Infertility in the third millennium: implications for the individual, family and society: condensed meeting report from the Bertarelli Foundation's second global conference

Primary infertility is a key issue in the developed world, while the developing world has high rates of secondary infertility. The impact of HIV/AIDS on fertility is insufficiently explored. One of the most important barriers to access to infertility treatment is cost; at the same time the role of social and cultural factors in restricting access should not be underestimated. IVF has become the standard therapy for female infertility, and ICSI for infertility of the male partner. However, the use of these therapies should not be initiated without a thorough investigation and, whenever possible, individual diagnosis of the underlying causes of infertility. Multiple gestation remains one of the most challenging and controversial issues in the treatment of infertility. Current IVF practices are often blamed for this; in this respect, attention should also be focused on the role of ovarian stimulation in ovulation induction. National guidelines and national registries for assisted reproductive technology (ART) are becoming more widespread and are expected to play an important role in promoting best practice in ART in the future.     

Fas and Fas-ligand are expressed in the uteroplacental unit of first-trimester pregnancy

PROBLEM: Fas and Fas-ligand (FasL) are thought to provide a strategy for reducing graft rejection in immunologically 'privileged' tissues by controlling injurious lymphocyte reactions. As the uteroplacental unit is often defined as an immune-privileged site, we investigated the expression of Fas and FasL in this tissue in the first trimester of pregnancy. METHOD OF STUDY: Western blotting, immunohistochemistry, and double immunofluorescence were used for this examination. RESULTS: Western blotting with purified first-trimester trophoblast cells revealed one specific band for FasL. The presence of FasL on different trophoblast populations could be confirmed by immunohistochemistry and double immunofluorescence. In the villous part of the placenta, FasL is mostly located on cytotrophoblast cells with no access to maternal blood flow, whereas in trophoblast-invaded uterine tissue, interstitial trophoblast cells, which are in close contact with maternal leukocytes, revealed a strong signal for FasL, but no staining for Fas on these cells. However, Fas was found on CD45+ maternal leukocytes. CONCLUSION: Based on our experimental findings, we speculate that the abundant presence of FasL on trophoblast cells within the maternal decidua may play an important role in the maintenance of immune privilege in the pregnant uterus by endowing fetal trophoblast cells with a defense mechanism against activated maternal leukocytes, whereas in the villous part of the placenta, the Fas FasL system seems to be involved in the regulation of placental growth.     

Spermatozoal nuclear determinants of reproductive outcome: implications for ART

A male factor is implicated in more than 50% of couples treated with IVF. However, neither the routine testing of male fertility potential nor its treatment address the specific mechanisms by which spermatozoal factors may impact upon reproductive outcome. An important function of spermatozoa is to deliver the paternal genome to the oocyte. Recently, a number of acquired spermatozoal nuclear factors that may have implications on reproductive outcome have been described. These include non-specific DNA strand breaks, numerical abnormalities in spermatozoal chromosome content, Y chromosome microdeletions and alterations in the epigenetic regulation of paternal genome. The exact mechanisms by which these factors affect reproduction are unknown and their implications for assisted reproduction technology outcome need to be further investigated. These recent findings point to the need for novel and more personalized approaches to test and treat male factor infertility.     

Reproductive risk factors in unilateral and bilateral renal agenesis

ABSTRACT  Renal agenesis (RA) appears to be a multifactorial condition with combined genetic and environmental influences. We performed a retrospective case-control study of reproductive history of 26 isolated RA live births cases referred to Sicilian Registry of Congenital Malformations. A statistical significant association for birth weight if we considered all RA together and for bilateral RA alone, an increasing risk for maternal age only in the bilateral RA subgroup and a male predominance both for unilateral and bilateral RA was found. Our results show that some reproductive risk factors may be associated with RA, moreover differences found between subgroups indicate that some risk factors may be different in unilateral and bilateral RA. The association between reproductive risk factors and RA may reflect pathogenetic interaction between genetic and environmental factors. Nevertheless further studies are needed to clarify these associations and to explore the role of perinatal factors in the etiology of renal agenesis. In fact if prenatal or perinatal risk factors are in a causal chain influencing the risk for developing RA, then these data could have important implications in the prevention or treatment of this condition.     

脑红蛋白在成年男性生殖系统的表达及意义

目的:探讨脑红蛋白(neuroglobin,Ngb)在成年男性生殖系统的表达及其意义。方法:用免疫组织化学SP法观测Ngb在成人男性生殖系统的表达、分布与定位。结果:Ngb在生殖系统内神经节细胞、睾丸间质细胞有较强表达,在睾丸支持细胞、生精细胞、附睾管腔上皮、前列腺腺上皮及精囊黏膜上皮呈弱阳性表达。结论:Ngb在男性生殖系统中分布广泛,其功能值得研究。     

Fibroids, infertility and pregnancy wastage

Uterine fibroids are often found in women of reproductive age. Different types of fibroids may affect reproductive outcome to a different extent, with submucous, intramural and subserosal fibroids being (in decreasing order of importance) a cause of infertility and pregnancy wastage. Fibroids may also produce a number of complications during pregnancy. Women who are scheduled for assisted conception should be advised to have submucous and possibly intramural fibroids removed prior to IVF. Large fibroids (>5 cm), wherever their location, should be considered individually, with the reproductive history being an important consideration. Miscarriage rates are significantly reduced following myomectomy. Open myomectomy should be the route of choice when there are large subserosal or intramural fibroids, multiple fibroids or entry into the uterine cavity is to be expected. Proper assessment of the benefits and risks of surgery for individual patients should be carefully considered before offering a procedure.     

