Comparison of sperm retrieval and reproductive outcome in azoospermic men with testicular failure and obstructive azoospermia treated for infertility

We assessed the rates of sperm retrieval and intracytoplasmic sperm injection outcomes, including the neonatal profile of infants conceived, in men with testicular failure. Three-hundred and sixty-five men with testicular failure who underwent micro-dissection testicular sperm extraction were included in this study. We compared their outcomes with 40 men with testicular failure who used donor sperm for injections due to failed retrieval, and 146 men with obstructive azoospermia who underwent percutaneous sperm retrieval. The retrieval rate in testicular failure was 41.4%, and the results were lower than the obstructed azoospermia （100%; adjusted odds ratio： 0.033; 95% Ch 0.007-0.164; P 〈 0.001）. Live birth rates after sperm injections were lower in men with testicular failure （19.9%） compared with donor sperm （37.5%; adjusted OR： 0.377 （95% Ch 0.233-0.609, P 〈 0.001）） and obstructive azoospermia （34.2%; adjusted OR： 0.403 （95% CI： 0.241-0.676, P= 0.001）. Newborn parameters of infants conceived were not significantly different among the groups. We concluded that the chances of obtaining sperm on retrieval and achieving a live birth after intracytoplasmic sperm injection （ICSI） are reduced in men with testicular failure. The profile of infants conceived after sperm injection does not seem to be negatively affected by testicular failure.

Can inhibin-B predict the outcome of microsurgical epididymal sperm aspiration in patients with suspected primary obstructive azoospermia？

Aim： To evaluate whether inhibin-B can predict the outcome of a microsurgical epidymal sperm aspiration （MESA） procedure in patients with suspected primary obstructive azoospermia （OA） and if inhibin-B can replace testicular biopsy in the diagnostic work-up of these patients. Methods： Inhibin-B levels and testicular biopsy scores were related to the outcome of MESA in 43 patients with suspected primary OA. MESA was considered to be successful when epididymal sperm could be identified during the procedure. Results： Spermatozoa were present in the epididymal aspirate in 28 out of the 43 patients （65%）. lnhibin-B values were not significantly different in patients with successful or unsuccessful MESA. The modified Johnsen score, however, was significantly lower in patients with unsuccessful MESA （P = 0.003）. A rete testis obstruction or epididymal malfunctioning was found in 15% of patients with suspected primary OA, reflected by unsuccessful MESA despite normal inhibin-B levels and normal testicular histology. Conclusion： Inhibin-B cannot replace testicular biopsy as a diagnostic tool in the work-up of patients with suspected primary OA. Testicular biopsy is useful in identifying patients with spermatogenic arrest, who might have normal inhibin-B values.

Clinical observation of loupe-assisted intussusception vasoepididymostomy in the treatment of obstructive azoospermia(analysis of 49 case reports)

To evaluate the clinical outcomes of loupe-assisted intussusception vasoepididymostomy(VE)in the treatment of epididymal obstructive azoospermia(EOA),we retrospectively analyzed data from 49 patients with EOA who underwent two-suture longitudinal intussusception vasoepididymostomy(LIVE)between 2000 and 2007.The data included the surgical method,postoperative motile sperm count per ejaculation,percentage of progressive motile sperm and patency and pregnancy outcomes.There were a total of 49 men undergoing scrotal exploration,and epididymal obstruction was found in all cases.Bilateral or unilateral anastomoses were performed in 40 and 6 men,respectively.The postoperative courses of 42 patients were followed up for more than 6 months,and the courses of 38 patients were followed up for more than 1 year.The overall patency and pregnancy rates were 71.4%and 26.3%,respectively.Moreover,progressive motile sperm was more frequently present in those patients who had undergone anastomosis at cauda than at corpus or caput.Pregnancy was achieved only in those patients who had undergone anastomosis at least on one side of the cauda epididymis.We think that the loupe-assisted method,with a lower overall cost and a simplified surgical procedure,can achieve satisfactory patency outcomes and pregnancy results.Data from this paper also suggest that paternity outcomes occur more frequently after anastomoses at cauda than at corpus or caput.

