This book is an honest and practical testimony to these achievements. It is an excellent compilation of the work of world's experts in the field from at least 14 countries spanning the six inhabited continents, thanks to the great efforts of the editors and, in particular, the incessant activity of Dr Gautam N Allahbadia. It covers all aspects of ovulation induction and controlled ovarian stimulation.

The section on the Fundamentals of Stimulation is a necessary introduction to the subject and bridges the gap between basic science and clinical application. It helps to clarify the intricate relationships between the different elements of the hypothalamic-pituitary-ovarian axis and the various hormones and molecules involved in the process of natural ovulation, and how this can be manipulated for induction of ovulation in anovulatory women, as well as for controlling superovulation in assisted reproduction. It also discusses the up-to-date techniques for monitoring ovarian stimulation and addresses the important questions of whether the repeated ovarian stimulation has an effect on the ovarian reserve and whether some LH activity is indispensable for proper ovulation induction.

The following section is a journey into the world of ovarian stimulation and its chapters span various subjects from mild stimulation protocols to more aggressive protocols for various applications in assisted reproduction. It starts by discussing the place of Clomiphene citrate in the modern world of assisted reproduction and the possibility of combining it with other preparations, namely hMG or FSH, a particularly important subject for low-resource settings in developing countries. It continues with the still hot debate between the GnRH agonist and antagonist protocols in the light of the latest evidence-based analyses. In addition, the different regimens of FSH and hMG administration are discussed, including the step-up and step-down protocols and the use of Clomiphene citrate and oral contraceptives to manipulate the cycle for better clinical outcomes. It also addresses the question of whether any of these regimens has an effect on the luteal phase and the best way of supporting it. It finally discusses the supplementation of the various protocols with LH, hCG and estradiol in order to achieve the ultimate goal of a livebirth.

The subsequent section discusses the role of aromatase inhibitors, embracing their advantages and disadvantages and comparing them to other ovulation induction therapies. This is followed by the special section on ovarian stimulation in the still enigmatic polycystic ovary syndrome (PCOS), addressing the subject from all angles. In particular, the role of Metformin in this group of patients is discussed in detail as in the use of corticosteroids. The section ends with the role of surgery in the light of recent evidence and is followed by a section on triggering ovulation. Here, the different methods of achieving the final step in ovarian stimulation are discussed including LH, hCG as well as triggering ovulation by GnRH agonists in patients with PCOS.

A special section is dedicated to the complications of controlled ovarian stimulation, including the ovarian hyperstimulation syndrome, multiple pregnancies, as well as the possible relationship between ovarian stimulation and gynecological tumors. This is followed by a section that addresses the subject of poor responders, its causes and the best management protocols in these unfortunate patients in the light of the most recent. The final section is a look into the future of the subspecialty and discusses the new long-term FSH preparations, as well as state-of-the-art methods of monitoring ovarian stimulation.

With such a widespread text, the book is an indispensable addition to our library and is an excellent companion to all clinicians working in the field. It is also essential reading material for young doctors aspiring to work in our exciting and expanding world of assisted reproduction. I finally hope that this edition will be followed by more to come as the subject continues to evolve.

However, the unpleasant complications of ovarian stimulation, such as ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies, that lurk in the background of these lucrative success rates, spiral us back to the thought-provoking questions: Mild, Milder, Mildest or Back to Nature? Which protocol should it be? What drug regimen and dose should be used for which patient? Is the pursuit of success with assisted reproductive technology (ART) financially, psychologically, emotionally and ethically justified for infertility patients, especially for those from developing countries with low-resource settings, poor responders to stimulation and advance-aged women? Is the treatment safe for women at risk for a flare response to stimulation?

