Evaluation and assessment of semen for IVF/ICSI

Evaluation and assessment of semen is very important for both diagnosis of male infertility and selection of patients for treatment with IVF or ICSI. In standard IVF, sperm function is essential for normal fertilization: sperm must be able to bind to zona pellucida (ZP), undergo the acrosome reaction and penetrate the ZP and fuse with the oolemma before fertilization takes place. In contrast, most sperm functions are not required for fertilization in ICSI since sperm bypass the ZP and oolemma by injection of a single sperm directly into cytoplasm of oocyte. Therefore, the clinical decision on treatment of patients with either IVF or ICSI is mostly dependent on results of sperm tests. However, conventional semen analyses do not provide accurate information about sperm fertilizing ability since many patients with subtle sperm defects can not be detected. More advanced sperm function tests are required to detect sperm defects that may lead to failure of fertilization in standard IVF. In the last 15 years we performed extensive studies on relationship between sperm functions and fertilization rates by logistic regression analysis in large numbers of IVF patients including 370 patients with zero fertilization rate by IVF. We confirmed sperm morphology assessed strictly was strongly related to fertilisation rate with standard IVF. Thus sperm morphology assessment is very useful for selection of patients for ICSI. We also developed a number of new tests including sperm-ZP binding, sperm-ZP penetration and the ZP-induced AR and evaluated the clinical value of these tests. Sperm-ZP binding and sperm-ZP penetration tests are the most powerful indicators for sperm fertilizing ability in vitro. The ZP-induced AR is highly correlated with sperm-ZP penetration. We discovered a condition we call disordered ZP-induced AR which causes serve infertility in up to 25% men with otherwise idiopathic infertility In conclusion, the combination of semen analysis with advanced sperm function tests provide important diagnostic and prognostic information for male infertility and is crucial for selection of patients for treatment with IVF or ICSI. (Asian J Androl 2002 Dec; 4: 281-285)

The human acrosome reaction

We developed tests of sperm-oocyte interaction:sperm-zona binding,zona-induced acrosome reaction,sperm-zona penetration and sperm-oolemma binding,using oocytes which failed to fertilise in clinical in vitro fertilization(IVF).Although oocyte defects contribute to failure of sperm oocyte interaction,rarely are all oocytes from one wom-an affected.Low or zero fertilization in standard IVFwas usually caused by sperm abnormalities.Poor sperm-zona pel-lucida binding was frequently associated with failure of standard IVF and obvious defects of sperm motility or morpholo-gy.The size and shape of the acrosome is particularly important for sperm binding to the oocyte.The proportion ofacrosome intact sperm in the insemination medium was related to the IVF rote.Inducing the acrosome reaction with acalcium ionophore reduced sperm-zona binding.Blocking acrosome dispersal with an acrosin inhibitor prevented sperm-zona penetration.Sperm-zona penetration was even more highly related to IVF rates than was sperm-zona binding.Some patients had low or zero fertilization rates with standard IVF but normal sperm by conventional tests and normalsperm-zona binding.Few of their sperm underwent the acrosome reaction on the surface of the zona and none penetrat-ed the zona.In contrast,fertilization and pregnancy rates were high with intmcytoplasmic sperm injection.We call thiscondition defective zona pellucida induced acrosome reaction.Discovery of the nature of the abnormalities in the signaltmnsduction and effector pathways of the human zona pellucida induced acrosome reaction should result in simpler testsand treatments for the patients and also provide new leads for contraceptive development.

