Y chromosome microdeletions, gene mutations and epigenetic modifications. At present, there is no unified and effective treatment strategy to restore spermatogenesis. The current treatment options include preoperative hormone optimization therapy, changing the testicular spermatogenesis microenvironment, and stem cell therapy. This article reviews the existing genetic etiology of NOA and related treatment methods, in order to provide reference for the clinical treatment.
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【Objective】 To investigate the sperm retrieval rate (SRR) of microdissection testicular sperm extraction (M-TESE) in patients with non-obstructive azoospermia (NOA) caused by different causes. 【Methods】 A retrospective analysis was performed on 225 NOA patients during Jan.2020 and Dec.2022. The relation between SRR and patients’ age,body mass index (BMI),testicular volume,endocrine hormones and different etiological classifications were analyzed. 【Results】 According to whether sperm was obtained by surgery,the patients were divided into two groups,including 107 cases in the sperm group and 118 cases in the non-sperm group. There were no significant differences in patients’ age,testicular volume and levels of endocrine hormones between the two groups (P>0.05). According to the different causes,NOA patients with mumps history,cryptorchidism history,AZFc deletion or Klinefelter syndrome (KS) had higher SRR,while idiopathic NOA patients had the lowest SRR (P<0.05). 【Conclusion】 M-TESE is an effective treatment of NOA. There is no correlation between SRR and patients’ age,MBI,testicular volume and levels of endocrine hormones. NOA caused by different etiological classifications may have different SRR.
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Sperm identification and selection is an essential task when processing human testicular samples for in vitro fertilization. Locating and identifying sperm cell(s) in human testicular biopsy samples is labor intensive and time consuming. We developed a new computer-aided sperm analysis (CASA) system, which utilizes deep learning for near human-level performance on testicular sperm extraction (TESE), trained on a custom dataset. The system automates the identification of sperm in testicular biopsy samples. A dataset of 702 de-identified images from testicular biopsy samples of 30 patients was collected. Each image was normalized and passed through glare filters and diffraction correction. The data were split 80%, 10%, and 10% into training, validation, and test sets, respectively. Then, a deep object detection network, composed of a feature extraction network and object detection network, was trained on this dataset. The model was benchmarked against embryologists' performance on the detection task. Our deep learning CASA system achieved a mean average precision (mAP) of 0.741, with an average recall (AR) of 0.376 on our dataset. Our proposed method can work in real time; its speed is effectively limited only by the imaging speed of the microscope. Our results indicate that deep learning-based technologies can improve the efficiency of finding sperm in testicular biopsy samples.
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We performed this study to evaluate the clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection (micro-TESE-ICSI) treatment that used fresh or cryopreserved sperm in patients with nonobstructive azoospermia (NOA). A total of 338 NOA patients with 344 consecutive cycles received treatment in the reproductive medicine center of Peking University Third Hospital in Beijing, China, from January 2014 to December 2017. Fresh oocytes and fresh sperm were used in 222 patients with 234 cycles (Group A). Fresh oocytes and cryopreserved sperm were used in 116 patients with 110 cycles (Group B). We compared patient characteristics, embryonic development, and pregnancy outcomes between Groups A and B. There was no statistical difference in the patient characteristics, and no differences were observed with fertilization or quality embryo rates between Groups A and B. The rates of clinical pregnancy and live birth were both higher for Group A than those for Group B (both P < 0.05). In conclusion, fresh testicular sperm appears to produce better ICSI outcomes than cryopreserved testicular sperm in patients with NOA.
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The aim of our study was to compare the sperm retrieval rates (SRRs) and clinical outcomes of patients with different causes of azoospermia who underwent microdissection testicular sperm extraction-intracytoplasmic sperm injection (micro-TESE-ICSI). We conducted a retrospective study at the Reproductive Medicine Center of Peking University Third Hospital in Beijing, China, from January 2014 to December 2017. This study examined 769 patients with nonobstructive azoospermia who underwent 347 cycles of micro-TESE-ICSI. Patients with azoospermia were classified into Group A (Klinefelter syndrome, n = 284, 125 cycles), Group B (azoospermia Y chromosome factor c [AZFc] microdeletion, n = 91, 64 cycles), Group C (cryptorchidism, n = 52, 39 cycles), Group D (previous mumps and bilateral orchitis, n = 23, 23 cycles), and Group E (idiopathic azoospermia, n = 319, 96 cycles). Clinical characteristics, SRR, embryonic development, and pregnancy outcomes of the patients were compared between all groups. Patients in Group D had the highest and most successful SRR. The average SRR for all patients was 46.0%. The rates of clinical pregnancy, implantation, and live birth in Group D were 78.3%, 65.0%, and 74.0%, respectively, which were higher than those in all other groups (P 0.05). Patients with orchitis had the highest SRR and best clinical outcomes. Although AZFc microdeletion patients had a higher SRR, their clinical outcomes were worse.