Surgical management of nonobstructive azoospermia

Nonobstructive azoospermia(NOA)is characterized by the complete absence of sperm in the ejaculate due to testicular failure.The evaluation and management of patients with NOA offer a challenge to the reproductive urologist.In the era of in vitro fertilization with intracytoplasmic sperm injection,surgical sperm extraction techniques can afford men with NOA biologic paternity.To provide a comprehensive review of surgical sperm retrieval approaches in the patient with NOA emphasizing complications,success rates and outcome optimization,a Medline search was conducted querying surgical approaches used to manage NOA.Four sperm extraction techniques are described including:testicular sperm aspiration,testicular sperm extraction,fine needle aspiration mapping and microdissection testicular sperm extraction.In addition,the roles for pre-extraction varicocelectomy and sperm cryopreservation are discussed.The management of NOA continues to evolve as newer tools become available.Several modalities of sperm acquisition exist.An understanding of their complications and success rates is fundamental to the treatment of NOA.

A susceptibility locus rs7099208 is associated with non-obstructive azoospermia via reduction in the expression of FAM160B1

Non-obstructive azoospermia （NOA） is a severe defect in male reproductive health that occurs in 1% of adult men. In a previous study, we identified that rs7099208 is located within the last intron of FAM160B1 at 10q25.3. In this study, we analysed expression Quantitative Trait Loci （eQTL） of FAM16OB1, ABLIM1 and TRUB1, the three genes surrounding rs7099208. Only the expression level of FAM16OB1 was reduced for the homozygous alternate genotype （GG） of rs7099208, but not for the homozygous reference or heterozygous geno- types. FAM160B1 is predominantly expressed in human testes, where it is found in spermatocytes and round sper- matids. From 17 patients with NOA and five with obstructive azoospermia （OA）, immunohistochemistry revealed that expression of FAM160B1 is reduced, or undetectable in NOA patients, but not in OA cases or normal men. We conclude that rs7099208 is associated with NOA via a reduction in the expression of FAM160B1.

Preliminary study of letrozole use for improving spermatogenesis in non-obstructive azoospermia patients with normal serum FSH

We investigated whether letrozole （2.5 mg day-1） improves sperm count in non-obstructive azoospermia （NOA） patients. Four men were included in this study, and they had folliculo-stimulating hormone and other hormone levels within the normal range and no varicoceles or chromosomal aberrations. These four patients were administered letrozole for 3 months. Sperm count, testicular volume, gonadotropin, testosterone （T） and estradiol （E2） blood levels were assessed before, during and 1 week after the suspension of treatment. All patients showed spermatozoa in their ejaculate, increased gonadotropin and T levels and lower E2 levels （P〈0.05 in all cases）, when letrozole was administered. This suggests that letrozole treatment might improve sperm count in an NOA sub-population; however, more studies, including the proper controls, are needed to confirm its efficacy.

The number of spermatozoa collected with testicular sperm extraction is a novel predictor of intracytoplasmic sperm injection outcome in non-obstructive azoospermic patients

The purpose of this study was to determine the relationships between monitors of spermatogenesis and predictors of the intracytoplasmic sperm injection （ICSI） outcome in patients with non-obstructive azoospermia （NOA） undergoing testicular sperm extraction （TESE）. Seventy-nine patients with NOA （mean age： 43.6±5.2 years）, each of whom yielded （97 000±3040） spermatozoa with conventional TESE, were considered in our analysis. Their partners （mean age： 35.8±5.1 years） underwent a total of 184 ICSI cycles; 632 oocytes were collected, 221 oocytes were injected, 141 oocytes were fertilized, 121 embryos were obtained, 110 embryos were transferred, 14 clinical pregnancies were achieved and only one miscarriage occurred. Multivariate regression analysis indicated relationships between the percentage of fertilized oocytes, transferred embryos and clinical pregnancies with the following variable values： female partner＇s age, number of spermatozoa collected, testicular volume, male partner＇s levels of follicle stimulating hormone （FSH）, number of oocytes collected, number of oocytes injected and number of ICSI cycles. A significant inverse relationship was found between female partner＇s age or male partner＇s FSH levels and biochemical pregnancies. A significant direct relationship emerged between the number of ICS! cycles and the percentage of oocytes fertilized, embryos transferred and biochemical pregnancies, and between the number of spermatozoa collected per testicular biopsy and biochemical pregnancies. The number of spermatozoa was positively linked to the number of clinical pregnancies, independent of the number of ICSI cycles and the number of oocytes collected/injected. The number of spermatozoa collected, FSH level and testicular volume are monitors of spermatogenesis linked to ICSI success.

