Human in vitro fertilisation and developmental biology: a mutually influential history.

This article describes the origins and development of in vitro fertilisation (IVF) and how it was influenced by, and influenced, basic research in developmental biology. It describes the technical and social challenges that confronted the pioneers in this field of study, and the considerable progress that has been made since those early days. It also considers how IVF has contributed, and continues to contribute, to our understanding of early human development.

Necessity is the mother of invention and the evolutionary force driving the success of in vitro fertilization.

During the last few decades, millions of healthy children have been born with the aid of in vitro fertilization (IVF). This success belies the fact that IVF treatment is comprised of a complex series of interventions starting with a customized control ovarian stimulation protocol. This is followed by the induction of oocyte maturation, the retrieval of mature oocytes and in vitro fertilization, which often involves the microinjection of a single sperm into the oocyte. After fertilization, the resulting embryos are cultured for up to 7 days. The best embryos are transferred into the uterus where the embryo implants and hopefully develops into a healthy child. However, frequently the best embryos are biopsied and frozen. The biopsied cells are analyzed to identify those embryos without chromosomal abnormalities. These embryos are eventually thawed and transferred with pregnancy rates as good if not better than embryos that are not biopsied and transferred in a fresh cycle. Thus, IVF treatment requires the coordinated efforts of physicians, nurses, molecular biologists and embryologists to conduct each of these multifaceted phases in a seamless and flawless manner. Even though complex, IVF treatment may seem routine today, but it was not always the case. In this review the evolution of human IVF is presented as a series of innovations that resolved a technical hurdle in one component of IVF while creating challenges that eventually lead to the next major advancement. This step-by-step evolution in the treatment of human infertility is recounted in this review.

Reconstructing Robert Edwards: biography and the history of reproduction.

This commentary assesses Let There Be Life: An Intimate Portrait of Robert Edwards and His IVF Revolution by Roger Gosden (Jamestowne Bookworks, Williamsburg, VA, 2019, xxix + 359 pp., £15.99 / $19.99), an authorized biography of the IVF pioneer who founded this journal. It reflects on the challenges of placing Edwards in the history of studying reproduction, especially the rise of interest in infertility. It analyses Gosden's narrative choices and practices of reconstruction, in particular of experiences of seeing human eggs, embryos and fetuses. And it suggests that further research should explore the full spectrum of communication around Edwards with a view to illuminating the roles of scientists in transforming reproduction and to feeding back into a richer view of his life.

A revolutionary joins the establishment: Reproductive Biomedicine Online turns 20.

This commentary highlights the publishing revolution achieved by Robert Edwards in founding Reproductive Biomedicine Online. It corrects some inaccuracies in the account given by Roger Gosden in his recently published book Let There Be Life: An Intimate Portrait of Robert Edwards and His IVF Revolution.

Ex ovo omnia? A letter to members of The Ovum Club on the 50th anniversary of the beginning of IVF.

This writing presents personal reflections on issues raised by the recent publication of texts concerning the developing story of infertility treatment since the delivery of Louise Brown in 1978. It is written by a woman whose own natural conception coincided with the commencement of Steptoe and Edwards's collaboration, and who herself received, as an adult, a treatment to which their work gave rise. It addresses itself to the as yet mostly anonymous and silent female subjects-the self-styled 'Ovum Club'-without whose involvement in the original research programme in Oldham in 1969-1978 Louise would never have been born, to be followed by millions of in vitro fertilisation (IVF) babies worldwide. It ponders a few of the characteristics of the celebratory narratives of the development of IVF as have so far been told and draws attention to some of the paradoxes, inconsistencies, misunderstandings and confusions apparent in texts which have played a crucial role in shaping public awareness of this branch of medical science for 50 years. In conclusion, it points out that without hearing a range of voices of those women involved in the original experimental research who mostly lost more than they gained, a more compassionate historiography, and a balanced and comprehensive History of this branch of medicine will never be attained.

THE JEREMIAH METZGER LECTURE: A BRIEF HISTORY OF EUGENICS IN AMERICA: IMPLICATIONS FOR MEDICINE IN THE 21ST CENTURY.

In the first half of the 20th century, the US was swept up in a multifaceted movement to enhance the genetic makeup of the country's population. This eugenics movement, based on flawed scientific principles promulgated by Galton in the UK and Davenport in the US included legally mandated compulsory sterilization in 27 states in the US and sharply restricted immigration from many parts of the world. Compulsory sterilization legislation was upheld by the Supreme Court in 1927. The American eugenics movement was a model for the compulsory sterilization implemented by the Nazis after they took power in Germany in 1933. The movement waned in America only following World War II when the US public became aware of the full extent of the Nazi Aryan racial superiority program. With the advent of major advances in molecular and cellular biology that are already being applied to clinical medicine in the 21st century, we have entered a new eugenics era. It is critical that we learn the lessons of our earlier eugenics movement if we are to avoid making the same flawed decisions now.

