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.

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.

Reproduction in domestic ruminants during the past 50 yr: discovery to application.

The study of reproductive physiology in domestic ruminants has progressed from the whole animal to the molecular level in an amazingly short period of time. The volume of information on this subject is enormous; therefore, we have focused on domestic ruminants, with an emphasis on cattle. To date, artificial insemination (AI) is perhaps the most powerful technique that reproductive physiologists and geneticists have provided the livestock industry for genetic improvement. Early efforts to establish AI as a tool were initiated in Russia around 1899 and since that time major advances in methods of semen collection, evaluation of male fertility, cryopreservation of sperm, sex-sorted semen, and estrous cycle control have occurred. The preceding advances not only led to the widespread use of AI, but also contributed to our fundamental understanding of ovulation control, timing of insemination, gamete biology, and cryopreservation. In regards to anestrus, our understanding of the concept of neuroendocrine control of the pituitary gland and the role of steroid feedback led to the Gonadostat Theory, which proposes that onset of puberty is due to a decrease in the negative feedback of gonadal steroids over time. Subsequent studies in prepuberal and postpartum sheep and cattle established that a short luteal phase frequently precedes the first normal length cycle that is accompanied by estrous expression. This observation led to the common practice of treating prepuberal heifers and anestrous postpartum cows with a short-term progestin treatment (e.g., Controlled Internal Drug Release) to induce normal estrous cycles. In domestic ruminants, fertilization rate is high (85% to 95%); however, significant embryonic mortality before or around the time of maternal recognition of pregnancy (MRP) reduces the pregnancy rate to a single breeding. Significant effort has been directed at determining the time of MRP, the signal for MRP, as well as elucidating the physiological, cellular, and molecular dialogue between the conceptus and uterine environment. Advancements have now led us to the ability to edit the genome to alleviate disease and possibly improve production traits. In summary, major advancements in our understanding of reproductive biology have stemmed from efforts to establish the AI and embryo transfer technique and reduce the negative impact of anestrus and embryonic mortality in domestic ruminants.

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.

Therio-ontology: a personal view of 40 years of farm animal embryo form and function.

The main purpose of this autobiographical reminiscence of 40 years of embryo research is to provide young theriogenologists with a firsthand account of how career development can depend strongly on early influences that become modified by changing circumstances. With no intention of being didactic, I hope that my experience of coping with enormous changes in techniques and attitudes may be of use to some of those embarking on a further 40 years of change of at least equal enormity.

Forty years of embryo transfer in cattle: a review focusing on the journal Theriogenology, the growth of the industry in North America, and personal reminisces.

After the first successful transfer of mammalian embryos in 1890, it was approximately 60 years before significant progress was reported in the basic technology of embryo transfer (ET) in cattle. Starting in the early 1970s, technology had progressed sufficiently to support the founding of commercial ET programs in several countries. Today, well-established and reliable techniques involving superovulation, embryo recovery and transfer, cryopreservation, and IVF are utilized worldwide in hundreds, if not thousands, of commercial businesses located in many countries. The mean number of embryos produced via superovulation has changed little in 40 years, but there have been improvements in synchrony and hormonal protocols. Cryopreservation of in vivo-derived embryos is a reliable procedure, but improvements are needed for biopsied and in vitro-derived embryos. High pregnancy rates are achieved when good quality embryos are transferred into suitable recipients and low pregnancy rates are often owing to problems in recipient management and not technology per se. In the future, unanticipated disease outbreaks and the ever-changing economics of cattle and milk prices will continue to influence the ET industry. The issue of abnormal pregnancies involving in vitro embryos has not been satisfactorily resolved and the involvement of abnormal epigenetics associate with this technology merits continued research. Last, genomic testing of bovine embryos is likely to be available in the foreseeable future. This may markedly decrease the number of embryos that are actually transferred and stimulate the evolution of more sophisticated ET businesses.

MC Chang--Reproductive biologist of distinction 1908-1991.

This article reviews the remarkable life and major scientific achievements of the reproductive biologist M.C. Chang. His scholarly career progressed from university in Peking, via Edinburgh, Scotland, and Cambridge, England, to the newly founded Worcester Foundation for Experimental Biology in Massachusetts. At each stage, the hand of fate is noted as are the support and encouragement of key professors. Chang's own contributions on capacitation of spermatozoa, in vitro fertilisation of mammalian eggs, and transplantation of oocytes and embryos are all brought out, as is his essential input to the creation and development of a steroid contraceptive pill. He strongly encouraged young reproductive biologists who worked in his laboratory, and applauded the world-wide distinction of his student and associate, R. Yanagimachi, as a specialist in mammalian fertilisation. Finally, Chang's continued feelings towards his homeland are contrasted with the reality of his American life after 1945, itself a study in poignancy.

