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The past three decades have seen considerable change in the understanding of clinical research methods. There has been an acceptance that RCTs are the best way of establishing treatment effectiveness and a recognition that, while single studies are useful, pooling knowledge from a complete body of work is likely to provide the best evidence. Advances in methodology have been mirrored by the many advances in the field of reproductive medicine, such as assisted reproduction, assessment of male fertility, ovulation induction and laparoscopic surgery. Together, they have led to welcome improvements in the outcomes of fertility treatments. In particular, systematic reviews have become important tools enabling clinicians and patients to make health-care decisions based on evidence from all the available high-quality studies. The move towards identifying and aggregating the highest quality evidence has been led by the Cochrane Collaboration, which this year celebrates 20 years of preparing and publishing systematic reviews. This paper outlines the achievements, progress and challenges of this enterprise to date, with a particular focus on systematic reviews of reproductive medicine.

This Views and Reviews series concerning future developments in in vitro fertilization will highlight various aspects of in vitro fertilization from the global perspective., (Copyright © 2013 American Society for Reproductive Medicine. All rights reserved.)

Purpose of Review: Germline stem cell research over the last decade has brought into question one of the basic tenets of reproductive biology that women are born with a finite number of oocytes without the potential for renewal. Evidence for the existence of oogonial stem cells in the postnatal ovary has gained momentum, but skepticism remains., Recent Findings: Several research studies claimed that they have identified functional oogonial stem cells in the postnatal ovary of several different species including humans. The scientific community has questioned both the methods and significance of these studies., Summary: Many speculate that germline stem cells could make a significant impact on the treatment of female infertility. However, this field of research is still in its infancy. There is still much to learn about the biology of oogonial stem cells and their potential clinical application. More research is needed before oogonial stem cells can become a viable treatment modality for women with infertility.

The American Society for Reproductive Medicine, one of the older professional medical societies in the United States, is devoted to education, support of research, and advocacy in the field of reproductive medicine. It is also the oldest and largest medical society devoted to reproductive medicine in the world. A multidisciplinary organization, the Society is composed of ∼8000 members from the United States and more than a hundred other countries and undertakes a large number of activities aimed at advancing the discipline of reproductive medicine., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Proteomic technologies have begun providing evidence that viable embryos possess unique protein profiles. Some of these potential protein biomarkers have been identified as extracellular and could be used in the development of a noninvasive quantitative method for embryo assessment. The field of assisted reproductive technologies would benefit from defining the human embryonic proteome and secretome, thereby expanding our current knowledge of embryonic cellular processes., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

A biomarker can be used for early diagnosis of a disease, identification of individuals for disease prevention, as a potential drug target, or as a potential marker for a drug response. A biomarker may also limit the use of drug (and therefore costs) to the population of patients for which the drug will be safe and efficacious. A biomarker in reproduction could be used to improve assessment of exposure, identify subgroups susceptible to treatment, predict outcome, and/or differentiate subgroups with potentially different etiologies of disease. Despite many potential uses there is low participation in reproductive biology to develop molecular biomarkers, which may be directly related to the low number of new molecular entities entering clinical trials. As the number of candidate markers in reproductive medicine is increasing, it is important to understand the pathway of development from discovery to clinical utility and recognize that the vast majority of potential markers will not be clinically useful, owing to a variety of pitfalls. Extensive testing, validation, and modification needs to be performed before a biomarker is demonstrated to have clinical utility. New opportunities and partnerships exist and should hasten the development of biomarkers in reproduction. As more biomarkers are moved into practice, a better-educated biomarker consumer will enhance the possibility that biomarker(s) will realize their great potential., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Problem: Reproductive immunology has evolved from basic research studies to clinical applications. In this study, we aim to investigate the actual application of reproductive immunology concepts and findings in clinical reproductive medicine such as recurrent pregnancy losses (RPL), repeated implantation failures (RIF), and failed in vitro fertilization (IVF) cycles., Method of Study: A web-based survey was performed on IVF-Worldwide.com. Collected data were analyzed by the computerized software., Results: A significant proportion of physicians recommend thrombophilia workups (86%), parental genetic study (79%), and immunologic evaluations (69%) to IVF candidates who have a history of RPL or chemical pregnancy losses. IVF physicians consider an immunologic workup when patients have two (30%) or three (21%) failed IVF cycles. Assays for anticardiolipin antibody, lupus anticoagulant, thyroid peroxidase antibody, and antinuclear antibody are the four most commonly ordered immunologic tests for RPL (88, 84, 50, 47% each) and RIF (68, 63, 38, 38% each). Cellular immune evaluations, such as NK assay, human leukocyte antigen study, Th1/Th2 study or immunophenotype assay, are less commonly ordered., Conclusions: Reproductive immunology principles have been applied to the clinical management of RPL, RIF, and failed IVF cycles, and a significant proportion of IVF physicians acknowledge the importance of immunologic alterations with reproductive outcomes., (© 2012 John Wiley & Sons A/S.)

