Like a Virgin

by Prasad, Aarathi

  The first authenticated case of artificial insemination was performed successfully about three hundred years later, around 1776. In this revolutionary year the renowned surgeon and human dissector John Hunter was approached by a ‘linen draper in the Strand’ of central London who came to consult him because of a deformity of his penis. The draper suffered from hypospadias, in which the opening of his urethra, from which a man would normally ejaculate semen, was in a position on his penis from which his sperm could not physically make it into his wife – the same condition that likely afflicted King Henry II (and his bride Catherine de Medici). Hunter armed his patient with a syringe, and advised him to use it to collect his semen after sex and inject its contents directly into his wife, while she would be most receptive. Presumably Hunter felt she would be more open to having a syringe inserted into her vagina around that time, but he may also have suspected that this moment would give the semen (and its sperm) a better chance of making its way well into the uterus. It was a simple but effective intervention. The wife became pregnant, and the baby was born healthy.

  Such hit-or-miss attempts were always in demand, though they were not always scrupulous. We have records of a French doctor by the name of Girault, who in 1838 used a hollow tube to blow sperm into the vaginas of infertile men’s wives. Another French doctor was forced by public disapproval to cease similar attempts to impregnate women artificially. After the American Civil War, James Marion Sims – credited as the father of American gynaecology – reported his own attempts at artificial insemination, in which he injected sperm past the vagina, directly into the womb.

  Sims had a reputation for medical miracles: he was also known for curing crossed eyes, clubbed feet, and a debilitating condition called vesico-vaginal fistulae (VVF), which affects women. VVF is a trauma commonly associated with a prolonged, obstructed labour, during which the baby’s head puts pressure on the tissue that normally forms a barrier between the mother’s vagina and her bladder. If the baby gets stuck and remains in this position too long, this tissue can be destroyed, and a hole opens between the vagina and the bladder. This often leads to constant, uncontrollable urinary incontinence – a debilitating situation, physically and emotionally. In Sims’s day, women with the condition were likely to become social outcasts. In his efforts to find a surgical solution to this problem, between 1845 and 1849 he carried out a series of operations on black slave women. In that day, any woman with VVF would probably have accepted the slimmest of chances to be rid of it, so the slaves he operated on may well have been consenting; however, anaesthesia had only recently been discovered, and some accounts say he performed what must have been incredibly painful procedures on the slaves without the anaesthetic that he later used with his white patients. The alleged practice has left his medical legacy in something of an ethical limbo.

  Regardless, Sims published his definitive work on women’s reproduction and ‘uterine surgery’ in 1866. In it, he also logged the fifty-five artificial inseminations he had conducted on six different patients using sperm from their husbands. Bypassing the vagina to put seminal fluid directly into the womb was excruciating for the patient; Sims himself states that his earliest insemination experiments were ‘often more painful than any operation’. Half of his attempts he considered to be utter failures, and only once did he achieve a pregnancy. Sims’s poor results probably had less to do with his technique than with the era’s limited knowledge about menstruation, and about where in a woman’s body conception actually happened. It was truly a guessing game. Unfortunately, the only time Sims guessed right and managed a successful artificial insemination, the woman miscarried, having experienced a ‘fall and a fright’ when she was four months into her pregnancy. The twenty-eight-year-old patient had undergone Sims’s procedure ten times. After that twist of fate, the doctor wrote, he gave up the practice altogether.

  Other doctors forged ahead, however. To test the limits of artificial insemination, they soon began to turn to donors, breaking from the tradition of exclusively using sperm from a woman’s husband. The world’s first case of such donor insemination was performed in 1884 by Professor William Pancoast, who was based at Philadelphia’s Jefferson Medical College. Pancoast used a hard rubber syringe to insert sperm donated by one of his medical students, whom he had judged to be the best-looking of the bunch. His patient, a woman who had been anaesthetized prior to the insemination, was unaware that Pancoast had even performed the procedure, and then, when her infertile husband was made aware of Pancoast’s procedure, the doctor instructed him never to tell her about the day’s events. Their son was never told the circumstances of his birth either. Only the medical archives have given the story to us.

  At the time, the thought of using ‘alien’ semen shocked many people. In the nineteenth century, the idea of sperm banks had inflamed the imagination of doctors and the public alike; as early as 1870, there was speculation that soon there would be places where you could buy the semen of a ‘thirty-year-old blond with black eyes’ or a nineteen-year-old virgin. These were not considered to be happy developments. This attitude persisted for decades – at least until the 1940s in the US, and into the 1970s in Australia, and was only supplanted after the first professional sperm banks were launched in these countries. Indeed, in Pancoast’s day, there were still so many dissenters opposed to impregnating a woman using sperm that was not her husband’s that he kept his work secret until his death, and it was only revealed in 1909. In fact, the obituary for him, printed in the New York Times on 6 January 1897, made no mention of his innovations in this field. Instead, he was remembered as the surgeon who performed the autopsy of Chang and Eng Bunker, the conjoined ‘Siamese twins’ who had been exhibited in Victorian freak shows nearly seventy years earlier.

