Background Vasoepididymostomy (VE) is an important surgical treatment to achieve natural conception for patients with obstructive azoospermia (OA), and only unilateral VE can be performed under certain conditions, such as OA patients with congenital unilateral absence of the vas deferens (CUAVD) and some acquired OA. There is a lack of relevant reports assessing the clinical outcomes of unilateral VE in OA patients with different causes. This study is aimed to describe the clinical features and evaluate treatments and outcomes of unilateral single-armed VE in OA patients. Methods From December 2015 to June 2021, 46 OA patients (including 13 CUAVD-associated OA and 33 acquired OA) underwent unilateral single-armed VE in Shanghai General Hospital (Shanghai, China). Patient information, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Results Obstruction in distal of unilateral vas deferens (16/46) was the most common cause for OA patients underwent unilateral VE, and CUAVD accounts for 28.4% (13/46). The overall patency rate was 50.0% (23/46), with 38.5% (5/13) for the CUAVD group and 54.5% (18/33) for the acquired group (p > 0.05). The natural pregnancy rates in CUAVD group and acquired group were 20.0% and 33.3%, respectively (p > 0.05). Conclusions These findings suggest unilateral single-armed VE can achieve high patency and pregnancy rates in OA patients, whether for CUAVD or acquired OA patients.

Post-transcriptional regulation mediated by RNA binding proteins is crucial for male germline development. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), an RNA binding protein, is specifically expressed in human and mouse male gonads and is involved in manifold biological processes and tumorigenesis. However, the function of IGF2BP1 in mammalian spermatogenesis remains poorly understood. Herein, we generated an Igf2bp1 conditional knockout mouse model using Nanos3-Cre. Germ cell deficiency of Igf2bp1 in mice caused spermatogenic defects in an age-dependent manner, resulting in decreased numbers of undifferentiated spermatogonia and increased germ cell apoptosis. Immunoprecipitation-mass spectrometry analysis revealed that ELAV-like RNA binding protein 1, a well-recognized mRNA stabilizer, interacted with IGF2BP1. Single cell RNA-sequencing showed distinct mRNA profiles in spermatogonia from conditional knockout versus wide type mice. Further research showed that IGF2BP1 plays a vital role in the modulation of spermatogenesis by regulating Lin28a mRNA, which is essential for clonal expansion of undifferentiated spermatogonia. Thus, our results highlight the crucial effects of IGF2BP1 on spermatogonia for the long-term maintenance of spermatogenesis. A study characterizes the in vivo function of RNA-binding protein IGF2BP1 during spermatogenesis and further identifies ELAVL1 as a binding partner and Lin28a mRNA as a downstream target.

Background Hemodynamic alterations in the spermatic vein are implicated in infertility among patients with varicocele (VC). Contrast-enhanced ultrasound (CEUS), a powerful tool for hemodynamic analysis, remains unexplored for VC. This study aimed to demonstrate the feasibility of using CEUS to evaluate spermatic vein hemodynamics in patients with VC and establish a clear correlation between specific hemodynamic patterns and impaired semen parameters. This study included 165 patients with left-sided VC and 50 healthy volunteers. All participants underwent CEUS of the spermatic veins, along with maximum venous diameter and testicular volume measurements and serum sex hormone levels and routine semen analyses. The sperm DNA fragmentation index was measured in 146 patients with VC and 37 healthy controls. Results The analyses revealed four distinct perfusion patterns ofthe spermatic vein: steady flow, intermittent stasis, intermittent reflux, and filling defect. In healthy spermatic veins, the predominant perfusion patterns included steady flow and intermittent stasis. Spermatic veins with VC exhibited a significant increase in the intermittent reflux and filling defect patterns, with the proportion rising as the clinical grade increased. The four patterns were further grouped into the “steady flow & intermittent stasis” and “intermittent reflux & filling defect” patterns for logistic regression analyses; the intermittent reflux & filling defect pattern was revealed as an independent risk factor for impaired sperm concentration, total sperm counts, progressive motility, morphology, and DNA fragmentation index. Conclusions This study validated the feasibility of CEUS for assessing the hemodynamics of the spermatic vein and established the intermittent reflux & filling defect pattern as an independent predictor of impaired semen parameters.