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This retrospective study demonstrates the clinical outcomes of patients with nonmosaic Klinefelter's syndrome (KS) who underwent preimplantation genetic testing (PGT) with frozen-thawed testicular spermatozoa. Microdissection testicular sperm extraction (micro-TESE) was performed for sperm retrieval. Next-generation sequencing (NGS) was conducted for embryo analysis. A total of 18 couples aged ≤35 years were included, and 22 oocyte retrieval cycles were completed. Euploidy was detected in 29 of 45 (64.4%) embryos. Additionally, the numbers of aneuploid and mosaic embryos detected were 8 (17.8%) and 8 (17.8%), respectively, regardless of a lack of sex chromosome abnormalities. Finally, 13 couples with euploid embryos completed 14 frozen embryo transfer (FET) cycles. Ten couples had clinical pregnancies, and 6 of them had already delivered 5 healthy babies and 1 monozygotic twin. There were also 4 ongoing pregnancies and 2 biochemical pregnancies, but no early pregnancy loss was reported. Based on our results, we speculate that for KS patients, when sperm can be obtained by micro-TESE, the cryopreservation strategy makes the ovarian stimulation procedure more favorable for female partners. The paternal genetic risk of sex chromosome abnormalities in their offspring is extremely low in men with KS. In addition to PGT, the intracytoplasmic sperm injection (ICSI) procedure is comparably effective but more economical for young nonmosaic KS couples. ICSI should be offered as an option for such couples, but monitoring by prenatal genetic diagnosis is recommended.
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Adulto , Feminino , Humanos , Gravidez , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Síndrome de Klinefelter/terapia , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Indução da Ovulação/estatística & dados numéricos , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas/métodosRESUMO
Prior studies have investigated sperm retrieval rates in men with nonobstructive azoospermia (NOA) secondary to specific etiologies, yet most cases of NOA are idiopathic. We compared sperm retrieval rates and testicular histopathology in idiopathic NOA (iNOA) and nonidiopathic NOA (niNOA). We performed a retrospective review of men with NOA who underwent microdissection testicular sperm extraction (microTESE) between 2000 and 2016. Men with no history of malignancy or cryptorchidism and negative genetic evaluation were considered idiopathic. Multivariable regression determined the association between idiopathic etiology and primary outcomes of sperm retrieval and active spermatogenesis on histopathology. Among 224 men, 86 (38.4%) were idiopathic, 75 (33.5%) were nonidiopathic, and 63 (28.1%) did not undergo genetic testing. Median age and serum testosterone were higher among iNOA or no testing versus niNOA. Median follicle-stimulating hormone (FSH) was lower among iNOA or no testing versus niNOA. A higher proportion of iNOA or no testing versus niNOA had a clinical varicocele. Sperm retrieval rates were similar between iNOA, niNOA, and no testing (41.8% vs 48.0% vs 55.6%, respectively; P = 0.255). Active spermatogenesis was seen in a higher proportion of iNOA or no testing versus niNOA (31.4% and 27.0% vs 16.0%, P = 0.073). On multivariaile analysis, iNOA was not associated with sperm retrieval or spermatogenesis (P = 0.430 and P = 0.078, respectively). Rates of sperm retrieval and spermatogenesis on testis pathology were similar in men with iNOA and niNOA. These data will be useful to clinicians in preoperative counseling for men with NOA and negative genetic evaluation.
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Non-obstructive azoospermia (NOA), which is defined as the absence of spermatozoa in the ejaculate secondary to impaired spermatogenesis within the testis, may be caused by a variety of etiologies, including varicocele-induced testicular damage, cryptorchidism, prior testicular torsion, post-pubertal mumps orchitis, gonadotoxic effects from medications, genetic abnormalities, chemotherapy/radiation, and other unknown causes currently classified as idiopathic (Cocuzza et al., 2013). The microdissection testicular sperm extraction (micro-TESE) technique involves a meticulous microsurgical exploration of the testicular parenchyma to identify and selectively extract larger seminiferous tubules that carry a higher probability of complete spermatogenesis (Schlegel, 1999). The Cornell group evaluated the efficacy of micro-TESE in 152 NOA patients with an associated history of cryptorchidism. In their series, spermatozoa were successfully retrieved in 116/181 attempts (64%), and the resulting pregnancy rate was 50% with a delivery rate of 38% (Dabaja and Schlegel, 2013). Franco et al. (2016) described a stepwise micro-TESE approach in NOA patients, which was considered to reduce the cost, time, and effort associated with the surgery. Alrabeeah et al. (2016) further reported that a mini-incision micro-TESE, carried through a 1-cm equatorial testicular incision, can be useful for micro-TESE candidates, particularly in patients with cryptozoospermia. We conducted a retrospective study of 20 consecutive NOA patients with a history of orchidopexy from May 2015 to March 2017.
