专家风采

黄荷凤 浙江大学求是特聘教授、妇产科主任医师、博导。国家“973”项目首席科学家，卫生部和浙江省有突出贡献中青年专家。现任浙江大学医学院附属妇产科医院院长、国家重点（培育）妇产科学学科带头人、教育部生殖遗传重点实验室主任、

北京大学第一医院男科中心辛钟成教授荣任亚太地区性医学学会（APSSM）理事长

第14届亚太地区性医学学会（Asia-pacific Society of Sexual Medicine, APSSM）于2013年5月31日－6月2日在日本金浞隆重召开。在此次将近500名亚太地区从事泌尿外科、男科学、生殖医学、内分泌学、精神心理学、老年医学领域基础科研和临床工作的医师和专家参加的盛会上，

ASIAN JOURNAL OF ANDROLOGY Information for Authors

The Asian Journal of Andrology is the official publication of the Asian Society of Andrology, and is sponsored by the Shanghai Institute of Materia Medica, Chinese Academy of Sciences. The Journal has been included in 11 international indexing systems, including BIOSIS, CAB Abstracts, CAB Health, Chemical Abstracts, Current Contents/Clinical Medicine, EMBASE, Index Medicus, MEDLINE, PASCAL, Research Alert, and SCI Expanded. The Impact Factor is 1.096 and the Journal ranks third among international andrology journals.

Clinical significance of the low normal sperm morphology value as proposed in the fifth edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen

The very low cut-off value for sperm morphology of 4% morphologically normal spermatozoa, as proposed in the new edition of the World Health Organization （WHO） manual on semen analysis, is in agreement with recently published values and reflects the trend of a decline in reported mean values for normal sperm morphology. The reduced value for morphologically normal spermatozoa over the years may be due to several factors. The first is the introduction of strict criteria for the evaluation of sperm morphology. Other reasons may include the introduction of additional criteria for sperm morphology abnormalities and the suggested decrease in semen parameters because of increasing negative environmental influences. Although on its own the newly proposed very low normal value may not provide the strong predictive value for a males＇ fertility potential, as originally reported for sperm morphology evaluated according to strict criteria, a good predictive value can still be obtained if the holistic, strict approach for sperm morphology evaluation is followed together with additional sperm morphology parameters now available, because certain morphology patterns and sperm abnormalities are now known to be of strong prognostic value. In addition, better international standardization of the technical methodology, consensus on the interpretation of sperm morphology evaluation criteria and standardized international external quality control （EQC） schemes, are of utmost importance to maintain the good predictive value of sperm morphology.

Commentary on: Mobley AJ, Lam YW, Lau KM, Pais VM, Lesperance JO, Steadman B, et al. Monitoring the serological Proteome Colon, the latest modality in prostate cancer detection. J Urol 2004; 172: 331-7.

This manuscript examines the utility, utilizing the Ciphergen Protein Biosystem II, to develop a fingerprint for the diagnosis of prostate cancer. The investigators compared samples from control individuals as well as those with prostate cancer. In doing so, they utilize several chip platforms on which to examine the resulting

Two-micron （thulium） laser resection of the prostate- tangerine technique： a new method for BPH treatment

Two-micron （thulium） laser resection of the prostate-tangerine technique （TmLRP-TT） is a transurethral procedure that uses a thulium laser fiber to dissect whole prostatic lobes off the surgical capsule, similar to peeling a tangerine. We recently reported the primary results. Here we introduce this procedure in detail. A 70-W, 2-um （thulium） laser was used in continuous-wave mode. We joined the incision by making a transverse cut from the level of the verumontanum to the bladder neck, making the resection sufficiently deep to reach the surgical capsule, and resected the prostate into small pieces, just like peeling a tangerine. As we resected the prostate, the pieces were vaporized, sufficiently small to be evacuated through the reseetoscope sheath, and the use of the mechanical tissue morcellator was not required. The excellent hemostasis of the thulium laser ensured the safety of TmLRP-TT. No patient required blood transfusion. Saline irrigation was used intraoperatively, and no case of transurethral resection syndrome was observed. The bladder outlet obstruction had clearly resolved after catheter removal in all cases. We designed the tangerine technique and proved it to be the most suitable procedure for the use of thulium laser in the treatment of benign prostatic hyperplasia （BPH）. This procedure, which takes less operative time than standard techniques, is safe and combines efficient cutting and rapid organic vaporization, thereby showing the great superiority of the thulium fiber laser in the treatment of BPH. It has been proven to be as safe and efficient as transurethral resection of the prostate （TURP） during the 1-year follow-up.

