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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Male factor infertility: Prediction models for assisted reproductive technology

Vitaly A. Kushnir & Norbert Gleicher


Nature Reviews Urology 11, 492-493 (2014)

Reproductive endocrinology: Maternal and fetal insulin levels at birth in women with PCOS

Renato Pasquali


Nature Reviews Endocrinology 10, 382-384 (2014)

Reproductive endocrinology: New guidelines for the diagnosis and treatment of PCOS

Francesco Orio & Stefano Palomba


Nature Reviews Endocrinology 10, 130-132 (2014)

Reproductive endocrinology: Menstrual dysfunction—a proxy for insulin resistance in PCOS?

Héctor F. Escobar-Morreale


Nature Reviews Endocrinology 10, 10-11 (2014)


The management of patients with polycystic ovary syndrome

Channa N. Jayasena & Stephen Franks


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


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


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


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


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.

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Vitamin D and male reproduction

Martin Blomberg Jensen


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.

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Energy metabolism and fertility—a balance preserved for female health

Sara Della Torre, Valeria Benedusi, Roberta Fontana & Adriana Maggi


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


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


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


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


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


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.

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Ageing of the male germ line

Catriona Paul & Bernard Robaire


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


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


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


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.

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Metabolic regulation is important for spermatogenesis

Luís Rato, Marco G. Alves, Sílvia Socorro, Ana I. Duarte, José E. Cavaco & Pedro F. Oliveira


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


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


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


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.