Searching for candidate genes for male infertility

<abstract>Aim: We describe an approach to search for candidate genes for male infertility using the two human genome databases: the public University of California at Santa Cruz (UCSC) and private Celera databases which list known and predicted gene sequences and provide related information such as gene function, tissue expression, known mutations and single nucleotide polymorphisms (SNPs). Methods and Results: To demonstrate this in silico research, the following male infertility candidate genes were selected: (1) human BOULE, mutations of which may lead to germ cell arrest at the primary spermatocyte stage, (2) mutations of casein kinase 2 alpha genes which may cause globozoospermia, (3) DMR-N9 which is possibly involved in the spermatogenic defect of myotonic dystrophy and (4) several testes expressed genes at or near the breakpoints of a balanced translocation associated with hypospermatogenesis. We indicate how information derived from the human genome databases can be used to confirm these candidate genes may be pathogenic by studying RNA expression in tissue arrays using in situ hybridization and gene sequencing. Conclusion: The paper explains the new approach to discovering genetic causes of male infertility using information about the human genome.

葡萄胎妊娠对心理症状、性功能及生活质量的影响

Background. Molar pregnancy is an unusual complication of pregnancy whereby abnormal placental tissue proliferates in the absence of a fetus. There is usually a protracted follow- up period where pregnancy is contra- indicated. Whilst the medical outcomes of the disease have been well explored, limited data have evaluated the impact on psychological symptomatology, sexual function, and quality of life. Methods. Institutional ethics approval and individual consent were obtained. All women listed on the hospital molar pregnancy register receiving active follow- up (n = 102) and a random sample of women who had been registered in the previous 30 years (n = 56) were sent a postal survey outlining the purpose of the study and an invitation to participate. Questionnaires included the Hospital Anxiety and Depression Scale (HADS), Satisfaction with Life Scale (SWLS), and Sexual History Form 12 (SHF- 12). Results. The response rate was 54% . The key findings were that 60% , 55% , and 18% of women scored ≥ 10 on the total HADS, ≥ 8 on HADS- A, and >8 on HADSD, respectively. The presence of children played a protective role and was associated with significantly better psychological function and quality of life. SWLS were in the lower end of ranges reported for community controls (mean of 23.9). Chemotherapy had an adverse impact on quality of life ratings (SWLS for chemotherapy yes = 21.7, no = 25). Sexual dysfunction was similar to community samples and was independent of age, time since diagnosis, chemotherapy requirement, and presence of children. Qualitative results complemented the quantitative data with similar emotional themes identified as well as issues related to the medical condition, care, and support networks. Conclusion. Women with a molar pregnancy may benefit from a multidisciplinary approach to management that addresses their psychological and sexual needs in addition to medical aspects of care.

Secondary sex ratio of assisted reproductive technology babies

Objective: To assess the secondary sex ratio (SSR) of assisted reproduction technology babies within a fertility clinic in Melbourne, Australia. Methods: A retrospective cohort study was conducted on 3369 babies who were born following single embryo transfer between 2011 and 2016. Variables examined included embryo creation date, maternal and paternal ages, maternal body mass index (BMI), type of infertility, sperm parameters, fertilization method, type of embryo and stage of transfer. Multivariate regression analysis was performed on the data set using STRATA V9.2. Results: More males were found to be born to embryos created in summer (adjusted odds ratio=1.46, 95% confidence interval: 1.08-1.95;P=0.01). Lower BMI of mother (≤30 kg/m 2) and younger age of parents (≤35 years) were associated with an increase in SSR (50.1% vs. 47.1%;50.6% vs. 48.8%;50.0% vs. 48.9%) respectively. Decreased SSR value was associated with primary subfertility, using in-vitro fertilization procedure and fresh embryo compared to those with secondary subfertility, using intracytoplasmic sperm injection procedure and thawed embryo (49.3% vs. 50.6%;47.1% vs. 50.8%;49.4% vs. 50.1%) respectively. Conclusions: The fertilization methods, type of embryo, stage of embryo transfer, parameters of the sperm and status of subfertility do not significantly affect the SSR. SSR is affected by the seasonality, maternal age, and BMI.

