A Xp22.11-p21.3 microdeletion in a three-generation family supports male lethality of POLA1 nullisomy resulting in reduced fertility of female carriers

POLA1 encodes a subunit of the DNA polymerase alpha, a key enzyme for the initiation of DNA synthesis. In males, hemizygous hypomorphic variants in POLA1 have been identified as the cause of X-linked pigmentary reticulate disorder (XLPDR) and a novel X-linked neurodevelopmental disorder termed Van Esch-O’Driscoll syndrome (VEODS), while female carriers have been reported to be healthy. Nullisomy for POLA1 was speculated to be lethal due to its crucial function, while the effect of loss of one allele in females remained unknown. Here, we report on a three-generation family harboring a deletion of POLA1 in females showing subfertility as the only phenotype. Our findings show that heterozygous deletions or truncating variants in females with skewed X inactivation do not cause VEODS and support the hypothesis of very early embryonic lethality in males with POLA1 nullisomy.     

Current Internet use and preferences of IVF and ICSI patients

BACKGROUND: Nowadays, the Internet has a tremendous impact on modern society, including healthcare practice. The study aim was to characterize current Internet use by IVF and ICSI patients and to identify their preferences regarding Internet applications in fertility care. METHODS: A total of 163 couples with fertility problems awaiting an IVF or ICSI procedure in the University Medical Centre Nijmegen, The Netherlands, was asked to complete a written questionnaire on Internet use in general, and also for fertility-related problems, preferences regarding Internet applications in fertility care and demographic characteristics. RESULTS: The response rate was 82%. In total, 81% of infertile couples used the Internet. Multivariate logistic regression analysis showed ethnic background and annual family income to be significant predictors of Internet use. Some 66% of Internet users and 54% of the total study population used the Internet for fertility-related problems. The female partners were the main Internet users with regard to fertility-related issues. In terms of preferences of the study participants, the majority favoured personal medical information online. CONCLUSIONS: Most infertile couples used the Internet with respect to fertility-related problems and were interested in implementation of Internet applications in fertility care. Healthcare providers should actively participate in the development and implementation of Internet applications in fertility care.     

Fertility knowledge and the timing of first childbearing: a cross-sectional study in Japan

Although fertility educational initiatives have increased in developed countries to prevent infertility and to broaden fertility choices, the relationship between knowledge and behaviour is still poorly understood. In order to investigate the association between fertility knowledge and timing of childbearing, we investigated male and female participants between 35 and 44 years of age who had children (n?=?640) from an online survey conducted in Japan in 2013. The age at which participants actually gave birth to or fathered their first child was compared between those who were aware for at least a decade of age-related decline in female fertility (hereinafter, those with past fertility knowledge) and those without. Age at first birth was significantly younger and more narrowly distributed among women with past fertility knowledge than among those without: 28.2?±?3.4 vs. 29.8?±?4.6 (mean?±?SD). A multivariate linear regression analysis showed that women with past fertility knowledge gave birth to their first child 2.34 [95% confidence interval (CI): 1.09–3.59] years earlier compared to those without such knowledge. No significant relation existed among men. Being informed in young adulthood about the facts of fertility might be related to starting a family at an earlier age, although further longitudinal evaluation will be necessary.     

Twin pregnancy: is it a risk factor for long-term cardiovascular disease?

Objective: To investigate whether twin pregnancy increases the risk for long-term maternal cardiovascular disease (CVD).

Study design: A retrospective population-based cohort study compared the incidence of long-term CVD in a cohort of women with and without a previous twin delivery.

Setting: Deliveries occurred between the years 1988 and 2012.

Patients: Patients who had a twin birth between years 1988 and 2012 were included in the study, patient that had a singleton delivery included in the control group.

Main outcome measures: CVD was divided into four categories according to severity and type. Kaplan–Meier survival curve was used to estimate cumulative incidence of cardiovascular hospitalizations. Cox proportional hazards model was used to estimate the adjusted hazard ratios (HR) for CVD.

Results: During the study period, there were 100?387 women that met the inclusion criteria, 4.6% (n?=?4647) delivered twins at least once during the period. The incidence of CVD was 1% in women who had a twin delivery and 1.12% in women who had a singleton delivery. There was no difference in the cumulative incidence of cardiovascular hospitalizations among women who had twin deliveries as compared with singletons. When performing a Cox proportional hazard model, a history of twin delivery did not increase the risk for long-term maternal cardiovascular hospitalizations (adjusted HR?=?1.0, 95% CI?=?0.8–1.1, p?=?0.698).

Conclusions: Twin pregnancy is not associated with an increased risk for long-term maternal CVD.     

Impact of physicians’ personal discomfort and patient prognosis on discussion of fertility preservation with young cancer patients

Objective

This study sought to determine if physician's personal discomfort with the topic of FP and a patient's prognosis would have an impact on the likelihood of discussing FP with cancer patients.

Methods

Data from larger studies of qualitative semi-structured interviews with pediatric and adult oncologists were analyzed using grounded theory and crystallizing immersion method to examine the themes of “personal comfort” and “patient prognosis” in relation to discussion.