目的:分析不同病因的非梗阻性无精子症(non-obstructive azoospermia,NOA)患者经显微镜下睾丸取精术(microdis-section testicular sperm extraction,micro-TESE)的治疗结局.方法:回顾性分析上海市第一人民医院2015年3月—2022年1月1 355例接受micro-TESE的患者,病因/危险因素包括克氏综合征(Klinefelter syndrome,KS)、Y染色体AZFc缺失、隐睾、腮腺炎性睾丸炎、放化疗、精索静脉曲张以及特发性NOA,研究分析各组患者精子获取率(sperm retrieval rate,SRR),并比较各组取精成功的妊娠结局.结果:NOA患者的总体SRR为26.2％(355/1 355),其中腮腺炎性睾丸炎SRR最高(75.9％,22/29),其次分别为隐睾(70.5％,43/61)、Y染色体AZFc缺失(55.6％,30/54)、KS(47.6％,71/149)、特发性NOA(18.6％,167/897)、放化疗(15.4％,2/13),精索静脉曲张SRR最低(13.2％,20/152).根据手术结局,将NOA患者分为取精成功组及取精失败组.特发性NOA及放化疗类型中,取精成功组卵泡刺激素(follicle-stimulating hormone,FSH)和黄体生成素(luteinizing hormone,LH)水平显著高于取精失败组;Y染色体AZFc缺失类型中,取精成功组FSH、LH水平显著低于取精失败组;腮腺炎性睾丸炎类型中,取精成功组睾丸体积高于取精失败组.回归分析发现年龄可作为预测特发性NOA患者取精结局的因素,年龄较高者拥有较好的取精结局.卵胞浆内单精子注射治疗的妊娠率为51.4％(200/389),活产率为73.5％(147/200).结论:不同病因/危险因素NOA患者的SRR具有显著差异,是影响micro-TESE取精结局的重要指标.

Meiotic arrest is a common pathologic phenotype of non-obstructive azoospermia (NOA), yet its genetic causes require further investigation. Meiotic nuclear divisions 1 (MND1) has been proved to be indispensable for meiotic recombination in many species. To date, only one variant of MND1 has been reported associated with primary ovarian insufficiency (POI), yet there has been no report of variants in MND1 associated with NOA. Herein, we identified a rare homozygous missense variant (NM_032117:c.G507C:p.W169C) of MND1 in two NOA-affected patients from one Chinese family. Histological analysis and immunohistochemistry demonstrated meiotic arrest at zygotene-like stage in prophase I and lack of spermatozoa in the proband's seminiferous tubules. In silico modeling demonstrated that this variant might cause possible conformational change in the leucine zippers 3 with capping helices (LZ3wCH) domain of MND1-HOP2 complex. Altogether, our study demonstrated that the MND1 variant (c.G507C) is likely responsible for human meiotic arrest and NOA. And our study provides new insights into the genetic etiology of NOA and mechanisms of homologous recombination repair in male meiosis.

Objective:To analyze the effectiveness and safety of reoperation for obstructive azoospermia (OA) with initial microsurgical anastomosis failure.Methods:A retrospective case series was performed for OA patients who underwent reoperation after initial microsurgical anastomosis failure, in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Institute of Urology, Urologic Medical Center from March 2015 to June 2020. Totally, 21 patients were enrolled in the study, and the clinical data, patency and pregnancy outcomes were reviewed.Results:During the initial surgery, 8 cases underwent vasovasostomy and 8 cases underwent vasoepididymostomy, while the other 5 cases underwent crossover anastomosis; 19 cases underwent reoperation because of reproductive needs, and 2 for post-vasectomy chronic testicular pain. During the reoperation, anastomotic stricture was found in 14 cases, and sperm granuloma was found in 6 cases, while spermatogenic dysfunction was confirmed in 1 case. Unilateral or bilateral anastomosis was performed successfully in 19 cases. Testicular sperm extraction was performed for 1 case with non-obstructive azoospermia (NOA) and 1 case with severe adhesion respectively. Totally 19 cases was followed for 3 to 58 months [(30.21±18.43) months], and 2 cases were lost to follow-up. Chronic testicular pain was relieved completely in 1 of the 2 cases suffering from the post-vasectomy testicular pain. Overall, 11 cases achieved patency, and 4 cases concieved naturally. Furthermore, 3 cases underwent in vitro fertilization cycle (1 case with semen sperm, and the other 2 cases with frozen testicular sperm). There were no severe post-operational complications in all cases. Conclusion:Microsurgical reoperation, which allows a favorable patency rate and natural pregnancy rate, is a valid option for the treatment of OA with initial microsurgical anastomosis failure.