  A contemporary of Pancoast’s working in Austria, Professor Leopold Schenck, decided to go one better. In a Petri dish, he mixed together the sperm and egg of rabbits in an attempt at developing a rabbit embryo – something close to in vitro fertilization proper. But Schenck never succeeded in making bunnies, let alone babies. His clinic instead became renowned for a different speciality: that he could influence the sex of a baby, as its parents desired. And for this, he was in great demand. So much so that in 1898, a visiting American doctor barely gained entrance to Schenck’s Parisian surgery. On a trip to Paris, Dr Victor Neesen, who was visiting from Brooklyn, noted, ‘When I called at Dr Schenck’s house I found the street blocked with carriages of all descriptions. A group of well-dressed people stood on the stoop of the house, waiting to be admitted. The anterooms were crowded to suffocation with visitors, most of them women, richly attired and genteel looking, all waiting to consult the professor.’

  Though there were those who objected on moral grounds, there was evidently quite a strong appetite for all sorts of reproductive manipulation. As long as it happened inside the body, and not in a test tube.

  Not surprisingly then, there was huge public interest in the first IVF baby. Before the birth of Louise Joy Brown was announced in the summer of 1978, the Oldham and District General Hospital enlisted a guard dog as backup to its usual entourage of security guards, to ensure that mum and baby could avoid the paparazzi and get some much-needed rest. Still, journalists besieged the hospital’s maternity unit. It was suspected that the tabloids may have even faked a bomb scare, in efforts to snap a photo of an exhausted Lesley Brown as she left the building.

  There had been a long wait for the child that many referred to as ‘our’ baby. The animal research into the potential for IVF had been encouraging, but there were fears that the process would not work in humans, or that terrible abnormalities would result. When Lesley and John Brown arrived in the office of Dr Patrick Steptoe at Oldham General Hospital outside of Manchester, they had nearly given up hope. Steptoe and the Cambridge physiologist Robert Edwards had been investigating options for fertilizing eggs outside the womb since the mid-1960s, but the eighty pregnancies they had managed had only lasted a few weeks before spontan
eously aborting. After extracting an egg from Lesley and fertilizing it with John’s sperm, they watched it divide into more cells – and they took a gamble. Rather than waiting four or five days, as they had in the past, they injected the fertilized egg into Lesley’s womb two days later. The egg attached itself to the uterus wall without any difficulties.

  Once news of the pregnancy leaked to the media, Lesley was forced into hiding. The press were chasing her all over Bristol, where she lived, and Edwards and Steptoe were concerned that she might lose the baby from the stress. Eventually, Steptoe drove Lesley to his mother’s house in Lincoln. For the rest of the pregnancy, the press could not uncover where she was.

  For weeks, things seemed to go well. Then, near to her due date, Lesley’s blood pressure spiked. The doctors chose to deliver the baby early, rather than risk complications from natural labour. ‘There were many times in the last ten years when we wondered if we would ever see that baby,’ one of the team of doctors who had been working with Steptoe and Edwards on IVF later told the BBC. On the night of Louise’s delivery, there was a buzz in the air. Some of the medical staff had even drawn lots to be present at the history-making birth.

  Louise may have been the first ‘superbabe’, but she was not to be the only one – even as she was born, there were reports of other mothers who were already pregnant using the new technology. By 1979, two more ‘test tube’ babies were born in the UK. The next year, Australia greeted its first IVF birth, with the United States matching this feat the year after that. Between 1978 and 1999, fifty thousand IVF babies were born in the UK, and more than four million worldwide. Each year, around eleven thousand IVF babies are now born in the UK, and around forty thousand in the US.

  It may seem strange, but the world’s first IVF baby was also a spur to much ideological controversy. As with some views about human cloning today, many then (as some still do now) felt that creating life ‘in a test tube’ was unnatural; they believed that conception was supposed to happen through biological sex – and sex between married partners, to be quite precise. Among those opposing IVF was the Catholic Church. ‘The fact that science now has the ability to alter this does not mean that, morally speaking, it has the right to do so,’ the general secretary of the National Conference of Catholic Bishops told the Washington Post. But reaction was mixed, and the Church’s sentiment was not wholly embraced by the public. A Gallup poll taken shortly after Louise’s birth attested that sixty percent of people favoured the new technology, because it would make children possible for those couples who would otherwise be unable to have them – a clear majority, but not an overwhelming one.

  Yet, for the five thousand or so childless couples who promptly signed up for the new technology, IVF couldn’t have come soon enough. Here was a dramatic addition to the arsenal against infertility, one that could make them parents, even if biology was against them.

  Today, assisted reproductive technology, or ART, involves far more than IVF, and includes any procedure in which eggs, sperm, or embryos are manipulated in vitro. Around one in six couples will seek medical assistance because they are having difficulty conceiving a child, and only about one in ten who consult a doctor will go on to use IVF. This is because, though it is probably the most widely discussed reproductive technology, IVF is not the only, or the first, choice when a problem with fertility is diagnosed.