精液分析现状:对《亚洲男性学杂志》出版的陆金春等所著的“中国118家实验室精液分析状况的调查”一文的评论

陆金春等^[1]所著的“中国118家实验室精液分析状况的调查”一文主要回顾了当前在中国采用的精液分析方法。调查使用的是作者自己设计的包括36个问题的“男科实验室精液分析调查表”。给145家精液实验室发放了调查表，收回118份答卷。调查表均由实验室专业技术人员填写。

维多利亚3个不同时期的极低出生体重儿童8岁时的感觉神经预后的改善

Aim: To determine neurosensory outcome at 8 years of age of extremely low birthweight (ELBW) children born in the 1990s, how it varies with birth weight, and how it compares with ELBW children born in the 1980s and 1970s. Methods: Subjects were born in the state of Victoria during 1991- 92 and comprised 224 of 241 consecutive survivors with a birth weight of 500- 999 g, and 223 of 262 normal birthweight (NBW) controls who had been randomly selected at birth. The comparison cohorts from earlier eras comprised 87 of 89 consecutive ELBW survivors born in 1979- 80, 206 of 212 consecutive ELBW survivors born in 1985- 87, and 51 of 60 randomly selected NBW survivors born in 1981- 82. Survivors were assessed for neurological impairments (cerebral palsy, blindness, deafness, intellectual impairment) and disabilities at 8 years of age by paediatricians and psychologists blinded to perinatal details. Results: For the 1991- 92 cohorts, the rate of neurosensory disability was substantially higher in ELBW children compared with NBW controls (P < 0.0001). Within the ELBW group, neurosensory disability was more prevalent in children with a birth weight of < 750 g compared with a birth weight of 750- 999 g (P=0.024). Disability rates were lower in the 1991- 92 ELBW cohort compared with the ELBW cohort born in 1979- 80 (p = 0.046). Conclusions: Neurosensory disability rates at school age were more common in ELBW children born in the 1990s compared with NBW controls, and were significantly more common in the 500- 749 g birthweight subgroup, but have improved compared with ELBW children born in earlier eras.

经鼻持续气道正压通气:通气流量是否能改善气体交换

In a randomised crossover trial, 26 babies, treated with Hudson prong continuous positive airway pressure (CPAP) from a bubbling bottle, received vigorous, high amplitude, or slow bubbling for 30 minutes. Pulse oximetry, transcutaneous carbon dioxide, and respiratory rate were recorded. The bubbling rates had no effect on carbon dioxide, oxygenation, or respiratory rate.

极低出生体重儿成功拔管的预测

Objective: To determine the accuracy of three tests used to predict successful extubation of preterm infants. Study design: Mechanically ventilated infants with birth weight < 1250 g and considered ready for extubation were changed to endotracheal continuous positive airway pressure (ET CPAP) for three minutes. Tidal volumes,minute ventilation (VE), heart rate,and oxygen saturation were recorded before and during ET CPAP. Three tests of extubation success were evaluated: (a) expired VE during ET CPAP; (b) ratio of VE during ET CPAP to VE during mechanical ventilation (VE ratio); (c) the spontaneous breathing test (SBT)- the infant passed this test if there was no hypoxia or bradycardia during ETCPAP. The clinical team were blinded to the results, and all infants were extubated. Extubation failure was defined as reintubation within 72 hours of extubation. Results: Fifty infants were studied and extubated. Eleven (22% ) were reintubated. The SBT was the most accurate of the three tests, with a sensitivity of 97% and specificity of 73% and a positive and negative predictive value for extubation success of 93% and 89% respectively. Conclusion: The SBT used just before extubation of infants < 1250 g may reduce the number of extubation failures. Further studies are required to establish whether the SBT can be used as the primary determinant of an infant’ s readiness for extubation.

在未成熟儿入选数项研究时其父母会考虑什么?

