In the developed world, birth rates are plummeting and, increasingly, individuals are delaying reproduction. At the same time, rising rates of obesity and cancer are affecting fertility (both by virtue of the disease burden and the effects of treatment). A number of factors have been shown to affect fertility in men and women, including oxidative stress, hormonal and metabolic dysfunction and physical deformity. This joint Nature Reviews Urology and Nature Reviews Endocrinology collection on fertility and reproduction contains Reviews and commentaries written by key opinion leaders on a range of topics pertinent to the subject, from the molecular mechanisms regulating fertility and reproduction to the preservation of fertility and treatment of infertility in both men and women.
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NEWS & VIEWS
Male factor infertility: Prediction models for assisted reproductive technology
Vitaly A. Kushnir & Norbert Gleicher
doi:10.1038/nrurol.2014.181
Nature Reviews Urology 11, 492-493 (2014)
Reproductive endocrinology: Maternal and fetal insulin levels at birth in women with PCOS
Renato Pasquali
doi:10.1038/nrendo.2014.61
Nature Reviews Endocrinology 10, 382-384 (2014)
Reproductive endocrinology: New guidelines for the diagnosis and treatment of PCOS
Francesco Orio & Stefano Palomba
doi:10.1038/nrendo.2013.248
Nature Reviews Endocrinology 10, 130-132 (2014)
Reproductive endocrinology: Menstrual dysfunction—a proxy for insulin resistance in PCOS?
Héctor F. Escobar-Morreale
doi:10.1038/nrendo.2013.232
Nature Reviews Endocrinology 10, 10-11 (2014)
REVIEWS
The management of patients with polycystic ovary syndrome
Channa N. Jayasena & Stephen Franks
doi:10.1038/nrendo.2014.102
Nature Reviews Endocrinology 10, 624-636 (2014)
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. This article provides an overview of the pathophysiology, aetiology, diagnosis, and management of the most common presenting features of PCOS, including hyperandrogenism, menstrual irregularity and infertility. Management of cardiometabolic risk, an important concern in these patients, is also discussed.
Possible fetal determinants of male infertility
Anders Juul, Kristian Almstrup, Anna-Maria Andersson, Tina K. Jensen, Niels Jørgensen, Katharina M. Main, Ewa Rajpert-De Meyts, Jorma Toppari & Niels E. Skakkebæk
doi:10.1038/nrendo.2014.97
Nature Reviews Endocrinology 10, 553-562 (2014)
Accumulating evidence suggests that common reproductive problems, such as male infertility and testicular cancer, originate during fetal development. In this Review, Anders Juul and colleagues discuss the current knowledge of a variety of male reproductive issues, focusing on the developmental origins of testicular pathologies in the context of male infertility.
Pros and cons of GnRHa treatment for early puberty in girls
Ruben H. Willemsen, Daniela Elleri, Rachel M. Williams, Ken K. Ong & David B. Dunger
doi:10.1038/nrendo.2014.40
Nature Reviews Endocrinology 10, 352-363 (2014)
The utility of gonadotropin-releasing hormone agonists (GnRHa) treatment in girls with early puberty are much debated, as are its limitations. Here, the authors outline the different types of early puberty, the short-term and long-term effects of GnRHa treatment, life-course consequences of early pubertal development and areas in need of additional research.
Seminal plasma as a diagnostic fluid for male reproductive system disorders
Andrei P. Drabovich, Punit Saraon, Keith Jarvi & Eleftherios P. Diamandis
doi:10.1038/nrurol.2014.74
Nature Reviews Urology 11, 278-288 (2014)
Seminal plasma is a potential source of biomarkers of male reproductive system disorders. Drabovich et al. describe the development of seminal plasma proteomics and the progress towards the clinical use of biomarkers of male infertility and prostate cancer.