目的:可膨胀性人工海绵体植入术常规将储水囊放置于耻骨后膀胱前间隙,而对于盆腔外伤或手术的重度勃起功能障碍患者,储水囊放置存在风险与困难.本研究旨在改良可膨胀性人工海绵体植入术的储水囊放置方法,评估其安全性与有效性.方法:回顾性分析2017年6月-2021年12月在上海市第一人民医院泌尿男科实施可膨胀性人工海绵体植入术患者的临床资料.其中对照组为常规将储水囊置于耻骨后膀胱前间隙的患者,试验组为因盆腔外伤手术实施改良储水囊植入的患者.通过门诊或电话交流对患者进行术后回访,分析改良方案的安全性、有效性.结果:30例可膨胀性人工海绵体植入术中采用改良储水囊放置的试验组患者有8例,其中放置于右侧腹壁下腹膜前间隙的有5例(16.67％),放置于左侧腹壁下腹膜前间隙的有3例(10.00％),均通过隧道法连接储水囊和泵阀.其余22例(73.33％)为对照组患者.30例手术的二次手术率为3.33％(1/30),为对照组中的1例术后泵阀故障的患者.试验组二次手术率为0(0/8),对照组为4.55％(1/22).试验组性生活满意度为100％(8/8),对照组为90.91％(20/22).试验组不良反应发生率为12.50％(1/8),对照组为13.64％(3/22).结论:可膨胀性人工海绵体植入术是治疗难治性勃起功能障碍的推荐治疗方法,然而对于曾行骨盆骨折或尿道断裂相关手术的严重外伤性勃起功能障碍患者实施常规放置储水囊于耻骨后膀胱前间隙的操作存在一定风险和困难.对这类患者实施储水囊放置于左右腹壁下腹膜前间隙并通过隧道法连接储水囊与泵阀的改良方案可以简化手术操作,降低手术风险,且与常规放置方案之间在二次手术率、性生活满意度和不良反应发生率等方面没有统计学差异,显示出良好的安全性及有效性.