Appropriate physical activity is one of the bases of healthy lifestyle. In fact, physical exercise and playing sport may be associated with both improvements and injury to both general and reproductive health. A biologically normal testosterone secretion appears fundamental in males to guarantee both a physiological exercise adaptation and safe sport participation. The reproductive system is highly sensitive to the effects of exercise-related stress and the reproductive hormones may both increase and decrease after different acute or chronic exercises. Exercise and sport participation may positively or negatively influence andrological health status depending on the type, intensity and duration of performed physical activity and on individual health status. In addition, prohibited substances administration (e.g. androgenic-anabolic steroids, and so forth) in competitive and non-competitive athletes represents the main cause of iatrogenic andrological diseases. Preventing and treating andrological problems in active healthy and unhealthy individuals is as important as promoting a correct lifestyle. Physicians need to be educated on the relationships between the male reproductive system and sport participation and on the great role of the pre-participation physical examination in the prevention of andrological diseases.

The Society for Gynecologic Investigation (SGI) hosted its 59th Annual Meeting in San Diego (CA, USA) on 21-24 March 2012. The program attracted 1313 attendees, 918 from the USA and Canada and 395 from the rest of the world. The event was hosted by the SGI president Stephen J Lye and the program director Stephen Matthews. The mission of the SGI is to discover, review, report and transfer new knowledge through creative research and training, community integration and partnerships that improve the reproductive health of women everywhere. More than 1100 abstracts were presented at the meeting, 172 of which were oral presentations. A selection of notable presentations are highlighted here.

Three experts in regenerative medicine explore the evidence and expanding future clinical applicability of the human ovarian and endometrial stem cell population, and tissue engineering of reproductive organs and tissues., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Stem cell-based strategies for ovarian regeneration and oocyte production have been proposed as future clinical therapies for treating infertility in women. However, utilization of embryonic stem cells or induced pluripotent stem cells to produce oocytes has had limited success in vitro. A recent report of the isolation and characterization of endogenous oocyte-producing or oogonial stem cells (OSCs) from ovaries of reproductive age women describes the first stable and pure human female germ cell culture model in which a subset of cells appear to initiate and complete meiosis. In addition, purified human OSCs introduced into adult human ovarian cortical tissue generate oocytes that arrest at the diplotene stage of meiosis and successfully recruit granulosa cells to form new primordial follicles. This overview examines the current landscape of in vitro and in vivo gametogenesis from stem cells, with emphasis on generation of human oocytes. Future research objectives for this area of work, as well as potential clinical applications involving the use of human OSCs, are discussed., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The 59th Annual Meeting of the Society for Gynecologic Investigation was held in San Diego, (CA, USA) on 21-24 March 2012, with a record number of registrants (over 1300) and submitted abstracts. The main 3-day meeting was preceded by a day of satellite meetings, covering topics such as placental function, endometrial bleeding and global issues for preterm birth. The meeting was opened by the President of the Society for Gynecologic Investigation for 2011-2012, Stephen J Lye, from the University of Toronto (ON, Canada), with 13 past presidents of the society (including this writer) in attendance.

