Antioxidants improve vascular function in children conceived by assisted reproductive technologies: A randomized double-blind placebo-controlled trial.

AIMS Children conceived by assisted reproductive technology (ART) display vascular dysfunction. Its underlying mechanism, potential reversibility and long-term consequences for cardiovascular risk are unknown. In mice, ART induces arterial hypertension and shortens the life span. These problems are related to decreased vascular endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) synthesis. The aim of this study was to determine whether ART-induced vascular dysfunction in humans is related to a similar mechanism and potentially reversible. To this end we tested whether antioxidants improve endothelial function by scavenging free radicals and increasing NO bioavailability. METHODS AND RESULTS In this prospective double-blind placebo controlled study in 21 ART and 21 control children we assessed the effects of a four-week oral supplementation with antioxidant vitamins C (1 g) and E (400 IU) or placebo (allocation ratio 2:1) on flow-mediated vasodilation (FMD) of the brachial artery and pulmonary artery pressure (echocardiography) during high-altitude exposure (3454 m), a manoeuver known to facilitate the detection of pulmonary vascular dysfunction and to decrease NO bioavailability by stimulating oxidative stress. Antioxidant supplementation significantly increased plasma NO measured by ozone-based chemiluminescence (from 21.7 ± 7.9 to 26.9 ± 7.6 µM, p = 0.04) and FMD (from 7.0 ± 2.1 to 8.7 ± 2.0%, p = 0.004) and attenuated altitude-induced pulmonary hypertension (from 33 ± 8 to 28 ± 6 mm Hg, p = 0.028) in ART children, whereas it had no detectable effect in control children. CONCLUSIONS Antioxidant administration to ART children improved NO bioavailability and vascular responsiveness in the systemic and pulmonary circulation. Collectively, these findings indicate that in young individuals ART-induced vascular dysfunction is subject to redox regulation and reversible.

Cardiovascular dysfunction in children conceived by assisted reproductive technologies.

Epidemiological studies demonstrate a relationship between pathological events during foetal development and future cardiovascular risk and the term 'foetal programming of cardiovascular disease' has been coined to describe this phenomenon. The use of assisted reproductive technologies (ARTs) is growing exponentially and 2-5% of children are now born by this procedure. Emerging evidence indicates that ART represents a novel important example of foetal programming. Assisted reproductive technology may modify the cardiovascular phenotype in two ways: (i) ART involves manipulation of the early embryo which is exquisitely sensitive to environmental insults. In line with this concern, ART alters vascular and cardiac function in children and studies in mice show that ART alters the cardiovascular phenotype by epigenetic alterations related to suboptimal culture conditions. (ii) Assisted reproductive technology markedly increases the risk of foetal insults that augment cardiovascular risk in naturally conceived individuals and are expected to have similar consequences in the ART population. Given the young age of the ART population, it will take another 20-30 years before data on cardiovascular endpoints will be available. What is clear already, however, is that ART emerges as an important cardiovascular risk factor. This insight requires us to revise notions on ART's long-term safety and to engage on a debate on its future. There is an urgent need to better understand the mechanisms underpinning ART-induced alteration of the cardiovascular phenotype, improve the procedure and its long-term safety, and, while awaiting this aim, not to abandon medicine's fundamental principle of doing no harm (to future children) and use ART parsimoniously.

Right ventricular dysfunction in children and adolescents conceived by assisted reproductive technologies.

Assisted reproductive technologies (ART) predispose the offspring to vascular dysfunction, arterial hypertension, and hypoxic pulmonary hypertension. Recently, cardiac remodeling and dysfunction during fetal and early postnatal life have been reported in offspring of ART, but it is not known whether these cardiac alterations persist later in life and whether confounding factors contribute to this problem. We, therefore, assessed cardiac function and pulmonary artery pressure by echocardiography in 54 healthy children conceived by ART (mean age 11.5 ± 2.4 yr) and 54 age-matched (12.2 ± 2.3 yr) and sex-matched control children. Because ART is often associated with low birth weight and prematurity, two potential confounders associated with cardiac dysfunction, only singletons born with normal birth weight at term were studied. Moreover, because cardiac remodeling in infants conceived by ART was observed in utero, a situation associated with increased right heart load, we also assessed cardiac function during high-altitude exposure, a condition associated with hypoxic pulmonary hypertension-induced right ventricular overload. We found that, while at low altitude cardiac morphometry and function was not different between children conceived by ART and control children, under the stressful conditions of high-altitude-induced pressure overload and hypoxia, larger right ventricular end-diastolic area and diastolic dysfunction (evidenced by lower E-wave tissue Doppler velocity and A-wave tissue Doppler velocity of the lateral tricuspid annulus) were detectable in children and adolescents conceived by ART. In conclusion, right ventricular dysfunction persists in children and adolescents conceived by ART. These cardiac alterations appear to be related to ART per se rather than to low birth weight or prematurity.