Endometriosis: pathogenesis and treatment
Paolo Vercellini, Paola Viganò, Edgardo Somigliana & Luigi Fedele
doi:10.1038/nrendo.2013.255
Nature Reviews Endocrinology 10, 261-275 (2014)
Endometriosis is a chronic inflammatory disease affecting around 5% of reproductive age women, often causing pelvic pain and infertility. This Review addresses current knowledge on the pathogenesis of the condition, medical, surgical and potential new treatments, the role of assisted reproduction, prevention of recurrences, and the association with ovarian cancer.
Featured article
Vitamin D and male reproduction
Martin Blomberg Jensen
doi:10.1038/nrendo.2013.262
Nature Reviews Endocrinology 10, 175-186 (2014)
Vitamin D receptor and enzymes that metabolize vitamin D are expressed in male reproductive organs. This Review highlights the role of vitamin D in male reproduction. Effects of vitamin D signalling on semen quality, estrogen responsiveness and the development of testicular germ cell tumours are discussed.
Featured article
Energy metabolism and fertility—a balance preserved for female health
Sara Della Torre, Valeria Benedusi, Roberta Fontana & Adriana Maggi
doi:10.1038/nrendo.2013.203
Nature Reviews Endocrinology 10, 13-23 (2014)
This Review highlights the reciprocal interaction of pathways that control female fertility and metabolism, a mechanism conserved by evolution. The authors focus on the role of estrogens and the potential of hormone replacement therapy for the treatment of metabolic disorders.
Endocrine autoimmune diseases and female infertility
Aritro Sen, Vitaly A. Kushnir, David H. Barad & Norbert Gleicher
doi:10.1038/nrendo.2013.212
Nature Reviews Endocrinology 10, 37-50 (2014)
Mounting evidence suggests that immune-mediated processes and autoimmunity affect female reproductive success. This Review summarizes the effect of individual autoimmune endocrine diseases on female fertility, and points towards selected developments expected in the near future.
Fertility preservation in women
Jacques Donnez & Marie-Madeleine Dolmans
doi:10.1038/nrendo.2013.205
Nature Reviews Endocrinology 9, 735-749 (2013)
Advances in cancer therapy over the past two decades have resulted in more patients surviving for longer after treatment. As many therapies can cause premature ovarian failure (POF), infertility in female cancer patients now needs to be addressed. This Review analyses the options that are currently available to preserve fertility in female patients with cancer and in women at risk of POF.
Sperm retrieval techniques
Daniel H. Shin & Paul J. Turek
doi:10.1038/nrurol.2013.262
Nature Reviews Urology 10, 723-730 (2013)
Overcoming male infertility resulting from azoospermia requires the retrieval of viable sperm for use in assisted reproduction. Shin and Turek compare the techniques available for sperm retrieval, and discuss considerations including DNA integrity and the ability to tolerate freezing and thawing of sperm from different anatomical locations.
Current and future applications of GnRH, kisspeptin and neurokinin B analogues
Robert P. Millar & Claire L. Newton
doi:10.1038/nrendo.2013.120
Nature Reviews Endocrinology 9, 451-466 (2013)
The reproductive hormone cascade affects all stages of life and provides a number of target points for therapeutic intervention in disease. This Review outlines the development and therapeutic applications of analogues of gonadotropin-releasing hormone, and of its upstream neuropeptide regulators kisspeptin and neurokinin B.
Current status of vasectomy reversal
J. Ullrich Schwarzer & Heiko Steinfatt
doi:10.1038/nrurol.2013.14
Nature Reviews Urology 10, 195-205 (2013)
Vasectomy reversal is the most common microsurgical treatment for male infertility; although assisted reproductive technology (ART) is an alternative, it is associated with higher costs without offering higher cumulative chances of a pregnancy. In this Review, Schwarzer and Steinfatt discuss the vasectomy reversal procedure, in terms of patient selection, surgical technique and alternative options, and consider the future directions of this complex procedure.
Featured article
Ageing of the male germ line
Catriona Paul & Bernard Robaire
doi:10.1038/nrurol.2013.18
Nature Reviews Urology 10, 227-234 (2013)
In this Review, Paul and Robaire discuss published data relating to the effect of paternal age on reproductive factors such as sperm quality, fertility, time to pregnancy, pregnancy loss, and congenital defects in offspring.
