A novel loss-of-function variant in PNLDC1 inducing oligo-astheno-teratozoospermia and male infertility

Male infertility is a major reproductive disorder,which is clinically characterized by highly heterogeneous phenotypes of abnormal sperm count or quality.To date,five male patients with biallelic loss-of-function(LOF)variants of PARN-like ribonuclease domain-containing exonuclease 1(PNLDC1)have been reported to experience infertility with nonobstructive azoospermia.The aim of this study was to identify the genetic cause of male infertility with oligo-astheno-teratozoospermia(OAT)in a patient from a Chinese Han family.Whole-exome and Sanger sequencing analyses identified a homozygous LOF variant(NM_173516.2,c.l42C>T,p.Gln48Ter)in PNLDC1.Hematoxylin and eosin staining revealed that the spermatozoa of the patient with OAT had an irregular head phenotype,including microcephaly,head tapering,and globozoospermia.Consistently,peanut agglutinin staining of the spermatozoa revealed a complete or partial loss of the acrosome.Furthermore,the disomy rate of chromosomes in the patient’s spermatozoa was significantly increased compared with that of a fertile control sample.We reported an LOF variant of the PNLDC1 gene responsible for OAT.

Thoughts and Approaches of Integrated Chinese and Western Medicine for the Treatment of Oligo-astheno-teratozoospermia

Oligo-astheno-teratozoospermia（OAT） which perplexes doctors and patients due to its complicated etiology, atypical symptoms and poor clinical efficacy, is a general term for the three pathological states of abnormal semen. OAT is the main factor of male infertility. It is also a hot and difficult point in present studies. Empiric drug is the most popular treatment of this disease in the modern medicine. Chinese medicine（CM） is one of the main methods for the treatment of this disease, and it has certain clinical effect. The author believes that the use of modern medical technology to make the diagnosis as clear as possible is the key to treat OAT. The combination of syndrome and disease differentiation is the main mode in the treatment of OAT. Microscopic syndrome differentiation and macroscopic evidence embodies the basic principle of ＂Si Wai Chuai Nei＂ and broadens the perspective of CM syndrome differentiation. Classification and treatment are basic methods for the treatment of OAT. The treatment should not be limited to the Shen（Kidney）, instead it should focus on the whole body condition. At different stages, the treatment should also pay attention to strengthening the Pi（Spleen）, nourishing the Gan（Liver） and promoting blood circulation. Complementing Chinese and Western medicine, and highlighting the characteristics and advantages of CM treatment, have a great guiding value for the treatment of OAT.

国内单独应用左卡尼汀与联合其他药物治疗少弱精子症有效性的Meta分析

目的应用Meta分析方法评价少弱精子症患者单独应用左卡尼汀与左卡尼汀联合其他药物治疗后精液质量改善的总有效率的变化。方法检索万方数据库、中国知网期刊数据库、中国生物医学文献数据库等数据库,全面收集相关文献。制定文献纳入标准,观察指标包括妊娠率、精子密度、精子活率及前向运动精子率,制定疗效等级评价标准。应用ReviewManager 5.2软件进行Meta分析。结果本项研究共有981名少弱精子患者入选,Meta分析结果显示采用口服左卡尼汀联合其他多种生精药物后的治疗总有效率明显高于单纯服用左卡尼汀口服液。结论应用左卡尼汀联合其他不同机制的生精药物治疗少弱精子症时比单独应用左卡尼汀具有更加积极的治疗效果。

不同来源精子行卵胞浆内单精子注射临床结局分析

目的:比较不同来源精子行卵胞浆内单精子注射的临床结局。方法:回顾性的分析2008年1月～2011年12月在我中心行ICSI助孕的患者,选取不孕原因为单纯性严重少、弱、畸精症和无精症的,且年龄在35岁或35岁以下的153例患者入组本研究,共完成165个取卵周期,146个移植周期。按精子来源分为两组:射出精子组(严重少、弱、畸精症组)和睾丸精子组,比较两组间的女方平均年龄、不孕年限、基础FSH值、Gn支数、Gn天数、HCG日E2值、内膜厚度、MII卵数、受精、卵裂、可移植胚胎、优质胚胎、临床妊娠及流产情况。结果:两组间的女方平均年龄、不孕年限、基础FSH值、Gn支数、Gn天数、HCG日E2值、子宫内膜厚度、MII卵数、2PN卵裂率、可移植胚胎率、优质胚胎率、流产率、多胎率无统计学差异;睾丸精子组的受精率、2PN受精率较射出精子组高(72.3%vs 82.0%,P<0.01;67.9%vs72.9%,P<0.05),差异均有统计学意义;虽然睾丸精子组的临床妊娠率、种植率(60.7%、42.0%)高于射出精子组(50.0%、35.6%),但是两组间的差异无统计学意义(P>0.05)。结论:睾丸精子行ICSI助孕可以得到较好的临床结局,不比严重少、弱、畸精子症患者精液中的精子差。

