The history and future of in vitro fertilization in the United States: the complex interrelationships among basic science, human medicine, and politics.

Although much of the foundational basic scientific and clinical research was conducted in the United States, the first in vitro fertilization (IVF) birth occurred in the United Kingdom. Why? For centuries, all research surrounding the field of "reproduction" has elicited bipolar passionate responses by the American public, and the issue of "test tube babies" has been no different. The history of conception in the United States is defined by complex interrelationships among scientists, clinicians, and politically charged decisions by various branches of the US government. With a focus on research in the United States, this review summarizes the early scientific and clinical advances important to the development of IVF and then addresses the potential future developments in IVF. We also consider what future advances are possible in the United States given the current regulations, laws, and funding.

Common practices among consistently high-performing in vitro fertilization programs in the United States: 10-year update.

OBJECTIVE: To evaluate similarities and differences in clinical and laboratory practices among high-performing fertility clinics. DESIGN: Cross-sectional questionnaire study of selected programs. SETTING: Academic and private fertility practices performing in vitro fertilization (IVF). PATIENT(S): Not applicable. INTERVENTION(S): A comprehensive survey was conducted of 13 IVF programs performing at least 100 cycles a year and having high cumulative singleton delivery rates for 2 years. MAIN OUTCOME MEASURE(S): Clinical and laboratory IVF practices. RESULT(S): Although many areas of clinical practice varied among top programs, some commonalities were observed. All programs used a combination of follicle-stimulating hormone and luteinizing hormone for IVF stimulation, intramuscular progesterone in frozen embryo transfer cycles, ultrasound-guided embryo transfers, and a required semen analysis before starting the IVF cycle. Common laboratory practices included vitrification of embryos at the blastocyst stage, air quality control with positive air pressure and high-efficiency particulate air filtration, use of incubator gas filters, working on heated microscope stages, and incubating embryos in a low-oxygen environment, most often in benchtop incubators. CONCLUSION(S): Some areas of consistency in clinical and laboratory practices were noted among high-performing IVF programs that are likely contributing to their success. High-performing programs focused on singleton deliveries. As the field of IVF is rapidly evolving, it is imperative that we share best practices in an effort to improve outcomes from all clinics for the good of our patients.

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.

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.

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.

Founding pioneers of IVF update: Innovative researchers generating livebirths by 1982.

This commentary adds accuracy and interesting information to the story of the founding pioneers of IVF which was published in this journal in 2018, at the 40th anniversary of the first IVF livebirth, namely Louise Joy Brown born 25 July 1978. Table 1 in that first publication is now updated to reflect extended information about Team 1 comprising the acknowledged "Fathers of IVF", but whose work is better tabulated as Team 1a from the NHS days in Oldham; and Team 1b covering the new period of private practice at Bourn Hall in Cambridge. With the passing of pioneer Ian Craft, co-author of the first article, further information came to light at his memorial service. There has now been some adjustment to the last few months of 1982, with correct inclusion of Israel into the list along with an interesting exposé of the two major pioneer facilities of that country. The previously cited third Australian groups (Team 12) have now been appropriately relegated to 1983, a year which experienced a plethora of IVF facilities around the world and the beginning of the IVF population boom.

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.

Preimplantation Genetic Testing for Aneuploidy: A Review.

IMPORTANCE: Preimplantation genetic testing for aneuploidy (PGT-A) has undergone many technical developments over recent years, including changes in biopsy timings, methodology, and genetic analysis techniques. The evidence surrounding the efficaciousness of PGT-A is sporadic and inconsistent; as such, significant doubt and concern remain regarding its widespread implementation. OBJECTIVE: This review seeks to describe the historical development of PGT-A and to analyze and summarize the current published literature. CONCLUSIONS: At times during its infancy, PGT-A failed to display conclusive improvements in results; with newer technologies, PGT-A appears to yield superior outcomes, including reductions in miscarriages and multiple gestations. Clinicians and patients should assess the use of PGT-A on a case-by-case basis, with laboratories encouraged to utilize blastocyst biopsy and next-generation sequencing when conducting PGT-A. Further studies providing cumulative live birth rates and time to live birth are required if PGT-A is to be proven as producing superior outcomes. RELEVANCE: PGT-A has the potential ability to impact in vitro fertilization success rates, and as it is increasingly adopted worldwide, it is crucial that clinicians are aware of the evidence for its continued use.

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.

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.

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.

A short history of in vitro fertilization (IVF).

The history of in vitro fertilization (IVF) in humans from the early attempts in the USA through to the first definitive achievement of IVF by Edwards, Steptoe and Purdy (1969-1978), and the brief period of innovative IVF achievements to Melbourne, Australia, cut short by the passage of restrictive legislation (1979-1984) is recorded. A summary of the key achievements since the mid 1980s is then given. The shameful connotations of engaging in IVF of those esrly days is contrasted with its wide acceptance today, in which IVF is setting the norms for modern families.

Looking into the Test Tube: The Birth of IVF on British Television.

The birth of Louise Brown, the world's first 'test-tube baby', has come to signify the moment at which technologically assisted human reproduction became a re ality. This was a highly mediated and visible reality, as this article explores through the example of a British television documentary about Louise Brown broadcast when she was just six weeks old, 'To Mrs Brown… A Daughter' (Thames Television, 1978). In the article, I discuss the programme alongside data from an interview with its producer, Peter Williams. Williams sought to convince the public that IVF was morally acceptable and to cultivate sympathy for the infertile through this film. I will consider how he went about this by focusing on the programme's visual presentation of Louise Brown, Peter Williams' aims in making the film and his sympathetic relationship with the 'pioneers' of IVF, gynaecologist Patrick Steptoe and physiologist Robert Edwards. I will conclude with a discussion of the political implications of this film and how it contributed to the normalisation of IVF at a pivotal moment in its history.

30 years of data: impact of the United States in vitro fertilization data registry on advancing fertility care.

OBJECTIVE: To summarize and assess the impact of key research generated through the Society of Assisted Reproductive Technology (SART)-initiated United States IVF registry and annual reporting system. DESIGN: Review. SETTING: Eligible studies included those that analyzed data generated by the National IVF data collection program (through SART or Centers for Disease Control and Prevention). PATIENT(S): Not applicable. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Summarize and report outcomes of research using National IVF registry data. RESULT(S): The Society of Assisted Reproductive Technology was founded in 1985 and published the first annual US IVF data report 30 years ago in 1988 in Fertility and Sterility. In 1995, the Centers for Disease Control and Prevention subsequently began collecting data from IVF programs and published their first report in 1997. This annual National IVF data collection and reporting is a significant responsibility and effort for IVF programs. Using these data sources, 199 articles have been published by clinicians and researchers from across the country. This research has guided the development of evidence-based assisted reproductive technology (ART) practice guidelines during the past 30 years, which have ultimately led to improved quality and patient care. CONCLUSION(S): Since the first SART National IVF data report publication 30 years ago, SART has achieved its original goals of creating a national IVF registry that successfully assesses clinical effectiveness, quality of care, and safety.

Founding Pioneers of IVF: Independent innovative researchers generating livebirths within 4 years of the first birth.

In this 40th anniversary year of the first IVF live birth, it is pertinent to look at all those teams endeavouring to generate live births from this unique technology and who succeeded within 4 years of the first. There were 9 teams who achieved this and a further 3 who were successful soon after, by the end of 1982. This historical review is compiled by 2 authors who were actively engaged in the field of IVF at the time of the first birth and who have remained active in Reproductive Medicine throughout their professional lives. They bring intimate and relevant knowledge of those pioneer researchers from the early years who can be classified as the "Founding Pioneers" of IVF.