Aging and erectile function.

The authors review and discuss numerous factors that influence erectile function and their interactions, based on the published literature. Of critical importance are vascular nitric oxide; nutrition; exercise; weight control and maintaining insulin sensitivity; early treatment of hypertension with attention to effects on erectile function; avoiding sources of oxidative stress such as obesity and smoking; reducing inflammation (e.g. from gingivitis); improving pelvic floor muscle strength; and inhibiting cyclic GMP break-down. The described interventions act on different aspects of erectile biochemistry and physiology. Therefore, combining multiple therapeutic approaches will yield maximum benefits for erectile and vascular and general health.

Forty years of IVF.

This monograph, written by the pioneers of IVF and reproductive medicine, celebrates the history, achievements, and medical advancements made over the last 40 years in this rapidly growing field.

Introduction: Management of the luteal phase in assisted reproductive technology.

The increasing utilization of a gonadotropin-releasing hormone agonist ovulation trigger and the widespread use of artificial cycles for the transfer of frozen-thawed or donated embryos has renewed interest in the luteal phase in assisted reproductive technology. The "luteal phase defect" phenomenon is now understood as a continuum: there is less impairment with milder stimulation than with more intense ovarian stimulation, and less impairment after controlled ovarian stimulation and human chorionic gonadotropin ovulation triggering than after gonadotropin-releasing hormone agonist ovulation triggering, the latter being associated with rapid luteolysis. The intensity of the support of luteal phase necessary to achieve optimal outcomes therefore depends on the degree of luteal phase defect encountered in different treatment protocols. Ultimately, the luteal phase of an artificial cycle in which ovulation is suppressed, a corpus luteum is therefore absent, and the establishment of endometrial receptivity completely relies on the orchestrated exogenous administration of sex steroids, is the litmus test situation for the study of the efficacy of different luteal phase support preparations, doses, regimens, and routes of administration.

Introduction: Obesity and reproduction.

Women bear the predominant burden of our obesogenic environment, with a higher incidence of obesity than men, more impact on their fertility and success with treatment, and significant maternal and perinatal morbidity and mortality. In this series, the causes, consequences, and solutions regarding the obesity pandemic, the mechanisms of the effect of obesity on the female and male, the epigenetic consequences of male obesity, the marked effects on perinatal outcomes, and the effects of weight loss before conception and during pregnancy are explored. Lifestyle modifications, in particular a healthy diet and exercise during the 3-6 months before conception and during treatment, should result in better outcomes than requiring weight loss before fertility treatments. Such fundamental changes toward a healthier lifestyle will achieve steady and sustainable weight loss and long-term benefits for general health. The role of bariatric surgery before pregnancy requires careful consideration.

Obesity pandemic: causes, consequences, and solutions-but do we have the will?

Obesity has become pandemic owing to an obesogenic environment (inexpensive calorie dense food, technologies and structure of communities that reduce or replace physical activity, and inexpensive nonphysical entertainment) and excessive emphasis on low fat intake resulting in excessive intake of simple carbohydrates and sugar. Effects are greater for women owing to their smaller size and extra weight gain with each pregnancy, with 38% of American adult women being obese. Women are responsible for more than three-fourths of the more than 400 billion dollars of excess direct health care expenditures due to obesity. They are less likely to conceive naturally and with fertility treatments, more likely to miscarry, and have more prematurity and other complications with their pregnancies. We describe the many causes, including key roles that a dysbiotic intestinal microbiome plays in metabolic derangements accompanying obesity, increased calorie absorption, and increased appetite and fat storage. Genetic causes are contributory if these other factors are present but have limited effect in isolation. The numerous health consequences of obesity are discussed. The authors itemize ways that an individual and societies can mitigate the pandemic. However, individual will power, the will of society to enact change, and willingness of the public to accept outside intervention frustrate efforts to stabilize or reverse this crisis. The most promising strategies are education and efforts by individuals to make responsible choices several times every day to protect, most effectively by prevention, their most valuable asset.

Effects of age on fertility and sexual function.

As paternal age increases in the developed world, more attention has been given to the effects of age on male reproductive and sexual function. Although the biologic potential for reproductive continues for most of a man's life, changes in sperm production do occur. In addition, erectile function changes with age, caused by the same factors that lead to other vascular disease.

The why, the how and the when of PGS 2.0: current practices and expert opinions of fertility specialists, molecular biologists, and embryologists.

