In vitro fertilization: four decades of reflections and promises.

BACKGROUND: In 2010, Robert Edwards was awarded the Nobel Prize in Medicine for his pioneering work in the development of in vitro fertilization, a field that has touched millions of lives across the globe. Edwards dedicated his career to helping couples overcome infertility. He first established principles of early embryo development that served as the foundation for his later work. In the 1960s, he achieved the first human fertilized oocyte in vitro while at the Johns Hopkins Hospital. He then continued his work at Cambridge University. In 1978, the world witnessed the birth of the first "test tube baby". This achievement is a landmark not only in the reproductive sciences but also in the history of mankind's technological evolution. SCOPE OF REVIEW: This article outlines the development and progression of IVF from its infancy to the refined and broadly utilized technology offered to patients today. We describe the evolution of the field and the current state of IVF, including its current technological and social challenges. MAJOR CONCLUSIONS: We congratulate Professor Edwards for his well-deserved recognition as Nobel Laureate in Medicine. GENERAL SIGNIFICANCE: This article is a tribute to Edwards for his exceptional accomplishments in this specific and rewarding field of modern medicine.

Thirty years of IVF: the legacy of Patrick Steptoe and Robert Edwards.

In this article, the author presents a review of the early collaboration between Patrick Steptoe and Robert Edwards, gynecologist and scientist, which ultimately led to the birth of Louise Brown in 1978, the first baby to be born as a result of in-vitro fertilisation. Following this momentous event, the author shows how Steptoe and Edwards continued to influence further developments in the treatment of infertile couples, both in the United Kingdom and Worldwide.

Recombinant human leukemia inhibitory factor does not improve implantation and pregnancy outcomes after assisted reproductive techniques in women with recurrent unexplained implantation failure.

In this randomized, double-blind, placebo-controlled, multicenter study, women (n = 149) with a history of at least two unexplained implantation failures after assisted reproductive techniques received recombinant human leukemia inhibitory factor, 150 microg SC twice daily for 7 days, or placebo. The clinical pregnancy rate after ET was significantly lower in patients receiving recombinant human leukemia inhibitory factor than in those receiving placebo (17.6% vs. 34.0%, respectively).

Optimal follicle and oocyte numbers for cryopreservation of all embryos in IVF cycles at risk of OHSS.

Ovarian hyperstimulation syndrome (OHSS) is a rare but potentially fatal complication of IVF treatment. The risk of OHSS increases with increasing numbers of follicles aspirated and oocytes retrieved, but there is little evidence to support whether threshold values of either can be used to correctly predict OHSS. Since the most severe forms of OHSS are usually associated with pregnancy, cryopreservation of all embryos may prevent this. The authors attempted to find thresholds of follicle and oocyte numbers that would optimally predict OHSS, through a retrospective analysis of 2253 consecutive cycles of IVF/intracytoplasmic sperm injection treatment reaching oocyte retrieval, between 1 January 2003 and 31 March 2006. Receiver operator characteristic (ROC) curves were calculated for both parameters, to determine threshold values that might predict OHSS in women with > or =20 oocytes. For the prediction of early onset OHSS, ROC curves showed that an optimal balance between sensitivity and specificity was achieved using thresholds of 24 oocytes (79%, 60%) and 29 follicles (82%, 65%) respectively. Using these thresholds, cryopreservation of all embryos may be offered as an alternative to cancellation of a treatment cycle due to excessive ovarian response, thus minimizing the number of unnecessary interventions while still correctly predicting most cases of early onset OHSS.

Oocyte number per live birth in IVF: were Steptoe and Edwards less wasteful?

As part of a learning exercise to assess the efficiency of oocyte utilization after controlled ovarian stimulation, we compared historical data from the publications of Steptoe and Edwards describing their early experiences in Oldham and at Bourn Hall with retrospective data from IVF and ICSI cycles carried out at Bourn Hall Clinic during the year 2000. For the purpose of analysing the more recent data, patients were subdivided into groups by age (< or = 37 years and > or = 38 years) and by oocyte yield (low, intermediate and high). In patients less than 38 years of age, live birth rates were equivalent in each group, irrespective of the number of oocytes retrieved. Patients who yielded low numbers of oocytes (1-5) utilized an average of 9.6 oocytes per live birth, compared with 25.1 and 51.5 in those who yielded intermediate (6-16) and high (16+) numbers of oocytes. The comparison with historical data suggests that the 'efficiency' of oocyte utilization has not improved significantly since the early 1980s, despite 25 years' experience of controlled ovarian stimulation for IVF treatment.

Gestational surrogacy.

