阴囊内输精管交叉显微吻合手术在不典型梗阻性无精子症患者中的临床应用

Clinical application of cross microsurgical vasovasostomy in scrotum for atypical obstructive azoospermia 阴囊内输精管交叉显微吻合手术在不典型梗阻性无精子症患者中的临床应用 1 first-author 1 1 1 1 2 1 corresp ‡Corresponding Author ‡Corresponding Author †E-mail:zhuyim@zju.edu.cn †E-mail:zhuyim@zju.edu.cn zhuyim@zju.edu.cn Department of Reproductive Endocrinology, Reproductive Medicine Center, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China Department of Reproductive Endocrinology, Reproductive Medicine Center, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China Department of Ultrasonography, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China Department of Ultrasonography, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China Seminal duct obstruction may result in obstructive azoospermia (OA) and severe oligoasthenoteratozoospermia (OAT) ( < 0.5 million/mL) (Nordhoff et al., 2015 2015 ). Cases of partial OA and OAT can be treated effectively by microsurgical anastomosis (Goldstein and Kim, 2013 2013 ) to obtain successful surgical reversal. However, microsurgical vasovasostomy (VV) (Dickey et al., 2015 2015 ) and vasoepididymostomy (VE) (Peng et al., 2017 2017 ) are not suitable for patients with atypical OA and poor epididymis conditions or unpredictable obstruction of the distal vas deferens. For those patients, cross anastomosis may be applied instead of routine VE or VV. A single-center, retrospective, comparison study was conducted, which assessed the usefulness of the cross VV (CVV) in the scrotum for indication and efficacy. A total of 77 cases with OA or OAT were included, and 20 cases implemented cross anastomosis, including unilateral CVV (UCVV) in 4 cases, unilateral VE plus CVV (UVE+CVV) in 11 cases, and unilateral VV-based CVV (UVV+CVV) in 5 cases. The other 57 cases received no cross-matching anastomosis. The patency and natural pregnancy rates in one year were 75.0% and 50.0%, respectively, in the UCVV group; 54.5% and 27.3%, respectively, in the UVE+CVV group; and 60.0% and 40.0%, respectively, in the UVV+CVV group. The CVV in the scrotum in the selected patients with OA and severe OAT could yield good results. We regard the CVV in the scrotum as an efficacious operation with a lower risk of injury in cases of atypical OA. 目的 2 探讨在不典型梗阻性无精子症患者中施行不同方式阴囊内输精管交叉显微吻合手术的指征及有效性. 创新点 2 分析不同方式阴囊内输精管交叉显微吻合手术的指征及有效性,建议使用损伤小且成功率较高的阴囊内单纯输精管交叉显微吻合手术方式. 方法 2 收集2012年1月至2016年6月浙江大学医学院附属妇产科医院68例不典型梗阻性无精子症和9例重度少弱精子症患者的临床资料,对施行不同手术方式的患者的特征、术后精子参数和配偶自然妊娠率结果等相关数据进行分析. 结论 2 不典型梗阻性无精子症患者中施行各种类型的输精管交叉吻合手术均是对传统原位吻合手术有益的补充,阴囊内单纯输精管交叉显微吻合手术损伤小且成功率较高. Vasovasostomy Azoospermia Microsurgery 输精管吻合 无精子症 显微手术 Seminal duct obstruction may result in obstructive azoospermia (OA) and severe oligoasthenoteratozoospermia (OAT) ( < 0.5 million/mL) (Nordhoff et al., 2015 2015 ). Cases of partial OA and OAT can be treated effectively by microsurgical anastomosis (Goldstein and Kim, 2013 2013 ) to obtain successful surgical reversal. However, microsurgical vasovasostomy (VV) (Dickey et al., 2015 2015 ) and vasoepididymostomy (VE) (Peng et al., 2017 2017 ) are not suitable for patients with atypical OA and poor epididymis conditions or unpredictable obstruction of the distal vas deferens. For those patients, cross anastomosis may be applied instead of routine VE or VV. A single-center, retrospective, comparison study was conducted, which assessed the usefulness of the cross VV (CVV) in the scrotum for indication and efficacy. A total of 77 cases with OA or OAT were included, and 20 cases implemented cross anastomosis, including unilateral CVV (UCVV) in 4 cases, unilateral VE plus CVV (UVE+CVV) in 11 cases, and unilateral VV-based CVV (UVV+CVV) in 5 cases. The other 57 cases received no cross-matching anastomosis. The patency and natural pregnancy rates in one year were 