STUDY QUESTION: We wanted to probe the opinions and current practices on preimplantation genetic screening (PGS), and more specifically on PGS in its newest form: PGS 2.0? STUDY FINDING: Consensus is lacking on which patient groups, if any at all, can benefit from PGS 2.0 and, a fortiori, whether all IVF patients should be offered PGS. WHAT IS KNOWN ALREADY: It is clear from all experts that PGS 2.0 can be defined as biopsy at the blastocyst stage followed by comprehensive chromosome screening and possibly combined with vitrification. Most agree that mosaicism is less of an issue at the blastocyst stage than at the cleavage stage but whether mosaicism is no issue at all at the blastocyst stage is currently called into question. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: A questionnaire was developed on the three major aspects of PGS 2.0: the Why, with general questions such as PGS 2.0 indications; the How, specifically on genetic analysis methods; the When, on the ideal method and timing of embryo biopsy. Thirty-five colleagues have been selected to address these questions on the basis of their experience with PGS, and demonstrated by peer-reviewed publications, presentations at meetings and participation in the discussion. The first group of experts who were asked about 'The Why' comprised fertility experts, the second group of molecular biologists were asked about 'The How' and the third group of embryologists were asked about 'The When'. Furthermore, the geographical distribution of the experts has been taken into account. Thirty have filled in the questionnaire as well as actively participated in the redaction of the current paper. MAIN RESULTS AND THE ROLE OF CHANCE: The 30 participants were from Europe (Belgium, Germany, Greece, Italy, Netherlands, Spain, UK) and the USA. Array comparative genome hybridization is the most widely used method amongst the participants, but it is slowly being replaced by massive parallel sequencing. Most participants offering PGS 2.0 to their patients prefer blastocyst biopsy. The high efficiency of vitrification of blastocysts has added a layer of complexity to the discussion, and it is not clear whether PGS in combination with vitrification, PGS alone, or vitrification alone, followed by serial thawing and eSET will be the favoured approach. The opinions range from in favour of the introduction of PGS 2.0 for all IVF patients, over the proposal to use PGS as a tool to rank embryos according to their implantation potential, to scepticism towards PGS pending a positive outcome of robust, reliable and large-scale RCTs in distinct patient groups. LIMITATIONS, REASONS FOR CAUTION: Care was taken to obtain a wide spectrum of views from carefully chosen experts. However, not all invited experts agreed to participate, which explains a lack of geographical coverage in some areas, for example China. This paper is a collation of current practices and opinions, and it was outside the scope of this study to bring a scientific, once-and-for-all solution to the ongoing debate. WIDER IMPLICATIONS OF THE FINDINGS: This paper is unique in that it brings together opinions on PGS 2.0 from all different perspectives and gives an overview of currently applied technologies as well as potential future developments. It will be a useful reference for fertility specialists with an expertise outside reproductive genetics. LARGE SCALE DATA: none. STUDY FUNDING AND COMPETING INTERESTS: No specific funding was obtained to conduct this questionnaire.

Introduction: Examining the many potential reasons why euploid blastocysts do not always result in viable pregnancies (and deliveries): part 2.

To result in a viable delivery: 1) a capable embryo must be accurately deposited and retained in an optimal location of the uterine cavity; 2) the endometrium must be receptive and synchronized to the developmental stage of the embryo; 3) the uterus must be physiologically and anatomically adequate; and 4) there should not be the presence of circulating factors capable of disrupting normal implantation and placentation, nor the absence of specific factors required for endometrial receptivity. The intricate interaction between the embryo and the uterus is discussed in this series of reviews.

Optimal uterine anatomy and physiology necessary for normal implantation and placentation.

The authors review aberrations of uterine anatomy and physiology affecting pregnancy outcomes with IVF. In the case of endometriosis and hydrosalpinx, pathologies outside of the uterus alter the uterine endometrium. In the case of endometriosis, Dominique de Ziegler outlines the numerous changes in gene expression and the central role of inflammation in causing progesterone resistance. With endometriosis, the absence of ovarian function inherent in deferred transfer, with or without a more lengthy suppression of ovarian function, appears to be sufficient to restore normal function of eutopic endometrium. Because laparoscopy is no longer routine in the evaluation of infertility, unrecognized endometriosis then becomes irrelevant in the context of assisted reproductive technology. With hydrosalpinx and submucus myomas, the implantation factor HOXA-10 is suppressed in the endometrium and, with myomas, even in areas of the uterus not directly affected. Daniela Galliano reviews various uterine pathologies, the most enigmatic being adenomyosis, where the endometrium also manifests many of the changes seen in endometriosis and deferred transfer with extended suppression appears to provide the best outcomes. Ettore Cicinelli's group has extensively studied the diagnosis and treatment of endometritis, and although more definitive diagnosis and care of this covert disorder may await techniques such as sequencing of the endometrial microbiome, it undoubtedly is an important factor in implantation failure, deserving our attention and treatment.