Gestational surrogacy is a treatment option available to women with certain clearly defined medical problems, usually an absent uterus, to help them have their own genetic children. IVF allows the creation of embryos from the gametes of the commissioning couple and subsequent transfer of these embryos to the uterus of a surrogate host. The indications for treatment include absent uterus, recurrent miscarriage, repeated failure of IVF and certain medical conditions. Treatment by gestational surrogacy is straightforward and follows routine IVF procedures for the commissioning mother, with the transfer of fresh or frozen-thawed embryos to the surrogate host. The results of treatment are good, as would be expected from the transfer of embryos derived from young women and transferred to fit, fertile women who are also young. Clinical pregnancy rates achieved in large series are up to 40% per transfer and series have reported 60% of hosts achieving live births. The majority of ethical or legal problems that have arisen out of surrogacy have been from natural or partial surrogacy arrangements. The experience of gestational surrogacy has been largely complication-free and early results of the follow-up of children, commissioning couples and surrogates are reassuring. In conclusion, gestational surrogacy arrangements are carried out in a few European countries and in the USA. The results of treatment are satisfactory and the incidence of major ethical or legal complications has been limited. IVF surrogacy is therefore a successful treatment for a small group of women who would otherwise not be able to have their own genetic children.

Models for future delivery of care in infertility: the role of the private sector.

An estimated 85% of infertility treatment at the tertiary level in the UK currently is funded by the infertile couples themselves. Of the 15% of couples who receive NHS funding for assisted reproductive technology (ART), a sizeable proportion is provided by private clinics. If the National Institute of Clinical Excellence (NICE) decides that the National Health Service (NHS) should provide funding for an increased number of treatments, then it is unlikely that wholly NHS ART clinics will be able to provide the extra number of cycles required. Those private clinics in the UK that bid to provide treatment funded by the NHS through primary care trusts (PCT) generally provide a cost-effective service in a 'patient friendly' environment. The case is made in this article that ART clinics in the private sector that wish to bid for PCT contracts, should be allowed to compete on an equal basis with NHS or NHS-private combined clinics. PCTs awarding contracts should be wholly driven by good evidence of clinical effectiveness, cost effectiveness and the provision of a quality service to patients.

Controlling the high order multiple birth rate: the European perspective.

The dramatic increase in the incidence of high order multiple pregnancies that has occurred since the mid-1970s is due to three main factors: increasing female age at conception; increasing use of ovulation induction agents and the introduction of sophisticated assisted reproduction techniques. High order multiple pregnancies are at significantly higher risk of complications than singleton pregnancies, for the fetuses, babies and the mothers. The aim of all fertility treatments is to achieve a healthy live child for each couple seeking treatment. Treatment of infertility by IVF and related techniques provides an ideal opportunity to limit the number of high order multiple pregnancies by reducing the number of embryos transferred to the woman. The realization that high order multiple pregnancy can and should be avoided has increasingly led, in most European countries, to a restriction of the number of embryos for transfer to two or even one, without a significant decrease in a couples' chance of achieving a pregnancy. The experience of European countries in reducing the number of embryos transferred is reviewed and a recommendation made that a responsible attitude to embryo transfer is adopted by all practitioners of assisted reproduction.

Is your IVF programme good?

Few standards exist today to assess the quality of an IVF centre. Although much focus is placed upon pregnancy rates, emphasis on this outcome alone is inadequate. The purpose of this report is to examine those factors that should be considered in assessing the overall quality of an IVF centre. Current methods to assess quality are reviewed. Many governing bodies throughout the world currently focus solely on pregnancy rates, which can be misguided if factors such as multiple pregnancies, ovarian hyperstimulation, patient satisfaction, and the proper evaluation of laboratory and clinical protocols are not taken into account. Measurements of quality and methods to improve it are critical in all business models, including IVF. We propose an international standard such as the ISO 9001 for IVF centres to properly evaluate and improve the delivery of their care.

Has clinical practice been changed by the Human Fertilisation and Embryology Act 1990?

The birth in 1978 of the first baby to be conceived through in vitro fertilization caused both wonder and controversy. Concerns that this technology would be abused led the Government of the United Kingdom to appoint a Committee of Enquiry into human fertilization and embryology, which led to the publication in 1984 of what has become known as the Warnock Report. This made recommendations on the creation of human embryos in vitro, the storage of human eggs, sperm and embryos, and research on human embryos. This report led eventually to the passing by Parliament of the Human Fertilisation and Embryology Act 1990 and the creation of the Human Fertilisation and Embryology Authority, which since 1991 has licensed and regulated all centres and practitioners of assisted reproductive technology. The effects of these regulations are considered in this article. Clinical practice has been affected by the Act, but it has generally led to higher standards of clinical and laboratory practice, improved patient information and care, and improved ethical standards.