The Dutch Minister of Health has proposed reducing the number of reimbursed in vitro fertilisation (IVF) cycles per couple from 3 to 1, in order to save 30 million euro per year. In the Netherlands, the number of IVF cycles has increased by 50% in the past 13 years, resulting in, on average, one child conceived through IVF in every classroom today. The increase in the number of IVF treatments is also caused by expansion of the indications for IVF, despite the lack of evidence proving the effectiveness of IVF for some of these indications. In a time of financial constraint, the restriction of reimbursed indications would be fairer than reducing the number of reimbursed treatments with IVF or intracytoplasmic sperm injection (ICSI) for all couples.

We asked seven senior and accomplished investigators from around the world to share their experiences conducting research in reproductive medicine., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Latin America is undergoing profound social, economic, political, demographic, and epidemiologic change. Reproductive health indicators have generally improved over the past two decades, but most pregnancies are still unintended and more than 4 million are terminated annually. Clandestine abortions necessitated by restrictive legal and social structures cause more than 1,000 deaths and 500,000 hospitalizations per year, primarily among poor and marginalized women. Abortions are becoming safer and less frequent, however, as a consequence of increased modern contraceptive use, misoprostol adoption, emergency contraception availability, and postabortion care provision, notwithstanding many impediments to these changes. Advocacy and conflict over abortion have grown. The contested policy shifts include Mexico City's 2007 legalization of first-trimester abortion. Drawing on numerous sources of evidence, this article provides a regional analysis of the rapidly changing practice and context of abortion in Latin America, and examines emerging issues, legal and policy developments, and contrasting country situations.

The prediction of extremes of ovarian response to stimulation and the irreversibility of reduced ovarian reserve remain important clinical and basic science research issues of IVF treatment. Recommending commencement of ovarian stimulation using any of the available exogenous compounds without knowledge of individual ovarian potentials is simplistic and dangerous because of the possible adverse consequences for the woman. The identification of groups of patients likely to benefit from one protocol than another is central to the workup process of IVF. Determining the agents for ovarian stimulation as well as the combination of them, the daily dose and duration according to some background information should be seen as the way to enhance safety and cost-effectiveness. This discussion paper aims to introduce the concept of individualized ovarian stimulation in routine clinical practice and to generate interest for tailored stimulation protocols., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

In view of the global burden of subfertility, efforts are required to make assisted reproduction more effective, less burdensome and more equally accessible. New reproductive technologies are frequently introduced in clinical practice without a sound evaluation of their efficacy, effectiveness and/or safety. Safety issues in this context refer both to patients (mostly women) undergoing the relevant medical procedures, and to the health of children born as a result. Responsible innovation requires making potentially risky reproductive technologies the subject of research, ideally proceeding through the steps of preclinical investigations, clinical trials and (long-term) follow-up studies. The European Society of Human Reproduction and Embryology is especially equipped to take the lead here.

OBJECTIVE Cryopreservation of supernumerary embryos resulting from IVF treatment offers extra chances to conceive. The objective of this study is to describe patients' decisions to continue or discontinue storage of their embryos after a minimum storage period of 2 years. METHODS Female patients who had embryos stored at the Infertility Centre of the Ghent University Hospital (Belgium) were sent a mail questionnaire to be completed anonymously. RESULTS The questionnaire had a response rate of 79% (326/412). After an embryo storage period of at least 2 years, 40% of the couples who were still together wished to continue storage of their embryos. Half of these had no concrete plans for a transfer and wanted to postpone the decision or keep all options open. For those who decided to discontinue storage (60%), the main reason was the completion of their families. Despite the fact that the patients' child wish was the main factor in their storage decision, two groups of patients with distinct profiles made decisions that were inconsistent with their child wish: those who wanted to continue storage while not wanting a(nother) child (7% of those with no child wish), and those who wanted a(nother) child but decided to discontinue storage (25% of those with a child wish). Overall, these patients more often expressed emotional difficulties regarding this decision. CONCLUSIONS This study demonstrates the importance of gaining more insight into patients' embryo storage decisions (along with their embryo disposition decisions) and into the emotional factors playing a role in patients' decision-making.