“Dishonourable disobedience” – Why refusal to treat in reproductive healthcare is not conscientious objection

In medicine, the vast majority of conscientious objection (CO) is exercised within the reproductive healthcare field – particularly for abortion and contraception. Current laws and practices in various countries around CO in reproductive healthcare show that it is unworkable and frequently abused, with harmful impacts on women's healthcare and rights. CO in medicine is supposedly analogous to CO in the military, but in fact the two have little in common. This paper argues that CO in reproductive health is not actually Conscientious Objection, but Dishonourable Disobedience (DD) to laws and ethical codes. Healthcare professionals who exercise CO are using their position of trust and authority to impose their personal beliefs on patients, who are completely dependent on them for essential healthcare. Health systems and institutions that prohibit staff from providing abortion or contraception services are being discriminatory by systematically denying healthcare services to a vulnerable population and disregarding conscience rights for abortion providers. CO in reproductive healthcare should be dealt with like any other failure to perform one's professional duty, through enforcement and disciplinary measures. Counteracting institutional CO may require governmental or even international intervention.

Use of ovary culture techniques in reproductive toxicology

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved. Acknowledgements The author's studies in this field are supported by MRC grants G1002118 (NS and RAA) and G110357 (RAA), MR/L010011/1 (PAF), the European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 212885 (PAF) and the Wellcome Trust (080388 to PAF). AS was funded by a BBSRC CASE Studentship co-funded by AstraZeneca.

Photoperiod- and Triiodothyronine-Dependent Regulation of Reproductive Neuropeptides, Proinflammatory Cytokines, and Peripheral Physiology in Siberian Hamsters (Phodopus sungorus).

Peer reviewed

Dimensions of gender relations and reproductive health inequity perceived by female undergraduate students in the Mekong Delta of Vietnam: a qualitative exploration

Introduction Increasing evidence indicates that gender equity has a significant influence on women’s health; yet few culturally specific indicators of gender relations exist which are applicable to health. This study explores dimensions of gender relations perceived by female undergraduate students in southern Vietnamese culture, and qualitatively examines how this perceived gender inequity may influence females’ sexual or reproductive health. Methods Sixty-two female undergraduate students from two universities participated in eight focus group discussions to talk about their perspectives regarding national and local gender equity issues. Results Although overall gender gaps in the Mekong Delta were perceived to have decreased in comparison to previous times, several specific dimensions of gender relations were emergent in students’ discussions. Perceived dimensions of gender relations were comparable to theoretical structures of the Theory of Gender and Power, and to findings from several reports describing the actual inferiority of women. Allocation of housework and social paid work represented salient dimensions of labor. The most salient dimension of power related to women in positions of authority. Salient dimensions of cathexis related to son preference, women’s vulnerability to blame or criticism, and double standards or expectations. Findings also suggested that gender inequity potentially influenced women’s sexual and reproductive health as regards to health information seeking, gynecological care access, contraceptive use responsibility, and child bearing. Conclusion Further investigations of the associations between gender relations and different women’s sexual and reproductive health outcomes in this region are needed. It may be important to address gender relations as a distal determinant in health interventions in order to promote gender-based equity in sexual and reproductive health.

Epidemiologic Features of Vulvovaginal Candidiasis among Reproductive-Age Women in India

Background. Vulvovaginal candidiasis is characterized by curd-like vaginal discharge and itching, and is associated with considerable health and economic costs. Materials and Methods. We examined the incidence, prevalence, and risk factors for vulvovaginal candidiasis among a cohort of 898 women in south India. Participants completed three study visits over six months, comprised of a structured interview and a pelvic examination. Results. The positive predictive values for diagnosis of vulvovaginal candidiasis using individual signs or symptoms were low (<19%). We did not find strong evidence for associations between sociodemographic characteristics and the prevalence of vulvovaginal candidiasis. Women clinically diagnosed with bacterial vaginosis had a higher prevalence of vulvovaginal candidiasis (Prevalence 12%, 95% CI 8.2, 15.8) compared to women assessed to be negative for bacterial vaginosis (Prevalence 6.5%, 95% 5.3, 7.6); however, differences in the prevalence of vulvovaginal candidiasis were not observed by the presence or absence of laboratory-confirmed bacterial vaginosis. Conclusions. For correct diagnosis of vulvovaginal candidiasis, laboratory confirmation of infection with Candida is necessary as well as assessment of whether the discharge has been caused by bacterial vaginosis. Studies are needed of women infected with Candida yeast species to determine the risk factors for yeast’s overgrowth.

Steroid Androgen Exposure during Development Has No Effect on Reproductive Physiology of Biomphalaria glabrata

Funding: The research presented in this manuscript was wholly funded by National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), https://www.nc3rs.org.uk/. ‘The Snail Assay as an Alternative to the Rodent Hershberger Assay for Detecting Androgens and Anti-androgens’ funding reference: G0900802/1 to SJ, EJR, CSJ, and LRN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Cyclical DNA methyltransferase 3a expression is a seasonal and oestrus timer in reproductive tissues

Acknowledgments This work was funded by the University of Aberdeen CLSM grant to TJS. EWJL was funded by a Society for Reproduction and Fertility undergraduate scholarship. TJS conceived the project, designed experiments, analyzed data and wrote the manuscript. EWJL conducted experiments and analyzed the data. CC conducted the immunocytochemistry. ML conducted HEK293 cell culture assays. EMC and ASB provided technical assistance. The authors thank Gerald Lincoln for critical feedback on a previous version of this manuscript.