Direct transfer of frozen-thawed bovine embryos and its application in cattle reproduction management.

Embryo transfer entails many procedures and techniques, of which embryo freezing is an important component in bovine embryo transfer. Embryo freezing techniques have been developed over the last 40 years, allowing practical availability, and have become essential for cattle reproduction management under field conditions. The direct transfer methods of frozen-thawed, in vivo-derived, and in vitro-produced (IVF) bovine embryos using 1.5 M ethylene glycol (EG) with or without sucrose (SUC) are used widely under on-farm conditions, not only in Japan but also globally. The direct transfer method using 1.5 M glycerol (GLY) and 0.25 M SUC (GLY-SUC) is used mainly in Japan. The pregnancy rate with direct transfer of frozen-thawed bovine embryos in either EG or GLY-SUC has been found to not differ from conventional freezing with GLY and traditional dilution techniques. Pregnancy rates following direct transfer of frozen-thawed bovine embryos were affected by the developmental stage of the embryos and the parity of the recipients. The use of ultrasound-guided on-farm ovum pickup is ushering in a new revolution for the commercial application of IVF embryos. Globally, for the first time more IVF bovine embryos were transferred in 2017 than produced in vivo. More than 60% of IVF embryos were transferred fresh due to a low pregnancy rate of frozen-thawed IVF embryos. Many factors seemed to be involved in improving the survival rate of frozen-thawed IVF embryos. Therefore, further research is needed to improve the freezing tolerance of IVF embryos to develop efficient direct transfer methods analogous to those used for in vivo embryos.

40 years of bovine IVF in the new genomic selection context.

The development of a complex technology such as in vitro fertilization (IVF) requires years of experimentation, sometimes comparing several species to learn how to create the right in vitro environment for oocytes, spermatozoa and early embryos. At the same time, individual species characteristics such as gamete physiology and gamete interaction are recently evolved traits and must be analysed within the context of each species. In the last 40 years since the birth of Louise Brown, IVF techniques progressed and are now used in multiple domestic and non-domestic animal species around the world. This does not mean that the technology is completely matured or satisfactory; a number of problems remain to be solved and several procedures still need to be optimized. The development of IVF in cattle is particularly interesting since agriculture practices permitted the commercial development of the procedure and it is now used at a scale comparable to human IVF (millions of newborns). The genomic selection of young animals or even embryos combined with sexing and freezing technologies is driving a new era of IVF in the dairy sector. The time has come for a retrospective analysis of the success and pitfalls of the last 40 years of bovine IVF and for the description of the challenges to overcome in the years to come.

The pioneering of intracytoplasmic sperm injection: historical perspectives.

Intracytoplasmic sperm injection (ICSI) has often been heralded as a ground-breaking technique that has transformed the treatment of couples with infertility. By injecting a single spermatozoon into the cytoplasm of the oocyte, ICSI bypasses the zona pellucida and increases the chances of fertilization and subsequent embryo development, independent of semen parameters. Ever since the first live births using ICSI were reported in 1992, ICSI has become the mainstay of treating male factor infertility as well as overcoming fertilization failure associated with conventional in vitro insemination. Today, ICSI is utilized in nearly 66% of all assisted reproductive treatments worldwide and has resulted in the birth of millions of babies. The primary goal of this review is to provide historical perspectives about the pioneering of ICSI. We begin by highlighting the scientific work of early investigators who elucidated the mechanisms central to mammalian fertilization. Furthermore, we briefly discuss how these findings contributed to the development of IVF for the treatment of infertility. We then emphasize the shortcomings of IVF in treating severe forms of male factor infertility and enumerate the micromanipulation techniques that were developed to circumvent these shortcomings. Finally, we indicate how the inadequacies of these micromanipulation techniques lead to the inception, application and popularity of ICSI.

A History of Developments to Improve in vitro Fertilization.

Methods of in vitro fertilization (IVF) have advanced dramatically since the first IVF baby was born in 1978. Originally yielding single-digit success rates, IVF is now successful in nearly 50% of cases in which the woman is younger than 35 years. Here, we describe the improvements in laboratory techniques and advances in our abilities to manipulate reproductive physiology that have facilitated this improvement. Additionally, we describe efforts to ensure safety standards in this competitive field.

