Approximately 30 years ago we faced many challenges and those of us involved at the time have witnessed, with awe, the astonishing progress of a new medical discipline – far outreaching the expectations of even the very small number of believers at the time, let al.ne the vast majority of lay and professionals who were detractors. Not least among these were the Nobel Laureate, James Watson, Professor Winston and the famous case of the Chief of Obstetrics and Gynecology of Columbia Presbyterian Hospital, NY, USA, in 1973. He believed that a baby conceived by IVF would be a ‘monster’ and ordered the destruction of a couple’s embryos that were developing in the hospital’s laboratory, thereby destroying their chance to have a baby Citation[1].
In general terms, before the advent of IVF, infertility was largely treated empirically, if at all; the emergence of IVF spawned the science of infertility and its remedy.
We have observed not just the development of a new medical field, but the introduction of a whole new specialty, which exercised the minds of moral philosophers, ethicists, lawyers, governments and regulators – as it still does today. Few of us have been fortunate to be engaged in many of these debates that have transcended geography, ethnicity and the enormous variety of communities in our shared world.
Among the many challenges, not least was learning how IVF could be undertaken with routine success for basic tubal infertility and, in time, how to undertake prospective treatments for conditions we had not previously faced. Over the years, we learned to dispel several myths concerning the physiology of human reproduction – from performing embryo transfer in an obligatory knee–chest position, to not undertaking embryo transfer until night-time. Once we had confidence that IVF was possible and routine for ‘female factors’, we gradually became aware of the clinical imperative for couples with ‘male factor’ infertility, ovarian dysfunction and premature menopause, the requirement to improve and develop cryopreservation of gametes and embryos, the need for surrogacy and even the prediction that one day we would involve ‘five ‘parents’ for one child’ Citation[1]. More recently, the use of these technologies, combined with equally remarkable parallel developments in molecular biology, has permitted fertile individuals access to IVF for healthcare options for inherited genetic disease or creating tissue-matched siblings. Moreover, a tangential ‘product’ of IVF has been the opportunity to research human embryonic stem cells, a prospective technology hopeful of seeding yet another medical breakthrough.
In the beginning, we had the ‘natural’ menstrual cycle – the ovulation of a single mature oocyte, at anytime of the day or night. Harvesting the preovulatory oocyte by having to predict the luteinizing hormone surge, then mobilizing a team of specialists any hour of the day or night, was a major enterprise – not to mention the aspiration of only a single follicle following pneumoperitineum during the laparascopic approach to egg retrieval.
During those early years, predicting ovulation was essential, whether the follicular phase was monitored during the natural cycle or following stimulation with clomiphene citrate or human menopausal gonadotrophins. Prediction was based on pinpointing the start of the luteinizing hormone surge; this required hospitalization and regular assessments of luteinizing hormone in urine eight times every 24 h; finding an appropriate assay some 30 years ago and assessing an accurate time delay from plasma to urine was a significant endeavor. Suffice to say, as the requirement for laparoscopy diminished in response to pioneering work using ultrasound-guided oocyte collection, with the introduction of gonadotrophin-releasing hormone agonists (towards the middle-end of the 1980s), and much later the antagonists, practitioners gained total control over the menstrual cycle. These, among many of the upcoming revolutions, turned IVF into an outpatient, almost office-based, process – greatly benefiting patients and practitioners alike.
Over a concentrated 15-year period, when IVF was now accepted worldwide and the field was benefiting from the involvement of many intellectual medical scientists, significant developments that occurred in many areas and technologies were refined. Follicular stimulation was becoming more bespoke for the vast array of patient endocrine and physiological profiles, and new recombinant technology introduced even more purified follicular stimulants into the arena.
During the 1980s, the achievement of a full-term pregnancy in a menopausal woman employing donated oocytes not only heralded a breakthrough, it eventually challenged many established dogmas regarding the immunology of implantation and the effects of age on the female reproductive organs. Moreover, with the introduction of donor oocytes, some successful programs have been developed to such an extent that this represents as much as 50% of their daily work. This is the consequence of a social trend towards delaying childbearing and is one of the major contributors to worldwide ‘reproductive migration’ (often referred to as ‘fertility tourism’). This is an effect of the varying availability of donors in different countries as a result of legislation, regulation restricting practice or prohibiting the procedure per se.
Until the late 1980s, the only option for ‘treating’ almost all male infertility cases was using donor sperm, which was widely practiced. In a battle to try to help the subfertile male, the early phases of differing sperm microinjection techniques eventually led to the direct approach of intracytoplasmic sperm injection that, in the early 1990s, entirely revolutionized treatment for male factor infertility almost overnight. Intracytoplasmic sperm injection rendered most infertile males the possibility, for the very first time, to become the father of their own genetic child.
Throughout the 1980s and 1990s a range of technologies improved that permitted highly successful micromanipulation of oocyte and zygote polar bodies, and early cleaving embryos (blastomeres and trophoblast cells), establishing the whole field of preimplantation genetic diagnosis – an important tool with which to diagnose monogenic mutations and avoid the hereditary transmission of many severe diseases. Furthermore, the screening of polar body and embryo chromosomal content was also introduced in the clinical setting as the most reliable method to select viable embryos for transfer, in the hope of improving IVF outcome. More recently however, this whole concept has been revisited, debated and is currently evolving as our knowledge increases; indeed it is thought that the embryo is able to undertake repair and self-correct to a level previously not understood.
As stated previously, IVF has not only been a revolutionary phenomenon in the treatment of infertility, but has also opened a series of continuing social, ethical and legal debates. IVF has made possible the creation of new types of families that may be controversial in some societies, but it has certainly changed the perception of many fundamental issues, such as the beginning of life, biological parenting and the whole concept of ‘being’ and ‘humanness’. In 1978 there were less than 20 publications on IVF-related topics; by 1981 it had gently risen to nearly 70 in that year, while in the years 1985/86 there were over 600 publications. The field now has several journals dedicated to the subject.
This issue brings together some of the finest practitioners and commentators of the ‘IVF revolution’, whose articles tell the remarkable story of a medical specialty, initially pilloried by most during its inchoative years, yet itself still in an embryonic stage – as commentary on its prospects for the future reveal. Few specialties have exercised the minds of practioners, ethicists, philosophers and even governments more than our dominion over conception in our own species. For those of us who were involved right at the beginning, those 30 years ago, we can express with some confidence how, during the period of a generation, the reward for perseverance has, in the face of extreme animosity, brought overwhelming support of the general population at large in almost every country of the world.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Reference
- Fishel S. IVF – historical perspective. In: IVF – Past, Present and Future. S Fishel and EM Symonds (Eds). IRL Press, Oxford, UK 1–16 (1986).