75.0% and 50.0%, respectively, in the UCVV group; 54.5% and 27.3%, respectively, in the UVE+CVV group; and 60.0% and 40.0%, respectively, in the UVV+CVV group. The CVV in the scrotum in the selected patients with OA and severe OAT could yield good results. We regard the CVV in the scrotum as an efficacious operation with a lower risk of injury in cases of atypical OA. The prevalence of azoospermia is less than 1% of the male population and about 10%–15% among infertile males. Furthermore, 40% of azoospermia cases involve OA resulting from seminal duct obstruction (Jarow et al., 1989 1989 ). Both microsurgical VV and VE can yield successful surgical reversal and allow infertile couples to have babies naturally in cases of OA. Such operations are not universally suitable for all cases. Those with poor epididymis conditions or unpredictable obstruction of the distal vas deferens could be referred to as atypical OA, and cross anastomosis might be applied instead of routine VE or VV. However, the efficacy of the cross methods has been only mentioned in a few previous reports (Chen et al., 2014 2014 ; Li et al., 2016 2016 ), and whether additional cross anastomosis can improve patency and pregnancy rates was unclear. Seventy-seven patients with clinically OA (67/77) and severe OAT (10/77) who sought treatment in our center were analyzed in this study from January 2012 to June 2016. Our center implemented cross anastomosis in 20 cases, and no-cross-matching cases in 57 cases. This retrospective comparison study was carried out in Zhejiang Women’s Hospital (Zhejiang, China). The Ethics Committee of Zhejiang Women’s Hospital, School of Medicine, Zhejiang University, approved the study protocol. All patients provided written informed consent to be in the study with guarantees of confidentiality. OA was confirmed by at least two consecutive semen analyses without sperm, and severe OAT by semen concentration less than 0.5 million/mL. For all patients, the following criteria were met: (1) azoospermia or severe OAT, (2) epididymis and/or vas deferens obstruction via scrotal ultrasonography and transrectal ultrasound (TRUS) (Lotti and Maggi, 2015 2015 ) for at least one side, (3) no history of acute urogenital infection, and (4) normal follicle-stimulating hormone levels and no chromosome abnormality. Cross anastomosis was performed with the steps as described below. A 24-gauge angiocatheter was cannulated into the lumen of the vas deferens, and diluted methylene blue was injected. After confirming the vas deferens patency and epididymal obstruction, we performed a microsurgical longitudinal 2-stuture intussusceptive VE (Hong et al., 2016 2016 ). For patients who underwent inguinal herniorrhaphy before adolescence, we could identify and dissociate the proximal obstruction site of the vas deferens with the guidance of a catheter in the vas deferens. The routine VV was performed in cases where the distal remnants were present. The microsurgical two-layer technique under operative microscopy was mandatorily required for VV according to literature (Silber, 1976 1976 ). However, because of sharply reduced wall thickness of the distal vasal remnants in some cases, one layer anastomosis was applied (Fig. 1a 1a ). (a) VV in situ (inguinal region); (b) CVV on the basis of unilateral VV in situ (UVV+CVV); (c) CVV plus unilateral vasoepididymostomy (UVE+CVV); (d) unilateral cross VV (UCVV) The microscopic examination of liquid in the vas deferens was critical (Ramasamy et al., 2015 2015 ). The identification of sperm and predominately sperm heads demonstrated an obstruction of the vas deferens instead of the epididymis. Cross anastomosis was applied with the following conditions. (1) For the UVV+CVV group: ipsilateral VV was accomplished in situ, absence of the contralateral distal vas deferens, and