to cryptozoospermia. After discussion with the couple, the patient elected to pursue conservative treatment to improve his sperm quality. As antioxidant supplements have emerged as a potential therapeutic approach in an attempt to treat male infertility, L-carnitine and vitamin E supplements were prescribed.3 However, his semen quality did not improve after 3 months of treatment, so he returned for surgical treatment by mVE. Surgery was performed under a Zeiss surgical microscope (Vario 700; Carl Zeiss AG, Oberkochen, Germany). During the surgery, testicular tissue was obtained and delivered immediately to the experienced laboratory experts. Many immotile spermatozoa were found under phase-contrast microscopy (Nikon Corporation, Tokyo, Japan) at 200× magnification. Dilated epididymal tubules in the caudae were identified easily, and many immotile spermatozoa were found in the aspirated fluid. The abdominal vas deferens were unobstructed, as confirmed by dilute methylene blue injection. A single-armed suture longitudinal intussusception vasoepididymostomy technique sparing the deferential vessels was adopted, and anastomosis was performed on both caudae. During the postoperative follow-ups, semen analyses indicated cryptozoospermia for the first 2 months, but the sperm recovered. The total progressively motile sperm count fluctuated but kept at a relative high level in most tests (Table 1). This indicated the success of the operation. Thirteen months after the operation, his wife conceived naturally, and a baby boy was born in due course. ICSI has now become an established therapy for cryptozoospermia.2 However, for cryptozoospermia caused by obstructive factors – as in this case – seminal duct reconstructive surgery is recommended. This enables spermatozoa to reappear in ejaculates, making natural conception possible. Compared with ICSI, it avoids oocyte retrieval and reduces medical expenses. In general, we recommend testicular sperm extraction (TESE) during surgery for the following reasons. First, TESE can be used to confirm normal spermatogenesis. Although uncommon, spermatogenic failure may be mistakenly considered normal spermatogenesis. Second, testicular sperm cryopreservation can be carried out for ICSI if the seminal duct reconstruction fails, avoiding reoperation for sperm extraction. In this case, the patient preferred to tolerate his epididymal obstruction. After all the treatment options were informed, the patient only accepted the surgical reconstruction surgery and refused TESE for sperm cryopreservation. The longitudinal intussusception vasoepididymostomy technique has been recognized as the gold standard to achieve a superior patency Dear Editor, Cryptozoospermia is defined as the apparent absence of spermatozoa from fresh semen samples, but they can be found in centrifuged pellets.1 It is usually caused by a spermatogenic disorder, while cryptozoospermia associated with seminal duct obstruction is less common.2 Because of the extremely low sperm counts in semen samples, men with cryptozoospermia are often reliant on intracytoplasmic sperm injection (ICSI) for paternity.2 However, for men with cryptozoospermia caused by seminal duct obstruction, reconstructive surgery might be an option. To our knowledge, there is no report of cryptozoospermia caused by epididymal obstruction. Here, we report a man with this condition who impregnated his wife successfully after undergoing microsurgical vasoepididymostomy (mVE). This study was approved by the Ethics Committee of Shanghai General Hospital (approval number: 2021KY084). Informed consent for this study was obtained from the patient. A 29-year-old man with a 2-year history of infertility presented for treatment in Shanghai General Hospital (Shanghai, China). He was diagnosed with azoospermia by repeated semen analyses but had been confirmed to have active spermatogenesis by fine-needle aspiration in another institution. He had impregnated a previous partner 4 years ago and had a history of epididymitis 3 years ago. He did not have other potential causes of infertility. The patient had well-developed testes. The bilateral epididymides were plump by palpation. The patient had no evidence of other abnormalities of the genitourinary system. Furthermore, no spermatozoa were found in ejaculates. The seminal fructose test was positive. The level of neutral α-glycosidase was 5.78 U l−1 (reference ≥10.12 U l−1). Endocrine evaluations showed a luteinizing hormone (LH) level of 9.98 mIU ml−1, follicle-stimulating hormone (FSH) level of 3.06 mIU ml−1, and total testosterone (T) level of 3.50 ng ml−1. Scrotal ultrasonography showed tubular ectasia in the bilateral corpus and caudae epididymides (Supplementary Figure 1). He was initially diagnosed with obstructive azoospermia (obstruction of epididymides) and was recommended to undergo mVE. Unexpectedly, the day before scheduled surgery, a semen analysis showed several immotile spermatozoa after centrifugation. Therefore, we revised his diagnosis LETTER TO THE EDITOR

Objective:To analyze the feasibility and safety of microsurgical anastomosis for obstructive azoospermia (OA) patients with prior intracytoplasmic sperm injection (ICSI) failure.Methods:From September 2015 to May 2020, the data of 20 OA patients with previous ICSI-assisted pregnancy failure admitted to the Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The characteristics of seminal tract microsurgical reconstruction were summarized, and the postoperative recurrence rate and clinical pregnancy rate were calculated.Results:Vasal obstruction was found in 8 patients and epididymal obstruction in 12 patients during microscopically reconstructed seminal tract. Among the patients with vasal obstruction, 1 patient developed OA after trauma and underwent laparoscopic-assisted right vasovasostomy (VV). Totally 7 patients developed OA after juvenile bilateral hernia, among whom 6 patients underwent further laparoscopic-assisted VV and 1 patient underwent vasovasostomy and epididymal cross anastomosis. Of the 8 patients who underwent VV, 6 achieved postoperative patency, and 2 couples achieved natural pregnancy. Patients with epididymal obstruction underwent microscopic vasoepididymostomy (VE), and 6 out of 12 patients achieved postoperative pregnancy, while 3 couples achieved natural pregnancy. No significant complications occurred in all patients during and after operation.Conclusion:Microsurgical anastomosis is an effective remedy for patients with OA after ICSI pregnancy failure, which can help patients achieve natural pregnancy.