Results

Results showed that, across both physician types, the majority of respondents’ personal comfort with the topic of FP was related to the likelihood of discussion. Personal discomfort manifested as: (a) lack of knowledge; (b) language/cultural barriers; (c) perception that subject of FP adds more stress to situation; (d) general uncertainty about success of FP methods. Data also indicate physicians do not feel discussions are appropriate for patients with poor prognosis.

Conclusion

Despite the ASCO guidelines suggesting physicians should discuss FP with all patients, the majority of physicians are not following these guidelines.

Practice implications

Improved training on recognition of such biases and communication strategies may improve the quality and frequency of such discussions. Involving the entire healthcare team in discussions may alleviate the need for physicians to have sole responsibility.     

Ovarian stem cells—Potential roles in infertility treatment and fertility preservation

One of the principal beliefs in reproductive biology is that women have a finite ovarian reserve, which is fixed from the time they are born. This theory has been questioned recently by the discovery of ovarian stem cells which are purported to have the ability to form new oocytes under specific conditions post-natally. Almost a decade after their discovery, ovarian, or oogonial, stem cells (OSCs) have been isolated in mice and humans but remain the subject of much debate. Studies in mice have shown that these cells can be cultured to a mature oocyte stage in vitro, and when injected into germ-cell depleted ovary they can form follicles and have resulted in the birth of healthy offspring. There are few data from human OSCs but this finding would open the door to novel fertility preservation strategies for women with both age-related and premature ovarian insufficiency (POI). As the number of girls and young women surviving cancer increases worldwide, POI secondary to gonadotoxic treatments, such as chemotherapy, is becoming more common. The ideal fertility preservation approach would prevent delays in commencing life-saving treatment and avoid transplanting malignant cells back into a woman after treatment: OSCs may offer one route to achieving this. This review summarises our current understanding of OSCs and discusses their potential clinical application in infertility treatment and fertility preservation.     

Vitamin D effects on musculoskeletal health,immunity, autoimmunity,cardiovascular disease,cancer, fertility,pregnancy, dementia and mortality—A review of recent evidence

Background

Optimal vitamin D intake and its status are important not only for bone and calcium-phosphate metabolism, but also for overall health and well-being. Vitamin D deficiency and insufficiency as a global health problem are likely to be a risk for wide spectrum of acute and chronic illnesses.

Methods

A review of randomized controlled trials, meta-analyses, and other evidence of vitamin D action on various health outcomes.

Results

Adequate vitamin D status seems to be protective against musculoskeletal disorders (muscle weakness, falls, fractures), infectious diseases, autoimmune diseases, cardiovascular disease, type 1 and type 2 diabetes mellitus, several types of cancer, neurocognitive dysfunction and mental illness, and other diseases, as well as infertility and adverse pregnancy and birth outcomes. Vitamin D deficiency/insufficiency is associated with all-cause mortality.

Conclusions

Adequate vitamin D supplementation and sensible sunlight exposure to reach optimal vitamin D status are among the front line factors of prophylaxis for the spectrum of disorders. Supplementation guidance and population strategies for the eradication of vitamin D deficiency must be included in the priorities of physicians, medical professionals and healthcare policy-makers.     

定义实验室参考值和决定限:人群,区间范围及其解读

简要概述多种分析人类精液检测结果的方法。参考区间(参考值范围)是最常用的解释临床实验结果的工具。参考值范围概念的发展,有赖于20世纪80年代临床化学专家国际联盟对这一概念的详尽阐述。这些指南要求:健康参考人群至少应包括120个健康个体,并对其进行分类,辨别最外延5%的参考值数据来确定双侧或单侧参考区间的界限值。最近,基于流行病学结果分析得出的决定限,也已用来解读分析检测结果。参考群体必须根据检验项目的临床使用要求严格定义:如果参考值范围用于评估男性生育能力,12个月内使配偶成功妊娠的男性应当是最合适的参考人群;如果用于精液检测结果的流行病学评估,随机选择的健康男性应该是最为理想的参考群体。虽然男性个体精液检测结果基于参考值和决定限无疑会在不久的将来成为解释结果的工具,但从长远看,解释精液检查结果的多因素方法或结合女性有关因素的分析,似乎是检测生育能力低下夫妇妊娠可能性的最佳方式。     

精液质量分析与正常生育力的概念

世界卫生组织(WHO)为对精液质量参数提供参考范围,对《世界卫生组织人类精液分析实验室技术手册》(简称手册)进行了大幅修订。这引发如何定义正常(不包括用此概念表示高斯分布)的问题。其可作为一个纯粹的统计学概念,使用生物学上主观设定的切点值表示异常水平,通常为末端5%的人群。正常的另一定义也可根据生物学上常态和非常态的概念,表示生物学功能受损的临界点。这两者都可以用于描述性流行病学,例如研究变化趋势。但在考虑生育时,精液质量和生育力(使配偶妊娠的时间)两者都是连续变量,缺乏确定的阈值。手册使用了生物学意义上的正常,因为提供的是在12个月或更短时间内使配偶妊娠男性的精液参数分布状态。但真正需要的却是反向的相同信息:获得一个特定的精液检测结果,预期生育能力如何,确定需要大概多长时间使配偶妊娠。从流行病学研究角度考虑,研究重点主要在于内部比较,而不是参考范围。如果更关注绝对值及其功能意义,换言之,如果精液分析数据从生物学角度上得到更好的校准,这将大有裨益。