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Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Azoospermia/cirurgia , Microdissecção/métodos , Orquidopexia , Estudos Retrospectivos , Recuperação EspermáticaRESUMO
Klinefelter's syndrome (KS) is a most frequent sex chromosomal disorder in males, which is characterized by hypogonadism and infertility. The development of assisted reproductive technology has made it possible for KS males to father children. Microdissection testicular sperm extraction (mTESE) is widely considered to be the best method for sperm retrieval in KS patients. This article presents an overview on mTESE for men with non-mosaic KS in the aspects of its predictors, sperm retrieval rate, operation procedure, preoperative hormonal therapy, and postoperative complications and testosterone reduction.
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Adulto , Humanos , Masculino , Síndrome de Klinefelter , Genética , Microdissecção , Métodos , Complicações Pós-Operatórias , Recuperação Espermática , Espermatozoides , Testículo , TestosteronaRESUMO
Objective@#To investigate the clinical application and outcomes of microdissection testicular sperm extraction (micro-TESE) in patients with nonmosaic Klinefelter syndrome (KS).@*METHODS@#A total of 143 nonmosaic KS patients underwent micro-TESE in the Center of Reproductive Medicine of Peking University Third Hospital between July 2012 and August 2016. We analyzed their clinical and follow-up data and evaluated the outcomes.@*RESULTS@#Spermatozoa were successfully retrieved from the testicular tissue in 44.76% (64/143) of the patients, 84.4% (54/64) by unilateral and 15.6% (10/64) by bilateral micro-TESE. Seventy-five of the KS patients were followed up in the years of 2014 and 2015. Of the 34 patients with successful sperm retrieval, 73.52% (25/34) achieved clinical pregnancy and 8 boys and 8 girls were already born in 14 of the 25 cases.@*CONCLUSIONS@#The micro-TESE is a useful method for sperm retrieval in nonmosaic KS patients, with high rates of sperm retrieval, clinical pregnancy, and birth of biological offspring.
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Feminino , Humanos , Masculino , Gravidez , Síndrome de Klinefelter , Microdissecção , Taxa de Gravidez , Injeções de Esperma Intracitoplásmicas , Recuperação Espermática , Espermatozoides , TestículoRESUMO
Objective · To assess the usefulness of contrast enhanced ultrasound (CEUS) in locating the testicular area to guide microdissection testicular sperm extraction (M-TESE) for patients with nonobstructive azoospermia (NOA). Methods · CEUS was performed in 95 NOA patients. M-TESE was performed in the best and poorest perfusion areas on CEUS and in the conventional area. Sperm retrieval rates (SRR) of the three areas were compared. Results · M-TESE was performed in 147 testicles (95 patients). SRRs in best perfusion area, poorest perfusion area and conventional area were 66.3%, 32.6% and 47.3% respectively, and the differences between groups were statistically significant (all P<0.05). The arriving time (AT), time to peak intensity (TTP), peak intensity (PI) and area under the curve (AUC) showed statistical significance (all P<0.05)between the successful retrieval group (94 points) and unsuccessful retrieval group (200 points). And the SRR showed statistical difference among the three pathological groups. In maturation arrest group and Sertoli cell only group, the SRR in the best perfusion area was higher than that in the conventional area (both P<0.05). Conclusion · SRR was different in different pathological groups. The locating of the best perfusion area could guide M-TESE so as to improve the SRRs of maturation arrest group and Sertoli cell only group.
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Objective · To assess the usefulness of contrast enhanced ultrasound (CEUS) in locating the testicular area to guide microdissection testicular sperm extraction (M-TESE) for patients with nonobstructive azoospermia (NOA). Methods · CEUS was performed in 95 NOA patients. M-TESE was performed in the best and poorest perfusion areas on CEUS and in the conventional area. Sperm retrieval rates (SRR) of the three areas were compared. Results · M-TESE was performed in 147 testicles (95 patients). SRRs in best perfusion area, poorest perfusion area and conventional area were 66.3%, 32.6% and 47.3% respectively, and the differences between groups were statistically significant (all P<0.05). The arriving time (AT), time to peak intensity (TTP), peak intensity (PI) and area under the curve (AUC) showed statistical significance (all P<0.05)between the successful retrieval group (94 points) and unsuccessful retrieval group (200 points). And the SRR showed statistical difference among the three pathological groups. In maturation arrest group and Sertoli cell only group, the SRR in the best perfusion area was higher than that in the conventional area (both P<0.05). Conclusion · SRR was different in different pathological groups. The locating of the best perfusion area could guide M-TESE so as to improve the SRRs of maturation arrest group and Sertoli cell only group.
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The development of testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) has made it possible for patients with non-obstructive azoospermia to have their own children. However, sperm retrieval by conventional TESE succeeds but in a subset of patients and, therefore, how to improve the success rate of sperm retrieval is becoming a focus of research. Recent studies suggest that microdissection TESE, although with its limitations, has obvious advantages over traditional sperm retrieval methods. This article presents an overview on the characteristics, predictive factors, sperm retrieval rate, post-operative complications, and improvement of microdissection TESE.