This monograph, divided into nine significant sections, with 67 carefully designed chapters, contributed by world authorities with clinical and scientific excellence, is a complete guide that aims to answer all these baffling questions and more in a single edition. The introductory section on the fundamentals of stimulation forms the scaffold, giving a thorough insight into the physiology of folliculogenesis and ovulation, regulation of gonadotropin secretion, their roles in follicular development and the menstrual cycle, and the effect of controlled ovarian hyperstimulation (COH) on cycle characteristics, indispensable to the understanding of cycle manipulation with ovulation indication (OI) drugs. The clinical significance of evaluating the ovarian reserve and monitoring folliculogenesis with ovarian reserve markers (AMH AFC, basal FSH, estradiol) to predict the ovarian response to COH is detailed, with particular relevance to high and poor responders to COH—the two most challenging patient groups. The value of LH supplementation, evaluation of the luteal phase and the significance of luteal phase support in COH are addressed to optimize the pregnancy outcomes with COH. The section on ovarian stimulation regimens that follows comprehensively, discusses the gamut of ovarian stimulation drugs (CC, urinary and recombinant gonadotropins, GnRH agonists and antagonists, and the novel recombinant long-acting Corifollitropin-alfa), the various protocols in which they are used (long, short, ultrashort, microdose-flare GnRH protocols, step-up protocols, step-down protocols), their clinical applications, comparative clinical efficacies, routes of administration and clinical outcomes, endowing the clinicians with the ability to appropriately individualize the treatment to patients. The mechanism of action of aromatase inhibitors and their indications, clinical outcomes, and their comparative clinical efficacy and safety with CC in women with polycystic ovary syndrome (PCOS) throws light on this particularly interesting alternative OI drug.

The versatile strategies for ovulation induction in PCOS patients, with an evidence-based approach to Metformin treatment, clears the cobwebs in the management of this still mysterious syndrome, leaving the reader with conclusive choices. While a critical evaluation of the roles of recombinant LH, recombinant hCG and GnRH agonist to trigger ovulation aims to present the ideal ovulation trigger to keep OHSS at bay, the possible benefit of a dual LH and FSH surge for final oocyte maturation forces a relook at the traditional hCG trigger. Complications of ovulation induction, specifically OHSS and multiple pregnancies, have been highlighted with precautions and strategies, such as in vitro maturation, natural cycle in vitro fertilization (IVF), minimal and modified natural cycle IVF, for their effective management. An entire section is dedicated to the optimal management of poor responders, an extremely challenging group that presents with a poor ovarian response to conventional stimulation, culminating in reduced oocytes and embryos, and thus, reduced pregnancy rates or canceled cycles.

A stimulating discussion on the when, why and how of embarking on mildstimulation protocols, natural cycle IVF and its advantages over conventional protocols, such as reduced medication, a physiological milieu, reduced complications, better clinical outcomes and higher cost-effective ratio, aims to increase its awareness to help make ovarian stimulation, softer, safer and cost-effective for patients. Combined with cryopreservation techniques, such as vitrification, and cryopreserved-thawed embryo transfer, this has important implications in low-resource settings.

The concluding section on advances in stimulation science is a window to technology at its ultimate. Remarkable advances in recombinant DNA technology, resulting in the highly potent, long-acting recombinant FSH (FSH-CTP, Corifollitropin-alfa), a single injection of which can sustain follicular growth for a week in a GnRH antagonist cycle, obviating the need for the daily painful injections for seven days, is now a relieving treatment option for patients undergoing COH for IVF/ICSI. The advantages of the applicability, reproducibility, and accuracy of Sonography-based Automated Volume Count (Sono AVC) for monitoring follicular growth, in addition to its value in time and patient management, and perhaps, even self-control by the patient, give it a special place in the clinic.

We earnestly hope that we have been able to effectively reach out to clinicians, infertility professionals, both medical and paramedical including postgraduate students through this practical, problem-orientated handbook, successfully platform evidence-based, and satisfying solutions to their clinical dilemmas, and inspire future path-breaking researches. We would like to thank the contributors for their scholarly contributions that have enabled us to further disseminate indispensable knowledge in this intriguing and rapidly advancing field of Reproductive Endocrinology.