patency of epididymis. The additional CVV in the scrotum based on the UVV was performed in situ (Fig. 1b 1b ). (2) For the UVE+CVV group: ipsilateral VE was performed, contralateral distal vas deferens obstruction, and patency of epididymis. The additional CVV in the scrotum plus UVE was applied (Fig. 1c 1c ). (3) UCVV group: ipsilateral patency of the vas deference and poor conditions of the epididymis or testis, contralateral obstruction of the distal vas deferens, and patency of epididymis. The UCVV in the scrotum was performed (Fig. 1d 1d ). For the CVV, we dissociated the vas deferens (obstruction side) for approximately 3 cm distal to the epididymis and resected it, then pulled it through the scrotal septum. A longitudinal incision with a diameter identical to the vas deferens was made in the contralateral vas deferens. The procedure was similar to the routine VV mentioned above. For all CVV cases, we implemented an end-to-side anastomosis instead of an end-to-end procedure (Figs. 2 2 and 3 3 ). All surgical approaches mentioned above were conducted under spinal anesthesia and under a surgical microscope (Carl Zeiss, S88, Germany). The sperm parameters were evaluated by semen analysis separately during the follow-ups at 3, 6, and 12 months. The couples’ pregnancy rates were recorded. The elevated sperm concentration at least 1.5 times after surgery demonstrated successful reversal for patients with OAT. All the patients’ characteristics are listed in Table 1 1 . Twenty patients underwent various types of CVV: 11/20 (55.0%) underwent UVE+CVV, 4/20 (20.0%) underwent UCVV, and 5/20 (25.0%) underwent UVV+CVV. The other 57 patients did not have cross anastomosis, including 35/57 (61.4%) for UVE group, 9/57 (15.8%) for UVV group, and 13/57 (22.8%) for bilateral VV (BVV group) with 9 patients in the scrotum (BVV-S group) and 4 patients in the inguen (BVV-I group) (Table 2 2 ). We achieved a 44.2% patency rate and 23.4% nature pregnancy rate separately (Table 1 1 ). The patency and nature pregnancy rates in each group with different methods are listed in Table 2 2 . The highest patency and natural pregnancy rates were in the BVV-S group (77.8% and 66.7%, respectively). We observed comparatively higher patency and natural pregnancy rates in the UCVV group (75.0% and 50.0%, respectively) compared with those of the UVE+CVV group (54.5% and 27.3%, respectively) and the UVE group (31.4% and 11.4%, respectively). The Pearson chi-square test or Fisher’s exact test was used to compare the patency and pregnancy rates among the different groups. One-way analysis of variance was used to compare the ages of men and women, and volume of surgical testis (Table 3 3 ). A P- value of < 0.05 was considered to be statistically significant. The mean patency rate of the BVV group was significantly higher than that of the UVV group (76.9% vs. 11.1%, P < 0.05), as well as that of the CVV group compared to the UVV group (60.0% vs. 11.1%, P < 0.05). There was no significant difference in the mean patency rate between the CVV and BVV groups (60.0% vs. 76.9%, P > 0.05). The mean natural pregnancy rate of the BVV group was higher than that of the UVV group (53.8% vs. 0%, P < 0.05), and no significant differences were observed between the CVV and BVV groups (35.0% vs. 53.8%, P > 0.05), as well as that between the CVV and UVV groups (35.0% vs. 0%, P > 0.05). Regarding the volume of average surgical testis, there were no significant differences between all the groups ( P > 0.05). Data are expressed as mean±standard deviation (SD) or number (percentage) Parameter Value Age, male (year) 32.6±6.5 Age, female (year) 28.9±4.5 Primary infertility 60 (77.9%) Secondary infertility 17 (22.1%) Obstructive azoospermia 68 (88.3%) Oligoathernotetrazoospermia 9 (11.7%) Infertility interval (year) 3.5±3.2 