BACKGROUND High-quality care for patients faced with infertility should be patient-centred. Few studies have provided in-depth insights into the patient's perspective on care and, to the best of our knowledge, no study has provided a model of the complex concept 'patient-centred infertility care'. Therefore, a qualitative study aimed at understanding 'patient-centred infertility care' from the patient's perspective was conducted. METHODS Fourteen focus group discussions were organized with patients (n = 103) from two European countries to find out about patients' positive and negative experiences with infertility care. Content analysis of the transcripts and analysis of patients' priority lists were conducted. RESULTS The patient-centredness of infertility care depends on 10 detailed dimensions, which can be divided into system and human factors, and there is a two-way interaction between both kinds of factors. System factors, in order of patient's priority, are: provision of information, competence of clinic and staff, coordination and integration, accessibility, continuity and transition and physical comfort. Human factors, in order of patient's priority, are: attitude of and relationship with staff, communication, patient involvement and privacy and emotional support. CONCLUSIONS This study provides a detailed patient's description of the concept 'patient-centred infertility care' and an interaction model that aids understanding of the concept. Fertility clinics are encouraged to improve the patient-centredness of their care by taking into account the detailed description of the dimensions of patient-centred infertility care, and by paying attention to both system and human factors and their interaction when setting up 'patient-centred improvement projects'.

Apart from medical and social implications of infertility, the problem of unfruitful marriages is of paramount importance in the context of state interests. The matter in question is how to improve overall reproductive potential of and quarantee proper upbringing of every child. The primary goal in this context is to realize an extensive rather than intensive reproduction strategy and thereby ensure the formation of a new generation of citizens able to address and solve the most complicated problems. The establishment of reproductive health centres is currently in order. Their primary activities should include the pre-conception assessment of the health status in pregnancy-planning couples, prophylaxis and treatment of possible diseases that are likely to have negative influence on the health of the future child.

Medical abortion is increasingly heralded as an ideal method for decreasing maternal mortality in health-care resource-deprived areas and as an answer to the shrinking pool of physicians willing to perform abortions. The advent of progesterone receptor modulators (PRMs) and the recent approval by the Food and Drug Administration of ella (ulipristal) as an emergency contraceptive put pharmacists in the center of abortion controversy. Pharmacists, worldwide, need to be aware of the controversy surrounding the introduction of PRMs, particularly with regard to the effect on health policy, their mechanism of action, associated adverse events, and common off-label uses. Once understood, genuine opportunity exists for pharmacists to serve a fundamental role in positively shaping public health policy.

Objective: Systemic lupus erythematosus (SLE) primarily affects women of reproductive age. Here we summarize the scientific evidence supporting recently developed quality indicators (QIs) pertaining to reproductive health., Methods: We used a modification of the RAND/UCLA Appropriateness Method to develop QIs for SLE. We performed systematic reviews of the literature pertaining to each proposed indicator. Three indicators focusing on reproductive health were included in the final set. Relevant literature was presented to an expert panel, who rated the validity and feasibility of the indicators., Results: Three QIs were rated as valid and feasible. These indicators specifically address laboratory testing during pregnancy in SLE, the treatment of antiphospholipid antibody syndrome, and counseling for drugs with teratogenic potential., Conclusion: We used a rigorous method to develop reproductive health QIs for SLE. In the future, these indicators can be used in the assessment and delivery of care to patients with SLE., (Copyright © 2011 by the American College of Rheumatology.)

Purpose of Review: There is heightened recognition that the environment is an important driver of human reproductive health. This article provides an overview of the nature and extent of the science in the field of reproductive environmental health and its implications for OB/GYN clinical practice., Recent Findings: Women of childbearing age incur ubiquitous contact to numerous toxic environmental contaminants. Even subtle perturbations caused by chemical exposures during critical and sensitive windows of development may lead to increased risks of disease and disability across the entire span of human life. The strength of the evidence is sufficiently high that leading scientists and clinicians have called for timely action to prevent harm., Summary: OB/GYNs are uniquely poised to intervene in critical stages of human development (i.e., preconception and during pregnancy) to prevent harm. Efforts are underway to provide clinicians with the evidence-based foundation to develop recommendations for prevention. If adopted, current directions in toxicity testing, risk assessment and policy are likely to create important changes in how environmental chemicals are evaluated and regulated in the future. Together, these changes have the potential to assist in clinical assessment of patient risk and reductions in patient exposure to environmental contaminants linked to adverse reproductive health outcomes.