Transverse testicular ectopia (TTE) associated with persistent Mullerian duct syndrome (PMDS) is a rare form of male pseudohermaphroditism usually unexpectedly found at surgery for cryptorchidism or inguinal hernia in children. Its etiology and prevalence are unclear, although defects in the gene that encodes anti-Mullerian hormone (AMH) or AMH receptor has been generally considered as the major cause. Adult cases of TTE associated with PMDS are even more peculiar, as the adult patients usually present more complex medical history, require more comprehensive medical examination and management. Two adult men with normal karyotype were referred to the urology outpatient clinic for infertility and cryptorchidism. Semen analysis showed both patients were azoospermic. Ultrasound and computed tomography (CT) found both testes were located at the same side of abdominal cavity or pelvic cavity, which was confirmed during the laparoscopic exploration. A tubular structure adhering to the spermatic cord was also found in both cases. Laparoscopic-assisted transabdominal orchiopexy was performed and the tubular mass was removed. Pathological examination confirmed the existence of Mullerian duct, which showed positive immunostaining of the uterus marker genes. The principles of treatment include the restoration of testes, the preservation of fertility, and the prevention of malignancy. Much attention should be payed to avoid damage of fertile testes and vas deferens in the surgery. Long-term postoperative follow-up is necessary for assessment of malignant transformation and infertility.

Objective:To explore the chromosomal genetic factors of maturation arrest non-obstructive azoospermia (NOA).Methods:A case of maturation arrest NOA patients with chromosome reciprocal translocation was retrospective analyzed with literature review.Results:The karyotype of 46,Y,t(X;19)(p22.1;q13.3) was detected in a NOA patient, and the karyotypes of his parents were normal. There were no micro-deletions of Y chromosome. Also, no obvious pathogenic gene mutations were found in whole-exome sequencing (WES). Furthermore, there were no pathogenic copy number variations (CNVs) detected by chromosomal microarray analysis (CMA) in the patient. The histopathological analysis revealed that the spermatogenesis arrested at spermatocyte stage.Conclusion:46,Y,t(X;19) chromosome reciprocal translocation could lead to maturation arrest NOA.

目的 探讨显微镜下睾丸取精术(m-TESE)在非梗阻性无精子症(NOA)治疗中的应用,并分析影响手术结局的因素和预测指标.方法 回顾性收集2017年6月-2020年1月在上海交通大学附属第一人民医院就诊的677例NOA患者资料,统计患者手术结局,分析患者无精子症相关病因分类、年龄、性激素[卵泡刺激素(FSH)、黄体生成素(LH)、睾酮(T)、雌二醇(E2)、泌乳素(PRL)、抗苗勒管激素(AMH)和抑制素B]水平与手术结局的关系.结果 纳入患者的FSH和LH分别为(27.5±15.7)和(14.3±9.1) U/L,均显著高于正常值上限.NOA患者病因分类依次为,特发性NOA 454例(67.1％),克氏综合征73例(10.8％),精索静脉曲张63例(9.3％),隐睾或有隐睾手术史45例(6.7％),Y染色体AZFc缺失19例(2.8％),睾丸炎16例(2.4％),辐射或放射治疗、化学治疗史7例(1.0％).成功获取179例(26.4％)患者的精子;其中,睾丸炎患者取精成功率最高,为13/16;辐射或化学治疗、放射治疗史患者最低,为1/7.根据手术结局,将特发性NOA患者分为成功组和失败组.成功组患者的FSH和LH水平均显著高于失败组,而AMH水平显著低于失败组(P值均＜0.05).logistic回归分析结果表明,AMH、FSH和LH均对手术结局有一定的预测价值,其中AMH的拟合优度最佳(x2=31.477,P=0.0001).绘制ROC曲线,AMH的AUC为0.713,FSH和LH分别为0.576和0.552.1例(0.1％)患者术后出现切口感染.结论 m-TESE是治疗NOA的有效方法,患者病因是影响手术结局的重要因素.对于特发性NOA患者,AMH对手术结局的预测能力最高.