Relationship between acrosin activity of human spermatozoa and oxidative stress

Aim: To study the association between seminal oxidative stress and human sperm acrosin activity. Methods: It is a prospective study consisting of 30 infertile men and 12 fertile normozoospermic volunteers. A full history, clinical examination and scrotal ultrasound were done to exclude other related factors such as smoking and varicocele. Presence of white blood cells (WBCs) in semen samples was evaluated by peroxidase staining. Lipid peroxidation in spermatozoa was induced after incubating with ferrous sulphate (4 mmol/L) and sodium ascorbate (20 mmol/L). Induced peroxidation of spermatozoa was assessed by determining the production of thiobarbituric acid reactive substances (TBARS). Acrosin activity was measured using the gelatinolysis technique. The halo diameters around the sperm heads and the percentages of spermatozoa showing halo formation were evaluated. An acrosin activity index was calculated by multiplying the halo diameter by the halo formation rate. Results: A significant difference was observed in acrosin activity parameters and TBARS levels between samples with WBCs (>1×106/mL of ejaculate) and those without. This difference was also noted between the normozoospermic and the oligoasthenoteratozoospermic semen samples. The TBARS production by spermatozoa had a significant negative correlation with the acrosin activity index (r = -0.89, P <0.001). Conclusion: The presence of oxidative stress in an individual with leukocytospermia and/or abnormal semen parameters is associated with impaired sperm function as measured by its acrosin activity.

The role of varicocele sclerotherapy in men with severe ol igo-astheno-teratozoos perm ia

The aim of this study was to verify the role of antegrade scrotal sclerotherapy for the treatment of varicoceles in infertile men with severe oligo-astheno-teratozoospermia （OAT）. The 59 patients with severe OAT in this study underwent antegrade scrotal sclerotherapy for the treatment of varicoceles. The outcome was assessed in terms of improvement in semen parameters and spontaneous conception rate. Semen parameters and reproductive hormones were evaluated before antegrade sclerotherapy （AS） and 6 months after AS. After an average follow-up time of 34.8_＋3.2 months, significant improvement was noted in the mean sperm concentration, motility and morphology in 36 patients （61%）. Spontaneous pregnancy occurred in nine couples （15%）. Six months after treatment, inhibin B levels were significantly higher （P〉0.04）, whereas follicle-stimulating hormone （FSH） levels were significantly lower （P〈0.001） than before treatment. Antegrade internal spermatic vein sclerotherapy can significantly improve seminal parameters and hormonal parameters in men with severe OAT and may even result in spontaneous pregnancy in couples who would otherwise be candidates for intracytoplasmic sperm injection （ICSI）.

左旋肉碱治疗男性不育症有效性的Meta分析

目的分析左旋肉碱治疗男性不孕症的有效性。方法计算机检索中国期刊全文数据库(1994—2014-03),中国生物医学文献数据库(1978—2014-03),中文科技期刊全文数据库(1989—2014-03),数字化期刊全文数据库(1997—2014-03),PubMed(1966 2014-03),EMBASE(1900 2014-03),SCI(1974—2014-03)和Cochrane Library(2013-01),并辅以其他检索,纳入左旋肉碱治疗男性不孕症的随机对照试验研究,使用PEDro量表进行质量评价并用RevMan 5.0进行Meta分析。结果共纳入9篇文献,643位患者。Meta分析结果显示:治疗组与对照组相比,妊娠率[OR=3.26,95%CI(1.74,6.11)]、精子密度[MD=12.49,95%CI(9.94,15.04)]、精子活力[MD=2.28,95%CI(0.63,3.93)]、前向运动精子率[MD=7.87,95%CI(6.71,9.03)]均高于对照组。结论左旋肉碱可以有效治疗男性不孕症,对精子质量具有改善作用。

无创胚胎染色体筛查在男性严重少弱畸精子症不育患者的临床应用

目的:探讨无创胚胎染色体筛查技术(NICS)对男性严重少弱畸精子症辅助生殖妊娠结局的应用价值。方法:随机选取2017年1月至2020年12月因男方严重少弱畸形精症行辅助生殖助孕的男性不育患者共计170例,接受NICS治疗的85对夫妻作为试验组,接受卵胞质内单精子注射(ICSI)85对夫妇作为对照组,比较两组女方年龄、女方体重质量指数(BMI)、抗苗勒氏管激素(AMH)、基础窦卵泡计数(AFC)、不孕年限、男方年龄、精子浓度、前向运动精子百分率、正常形态精子百分率、精子DNA碎片化指数(DFI)、获卵数、正常受精数、优质囊胚数、临床妊娠率、流产率的差异。结果:NICS组与ICSI组相比,女方年龄、女方BMI、AMH、AFC、不孕年限、男方年龄、精子浓度、前向运动精子百分率、正常形态精子百分率、精子DFI、获卵数、正常受精数、优质囊胚数均无统计学差异(P均>0.05),NICS组明确诊断率88.24%,检测胚胎染色体整倍体率48.56%,NICS组挑选整倍体胚胎移植后临床妊娠率高于ICSI组(66.28%vs 51.09%)、而流产率低于ICSI对照组(12.28%vs 29.79%),差异均有统计学意义(P<0.05)。结论:对于男性严重少弱畸形精子症不育患者,NICS技术可以提高临床妊娠率、降低流产风险。