Chronic pelvic pain in women of reproductive and post-reproductive age : a population-based study

Abimbola Ayorinde’s PhD funded by the Medical Research Council. This study was funded by the British Pain Society (Mildred Clulow Award) and preparatory work by National Health Service Grampian.

Cyclical DNA Methyltransferase 3a Expression Is a Seasonal and Estrus Timer in Reproductive Tissues

Acknowledgments This work was funded by the University of Aberdeen CLSM grant to TJS. EWJL was funded by a Society for Reproduction and Fertility undergraduate scholarship. TJS conceived the project, designed experiments, analyzed data and wrote the manuscript. EWJL conducted experiments and analyzed the data. CC conducted the immunocytochemistry. ML conducted HEK293 cell culture assays. EMC and ASB provided technical assistance. The authors thank Gerald Lincoln for critical feedback on a previous version of this manuscript.

Reproductive decisions of couples living with HIV in Malawi: What can we learn for future policy and research studies?

Background The rapid scale-up of free antiretroviral therapy has lead to decline in adult mortality at the population level and reduction of vertical transmission. Consequently, some couples living with HIV are maintaining their reproductive decisions; marrying and having children. This paper analyses policies and guidelines on HIV, AIDS and sexual and reproductive health in Malawi for content on marriage and childbearing for couples living with HIV. Methods A qualitative study using interpretive policy analysis approach was conducted from July to December 2010 in two phases. First, data on access to HIV, AIDS and sexual and reproductive health services were collected using in-depth interviews with twenty couples purposively sampled in matrilineal Chiradzulu and patrilineal Chikhwawa communities. Secondly, data were collected from Malawi policies and guidelines on HIV, AIDS and sexual and reproductive health. The documents were reviewed for content on marriage and childbearing for couples living with HIV. Data were analysed using framework approach for applied policy analysis. Results Four categories emerged from each phase. From the study, we extracted health workers attitudes, weak linkage between HIV, AIDS and sexual and reproductive health services, contradictory messages between media and the hospitals and lack of information as factors directly related to guidelines and policies. Analysis of guidelines and policies showed nonprescriptiveness on issues of HIV, AIDS and reproduction: they do not reflect the social cultural experiences of couples living with HIV. In addition, there is; lack of clinical guidelines, external influence on adoption of the policies and guidelines and weak linkages between HIV and AIDS and sexual and reproductive health services. Conclusion This synthesis along with more detailed findings which are reported in other published articles, provide a strong basis for updating the policies and development of easy-to-follow guidelines in order to effectively provide services to couples living with HIV in Malawi.

The “Iranian ART Revolution”: infertility, assisted reproductive technology, and third-party donation in the Islamic Republic of Iran

Infertility is a social onus for women in Iran, who are expected to produce children early within marriage. With its estimated 1.5 million infertile couples, Iran is the only Muslim country in which assisted reproductive technologies (ARTs) using donor gametes and embryos have been legitimized by religious authorities and passed into law. Th is has placed Iran, a Shia-dominant country, in a unique position vis-à-vis the Sunni Islamic world, where all forms of gamete donation are strictly prohibited. In this article, we first examine the “Iranian ART revolution” that has allowed donor technologies to be admitted as a form of assisted reproduction. Then we examine the response of Iranian women to their infertility and the profound social pressures they face. We argue that the experience of infertility and its treatment are mediated by women’s socioeconomic position within Iranian society. Many women lack economic access to in vitro fertilization (IVF) technologies and fear the moral consequences of gamete donation. Thus, the benefits of the Iranian ART revolution are mixed: although many Iranian women have been able to overcome their infertility through ARTs, not all women’s lives are improved by these technologies.

Major depressive disorder and nutritional medicine : a review of monotherapies and adjuvant treatments

A literature review was conducted to examine the evidence for nutritional interventions in depression. It revealed a number of significant conclusions. Interestingly, more positive clinical trials were found to support adjuvant, rather than monotherapeutic, use of nutrients to treat depression. Much evidence exists in the area of adjuvant application of folic acid, S-adenosyl-methionine, omega-3, and L-tryptophan with antidepressants. Current evidence does not support omega-3 as an effective monotherapy to treat depression. However, this may be due, at least in part, to olive oil being used as the control intervention, some studies using docosahexaenoic acid alone or a higher docosahexaenoic acid to eicosapentaenoic acid ratio, and significant heterogeneity regarding depressive populations. Nevertheless, adjunctive prescription of omega-3 with antidepressants, or in people with dietary deficiency, may be beneficial. Inositol lacks evidence as an effective antidepressant and cannot be currently recommended. Evidence on the use of L-trytophan for depression is inconclusive and additional studies utilizing a more robust methodology are required.