Insight into oxidative stress in varicocele-associated male infertility: part 1
Ashok Agarwal, Alaa Hamada & Sandro C. Esteves
doi:10.1038/nrurol.2012.197
Nature Reviews Urology 9, 678-690 (2012)
Oxidative stress is the central element contributing to infertility in men with varicocele, to which the testis responds by way of a number of mechanisms, including heat stress. In this comprehensive Review, Agarwal et al. discuss these responses, which have their own implications in exacerbating the underlying oxidative stress and on the subsequent infertility.
Insight into oxidative stress in varicocele-associated male infertility: part 2
Alaa Hamada, Sandro C. Esteves & Ashok Agarwal
doi:10.1038/nrurol.2012.198
Nature Reviews Urology 10, 26-37 (2013)
Current evidence suggests that oxidative stress is the central element contributing to infertility in men with varicocele. In this second part of their two-part Review, Hamada et al. discuss the clinical parameters and treatment options for men with varicocele-associated male infertility, focussing on alleviating oxidative stress as the major parameter and target for therapy.
Analysing the sperm epigenome: roles in early embryogenesis and assisted reproduction
Undraga Schagdarsurengin, Agnieszka Paradowska & Klaus Steger
doi:10.1038/nrurol.2012.183
Nature Reviews Urology 9, 609-619 (2012)
Aberrant epigenetic mechanisms have been implicated in impaired spermatogenesis, abnormal semen parameters and idiopathic male fertility. This Review covers the unique features of sperm chromatin, the methods used to analyse epigenetics in sperm and the possible roles of the sperm epigenome in early embryo development and assisted reproduction.
Featured article
Metabolic regulation is important for spermatogenesis
Luís Rato, Marco G. Alves, Sílvia Socorro, Ana I. Duarte, José E. Cavaco & Pedro F. Oliveira
doi:10.1038/nrurol.2012.77
Nature Reviews Urology 9, 330-338 (2012)
Sertoli cells provide nutritional support for germ cells by secreting nutrients or metabolic intermediates, such as amino acids, carbohydrates, lipids, vitamins, and metal ions. Here, the authors discuss the importance of Sertoli cell metabolism in the formation of the mature spermatozoa, and the regulation of this metabolism, which could have a direct influence on male fertility.
Anti-Müllerian hormone: an ovarian reserve marker in primary ovarian insufficiency
Jenny A. Visser, Izaäk Schipper, Joop S. E. Laven & Axel P. N. Themmen
doi:10.1038/nrendo.2011.224
Nature Reviews Endocrinology 8, 331-341 (2012)
A marker that predicts whether women are at risk of primary ovarian insufficiency (POI) would aid in early diagnosis and fertility counselling. This Review summarizes the current studies on anti-Müllerian hormone (AMH) in women with POI of various aetiologies and discusses its possible application as a marker to determine ovarian reserve.
Physical deformities relevant to male infertility
Rajender Singh, Alaa J. Hamada, Laura Bukavina & Ashok Agarwal
doi:10.1038/nrurol.2012.11
Nature Reviews Urology 9, 156-174 (2012)
In this thorough and comprehensive Review, Singh and colleagues describe a number of physical deformities associated with the testes, scrotum, epididymis, vasa deferentia, ejaculatory ducts and prostate that either commonly occur in infertile men or are potentially associated with male infertility. They include brief outlines of the available treatment options.
Neuroendocrine control by kisspeptins: role in metabolic regulation of fertility
Victor M. Navarro & Manuel Tena-Sempere
doi:10.1038/nrendo.2011.147
Nature Reviews Endocrinology 8, 40-53 (2012)
This Review highlights the milestones in the field of kisspeptin research, in particular developments in the putative interplay of kisspeptins and their cotransmitters, such as neurokinin B, in the central control of GnRH neurons; and the possible role of Kiss1 neurons as conduits for the metabolic regulation of puberty and fertility, with emphasis on intermediate regulatory signals and mechanisms involved.