In 1978, two children came into the world as a result of laboratory fertilisation techniques (in vitro fertilisation, or IVF). Louise Joy Brown was born in the UK on 25 July, and Kanupriya Agarwal , or âBaby Durgaâ, was born in India on 3 October.1 In Oldham, near Manchester, Patrick Steptoe, an obstetrician and gynaecologist, and Robert Edwards, a reproductive physiologist, led the clinical and scientific work that facilitated Lesley and John Brownâs attempt to have a child. Steptoe and Edwards achieved instant international fame; Jean Purdy, a nurse and scientist, is now acknowledged as having been a crucial member of the team.2 In Kolkata, the key figure was Subhas Mukerji, a clinician, reproductive physiologist and endocrinologist. With colleagues Saroj Bhattacharya, an obstetrician and gynaecologist, Sunit Mukherjee, a cryobiologist, and two nurses unnamed in reports, he used laboratory and clinical techniques quite different from those of Steptoe, Edwards and Purdy.3
Remarkably, after decades of research and experimentation, two disparate sets of clinical and laboratory techniques in the UK and India succeeded within a few months of each other in producing a living child. In âa race in two different corners of the worldâ, the British team relied on Lesley Brownâs natural ovulatory cycle, using just one egg for fertilisation; Mukerjiâs used fertility drugs to increase the number of ova available for fertilisation.4 Where Patrick Steptoe used the surgical technique of laparoscopy to reach the sole egg, the Kolkata team used a transvaginal technique (colpotomy) to access multiple ova for laboratory fertilisation. The British team used a fresh embryo; Mukerji froze the embryos for fifty-three days prior to implanting three of them.5 These two teams came in ahead of other scientist-clinician groups in the United States and Australia, who had also been trying for years to facilitate a human IVF birth.6
Reports of both births went rapidly around the world, giving rise to excitement, apprehension and even, to varying degrees, scepticism about the authenticity of the claims. Colleagues peppered Steptoe and Edwards with requests for more clinical details before they would credit them with having achieved an IVF birth, some still expressing doubt years after the fact.7 Tragically, institutional scepticism led Subhas Mukerji to take his own life in 1981, after three years in which he had been unable to convince medical authorities of his claims, now vindicated, to have achieved IVF in India more or less concurrently with the British team.8
Today an estimated ten million people have been born following the use of IVF and assisted reproduction (AR).9 More than forty years after the first two births, providers have built on, modified or set aside the original successful techniques, creating new kinds of assisted reproductive treatment for an expanded range of clinical indications and fertility goals. As at 2018, the International Federation of Fertility Societies (IFFS) estimated that AR was available in 132 countries.10 In most countries with established programs, the proportion of AR births annually is around 1â4% of the total number of births.11 In Israel and Japan, the figure is closer to 5%, while in Denmark reports suggest around 10% of births result from some form of assisted reproduction.12 A significant proportion of AR offspring, perhaps as many as 50%, belong to sets of twins, triplets or even higher-order multiple births.13
An individual or a couple who want to obtain a child through AR can now create an embryo using either their own gametes (oocytes , ova or, colloquially, eggs, and sperm), or those of a donor provider, while clinics can source gametes and embryos from across the world.14 Someone about to undergo a major medical treatment or a gender transition can have gametes frozen in anticipation of later use, while women hoping to use their own eggs to become pregnant in the future can have oocytes removed, frozen and stored. Techniques of preimplantation genetic testing (PGT) of embryos extend AR to cases in which a potential child is at risk from a genetic or chromosomal defect.15 If people who seek a child through AR are ineligible to use a technique for legal reasons, or, if they find their local clinics in some way unsuitable, they might travel across borders for treatment. Regulatory differences resulting from âlaws and religious bans [and] denial of treatment to certain categories of personsâ, in particular, have been a major reason for people to opt for reproductive travel; cost and quality factors, as well as a desire for privacy, are among the others.16
According to the European Society of Human Reproduction and Embryology (ESHRE), one in six male-female couples will âexperience some form of infertility problem at least once during their reproductive lifetimeâ.17 Infertility can be the result of factors in the female, the male or both partners, while 10â20% of cases are unexplained, termed âidiopathic infertilityâ.18 These statistics relate to heterosexual couples, but infertility is now understood more broadly as the unmet desire to parent a child: sexual preference, marital status or an event such as early bereavement can lead people to seek AR. Several subcategories of infertility have at different times been identified, including primary infertilityâthe physical inability to establish a first clinical pregnancyâand secondary infertility, meaning the physical inability to establish a second or subsequent pregnancy.19 Subfertility, meaning a âreduced fertility with a prolonged time of unwanted non-conceptionâ, is now covered by the term âinfertilityâ.20 âSocial infertilityâ, arising principally from social factors, such as single status or a same-sex partnership, is a more contested but still widely used term.21
Assisted reproduction is expensive and âmore common in the rich worldâ.22 Denmark, for example, uses AR at twenty-eight times the rate per million of population than does India.23 The highest prevalence of infertility, however, is to be found in South Asia, sub-Saharan Africa, North Africa, the Middle East, Central and Eastern Europe, and Central Asia.24 In a place such as the United States, with high availability of AR treatment, âfertility financingâ schemes exist for the many clients without insurance support who are prepared to take out a debt to obtain treatment.25
A constellation of global fertility treatment âhotspotsâ reflects regulatory diversity, geographical suitability and recognised expertise. At present, Belgium is the go-to nation for the increasingly sought-after procedure of intracytoplasmic sperm injection (ICSI), a technique that has outstripped the use of IVF, originally being used for cases of male infertility but now often used instead of IVF. Spain and Romania are major sites for egg provision, and Denmark for sperm.26 The volatile surrogacy industry is constantly adapting to regulatory changes: India, Thailand, the United Arab Emirates (Dubai) and Mexico have been major fertility treatment destinations at different stages, but new laws have reduced treatment availability, notably for international visitors. In several well-publicised cases, women providing children through surrogacy, the children themselves and fertility clients have faced social dislocation when new laws have come into being.27 As some markets have shut down, they have left a vacuum that other markets try to fill.
There are around 6000 AR clinics currently in operation worldwide. India has the largest number, with an estimated 1500, but China, with fewer officially registered clinics, may provide more treatments than any other country.28 Israel has the highest number of clinics per head of population.29 In Japan, where there are 574 clinics, subsidies to AR patients reflect government fears about a declining national birth rate.30 High-end investment, high-tech products and international fertility companies are now standard for AR.31 International investment advisors expect that th...