Background To evaluate the clinical outcomes and the duration required for the sperm to return to the ejaculate after a modified single-armed 2-suture longitudinal intussusception vasoepididymostomy (SA-LIVE). Methods From March 2015 to December 2018, 134 patients with epididymal obstruction azoospermia underwent the modified single-armed vasoepididymostomy at Shanghai General Hospital. The outcomes and clinical findings were documented and evaluated. The mean follow-up period was 17 (range: 3–36) months. Results Patency was assessed by the return of sperm in the ejaculate. The overall patency rate was 55.2%, and the patency rates were 58.9, 40.7, 36.4, and 58.9% for bilateral surgery, unilateral surgery, proximal anastomosis, and distal anastomosis, respectively. The average time to achieve patency was 4.11 ± 2.74 months. In the first 6 months, 87.8% (65/74) patency patients reported sperm in the ejaculate. The overall pregnancy rate was 40.9% (29/66) at the follow-up of 3–36 months, and the natural pregnancy rate was 30.3% (20/66). The natural pregnancy rate was 32.1% post-bilateral surgery and 33.3% for the site of distal anastomosis; surprisingly, it was 0% for the site of proximal anastomosis. Conclusion Modified SA-LIVE is safe and may achieve favorable patency and pregnancy rates. When double-armed sutures are not accessible, single-armed may be preferable. The expected patency time was within 1 year. Moreover, because of the low natural pregnancy rate for proximal anastomosis, sperm banking is preferred to SA-LIVE.

Clinical efficacy of treatments against non-obstructive azoospermia (NOA), which affects 1% of men, are currently limited by the incomplete understanding of NOA pathogenesis and normal spermatogenic microenvironment. Here, we profile >80,000 human testicular single-cell transcriptomes from 10 healthy donors spanning the range from infant to adult and 7 NOA patients. We show that Sertoli cells, which form the scaffold in the testicular microenvironment, are severely damaged in NOA patients and identify the roadmap of Sertoli cell maturation. Notably, Sertoli cells of patients with congenital causes (Klinefelter syndrome and Y chromosome microdeletions) are mature, but exhibit abnormal immune responses, while the cells in idiopathic NOA (iNOA) are physiologically immature. Furthermore, we find that inhibition of Wnt signaling promotes the maturation of Sertoli cells from iNOA patients, allowing these cells to regain their ability to support germ cell survival. We provide a novel perspective on the development of diagnostic methods and therapeutic targets for NOA.

Objective:To evaluate the safety and effectiveness of The Stork OTC conception aid kit for the treatment of male infertility compared with natural sexual intercourse.Methods:A multi-center, prospective, open, self-controlled, randomly crossed trial was performed in 57 infertility couples who were unable to naturally conceive, and were selected in Shanghai General Hospital, Shanghai Jiao Tong University, Reproductive Medicine Center,Tongji Medical College, Huazhong University of Science and Technology and Anhui Provincial Hospital from July 2017 to September 2018. Patients were required to participate both the conception aid kit and natural sexual intercourse in two consecutive periods of ovulation. A random envelope method was used to determine the application sequences of two methods. Twenty-nine couples were treated with the conception aid kit in the first month of ovulation, and applied the natural sexual intercourse in the second month of ovulation as group A. Twenty-eight couples were applied the natural sexual intercourse in the first month of ovulation, and were treated with the conception aid kit in the second month of ovulation as group B. Test results collected from all couples who used the conception aid kit were categorized as the test group data. Meanwhile, test results out of those couples who completed natural sexual intercourse were collected as control group data. Compared with its self-controlled natural sexual intercourse two months before and after, the effectiveness and safety of the conception aid kit was verified by general vaginal examination, routine leucorrhea examination, motile sperm score from post coital test (PCT), pregnancy rate comparison and other methods.Results:The trial was conducted at three clinical trial centers. A total of 57 infertility couples were enrolled. A total of 54 couples were validated eventually including 26 couples in group A and 28 infertility couples in group B. Effectiveness was evaluated. The PCT results showed that the sperm score of test group was 6.11±3.00, and the score of the sperm score of control group was 1.22±0.79. The motile sperm score of test group was 5 times ( P<0.001) than that in control group. In the follow-up, 7 (13.0%) of the couples successfully achieved pregnancy with the conception aid kit, 6 (85.7%) of them had healthy offspring, 1 (14.3%) had spontaneous abortion. No couples were pregnant after natural sexual intercourse. Safety was evaluated. The general examination of the vagina and the routine tests of the vaginal leukorrhea showed no difference between test group and control group. All 54 effective couples who completed the test can successfully use the conception aid kid to place the seminal vesicles containing semen and remove them with the attached pulling thread on time without obvious discomfort. Conclusion:The Stork OTC conception aid kits can effectively treat infertility, significantly increase the number of forward-moving sperm entering the cervix, and significantly increase the pregnancy rate. It is safe, non-invasive, simple, can be easily operate by patients themselves, and meets the needs of clinical applications.