Studies on the integration of hepatitis B virus DNA sequence in human sperm chromosomes

Aim: To study the integration of hepatitis B virus (HBV) DNA into sperm chromosomes in hepatitis B patients and the features of its integration. Methods: Sperm chromosomes of 14 subjects (5 healthy controls and 9 HB patients, including 1 acute hepatitis B, 2 chronic active hepatitis B, 4 chronic persistent hepatitis B, 2 HBsAg chronic carriers with no clinical symptoms) were prepared using interspecific in vitro fertilization between zona-free hamster oocytes and human spermatozoa. Fluorescence in situ hybridization (FISH) to sperm chromosome spreads was carried out with biotin-labeled full length HBV DNA probe to detect the specific HBV DNA sequences in the sperm chromosomes. Results: Specific fluorescent signal spots for HBV DNA were seen in sperm chromosomes of one patient with chronic persistent hepatitis B. In 9(9/42) sperm chromosome complements containing fluorescent signal spots, one presented 5 obvious FISH spots and the others 2 to 4 signals. The fluorescence intensity showed significant difference among the signal spots. The distribution of signal sites among chromosomes seems to be random. Conclusion: HBV could integrate into human sperm chromosomes. Results suggest that the possibility of vertical transmission of HBV via the germ line to the next generation is present.

Microdissection testicular sperm extraction： an update

Patients with non-obstructive azoospermia （NOA） were once considered to be infertile with few treatment options due to the absence of sperm in the ejaculate. In the last two decades, the advent of intracytoplasmic sperm injection （ICSI）, and the application of various testicular sperm retrieval techniques, including fine needle aspiration （FNA）, conventional testicular sperm extraction （TESE） and microdissection testicular sperm extraction （micro-TESE） have revolutionized treatment in this group of men. Because most men with NOA will have isolated regions of spermatogenesis within the testis, studies have illustrated that sperm can be retrieved in most men with NOA, including Klinefelter＇s syndrome （KS）, prior history of chemotherapy and cryptorchidism. Micro-TESE, when compared with conventional TESE has a higher sperm retrieval rate （SRR） with fewer postoperative complications and negative effects on testicular function. In this article, we will compare the efficacy of the different procedures of sperm extraction, discuss the medical treatment and the role of testosterone optimization in men with NOA and describe the micro-TESE surgical technique. Furthermore, we will update our overall experience to allow counseling on the prognosis of sperm retrieval for the specific subsets of NOA.

Disposable circumcision suture device： clinical effect and patient satisfaction

In our experience patients undergoing circumcision are mostly concerned about pain and penile appearances. We conducted a prospective randomized trial to assess the benefits of a new disposable circumcision suture device （DCSD）. A total of 942 patients were equally divided into three groups （conventional circumcision, Shang ring and disposable suture device group）. Patients in the DCSD group were anesthetized with compound 5% lidocaine cream, the others with a 2% lidocaine penile block. Operation time, intra-operative blood loss, incision healing time, intra-operative and post-operative pain, the penile appearance and overall satisfaction degree were measured. Operation time and intra-operative blood loss were significantly lower in the Shang ring and suture device groups compared to the conventional group （P 〈 0.001）. Intra-operative pain was less in the suture device group compared With the other two groups （P 〈 0.001）; whereas post-operative pain was higher in the conventional group compared to the other two groups （P 〈 0.001）. Patients in the suture device （80.57%） and Shang ring （73,57%） groups were more satisfied with penile appearances compared with the conventional circumcision group （20.06%, P 〈 0.05）. Patients in suture device group also healed markedly faster than the conventional group （P 〈 0.01）. The overall satisfaction rate was better in the suture device group （78.66%） compared with the conventional （47.13%） and Shang ring （50.00%） groups （P 〈 0.05）. The combination of DCSD and lidocaine cream resulted in shorter operation and incision healing times, reduced intra-operative and post-operative pain and improved patient satisfaction with the cosmetic appearances.