Outcome of repeated micro-surgical testicular sperm extraction in patients with non-obstructive azoospermia

Aim： To evaluate the outcome of repetitive micro-surgical testicular sperm extraction （mTESE） attempts in non-obstructive azoospermia （NOA） cases, in relation to patients＇ initial testicular histology results. Methods： A total of 68 patients with NOA in whom mTESE had been performed in previous intracytoplasmic sperm injection （ICSI） attempts were reviewed. Results： Among the 68 patients with NOA, the first mTESE yielded mature sperm for ICSI in 44 （64%） （Sp^＋）, and failed in the remaining 24 （36%） （Sp^-）. Following their first trial, 24 patients decided to undergo a second mTESE. Of these 24 patients, no spermatozoa were obtained in 5 patients, and Sp^＋ but no fertilization/pregnancy were achieved in 19. In these 24 cases, mTESE was successively repeated for two （n = 24）, three （n = 4） and four （n = 1） times. The second attempt yielded mature sperm in 3/5 patients from the Sp group and 16/19 patients from the Sp^＋ group. At the third and fourth trials, 4/4 and 1/1 of the original Sp^＋ patients were Sp^＋ again, respectively. Distribution of main testicular histology included Sertoli cell-only syndrome （16%）, maturation arrest （22%）, hypospermatogenesis （21%） and focal spermatogenesis （41%）. Overall, in repetitive mTESE, 24/29 （82%） of the attempts were finally Sp^＋. Conclusion： Repeated mTESE in patients with NOA is a feasible option, yielding considerably high sperm recovery rate. In patients with NOA, mTESE may safely be repeated one or more times to increase sperm retrieval rate, as well as to increase the chance of retrieving fresh spermatozoa to enable ICSI.

Intracytoplasmic sperm injection in the treatment of male infertility due to obstructive or non-obstructive azoospermia

Objective: To evaluate the effects of intracytoplasmic sperm injection (ICSI) ontreatment of infertility due to obstructive and non-obstructive azoospermia..Methods: A retrospective analysis of fertilization, cleavage, embryo implantationand pregnancy rates was done in 158 ICSI cycles including 112 obstructive azoospermiaand 46 non-obstructive azoospermia. Ovarian hyperstimulation and ICSI procedureswere performed by conventional protocol. The sperm was collected by percutaneous epi-didymal sperm aspiration (PESA) or testicular sperm extraction (TESE).Results:The fertilization rate (73.1% vs. 67.0%), cleavage rate (88.6% vs. 86.3%), embryo implantation rate (20.7% vs. 11.4%), clinical pregnancy rate per trans-fer cycle (35.7% vs. 19.6%) were obtained for obstructive and non-obstructiveazoospermia, respectively.Conclusion: The results revealed that in the cases of obstructive azoospermia, ferti-lization rate, embryo implantation rate and clinical pregnancy rate were significantlyhigher than those of non-obstructive azoospermia. But there was no significant differ-ence of the cleavage rate between two groups.

Identification of CFTR Gene Mutations in Chinese Patients with Congenital Obstructive Azoospermia

ve To analyze the frequency and hot spot of CFTR gene mutations in Chinese patients with congenital obstructive azoospermia

Obstructive Azoospermia in a Patient with VATER Association

VATER association was first described in 1968 by Say and Gerald and is an association of congenital anomalies including V (vertebral defect), A (anal atresia), TE (tracheoesophegeal fistula), and R (radial dysplasia and renal defects). This report described a 26 year-old man with VATER association presented with infertility. Hormone tests including follicular stimulating hormone, luteinizing hormone and testosterone were normal. Semen analysis showed azoospermia. A testicular biopsy was performed and showed the presence of all of germinative components, germ cell sloughing, and mild hypospermatogenesis. The findings were compatible with obstructive azoospermia. No evidence of intratubular germ cell neoplasia unclassified was identified.