Azoospermia accounts for 10%-15% of male infertility, with the prevalence of 1% in male population. Obstructive azoospermia (OA) accounts for 40% of azoospermia and can be caused by a variety of factors, including male reproductive duct inflammation and genetic factors. Given the fact that the spermatogenesis is normal in the testis of OA patients, the OA patients can have their own offspring through testicular biopsy and sperm retrieval followed by assisted reproductive technology (ART). Therefore, the genetic etiology of OA is often overlooked. Subsequently, studies of the following ART strategies and offspring birth defects are also ignored. This article reviewed the genetic disorders of OA patients, and the animal model with OA, providing new ideas for management of OA patients, genetic counseling, and development of male contraceptives.

Objective: To study the efficacy and safety of low-intensity pulsed ultrasound (LIPUS) at different intervals by mechanical force in treating erectile dysfunction (ED). Method: Forty patients with mild to moderate ED were randomized in a 1∶1 ratio to receive 16-treatment sessions of LIPUS in group A and group B, applied 3 times per week and 2 times per week, respectively. End-point assessments were made at 8th week after treatment. Efficacy were evaluated using International Index of Erectile Function-Erectile Function domain score (IIEF-EF), Erectile Hardness Score (EHS), Self-Esteem and Relationship Questionnaire (SEAR), Sexual Encounter Profile (SEP), Global Assessment Question (GAQ), and pain were assessed by Visual Analogue Score (VAS).Treatment response was confirmed by a minimal clinically importance difference (MCID) at 8th week. Results: Compared with baseline, IIEF-EF score [(17.1±5.48 vs 23.4±3.75, P<0.05) and (18.9±4.34 vs 24.1±4.32, P<0.05)], proportion of EHS 4 [(0 vs 40%, P<0.05) and (16.7% vs 55.6%, P<0.05)], and Overall Relationship score [(50.6 vs 67.5, P<0.05) and (44.4 vs 70.1, P<0.05)] were significantly improved at 8th week in two groups, respectively. Compared with baseline, the positive responses to SEP-3 increased significantly at 8th week in two groups (50.0% vs 80.0%,P<0.05) and (44.4% vs 88.9%, P<0.05), respectively. The positive responses to GAQ-2 were 90.0% and 88.9% at 8th week in two groups, respectively. There were no significant differences in IIEF-EF, EHS, SEAR, SEP and GAQ at 8th week between two groups. There was no significant difference in treatment response using MCID between two groups at end-point (80.5% vs 77.5%). The treatment duration for full sessions were 2.5 weeks less in group A than group B. No adverse effects were reported in all cases. Conclusion: LIPUS at two different intervals is effective and safe for mild to moderate ED, and the regimen at 3 times per week can achieve quite good effect in relatively short duration,while the long-term effects is still be clarified in further study.