Expression of hepatitis B virus genes in early embryonic cells originated from hamster ova and human spermatozoa transfected with the complete viral genome

Aim： To detect the expression of hepatitis B virus （HBV） genes （HB S and C genes） in early embryonic cells after introducing motile human sperm carrying HBV DNA into zona-free hamster oocytes via the in vitro fertilization （IVF） technique. Methods： Human sperm-mediated HBV genes were delivered into zona-free hamster oocytes by the IVF method. Polymerase chain reaction （PCR） was used to detect HB S and pre-Core/Core （pre-C/C） coding genes both in one- and two-cell embryos. Reverse transcription-PCR （RT-PCR） analysis was used to study the expression of the two genes. Fluorescence in situ hybridization （FISH） analysis using the full-length HBV DNA as the hybridization probe was performed to confirm the integration of viral DNA in the host embryonic genome. Results： Both HB S and pre-C/C coding genes are present and transcribed in one- and two-cell embryos originated from hamster ova IVF with human spermatozoa carrying HBV DNA sequences. Conclusion： Sperm-mediated HBV genes are able to replicate and express themselves in early embryonic cells. These results provide direct evidence that HBV DNA could transmit vertically to the next generation via the male germ line.

Microsurgical varicocelectomy： a review

Varicocelectomy is the most commonly performed surgical procedure for the treatment of male infertility. Although several different techniques for varicocele repair have been described in the literature, microsurgical varicocelectomy performed through a subinguinal or inguinal incision is recognized as the gold-standard approach for varicocelectomy, due to high success rates with minimal complications. Standard indications for varicocelectomy include palpable varicocele（s）, with one or more abnormal semen parameters, and, for the couple trying to conceive, in the setting of normal or correctable female infertility. However, varicocele repair is often recommended and undertaken for reasons other than infertility, including low serum testosterone, testicular pain, testicular hypotrophy and poor sperm DNA quality. This article reviews the technical aspects of microsurgical varicocelectomy, and its indications in adults and adolescents.

Protective effect of ascorbic acid on cyclophosphamide induced testicular gametogenic and androgenic disorders in male rats

Aim:To study the detrimental effects of cyclophosphamide on the testicular androgenic and gametogenic activities through endocrine inhibition and/or induction of oxidative stress in male albino rats and to evaluate the protective effect of ascorbic acid.Methods:The testicular△^(5),3β-hydroxysteroid dehydrogenase(HSD),17β-HSD,peroxidase and catalase activities along with the levels of malondialdehyde(MDA)and conjugated dienes in testicular tissue were measured for the evaluation of testicular oxidative stress.The plasma testosterone(T)level was measured by immunoassay.Various germ cells at stageⅦof spermatogenic cycle were quantified from testicular stained sections.Results:Cyclophosphamide treatment results in a significant inhibition in the testicular△^(5),3β-HSD and 17β-HSD activities,a decrease in plasma T level and a diminution in the counts of various germ cells.Moreover,this treatment was also associated with a significant inhibition of the peroxidase and catalase activities along with high levels of MDA and conjugated dienes in the testis.All these changes were reversed by ascorbic acid co-administration.Conclusion:Cyclophosphamide treatment at the dosage used caused testicular gametogenic and androgenic disorders as well as induced testicular oxidative stress that can be reversed by ascorbic acid co-administration.

Comparison of semen quality and outcome of assisted reproductive techniques in Chinese men with and without hepatitis B

