育婴生精颗粒治疗精液异常性不育症临床观察

选用雄蚕蛾、鹿角片、熟地、炒山甲、急性子等15味名贵中药制成颗粒剂,治疗精液异常性不育症260例,其中治愈(受孕)165例,占63.5%,显效71例,占27.3%,总有效率达93.8%。临床研究实践证明,育婴生精颗粒疗效确切、效果满意。

New understandings of the genetic basis of isolated diopathic central hypogonadism

Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary-gonadal axis by gonadotrophin-releasing hormone （GnRH） action. Because reduced or normal luteinizing hormone （LH）/follicle-stimulating hormone （FSH） levels may be observed in the affected patients, the term idiopathic central hypogonadism （ICH） appears to be more appropriate. This disease should be distinguished from central hypogonadism that is combined with other pituitary deficiencies. Isolated ICH has a complex pathogenesis and ~s fivefold more prevalent in males. ICH frequently appears in a sporadic form, but several familial cases have also been reported. This finding, in conjunction with the description of numerous pathogenetic gene variants and the generation of several knockout models, supports the existence of a strong genetic component. ICH may be associated with several morphogenetic abnormalities, which include osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann syndrome （KS）. KS accounts for approximately 40% of the total ICH cases and has been generally considered to be a distinct subgroup. However, the description of several pedigrees, which include relatives who are affected either with isolated osmic defects, KS, or normo-osmic ICH （nlCH）, justifies the emerging idea that ICH is a complex genetic disease that is characterized by variable expressivity and penetrance. In this context, either multiple gene variants or environmental factors and epigenetic modifications may contribute to the variable disease manifestations. We review the genetic mechanisms that are presently known to be involved in ICH pathogenesis and provide a clinical overview of the 227 cases that have been collected by the collaborating centres of the Italian ICH Network.

A novel missense mutation in QRICH2 causes male infertility due to multiple morphological abnormalities of the sperm flagella

Multiple morphological abnormalities of the sperm flagella(MMAF)are characterized by bent,irregular,short,coiled,and absent flagella.MMAF is caused by a variety of genes,some of which have been identified.However,the underlying genetic factors responsible for the majority of MMAF cases are still largely unknown.The glutamine-rich 2(QRICH2)gene plays an essential role in the development of sperm flagella by regulating the expression of essential sperm flagellar biogenesis-associated proteins,and genetic variants of QRICH2 have been identified as the primary cause of MMAF in humans and mice.Here,we recruited a Pakistani consanguineous family to identify the genetic variant causing infertility in patients with MMAF.Whole-exome sequencing and Sanger sequencing were conducted to identify potentially pathogenic variants causing MMAF in infertile patients.Hematoxylin and eosin(HE)staining was performed to analyze sperm morphology.Quantitative polymerase chain reaction,western blot,and immunofluorescence staining analyses were conducted to observe the expression of QRICH2 in spermatozoa.A novel homozygous missense variant(c.4618C>T)in QRICH2 was identified in the affected patients.Morphological analysis of spermatozoa revealed the MMAF phenotype in infertile patients.qPCR revealed a significant reduction in the level of sperm QRICH2 mRNA,and immunofluorescence staining revealed a lack of sperm QRICH2 expression.Additionally,patients harboring a homozygous QRICH2 mutation presented reduced expression of outer dense fiber 2(ODF2)in sperm,whereas sperm expression of A-kinase anchor protein 4(AKAP4)was normal.These findings expand our understanding of the genetic causes of MMAF-associated male infertility and emphasize the importance of genetic counseling.

Relationship between microdeletion on Y chromosome and patients with idiopathic azoospermia and severe oligozoospermia in the Chinese

Objectives To evaluate the relationship between microdeletion or mutation on the Y chromosome and Chinese patients with idiopathic azoospermia and severe oligozoospermia and to establish a molecular detection method.Methods Microdeletion or mutation detection at the AZFa (sY84 and USP9Y), AZFb, AZFc/DAZ and SRY regions of the Y chromosome. Seventy-three azoospermia and 28 severe oligozoospermia patients were evaluated using PCR and PCR-SSCP techniques.Results Twelve of 101 patients (12%) with the AZFc/DAZ microdeletion were found, including 8 with azoospermia (11%) and 4 with severe oligozoospermia (14.3%), and 1 patient had a AZFb and AZFc/DAZ double deletion. No deletions in the AZFa or SRY regions were found. No deletions in AZFa, AZFb, AZFc/DAZ or SRY regions were found in 60 normal men who had produced one or more children.Conclusions Microdeletion on the Y chromosome, especially at its AZFc/DAZ regions, may be a major cause of azoospermia and severe oligozoospermia leading to male infertility in China. It is recommended that patients have genetic counseling and microdeletion detection on the Y chromosome before intracytoplasmic sperm injection.