Chang's meaning of capacitation: A molecular perspective.

Dr. Min Chue Chang's contributions to the field of reproductive biology set the stage for the development of the contraceptive pill and in vitro fertilization. Throughout his publications, Dr. Chang was also able to transmit his view of the fertilization process in ways that organized research for newer generations of reproductive biologists. Particularly relevant for the achievement of in vitro fertilization in mammals was the discovery that the sperm required a period of residence in the female tract to become fertilization-competent; Dr. Chang and Dr. Austin, in Australia, independently reported this process, now known as sperm capacitation. This review discusses Dr. Chang's views on capacitation, and puts them in the context of recent advances in the understanding of the molecular basis of this process. Mol. Reprod. Dev. 83: 860-874, 2016 © 2016 Wiley Periodicals, Inc.

Obstetricians' and Gynecologists' Opinion on Surrogacy in Japan: The Successful Use of Human In Vitro Fertilization in 1983.

This study confirmed opinions on surrogacy conducted by obstetricians who were affiliated with a university in the 1980s, based on the clue that a child was born using human in vitro fertilization (IVF) in 1983. This research also examined the question of why Japanese obstetricians limited the target population for IVF to legally married couples and excluded women (wives) who had undergone total hysterectomies. The women's movement has criticized the gender discrimination that occurred in IVF. Obstetricians had predicted the advancement of human IVF, and that it would raise legal and ethical issues regarding this form of surrogacy. Around this time, there was a lawsuit known as the Fujimi Obstetrics and Gynecology Hospital Case, which exposed the realities of performing a total hysterectomy after an unjustified diagnosis. It was believed that obstetricians had obstructed the normal sequence of events in which a patient selects surrogacy after undergoing a hysterectomy.

In vitro fertilization in Japan - early days of in vitro fertilization and embryo transfer and future prospects for assisted reproductive technology.

Assisted reproductive technology (ART) such as in vitro fertilization (IVF) and embryo transfer (ET) has been essential in the treatment of infertility. The world's first IVF-ET baby was born in 1978 based on the technique developed by Dr. Robert Edwards and Dr. Patrick Steptoe. In Japan, the first IVF-ET birth was reported in 1983 by Prof. Masakuni Suzuki at Tohoku University School of Medicine. IVF-ET is a procedure used to achieve pregnancy that consists of extracting oocytes from an infertile woman, fertilizing them in vitro, and transferring fertilized eggs into the patient's uterine cavity (Fig. 1). Since the first report of successful IVF-ET, numerous techniques related to ART, such as cryopreservation of oocytes and embryos, gamete intrafallopian transfer (GIFT), and microinsemination, have been developed and refined (Table 1). Herein we describe the history of basic research in IVF-ET that led to human applications, how the birth of the first IVF-ET baby was achieved in Japan, the current status of ART in Japan, issues related to ART, and future prospects for ART.

IVF endocrinology: the Edwards era.

Through pioneering human IVF as a global infertility treatment, Robert Edwards and his clinical partner Patrick Steptoe launched the field of IVF endocrinology. Following repeated failures with oocytes collected in human menopausal gonadotrophin (HMG) primed cycles timed to injection of human chorionic gonadotrophin (HCG), the first successful IVF pregnancy came from a spontaneous menstrual cycle. Intensive endocrine monitoring was used to track pre-ovulatory follicular development and collect a single ripe egg timed to the natural LH surge. Despite this groundbreaking achievement, ovulation induction was clearly required to make IVF treatment clinically robust and reliable. Ovarian stimulation with clomiphene citrate was used to achieve the first maternity from a superovulated human IVF cycle in 1980. HMG/HCG regimens were then successfully introduced-including substitution of 'pure' follicle-stimulating hormone as the principal ovarian stimulant. The application and success of IVF treatment were dramatically enhanced by the introduction of gonadotrophin-releasing hormone analogues that enabled elective control of endogenous gonadotrophin release during ovarian stimulation. Programmed gonadotrophin regimes yielding double-digit oocyte numbers became normal: 'more is better' was the ethos. Bob Edwards expressed increasing concern over the cost, complexity and potential long-term health risks of such high-order ovarian stimulation. In later life he repeatedly called for a return to minimalist approaches based on the natural menstrual cycle to improve oocyte quality over quantity. This article reviews the application of ovulation induction to human IVF and celebrates Edwards' abiding impact on the field, which firmly grounds him in the reproductive endocrinology pantheon.