Objective: To investigate parent’s opinions about enrolling their premature b aby into several research studies in the few days after birth. Methodology: A qu estionnaire was given to parents of premature babies in the neonatal intensive c are unit who had been invited to join several studies (two to seven). Results: A ll 50 mothers and 42 of 48 fathers completed the questionnaire independently; 28 %had been asked to join two studies, 32%three, 24%four, 14%five, and 2%six studies. There were 61 babies with mean (SD) gestational age 26.9 (1.6) weeks an d birth weight 877 (249) g. Nearly three quarters (71%) of the parents thought it was very good for their baby to be in a hospital that was carrying out a lot of research. Most (93%)-thought that their baby would get the same or better c are in a study. Only 15%thought their baby was too small for research studies. Almost all (98%) wanted to be involved in the decision about their baby joining a study. Only 22%were worried about the number of studies; 10%would not enrol their baby in any studies, but 74%were willing for their baby to join two or m ore studies, and 10%would enrol in all the studies. Most (94%)-believed that their baby’s participation would improve care of future babies. Conclusions: Mo st of these parents were willing to join several studies. The majority were not worried about their baby participating in the studies. The profession needs to b e aware that parents are supportive of neonatal research and participation in mu ltiple studies.

Continuity of care by a primary midwife(caseload midwifery):a cost analysis using results from the COSMOS randomised controlled trial

Introduction Caseload midwifery(continuity of midwifery carer)offers benefits including lower caesarean section rates,lower risks of preterm birth and stilbirth,and improved maternal satisfaction of care.Despite these advantages,concerns about additional costs hinder widespread implementation.This study examinesthecost of caseload midwifery compared with standard maternity care from the perspective of both public hospitals and public funders.Methods A cost analysis was conducted using data from a randomised controlled trial of 2314 low-risk pregnant women in Melbourne,Australia.Women randomised to caseload care received antenatal,intrapartum and postpartum care from a primary midwife,with some care provided by a‘back-up'midwife.Women in standard care received midwifery-led care with varying levels of continuity,junior obstetric care or community-based medical care.The cost analysis compared differences in mean costs of health resources to public hospitals and to public funders.Additionally,a budget impact analysis estimated total costs to the health system between 2023 and 2027.Results For public hospitals,there was no significant difference in overall costs between women receiving caseload midwifery(n=1146)versus standard care(n=1151)($SA12363(SD:$A4967)vs$A12323(SD:$A7404);p=0.85).Conversely,public funders incurred lower expenditures for women receiving caseload midwifery($A20330(SD:$A8312))versus standard care($A21637(SD:$A11818);p<0.001).The budget impact analysis estimated savings of sA625million to the health system over the next 5 years with expanded access to caseloadmidwifery inAustralia.Conclusion Caseloadmidwifery in low-risk women is cost-neutral to public hospitals and cost-saving to public funders.Tweetable abstract Continuity of midwifery for low-risk women reduces costs to public funders,with no additional costs to hospitals.

宫颈细胞学诊断未能除外高度上皮内瘤样病变的不典型鳞状细胞的临床意义及处理

目的探讨宫颈细胞学诊断在未能除外高度上皮内瘤样病变(内瘤变)的不典型鳞状细胞(ASC-H)的意义和临床处理。方法1999-10-20-2004-01-24墨尔本皇家妇女医院宫颈病变门诊(DysplasiaClinicoftheRoyalWomen’sHospital,Melbourne)对96例宫颈细胞学诊断为ASC-H的患者进行阴道镜检查、阴道镜下活检或行宫颈锥切组织诊断学检查和高危型HPV-DNA测定,分析其结果之间关系。结果96例ASC-H中,87例有组织病理学诊断,58例诊断为宫颈鳞状上皮内瘤变(SIL)占66.6%(58/87),其中高度鳞状上皮内瘤变(HSIL)为44.8%(39/87),低度鳞状上皮内瘤变(LSIL)为21.8%(19/87)。96例行阴道镜检查,78例阴道镜下活检,阴道镜诊断与阴道镜下活检组织学诊断的符合率为64.1%(50/78),45例同时有阴道镜下活检病理和宫颈术后病理,两种方法病理诊断的符合率为73.3%(33/45)。以病理诊断为标准,阴道镜诊断的敏感性是89.4%,特异性是36.8%,阳性预测值是83.1%。32例做了HPV-DNA测定,阳性率为59.4%(19/32),阳性者中68.4%(13/19)经组织学诊断为HSIL。结论宫颈细胞学诊断为ASC-H高度提示宫颈鳞状上皮内瘤变(SIL)的存在。阴道镜检查、阴道镜下活检和高危型HPV-DNA的测定,对ASC-H的处理有重要的指导意义。