New high yield Cu(I) assisted 123I radioiodination of 15(p-I-phenyl)-9-methyl pentadecanoic acid,a potential myocardial tracer

A new high yield ¹²³I radioiodination (97%), based on the Cu(I) assisted isotopic exchange in an ethanol water mixture, of 15(p-I-phenyl)-9 methyl pentadecanoic acid, a potential myocardial tracer, is proposed. The method allows a true kit preparation of radioiodinated phenyl fatty acids for a substrate concentration of ±10^-6 moles. High specific activities (>0.1 mCi/g) can be obtained when coupling the labelling method to HPLC purification with an overall radiochemical yield of 75%.     

Reported Challenges in Health Technology Assessment of Complex Health Technologies

ObjectivesWith complex health technologies entering the market, methods for health technology assessment (HTA) may require changes. This study aimed to identify challenges in HTA of complex health technologies.MethodsA survey was sent to European HTA organizations participating in European Network for HTA (EUnetHTA). The survey contained open questions and used predefined potentially complex health technologies and 7 case studies to identify types of complex health technologies and challenges faced during HTA. The survey was validated, tested for reliability by an expert panel, and pilot tested before dissemination.ResultsA total of 22 HTA organizations completed the survey (67%). Advanced therapeutic medicinal products (ATMPs) and histology-independent therapies were considered most challenging based on the predefined complex health technologies and case studies. For the case studies, more than half of the reported challenges were “methodological,” equal in relative effectiveness assessments as in cost-effectiveness assessments. Through the open questions, we found that most of these challenges actually rooted in data unavailability. Data were reported as “absent,” “insufficient,” “immature,” or “low quality” by 18 of 20 organizations (90%), in particular data on quality of life. Policy and organizational challenges and challenges because of societal or political pressure were reported by 8 (40%) and 4 organizations (20%), respectively. Modeling issues were reported least often (n = 2, 4%).ConclusionsMost challenges in HTA of complex health technologies root in data insufficiencies rather than in the complexity of health technologies itself. As the number of complex technologies grows, the urgency for new methods and policies to guide HTA decision making increases.     

冻融胚胎移植周期中不同辅助生殖技术助孕方式和移植不同发育阶段胚胎对出生性别比的影响

目的探讨冻融胚胎移植(frozen-thawed embryo transfer,FET)周期中不同辅助生殖技术(assisted reproductive technology,ART)助孕方式和移植不同发育阶段胚胎对新生儿性别的影响。方法回顾性队列研究分析2010年4月至2018年10月期间于广州市妇女儿童医疗中心生殖中心接受体外受精(in vitro fertilization,IVF)、卵胞质内单精子注射(intracytoplasmic sperm injection,ICSI)和胚胎植入前遗传学检测(preimplantation genetic testing,PGT)治疗并进行FET且成功分娩的患者和新生儿临床资料。比较不同助孕方式及移植不同发育阶段胚胎对新生儿性别的影响。结果①IVF-FET共898对夫妇(920个周期),1166名新生儿,出生性别比为106.7。移植桑葚期前、桑葚期或囊胚期胚胎,出生性别比逐渐增高(99.0,135.4,142.6),但各组间差异无统计学意义(P>0.05)。②ICSI-FET(含PGT)共415对夫妇(433个周期),555名新生儿,出生性别比为111.0。移植不同发育阶段胚胎,出生性别比(116.0、87.2、137.5)差异无统计学意义(P>0.05)。③PGT-FET共33对夫妇(33个周期),33名新生儿,出生性别比为153.8。移植IVF、ICSI或PGT解冻囊胚对出生性别比没有显著影响(P>0.05)。结论在FET周期中,采用IVF技术助孕,移植较晚发育阶段胚胎可能会增加出生性别比的风险;ICSI技术移植不同发育阶段胚胎或移植IVF、ICSI或PGT囊胚对新生儿性别没有显著影响。     

Characterizing Emergency Department Use in Assisted Living

ObjectivesLittle is known about emergency department (ED) utilization among the nearly 1 million older adults residing in assisted living (AL) settings. Unlike federally regulated nursing homes, states create and enforce AL regulations with great variability, which may affect the quality of care provided. The objective of this study was to examine state variability in all-cause and injury-related ED use among residents in AL.DesignObservational retrospective cohort study.Setting and ParticipantsWe identified a cohort of 293,336 traditional Medicare beneficiaries residing in larger AL communities (25+ beds).MethodsWith Medicare enrollment and claims data, we identified ED visits and classified those because of injury. We present rates of all-cause and injury-related ED use per 100 person-years in AL, by state, adjusting for age, sex, race, dual-eligibility, and chronic conditions.ResultsRisk-adjusted state rates of all-cause ED visits ranged from 100.9 visits/100 AL person-years [95% confidence interval (CI) 92.8, 109.9] in New Mexico to 162.3 visits/100 AL person-years (95% CI 154.0, 174.7) in Rhode Island. The risk-adjusted rate of injury-related ED visits ranged from 18.7 visits/100 AL person-years (95% CI 17.2, 20.3) in New Mexico to 35.7 visits/100 AL person-years (95% CI 34.7, 36.8) in North Carolina.Conclusions and ImplicationsWe observed significant variability among states in all-cause and injury-related ED use among AL residents. There is an urgent need to better understand why this variability is occurring to prevent avoidable visits to the ED.