In this study, we aimed to determine the effects of hepatitis B virus （HBV） infection on sperm quality and the outcome of assisted reproductive technology （ART）. A total of 916 men （457 HBV-positive and 459 HBV-negative） seeking fertility assistance from January 2008 to December 2009 at the Women＇s Hospital in the School of Medicine at Zhejiang University were analysed for semen parameters. Couples in which the men were hepatitis B surface antigen （HBsAg）-seropositive were categorized as HBV-positive and included 587 in vitrofertilisation （IVF） and 325 intracytoplasmic sperm injection （ICSI） cycles from January 2004 to December 2009; negative controls were matched for female age, date of ova retrieval, ART approach used （IVF or ICSI） and randomized in a ratio of 1：1 according to the ART treatment cycles （587 for IVF and 325 for ICSI）. HBV-infected men exhibited lower semen volume, lower total sperm count as well as poor sperm motility and morphology （P〈O.05） when compared to control individuals. Rates of two-pronuclear （2PN） fertilisation, high-grade embryo acquisition, implantation and clinical pregnancy were also lower among HBV-positive patients compared to those of HBV-negative patients after ICSI and embryo transfer （P〈0.05）; IVF outcomes were similar between the two groups （P〉0.05）. Logistic regression analysis showed that HBV infection independently contributed to increased rates of asthenozoospermia and oligozoospermia/azoospermia （P〈0.05） as well as decreased rates of implantation and clinical pregnancy in ICSI cycles （P〈0.05）. Our results suggest that HBV infection in men is associated with poor sperm quality and worse ICSI and embryo transfer outcomes but does not affect the outcome of IVF and embryo transfer.

Chromosomal disorders and male infertility

Infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family. Despite this, the molecular and genetic factors underlying the cause of infertility remain largely undiscovered. Nevertheless, more and more genetic factors associated with infertility are being identified. This review will focus on our current understanding of the chromosomal basis of male infertility specifically： chromosomal aneuploidy, structural and numerical karyotype abnormalities and Y chromosomal microdeletions. Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans. Aneuploidy is predominantly maternal in origin, but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts. Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm. Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed, as well as the application of preimplantation genetic diagnosis （PGD） in such cases. Clinical recommendations where possible will be made, as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility.

Oxidative stress and male reproductive health

One of the major causes of defective sperm function is oxidative stress, which not only disrupts the integrity of sperm DNA but also limits the fertilizing potential of these cells as a result of collateral damage to proteins and lipids in the sperm plasma membrane. The origins of such oxidative stress appear to involve the sperm mitochondria, which have a tendency to generate high leve｜s of superoxide anion as a prelude to entering the intrinsic apoptotic cascade. Unfortunately, these cells have very little capacity to respond to such an attack because they only possess the first enzyme in the base excision repair （BER） pathway, 8-oxoguanine glycosylase 1 （OGG1）. The latter successfully creates an abasic site, but the spermatozoa cannot process the oxidative lesion further because they lack the downstream proteins （APE1, XRCC1） needed to complete the repair process. It is the responsibility of the oocyte to continue the BER pathway prior to initiation of S-phase of the first mitotic division. If a mistake is made by the oocyte at this stage of development, a mutation will be created that will be represented in every cell in the body. Such mechanisms may explain the increase in childhood cancers and other diseases observed in the offspring of males who have suffered oxidative stress in their germ line as a consequence of age, environmental or lifestyle factors. The high prevalence of oxidative DNA damage in the spermatozoa of male infertility patients may have implications for the health of children conceived in vitro and serves as a driver for current research into the origins of free radical generation in the germ line.

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.

New insights on premature ejaculation： a review of ：lefinition, classification, prevalence and treatmeni

There are ongoing debates about the definition, classification and prevalence of premature ejaculation （PE）. The first evidence-based definition of PE was limited to heterosexual men with lifelong PE who engage in vaginal intercourse. Unfortunately, many patients with the complaint of PE do not meet these criteria. However, these men can be diagnosed as one of the PE subtypes, namely acquired PE, natural variable PE or premature-like ejaculatory dysfunction. Nevertheless, the validity of these subtypes has not yet been supported by evidence. The absence of a universally accepted PE definition and lack of standards for data acquisition have resulted in prevalence studies that have reported conflicting rates. The very high prevalence of 20%-30% is probably due to the vague terminology used in the definitions at the time when such surveys were conducted. Although many men may complain of PE when questioned for a population-based prevalence study, only a few of them will actively seek treatment for their complaint, even though most of these patients would define symptoms congruent with PE. The complaints of acquired PE patients may be more severe, whereas complaints of patients experiencing premature-like ejaculatory dysfunction seem to be least severe among men with various forms of PE. Although numerous treatment modalities have been proposed for management of PE, only antidepressants and topical anaesthetic creams have currently been proven to be effective. However, as none of the treatment modalities have been approved by the regulatory agencies, further studies must be carried to develop a beneficial treatment strategy for PE.