Clinical Observation of Combined Acupuncture ＆ Medications in Treating Dysspermia Infertility

Objective： To observe the curative effect of combined acupuncture and medication on infertility due to seminal abnormality. Method： Thirty-eight patients with seminal abnormality were separately treated by acupuncture and traditional Chinese medications （“Erxian Decoction”） plus Clomiphene. Results and Conclusion： The total effective rate was 96.0% in the acupuncture plus traditional Chinese medication group （26 cases） and 66.7% in the acupuncture and western medication groups （12 cases）. Statistical analysis showed a significant difference （P〈0.05）. The cure rate and the pregnancy rate were 38.5% and 30.8% respectively in the acupuncture and traditional Chinese medication group. Both of them were higher than 8.3% and 8.3% in the acupuncture and western medication group respectively, but there were no statistically significant differences. In the two groups of patients, seminal volume, liquefaction time and viscosity and spermatozoal density, death rate and one-hour survival rate took a significant turn for the better after treatment as compared with before treatment （P〈 0.05）. In the acupuncture and traditional Chinese medication groups of patients, symptoms markedly improved after treatment as compared with before treatment.

Effect of a comprehensive therapy plus Gushenyutai plaster administered at Guanyuan(CV 4) on male infertility associated with semen non-liquefaction

OBJECTIVE: To observe the clinical effect of Gushenyutai plaster administered at the Guanyuan(CV4) acupoint on male infertility associated with semen non-liquefaction.METHODS: Sixty-two male patients with infertility caused by semen non-liquefaction were random-ized into a treatment and control group. The control group received comprehensive therapy, which included oral administration of clarithromycin sustained release tablets, hip bath with Zhongyaoxiaoyan granules, prostate massage, and transurethral microwave treatment. The treatment group was administered Gushenyutai plaster in addition to the comprehensive therapy. Both groups were treated for 8 weeks. After treatment, the clinical effect and pregnancy rate were assessed and compared between the two groups.RESULTS: The effective rate of the treatment group was significantly higher than that of the control group(96.77% vs 70.97%, P<0.05) and the pregnancy rates of the treatment group and control groups were 38.71% and 16.13%, respectively(P<0.05).CONCLUSION: The effect of Gushenyutai plaster plus comprehensive therapy was better than that of the comprehensive therapy alone on male infertility induced by semen non-liquefaction.

Mutations in CCIN cause teratozoospermia and male infertility

Teratozoospermia is usually associated with defective spermiogenesis and is a disorder with considerable genetic heterogeneity. Although previous studies have identified several teratozoospermia-associated genes, the etiology remains unknown for a majority of affected men. Here, we identified a homozygous missense mutation and a compound heterozygous mutation of CCIN in patients suffering from teratozoospermia. CCIN encodes the cytoskeletal protein Calicin that is involved in the formation and maintenance of the highly regular organization of the calyx of mammalian spermatozoa, and has been proposed to play a role in sperm head structure remodeling during the process of spermiogenesis. Our morphological and ultrastructural analyses of the spermatozoa obtained from all three men harboring deleterious CCIN mutants reveal severe head malformation. Further immunofluorescence assays unveil markedly reduced levels of Calicin in spermatozoa. These patient phenotypes are successfully recapitulated in mouse models expressing the disease-associated variants, confirming the role of Calicin in male fertility.Notably, all mutant spermatozoa from mice and human patients fail to adhere to the zona mass, which likely is the major mechanistic reason for CCIN-mutant sperm-derived infertility. Finally, the use of intracytoplasmic sperm injections(ICSI) successfully makes mutated mice and two couples with CCIN variants have healthy offspring. Taken together, our findings identify the role of Calicin in sperm head shaping and male fertility, providing important guidance for genetic counseling and assisted reproduction treatments.

Genetic polymorphisms of CYP2D6*10 and the effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in infertile men with idiopathic oligozoospermia

Tamoxifen citrate, as the first line of treatment for infertile men with idiopathic oligozoospermia, was proposed by the World Health Organization （WHO）, and testosterone undecanoate has shown benefits in semen values. Our objective was to assess the effectiveness of treatment with tamoxifen citrate and testosterone un- decanoate in infertile men with idiopathic oligozoospermia, and whether the results would be affected by polymor- phisms of CYP2D6＊10. A total of 230 infertile men and 147 controls were included in the study. Patients were treated with tamoxifen citrate and testosterone undecanoate. Sex hormone, sperm parameters, and incidence of spontaneous pregnancy were detected. There were no significant differences between the control and patient groups with respect to CYP2D6＊10 genotype frequencies （P〉0.05）. The follicle-stimulation hormone （FSH）, luteinizing hormone （LH）, and testosterone （T） levels were raised, and sperm concentration and motility were increased at 3 months and became significant at 6 months, and they were higher in the wild-type allele （C/C） than in the heterozygous variant allele （C/T） or homozygous variant allele （T/T） subgroups （P〈0.05）. In addition, the percentage of normal morphology was raised at 6 months, and represented the highest percentage in the C/C subgroup （P〈0.05）. The incidence of spontaneous pregnancy in the C/C subgroup was higher than that in the C/T or T/T subgroups （P〈0.01）. This study showed that the CYP2D6＊10variant genotype demonstrated worse clinical effects in infertile men with idiopathic oligozoospermia.