Despite the controversial discussions, which have accompanied it since its first introduction of into clinical medicine particularly in Switzerland, assisted reproductive medicine has come to acquire a firm standing in present-day society. This broad acceptance is the logical consequence of the availability of efficient methods of family planning which started with the introduction of oral contraception in the early sixties. Over time assisted reproductive medicine has grown with a considerable degree of efficacy due to improvements in the culture conditions in the embryology laboratory and due to sophisticated ovarian hyperstimulation. In conjunction with steadily rising treatment numbers the latter has contributed to a high incidence of multiple deliveries, which now is considered a complication of assisted reproduction and current opinion demands that multiple pregnancies must be avoided as much as possible. The experience in various countries has demonstrated that through the selection of one single embryo with high developmental capacity the incidence of multiple gestations can be lowered to virtually none. However, the restrictive legislations in vigour both in Switzerland and in Germany impede such an endeavour. Still, the significantly higher pregnancy rates achieved by extending the culture of embryos up to the blastocyst stage clearly demonstrate that embryology holds the clues to further considerable improvements of assisted reproductive technology. Through the rapid development of three-dimensional culture techniques, immature ovarian follicles e.g. primordial follicles may be cultured up to the mature Graafian stage thereby avoiding the need to stimulate the ovaries.

The HIV epidemic has changed the face of women's reproductive health across southern Africa. In some circles, there have been calls for restrictions on women's reproductive rights, focusing particularly on the spread of HIV between sexual partners and from mother to child. However, during the past decade, public health attention and resources for the clinical care of HIV-infected individuals living in Africa have led to advances in women's reproductive health services. As many programs have recognized that effective HIV care and treatment services must link to other areas of primary care, key reproductive health services such as those providing contraception and barrier methods are commonly integrated into antiretroviral therapy services. In much of the region, this programmatic focus has helped increase attention on the ground to women's reproductive rights. However, in many settings, policies explicitly supporting the reproductive rights of HIV-infected women have lagged. Important gaps remain both in policy development and in the design, evaluation, and implementation of interventions promoting women's reproductive health and rights at the service delivery level.

The FIVCAT. NET database in Catalonia is the only official obligatory registry of human assisted reproduction practitioners in Spain. The present study assessed the effectiveness and outcomes of assisted reproduction over the period 2001-2005 relative to other established worldwide registries. The data analysed were derived from all centres conducting assisted reproduction in Catalonia, and included users of the services (resident and non-resident); all cycles performed; descriptive characteristics of the assisted reproduction procedures; and sociodemographic characteristics of the women. Effectiveness of assisted reproduction was measured by standard indicators such as rates of pregnancy and rates of live births per pregnancy. The results indicated that the preferred number of embryos for transfer changed from three to two over this period. Pregnancies per transfer improved from 33.2% to 37.1% (from 36.9% to 40.2% using fresh embryos and from to 18.4% to 27.0% with frozen embryos). Multiple births decreased from 50.1% to 38.6%, premature births from 37.5% to 28.3% and low-birth-weight infants from 38.0% to 25.6%. It is concluded that the conduct of assisted reproduction in Catalonia has improved considerably and compares favourably with other countries, not only with respect to the level of activity, but also the effectiveness and outcomes achieved, although the quality of the sociodemographic information requires improvement.

Reproductive rights continue to be under threat, even some 15 years after the landmark International Conference on Population and Development in Cairo declared the importance of a satisfying and safe sex life, the capability to have children, and the right to decide on the timing, number, and spacing. The right to choose whether and when to have children is at risk both from some who seek to increase birth rates through pronatalist policies and from some who seek a return to "population control" as a response to global climate change, environmental degradation, endemic poverty, global recession, and food shortages. This paper argues the success of the rights-based approach to family planning, reproductive health and health education, and outlines issues and policy responses related to low fertility. This is contrasted with the unmet need for family planning in the poorest countries. It calls for health providers to advocate for reproductive rights, affirming that the freedom of women to control their fertility is the basis for other essential freedoms.

An attitude shift toward ART in developing countries has resulted in attempts exploring low-cost ART suitable to limited resource settings. This is a positive and needed development. Future steps should consider national infertility needs, position of infertility services within comprehensive reproductive health programs, ART surveillance, and equitable access.