Objective:To investigate the novel genetic cause associated with hypospadias and the strategy for preventing offspring genetic defects in these patients.Methods:In March 2019, a patient with gonadal dysplasia (hypospadias associated with cryptorchidism) was referred to Shanghai General Hospital. His secondary sex characters, level of sex hormones and the development of male reproductive system was assessed through physical examination, sex hormone examination, male reproductive system B-ultrasound and computed tomography (CT). Whole-exome sequencing (WES) was preformed to investigate the pathogenic genetic variations associated with hypospadias and cryptorchidism. Also, Sanger sequencing was conducted to verify the WES results in the pedigree. Semen analysis was used to assess the fertility of the proband and the SRD5A2 gene analysis of his spouse was performed to assess the risk of genetic defects in the offspring.Results:The patient suffered from gonadal dysplasia (hypospadias associated with cryptorchidism). Physical examination showed an inverted triangular distribution of pubic hair, small penis and the volume of the testis was 8 ml. Sex hormone examination revealed the level of FSH, LH, Pituitary prolactin (PRL), estrogen (E 2), testosterone (T), and sex hormone-binding globulin (SHBG) was 25.81 U/L, 10.84 U/L, 21.09 μg/L, 153 pmol/L, 16.95 nmol/L, and 36.15 nmol/L respectively. B-ultrasound and computed tomography (CT) showed left inguinal testis. Also, semen analysis illustrated that the volume was 0.05 ml and sperm concentratio n<2×10 6/ml, suggesting oligospermia in this case. WES sequencing and Sanger sequencing showed compound heterozygous LoF mutations in SRD5A2 [NM_000348.3:C.679C>T(p.Arg227Ter) and NM_000348.3:C.16C>T(p.Gln6Ter)] in this patient. And there were no pathogenic genetic variations of SRD5A2 in the spouse. Conclusion:Novel compound heterozygous LoF mutations in SRD5A2[NM_000348.3:C.679C>T(p.Arg227Ter) and NM_000348.3:C.16C>T(p.Gln6Ter)] may be the primary cause of disorders of sex development.

精子发生障碍导致严重精子畸形与无精子症,由此引起的不育症与出生缺陷至少影响500万家庭.目前人类对生精障碍发病机制的认识有限,仅认识到Klinefelter综合征、Y染色体微缺失、隐睾、腮腺炎性睾丸炎影响精子发生.由遗传、环境、生活方式导致精子发生障碍的研究,多集中于啮齿类动物,缺乏对人类精原干细胞增殖分化的研究,尤其对调控信号的分子通路所知不多.人类精子发生障碍研究的重点和难点在于:缺乏基于临床家系的致病基因研究,缺少充足组织样本量支持的应用研究,尚无精子无创评估技术和规范化诊疗体系.本项目针对生精障碍,建立多学科研究团队,指导规范化样本收集,深入开展转化应用研究,建立体内体外向精子分化的研究模型.以此为基础,解析精子形成障碍的遗传学因素,建立精原干细胞向精子定向分化新体系,构建拉曼评估精子与生精小管无创平台并将其用于临床,制订精子发生障碍诊疗路径与诊疗新体系.本项目主要创新和研究成果如下.

Objective: To discuss the efficacy and safety of subinguinal microsurgical varicocelectomy in the treatment of non-obstructive azoospermia (NOA) with varicocele. Methods: The clinical data of 141 patients with NOA and varicocele who underwent subinguinal microsurgical varicocelectomy from March 2015 to June 2017 in Shanghai General Hospital was collected.One hundred and ten patients suffered from varicocele on the left side, 1 on the right side, and the rest (30 cases) were bilateral varicocele. Grade Ⅰ varicocele were found on 7 sides (the right and left side was count respectively), grade Ⅱ on 121 sides, and grade Ⅲ on 43 sides. Sperm analysis, pregnancy rate and complications were recorded after at least 6 months since operation. Results: Eleven cases were lost during the follow-up. Eighteen of the remaining 130 NOA patients processed successful sperm retrieval in post-operative semen analysis (18/130, 13.8%). Six couples(6/130, 4.6%) succeeded in natural pregnancy. Five couples (5/130, 3.8%)underwent successful pregnancy following with intracytoplasmic sperm injection(ICSI). Twenty-six out of the remaining 112 patients underwent the micro dissection testicular sperm extraction (micro-TESE), and 4 patients got a successful sperm retrieval (4/26, 15.4%). Among them, 2 couples had successful pregnancy with ICSI. Totally 2 cases of postoperative infection of incision were found. Conclusions: Microsurgical varicocelectomy had a beneficial effect on sperm quality of patients suffered from NOA with varicocele to some extent, even leading to unassisted pregnancy or avoiding micro-TESE before ICSI. Microsurgical varicocelectomy could be applied in the treatment of NOA with varicocele.