Senescent remodeling of the immune system and its contribution to the predisposition of the elderly to infections

Objective To review the senescent remodeling of the immune system with aging and its relevance to the increased susceptibility of the elderly to infectious diseases, along with an outlook on emerging immunological biomarkers. Data sources The data selected were from PubMed with relevant published articles in English or French from 1995 to the present. Searches were made using the terms immunosenescence and aging paired with the following： innate immunity, T-celr, B-cell, adaptive immunity and biomarkers. Articles were reviewed for additional citations and some information was gathered from web searches. Study selection Articles on aging of both the innate and adaptive immunity were reviewed, with special attention to the remodeling effect on the ability of the immune system to fight infectious diseases. Articles related to biomarkers of immunosenescence were selected with the goal of identifying immunological biomarkers predisposing the elderly to infections. Results Innate immunity is generally thought to be relatively well preserved or enhanced during aging compared with adaptive immunity which manifests more profound alterations. However, evidence, particularly in the last decade, reveals that both limbs of the immune system undergo profound remodeling with aging. Reported data on adaptive immunity is consistent and changes are well established but conflicting results about innate immunity were reported between in vivo and in vitro studies, as well as between murine and human studies. Epidemiological data suggests increased predisposition of the elderly to infections, but no compelling scientific evidence has directly linked senescent immune remodeling to this increased susceptibility. Recently, growing interest in identifying immunological biomarkers and defining immune risk phenotypes/profiles （IRP） has been expressed. Identification of biomarkers is in its early days and few potential biomarkers have been identified, with the Swedish having defined one IRP based on the adaptive immune response. Conclusions Aging does not necessarily lead to an unavoidable decline in immune functions. Instead, a complex remodeling occurs. Despite the lack of compelling scientific evidence, senescent immune remodeling surely is a significant contributing factor to the increased risk and severity of infections in the elderly. Although, no immunological biomarker has been formally linked to the increased risk of infections in the elderly, biomarkers remain a promising tool to predict the likelihood of healthy aging, the level of immune competence, and mortality risk in the elderly. Hence, more research is required to define healthy aging and identify immunological biomarkers.

子宫肌瘤的诊断与管理

子宫平滑肌瘤（简称子宫肌瘤）是女性最常见的良性肿瘤，可表现为单发或多发，从几毫米到几十厘米或更大，大小不一。据调查，近70％的50岁白人女性及80％以上的50岁黑人女性均可检出至少一个子宫肌瘤。框图1罗列了子宫肌瘤的几种危险因素。症状性肌瘤往往需要手术治疗，造成相当大的医疗费用负担。这篇综述旨在为非专业人士提供关于子宫肌瘤的检查及处理的最新知识。本文也特别描述了当前知识的缺口。

关于绝经期的NICE指南--缺少对激素治疗风险的定量汇总估计

关于绝经期的英国国家健康与优选研究所（NICE）指南，第一次强调绝经期症状对女性生活质量和功能造成不良影响，有些女性的这些症状可持续许多年。该指南促进了个体化照护，并强调需要足够的临床服务以及进一步研究。

Commentary on ＂Altered PIWI-LIKE 1 and PIWI-LIKE 2 mRNA expression in ejaculateC spermatozoa of men with impaired sperm characteristics＂

Infertility affects approximately 15% of couples who have regular intercourse with male partners for over 12-month periods, without using any contraceptives. Among these infertile couples, the male factor accounts approximately 40%-50%. A significant proportion of male infertility is due to idiopathic azoospermia, severe oligozoospermia, and teratozoospermia. While some severe male infertility is associated with possible genetic alterations in germ cell lines or spermatogenesis, the cause of severe male infertility is still largely unknown.