Etiology  Childhood inguinal herniorrhaphy (sides) 31 (20.1%)  Inflammatory (sides) 79 (51.3%)  Absences of vas (sides) 4 (2.6%)  Atrophy (sides) 10 (6.5%)  Suspected epididymal dysplasia (sides) 6 (3.9%)  Vasectomy (sides) 24 (15.6%) Average volume of surgical testis (mL) 15.5±3.6 Dilated vas deferens in ultrasound 35 (45.5%) Total patency 34 (44.2%) Total nature pregnancy 18 (23.4%) UVV: unilateral vasovasostomy; CVV: cross vasovasostomy; BVV-S: bilateral vasovasostomy in the scrotum; BVV-I: bilateral vasovasostomy in the inguen; UCVV: unilateral cross vasovasostomy; UVE: unilateral vasoepididymostomy. Data are expressed as number (percentage) Group Case Patency * * Nature pregnancy * * UVV+CVV 5 3 (60.0%) 2 (40.0%) BVV-S 9 7 (77.8%) 6 (66.7%) BVV-I 4 3 (75.0%) 1 (25.0%) UVV 9 1 (11.1%) 0 (0%) UCVV 4 3 (75.0%) 2 (50.0%) UVE+CVV 11 6 (54.5%) 3 (27.3%) UVE 35 11 (31.4%) 4 (11.4%) CVV: cross vasovasostomy (including unilateral vasovasostomy (UVV)+CVV, unilateral cross vasovasostomy (UCVV), unilateral vasoepididymostomy (UVE)+CVV). BVV: bilateral vasovasostomy. Male age: P =0.027 vs. BVV; P =0.043 vs. BVV. Female age: * P =0.034 vs. BVV. Patency: * P < 0.05 vs. UVV. Natural pregnancy: * P < 0.05 vs. UVV. Data are expressed as mean±standard deviation (SD); Data are expressed as number (percentage) 2 Group 2 Case 2 Age (year) 1 1 2 Volume of surgical testis (mL) 1 1 2 Patency 2 2 2 Natural pregnancy 2 2 Male Female CVV 20 31.4±4.4 * * 28.3±3.7 * * 14.9±2.5 12 (60.0) * * 7 (35.0) UVV 9 30.8±6.1 # # 28.2±5.2 16.2±4.6 1 (11.1) 0 (0) BVV 13 37.3±10.6 32.0±5.9 15.4±4.8 10 (76.9) * * 7 (53.8) * * 7 P -value 0.05 0.08 0.68 0.01 0.01 We found a significant difference in the patency rate between the CVV and UVV groups, and no significant difference between the CVV and BVV groups (Table 3 3 ), which implied that any kind of CVV may provide good supplementation to the unilateral anastomosis in situ. The higher rates in the UVE+CVV group compared to the UVE group suggest that additional CVV may be a better alternative than UVE. Similar results of the UVV+CVV group compared to the UVV group corroborate the conclusion (Table 2 2 ). It was interesting that UCVV in the scrotum has comparatively higher patency and pregnancy rates. This may have been because: (1) Compared with the inguinal area, the CVV area in the scrotum was well exposed and under less anastomotic tension. Microsurgery techniques are more difficult for surgeons to perform in the deep inguinal region. Furthermore, the internal diameter and wall thickness of the vas deferens are inconsistent. (2) According to the literature, the patency and natural pregnancy rates of VV were higher than those of VE (Chan, 2013 2013 ; Dickey et al., 2015 2015 ). (3) The additional manipulation on the ipsilateral vas deferens might lead to insufficient blood supply or unpredictable scar formation. However, the implementation of additional cross anastomosis might affect blood supply to the vas deferens, and whether additional anastomosis increases scar formation and decreases the patency remains unknown. 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Microscopic technique for reversal of vasectomy Compliance with ethics guidelines Zhong-yan LIANG, Feng-bin ZHANG, Le-jun LI, Jing-ping LI, Jing-gen WU, Chong CHEN, and Yi-min ZHU declare that they have no conflict of interest. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). Informed consent was obtained from all patients for being included in the study. 10.1631/jzus.B1800303 Project supported by the Medical Scientific Research Foundation of Zhejiang Province (No. 2015KYB197),China 2018-05-29 2018-12-19 2022-01-05 Copyright © Zhejiang University and Springer-Verlag GmbH Germany, part of Springer Nature 2019 2019 Journal of Zhejiang University-SCIENCE B (Biomedicine and Biotechnology) 03 20