  For instance, many couples will turn to induced ovulation, where a woman is treated with hormones to stimulate her ovaries to release eggs. While the ovaries are being manipulated through biochemistry, a couple may conceive merely by timing their sex; they know when the woman’s egg should be triggered for release by the hormone soup she’s taking. That’s much better than guessing.

  For couples with unexplained infertility, induced ovulation is sometimes accompanied with intra uterine insemination, or IUI, which can help to get underperforming sperm or eggs in the same place, at the same time. In IUI, semen is first processed in the lab, so that only sperm that are moving can be selected. These ‘good’ – or, at least, somewhat mobile – sperm are then delivered directly into the womb, near where the egg is preparing itself to be fertilized, bypassing the hazards that might assault them in the vagina and cervix, namely, unfavourable pH environment and tricky-to-navigate mucus. The vast majority of sperm are normally killed somewhere en route. Among couples with no clear fertility dysfunction, there seems to be a significantly higher chance of a successful pregnancy when IUI is used with ovarian stimulation rather than on its own, although simply having sex at the right time, which is much easier to pinpoint with ovarian stimulation, might work just as well.

  It may also be the case, as with Lesley Brown, that the reason a woman cannot get pregnant is because there is a blockage in her Fallopian tubes, the two passages that connect the ovaries to the womb. If this is the problem, a woman might choose to have surgery to unblock the tubes. But if this fails, or if the woman is already in her mid- to late thirties, when the biological clock is ticking away, IVF may indeed be the best bet.

  In IVF, an egg is extracted from a woman and incubated with around fifty thousand sperm. The in vitro part of IVF literally means ‘within glass’, because it originally referred to the fact that the experiments were performed in glassware, which was commonly used in labs instead of plastic. (This is in opposition to ‘in vivo’ fertilization, which comes from the Latin for ‘within the living’.) Fertilization in vitro thus means that the egg and sperm are effectively left to mingle and ‘introduce themselves’ in a specially created, artificial environment, something like a speed-dating night. With the plethora of obstacles in its way safely removed, a sperm can make a direct hit on the egg – as long as it can beat its competitors to it. It follows from the particulars of the set-up that for men whose sperm cannot move properly to the egg or penetrate it to begin fertilization, IVF may simply not work.

  By the late 1980s, fertility doctors had found a way to solve this matchmaking problem, without having to resort to donor sperm. Several techniques emerged that could improve an infertile man’s chances of making a baby, with one frontrunner quickly establishing itself: intra-cytoplasmic sperm injection, or ICSI. Like IVF, ICSI does not correct defects in the sperm, but it requires a much smaller number of sperm: instead of fifty thousand sperm, just one will do. ICSI does not leave fertilization to chance. This single sperm – possibly immobile, but otherwise picked for its ‘good looks’ – is first stunned, for example by rubbing its tail. It is next sucked up, tail first, into a sharp-tipped glass pipette and injected directly into an egg. Or, instead of a whole sperm, the doctor can pluck just a single sperm head or nucleus, containing the DNA that provides all the necessary genetic instructions for making a baby – the rest of the sperm is simply a vehicle to get the male DNA into an egg.

  Neither IVF nor ICSI are without limitations – their success rates are, at best, only around thirty percent. These remain techniques for assisting natural reproduction, not for replacing it.

  But as the use of ART increases worldwide, it is certainly also important to consider some potential long-term consequences. For a start, in both IVF and ICSI, eggs need to be removed from a woman in order to ensure sperm access to them. But eggs are tucked away in the ovaries, and released only infrequently following a biological programme, which makes them far trickier to acquire than sperm. To harvest her eggs, the doctor places the patient under local anaesthetic, and then, guided by ultrasound, passes a long, thin needle through her vagina to the ovaries. The needle is used to suck the fluid out of mature follicles, or egg-containing sacs. If an egg happens to be retrieved with this fluid, it is gingerly removed and tucked into an incubator. And then the process is repeated, until several more eggs join it.

  This process of extracting eggs is not just invasive; it carries very real health risks as well. To persuade the ovaries to release multiple eggs from their grip, these organs must be stimulated with a suite of hormones that the body itself uses for that purpose, but often at hi
gher than normal doses. These include a drug to stop eggs from being released until they are mature (a gonadotropin-releasing hormone, or GnRH, agonist or antagonist; a follicle-stimulating hormone, or FSH, that kick-starts the development of multiple eggs; and human chorionic gonatotropin hormone, or HCG, which forces the eggs to mature properly (and is the hormone that causes over-the-counter tests to test positive for pregnancy). Without stimulating medications, the ovaries generally produce one egg a month. With them, they churn out anywhere from five to twenty-five eggs that might be harvested, and some young women have been reported to produce fifty to seventy eggs from one high-dose stimulation. This sounds like good news, but this stimulation can cause severe ovarian hyperstimulation syndrome, or OHSS – most likely as a result of too high a dose of HCG. When OHSS sets in, the woman’s blood vessels become much more permeable than they should be. This leads to a drop in blood volume, so that her blood thickens. It can lead to organ failure, and is a life-threatening condition.