Testicular fine needle aspiration for sperm retrieval in non-obstructive azoospermia

Objective: To investigate the feasibility of obtaining mature spermatozoa for intracytoplasmic sperm injection (ICSI) by testicular fine needle aspiration (TEFNA) in men diagnosed non-obstructive azoospermia. Methods: TEFNA was performed in 121 patients with a mean of 15 punctures and aspirations from each testis with a #23 butterfly needle connected to a 20 mL syringe with an aspiration handle. Results: One hundred and twenty-one patients underwent 176 TEFNA cycles. Testicular sperm were recovered in 56.3 % (99/176) cycles from 57 % (69/121) of patients. The sperm recovery rate was 46.7 % (21/45) in patients with Sertoli cell-only syndrome, 45.7 % (16/35) in patients with maturation arrest, 96.1 % (25/26) in patients with hypospermatogenesis and 63.6 % (7/11) in patients of non-mosaic Klinefelter's syndrome as judged by testicular histology. No sperm were found in 3 cases with post-irradiation fibrosis and one, after resection and chemotherapy of unilateral testicular cancer. In 87 cycles of ICSI using the husbands' sperm, 591 mature oocytes were injected, 218 (36.9 %) were normally fertilized and 202 embryos developed; 178 were transferred in 62 cycles resulting in 26 pregnancies (41.9 %) with 44 gestational sacs (implantation rate: 24.7 %). Conclusion: TEFNA was an efficient, easy to learn, safe and well tolerated treatment in patients with non-obstructive azoospermia.

Combined evaluation of inhibin B, follicle stimulating hormone and luteinizing hormone improve sperm retrieval prediction in patients with non-obstructive azoospermia

Introduction: Non-invasive methods that can predict sperm recovery in patients with non-obstructive azoospermia (NOA) arouse interest of clinicians. The aim of this study was to evaluate the predictive value of sperm retrieval in NOA. Materials and Methods: In the retrospective study, fine needle aspiration (FNA) was performed on 306 patients with NOA at the department of andrology, Wuhan Tongji Reproductive Medical Hospital. Inhibin B, FSH and LH plasma levels were analyzed and sperms were retrieved in 67 of 306 cases (21.89%). Results: There were statistically significant differences between successful and unsuccessful sperm recoverygroups in terms of mean serum inhibin B, FSH and LH levels. The areas under the curve (AUC) of inhibin B, FSH and LH were 0.696, 0.729 and 0.747 respectively, and the AUC for the combined value of the three hormones is 0.832. The cut-off points were 27.31 pg/ml, 11.68 IU/L and 4.04 IU/L for inhibin B, FSH and LH respectively. Conclusions: This study suggests that the combined evaluation of inhibin B, FSH and LH is a more effective predictor for successful sperm retrieval in patients with NOA before decision making of an invasive procedure than any single factor.

Multivariate analysis to predict letrozole efficacy in improving sperm count of non-obstructive azoospermic and cryptozoospermic patients： a pilot study

We tested the hypothesis that letrozole increases sperm count in non-obstructive azoospermic or cryptozoospermic patients with a testosterone （T）/17-beta-2-oestradiol （E2） ratio 〈 10. Forty-six patients with no chromosomal aberrations were randomized into two groups： 22 received letrozole 2.5 mg per day for 6 months （Group 1：6 azoospermic＋ 16 cryptozoospermic patients）, while 24 received a placebo （Group 2：5 azoospermic＋19 cryptozoospermic patients）. The following data were collected： two semen analyses, clinical history, scrotal Duplex scans, body mass index （BMI）, Y microdeletion, karyotype and cystic fibrosis screens and follicle-stimulating hormone （FSH）, luteinizing hormone （LH）, E2, T and prolactin levels. Both before and after letrozole or placebo administration, the patients underwent two semen analyses and hormonal assessments. The differences were evaluated using the Mann-Whitney Utest. The relationships between sperm concentration after letrozole administration with respect to FSH, TIE2 ratio, bilateral testicle volume and BMI before letrozole administration were assessed using multivariate analysis. The side effects were assessed using the chi-square test. Group 1 had sperm concentration （medians： 400-1.290× 10^6 ml^-1; P〈0.01） and motility （medians： class A from 2% to 15%; P〈0.01）, FSH, LH and T significantly increased, while Group 2 did not. E2 levels diminished significantly in Group 1, but not in Group 2. Eight patients in Group 1 demonstrated side effects, whereas no patient side effects were observed in Group 2. The sperm concentration after letrozole administration is inversely related to TIE2, FSH and BMI; a direct relationship emerged between sperm concentration and testicular volume.