Emodin induces apoptosis in human prostate cancer cell LNCaP

Aim： To elucidate effects and mechanisms of emodin in prostate cancer cells. Methods： Viability of emodin-treated LNCaP cells and PC-3 cells was measured by MTT assay. Following emodin treatments, DNA fragmentation was assayed by agarose gel electrophoresis. Apoptosis rate and the expression of Fas and FasL were assayed by flow cytometric analysis. The mRNA expression levels of androgen receptor （AR）, prostate-specific antigen （PSA）, p53, p21, Bcl-2, Bax, caspase-3, -8, -9 and Fas were detected by RT-PCR, and the protein expression levels of AR, p53 and p21 were detected by Western blot analysis. Results： In contrast to PC-3, emodin caused a marked increase in apoptosis and a decrease in cell proliferation in LNCaP cells. The expression of AR and PSA was decreased and the expression of p53 and p21 was increased as the emodin concentrations were increased. In the same time, emodin induced apoptosis of LNCaP cells through the upregulation of caspase-3 and -9, as well as the increase of Bax/Bcl-2 ratio. However, it did not involve modulation of Fas or caspase-8 protein expression. Conclusion： In prostate cancer cell line, LNCaP, emodin inhibites the proliferation by AR and p53-p21 pathways, and induces apoptosis via the mitochondrial pathway.

Late-onset hypogonadism： current concepts and controversies of pathogenesis, diagnosis and treatment

Although suppressed serum testosterone （T） is common in ageing men, only a small proportion of them develop the genuine syndrome of low T associated with diffuse sexual （e.g., erectile dysfunction）, physical （e.g. loss of vigor and frailty） and psychological （e.g., depression） symptoms. This syndrome carries many names, including male menopause or climacterium, andropause and partial androgen deficiency of the ageing male （PADAM）. Late-onset hypogonadism （LOH） describes it best and is therefore generally preferred. The decrease of T in LOH is often marginal, and hypogonadism can be either due to primary testicular failure （low T, high luteinizing hormone （LH）） or secondary to a hypothalamic-pituitary failure （low T, low or inappropriately normal LH）. The latter form is more common and it is usually associated with overweight/obesity or chronic diseases （e.g., type 2 diabetes mellitus, the metabolic syndrome, cardiovascular and chronic obstructive pulmonary disease, and frailty）. A problem with the diagnosis of LOH is that often the symptoms （in 20%-40% of unselected men） and low circulating T （in 20% of men 〉70 years of age） do not coincide in the same individual. The European Male Ageing Study （EMAS） has recently defined the strict diagnostic criteria for LOH to include the simultaneous presence of reproducibly low serum T （total T 〈11 nmol 1-1 and free T 〈220 pmol 1-1） and three sexual symptoms （erectile dysfunction, and reduced frequency of sexual thoughts and morning erections）. By these criteria, only 2% of 40- to 80-year-old men have LOH. In particular obesity, but also impaired general health, are more common causes of low T than chronological age per se. Evidence-based information whether, and how, LOH should be treated is sparse. The most logical approach is lifestyle modification, weight reduction and good treatment of comorbid diseases. T replacement is widely used for the treatment, but evidence-based information about its real benefits and short- and long-term risks, is not yet available. In this review, we will summarize the current conceets and controversies in the Dathogenesis, diagnosis and treatment of LOH.

Do Ureaplasma urealyticum infections in the genital tract affect semen quality?

Aim： To investigate the relationship between Ureaplasma urealyticum （UU） infection and semen quality. Methods： From 2001 to 2003, 346 eligible patients aged 20-45 years were invited from two hospitals in Shanghai, China, to participate in an investigation which included questionnaires about general and reproductive health, an external genital tract examination, UU culture and semen analysis. Multiple linear regression models were used to examine whether UU had a significant effect on semen quality after adjustment for confounding factors. Results： Findings suggested that UU infection was associated with higher semen viscosity and lower semen pH value. Sperm concentration was lower in UU positive subjects than that in UU negative subjects （54.04 × 10^6/mL vs.70.58 × 10^6/mL）. However, UU did not significantly affect other semen quality indexes. Conclusion： UU infection of the male genital tract could negatively influence semen quality.