IVF and embryo transfer: historical origin and development.

IVF and embryo transfer for the treatment of human infertility has now resulted in the birth of over 4 million babies. The technique did not arise as a quantum event but was built on the efforts of many earlier workers in the fields of reproductive endocrinology and development. One should remember the famous saying of Isaac Newton: 'If I have seen further than most, it is because I have stood on the shoulder's of giants'. Ethical and moral issues have always arisen when investigators study early mammalian development, particularly human development. This paper documents these earlier studies and also draws attention to the ethical and moral arguments that inevitably arose.

[The establishment of in vitro fertilization-embryo transfer (IVF-ET) and the development of its derivative techniques].

On 25th July, 1978, a test-tube baby from the first use of IVF-ET was born, which opened a new chapter for the development of ART for human beings. Thereafter, some derivative techniques such as POST, GIFT, ICSI and PDG, etc., emerged in succession, which were a comprehensive supplement to IVF-ET, and further perfected ART. With the review of this technique and its derivative techniques, people can more comprehensively understand the techniques and provide experience and enlightenment for its more healthy development.

The work of the Animal Research Station, Cambridge.

This paper traces the history of the Animal Research Station, Cambridge from its establishment in 1932 to its closure in 1986. The author worked there for forty years and was Director from 1979. Originally set up as a field station for Cambridge University's School of Agriculture, the Station was expanded after World War II as the Agricultural Research Council's Unit of Animal Reproduction. Beginning with semen and artificial insemination, research at the Station soon embraced superovulation and embryo transfer in farm animals. Many other technologies were also developed here, including IVF in pigs, cloning by nuclear transplantation of early embryonic cells, and the first genetically modified farm animals in Britain. This account recalls the Directors of the Station and their research teams together with details of their pioneering contribution to reproductive biology.

Charles Thibault and assisted reproduction in France.

Charles Thibault was liked by French gynaecologists. There was not a year that Charles Thibault did not attend clinician gynaecology conferences. He made great strides in research on in vitro fertilisation, being the first to perform in vitro fertilised (IVF) oocyte transfers in rabbits. Later, in 1978 the first human pregnancy following IVF was achieved in the UK when Louise Brown was born. In 1980, two French teams,one at the Sèvres hospital and the other at the Clamart University Teaching Hospital, carried out egg retrievals in patients with natural cycles, after determination of the urinary LH peak, under general anaesthesia and by laparoscopy. The Clamart team developed LH SIR, which enabled a more accurate determination of the ideal time for egg collection. In 1983, the same team reported the first ambulatory oocyte retrievals by ultrasound, under local anaesthesia. This new technique did not require general anaesthesia. Finally, in 1983, the rate of births, per transfer, for the Sèvres team rose to 5.31%. 1984 showed considerable improvement: 13.83%. The first step in establishing IVF in France was completed with the Carghese symposium, in September 1984, where Charles Thibault pleaded for animal experimentation before human clinical trials. It was only later that ART developed significantly, necessitating a legislative framework and organisations such as GEFF and FIVNAT.

A history of farm animal embryo transfer and some associated techniques.

Events over the last 125 years that have been particularly important to the development of embryo transfer in farm animals are reviewed, arguing that an appreciation of the history of a discipline helps shape its future. Special attention is paid to how the motivations of the scientists involved have changed over time, and how these changes have influenced the practical application of embryo transfer to animal breeding.

Tribute to Georgeanna and Howard Jones.

This tribute is divided into three sections. The first of these is a description of six weeks of research involving Georgeanna and Howard Jones and me over a few weeks in Johns Hopkins in 1965. Initially, it describes details of preliminary work and then completion of the maturation programme of the mature human oocyte and the first serious attempts at IVF. Scientific discoveries in those exciting weeks contributed to the earliest beginnings of IVF. A second section on knowledge of the human preimplantation embryo today concentrates on the problem of poor-quality embryos and how to overcome it, and on new knowledge on the regulation of human embryonic development. Lastly, the ethics of assisted conception are debated in relation to early practice and to some international features of modern ethical adjudication. A brief conclusion describes some of the friendships initiated in Johns Hopkins and still intact today.