生精细胞形态学检查联合血清FSH水平检测在NOA患者M-TESE中的应用价值

目的探讨精液生精细胞形态学检查联合血清卵泡刺激素(FSH)水平检测在非梗阻性无精子症(NOA)患者睾丸显微取精术(M-TESE)中的应用价值。方法以2019年10月至2021年10月在该院生殖医学中心接受M-TESE的41例NOA患者为研究对象,采集精液标本进行生精细胞形态学检查和血清FSH水平检测。将精液生精细胞形态学检查检出生精细胞的患者作为阳性组,未检出生精细胞的患者作为阴性组;显微镜下找到成熟精子为M-TESE成功,未找到成熟精子为M-TESE未成功。分析两组患者的血清FSH水平和M-TESE的成功率。结果41例NOA患者中,阳性组18例,占43.9%;阴性组23例,占56.1%。M-TESE成功15例,未成功26例,总成功率为36.6%,其中阳性组M-TESE成功率为66.7%(12/18),阴性组M-TESE成功率为13.0%(3/23),两组的M-TESE成功率比较,差异有统计学意义(P<0.001)。阳性组血清FSH水平为(27.2±14.2)mIU/mL,阴性组为(39.3±15.0)mIU/mL,差异有统计学意义(P=0.012)。结论NOA患者精液生精细胞形态学检查联合血清FSH水平检测对M-TESE成功率有一定的预测作用。

显微镜下单针法纵向套叠输精管附睾吻合术后附睾管-输精管精道复通的影响因素

目的分析显微镜下单针法纵向套叠输精管附睾吻合术治疗附睾梗阻性无精子症术后附睾管-输精管精道复通的影响因素,为临床提高复通率提供参考。方法回顾性分析郑州大学第一附属医院男科于2020年9月—2023年1月行显微镜下单针法纵向套叠输精管附睾吻合术的82例附睾梗阻性无精子症患者的临床资料,术后门诊和/或电话随访患者术后复通情况及配偶受孕情况。分析患者年龄、病程、身体质量指数(BMI)、既往病史(附睾炎、手术史、无)、术前精浆弹性蛋白酶(SPE)水平、吻合部位、吻合侧别、附睾液镜检精子质量、手术时长及住院时间对术后复通率的影响。结果82例患者的手术均成功实施,随访率95.12%(78/82),78例随访患者中已婚73例,复通率78.21%(61/78),61例复通患者中已婚56例,已婚患者配偶自然受孕率45.21%(33/73)。单因素分析结果显示年龄<30岁、病程<2年、术前SPE水平<290 ng/mL、双侧吻合、体尾部吻合及附睾液镜检有活动精子的患者有更高的术后复通率(P<0.05);BMI、既往病史、附睾液镜检活动精子数量、手术时间及住院时间对术后复通的影响无显著相关性(P>0.05)。多因素logistic回归分析结果显示患者术前SPE水平(OR=0.998,95%CI:0.997~1.000,P=0.008)、吻合部位(OR=10.724,95%CI:2.243~51.283,P=0.003)与术后复通显著相关。结论术前SPE水平和吻合部位是显微镜下输精管附睾吻合术后复通的显著影响因素。年龄<30岁、病程<2年、术前SPE水平<290 ng/mL、双侧吻合、体尾部吻合及附睾液镜检有活动精子的患者术后复通率较高。

贵州苗族非梗阻性无精男性3例的Y染色体微缺失及致病候选基因

目的研究贵州苗族无精症男性的Y染色体微缺失和致病候选基因突变。方法本研究招募苗族非梗阻性无精症男性3人,使用目标区域捕获测序及全外显子测序,分析注释到相关基因区域,解析苗族无精症男性的Y染色体微缺失及致病候选位点。结果3例苗族非梗阻性无精症患者中未发现Y染色体微缺失位点。全外显子测序结果发现USP9Y、CFTR、ZMYND15、DNAH1的突变位点,可能是苗族非梗阻性无精症的候选致病突变。结论贵州苗族男性Y染色体微缺失阴性的非梗阻性无精症可能具有特异的基因致病突变位点,在男性不育研究及临床中应引起关注。

显微镜下改良单针LIVE对梗阻性无精子症患者的应用效果

目的:探讨显微镜下改良单针纵向套叠输精管附睾管吻合术(LIVE)对梗阻性无精子症(OA)患者的应用效果。方法:选取2019年10月至2023年5月郑州大学第一附属医院收治的OA患者91例作为研究对象,其中45例行显微镜下改良单针LIVE患者设为改良单针组,46例行显微镜下双针LIVE患者设为双针组。对两组患者手术、住院时间、复通率、术后3、6个月两组精子前向运动总活力、精子浓度、总活力水平和配偶妊娠结果进行比较。结果:与双针组患者相比较,改良单针组的手术时间较长,差异具有统计学意义(P <0.05);两组患者的住院时间比较,差异无统计学意义(P> 0.05);术后3个月,改良单针组患者的复通率为68.88%,双针组为71.73%,组间比较,差异无统计学意义(P> 0.05);相较于术后3个月,术后6个月两组患者精子前向运动总活力、精子浓度、总活力水平均有所提高,差异均具有统计学意义(P <0.05);两组患者术后3、6个月的精子前向运动总活力、精子浓度、总活力水平比较,差异均无统计学意义(P> 0.05);术后随访6个月,改良单针组患者的配偶妊娠率为35.55%,双针组为39.13%,组间比较,差异无统计学意义(P> 0.05)。结论:显微镜下改良单针LIVE治疗OA患者与双针LIVE疗效相当,相较于双针LIVE,单针LIVE的手术时间虽稍长,但其操作简单,手术材料更易获取,因此更容易普及。

非梗阻性无精子症患者睾丸显微取精病理学检查与睾丸活检组织剥离检查精子检出情况比较

目的探讨非梗阻性无精子症(NOA)患者组织病理学检查与睾丸活检组织剥离检查检出精子的一致性。方法回顾性分析2020年1月至2022年12月就诊于山东大学附属生殖医院的197例男性NOA患者,均于睾丸显微取精活检手术后对睾丸组织同时进行病理学检查和睾丸活检组织剥离检查,对其精子获取率进行分析。结果将患者根据病理学检查结果分为未见精子组[生精功能阻滞(MA)+唯支持细胞综合征(SCOS)]170例(86.3%)与查见精子组[生精功能低下(HS)]27例(13.7%)。睾丸活检组织剥离精子检出29例(14.7%),7例SCOS患者通过睾丸组织剥离查见精子并实施卵胞质内单精子注射(ICSI)。两种方法的精子检出率比较,差异无统计学意义(P>0.05)。卵泡刺激素(FSH)水平在两组间差异具有统计学意义(P<0.05)。结论两种方法查找精子一致率高,睾丸活检病理学检查作为病因学分析,对NOA患者再次体外取精能否成功提供预测依据,FSH水平也有助于预测能否成功取精,而睾丸组织剥离找到精子后可直接应用于人工辅助生殖技术,因此更具有决定性意义。

Microsurgical vasoepididymostomy for patients withinfectious obstructive azoospermia, cause, outcome,and associated factors

Azoospermia is of great importance to male infertility. Obstructive azoospermia （OA） due to infection is the most prevalent form of OA in China and has been less studied. We aim to observe the treatment outcome of microsurgical vasoepididymostomy （VE） and also to identify the factors relative to the result after reconstructive surgery. Two hundred and eight men presenting with OA due to infection during the study period from July 2010 to July 2013 were prospectively evaluated. Clinical examination, semen analysis, serum follicle stimulating hormone （FSH）, and scrotal ultrasound were done before surgical exploration. Among the 198 men who were selected for surgical procedures, 159 candidates underwent microsurgical VE with sperm detected in the epididymal fluid. As for the other 39 cases, reconstruction was not feasible. The average age was 28.5 ＋ 3.9 years （range 22-38）, with average follow-up being 16.5 ~ 5.9 months （range 4-28）. According to the 150 cases being followed after VE procedures, the total patency rate was 72% （108/150）. During follow-up, 38.7% （58/150） natural pregnancies occurred, with overall live birth rate being 32.7% （49/150）. Our data suggested that microsurgical VE is an effective therapy for postinfectious epididymal OA. Individualized counseling with prognosis based on etiology should be offered to patients to select optical therapy.