IMMACULATE DECEPTION

Test tube baby techniques make many miracles. They also have horrific side effects and may leave you with some terrible choices.

Louise Brown-the world’s first test tube baby is more than l0 years old and so is “test tube” baby technology. In that time, the media has largely painted a pretty picture of “assisted conception”, as it is known in medical circles, as a brilliant breakthrough for the heretofore hopelessly infertile. Two hundred and fifty thousand British couples can benefit from these techniques, claims a report from the Interim Licensing Authority, created as a temporary body to monitor so called “test tube” baby clinics. And as the Human Fertilization and Embryology Bill becomes law, even more press is likely to be given to what is undoubtedly one of the miracles of modern science.As the percentage of infertile couples increases the latest estimates are that one out of every seven couples of childbearing age has trouble conceiving infertility drugs or techniques are becoming the first port of call for the childless.

But what your gynaecologist probably hasn’t told you about are the potential dangers of the drugs employed, the poor success rates of the techniques, the increased potential for abnormalities and perinatal deaths, and the terrible ethical considerations you may be faced with in undergoing any sort of assistance involving fertility drugs.

This edition of WDDTY reports on the various techniques that attempt to assist or in some cases improve upon nature, the problems you may face with them and some alternatives to consider before allowing medical science to be the stork.

According to conventional medicine, half of all infertility cases are caused by, on the woman’s side, mechanical problems (blocked tubes, for instance), menstrual problems (ie, failure to ovulate), endometriosis or polycystic ovaries, or, rarely, mucus that is hostile to sperm. In one third of cases, the problem is with the man’s sperm low count or motility, usually, or, rarely, an obstruction in the testes. In about a quarter of all cases, the cause is unexplained.

There are three main ways that medical science helps nature chemically:

In vitro fertilization (IVF), or embryo transfer, is supposed to be used when women have blocked tubes, sperm cannot manage to get through the cervical mucus or other conditions where sperm cannot unite with egg. This technique involves removing one or more eggs from the woman, fertilizing the eggs with her partner’s sperm outside the body in a petrie (shallow) laboratory dish and reinserting the embryos (fertilized egg) into the woman’s uterus.

GIFT (gamete intrafallopian transfer) is a means of giving nature a gentle nudge. Although eggs are removed from the woman and sperm from her partner, they are placed separately into the outer ends of the woman’s fallopian tubes. In this way, goes the theory, sperm of low motility won’t have so far to go as they would having to travel the long and precarious journey through a woman’s reproductive canal in order to make it to their target.

Fertility drugs, now used for some 20 years, are supposed to be offered only to women who have trouble ovulating. Drugs like Clomid or, in the States, Serophene (clomiphene citrate) work by blocking the production of oestrogen and fooling the brain into thinking the body is not ovulating. The brain then produces larger amounts of Follicle Stimulating Hormone (FSH) causing the ovaries to “superovulate”, often producing two, three or more eggs.

Although Louise Brown resulted from the reimplantation of a single fertilized egg, test tube pioneers Patrick Steptoe and Professor Bob Edwards then came up with an idea to improve what is ordinarily a low success rate. It stood to reason that woman’s chances of having the pregnancy “take” would improve if they put back more than one egg. (It would also save the cost and trouble of going through multiple treatments.) They then began offering women fertility drugs to make them “super ovulate” and produce more than one egg at a go, which they would return all at once. Drugs like Pergonal and Metrodin, which are even more potent than Clomid, produce anywhere from three to 30 eggs at a time.

“It is in stimulating women’s ovaries to produce more eggs that doctors have made one of the major breakthroughs in IVF treatment<" says an Independent leaflet "How to Choose a Test Tube Baby Clinic"< echoing the usual laudatory press view.

Those are the official reasons for using the various therapies. In practice, however, many of the more extreme measures are employed as a matter of course at the first sign that a couple is having a problem, and even before the nature of the fertility problem is sorted out, and despite the fact that many are known to have a low success rate.

The super ovulation fertility drugs tend to be handed out indiscriminately by GPs when a couple first reports that they’ve been trying without success. Naomi Pfeffer, author of The Experience of Infertility (Virago) and the Greater London Association of Community Health Councils’ leaflet (Infertility Services: A Desperate Case” says that most women complaining that they haven’t got pregnant are handed out a fertility drug even before they’ve been investigated. “What’s frightening,” says Ellen Grant, a consultant to preconception care group Foresight and author of The Bitter Pill, “is that consultants so used to seeing suppressed hormone levels that they are just given them out like candy.” This is despite the fact that in the view of experienced IVF specialist Michael Ah-Moye, medical director of Holly House Hospital, Clomid and other drugs “don’t have a very good success rate” other than with those clearcut cases in which the problem is the fact that the woman isn’t ovulating. Indeed, even the manufacturers of one of the drugs says that it is less effective after three goes and shouldn’t be used indefinitely: “If pregnancy has not been achieved after three ovulatory responses to Serophene, further treatment is not generally recommended.”

Fertility drugs are often given to men with low sperm counts, says Ah-Moye, even though most studies have shown they do very little good. “I rarely rarely given the drug to men unless they insist,” he says.

These fertility drugs are known to have substantial side effect many of which will affect your pregnancy or baby if you do get pregnant while taking them. Although doctors tend to describe the side effects of the fertility drugs are limited to hot flashes or abdominal discomfort, here’s what Swiss based pharmaceutical firm Serono, which has the corner on most fertility drugs, reports about Serophene in the America’s drugs bible, The Physician’s Desk Reference: blurred vision (for reasons they don’t understand), ovarian enlargement (in about l4 per cent of patients). This has particular repercussions for patients with endometriosis or ovarian cysts, as it will make the problem worse and possibly permanently affect fertility. Furthermore, says Serono, “maximum enlargement of the ovary. . . does not occur until several days” after discontinuation of the drug.

With super ovulation drugs like Metrodin, also produced by Serono, the drug company warns that its usage should be limited to those doctors “thoroughly” familiar with infertility problems. Besides ovarian enlargement, it also cases Ovarian Hyperstimulation Syndrome (OHSS), a serious medical problem causing a sudden increase in rapid accumulation of flue in the abdominal cavity, the thorax and even the sac surrounding the heart, requires immediate hospitalization. This situation can worsen if the patient is also pregnant. “With OHSS there is an increased risk of injury to the ovary,” says Serono in the PDR. “Pelvic examination may cause rupture of an ovarian cyst. “If this does occur, surgery may be necessary to remove the ovary and control bleeding. The manufacturer suggests that as much ovarian tissue be retained as possible.

If that isn’t enough to make you think twice before taking one of these drugs casually, Serono also warns of pulmonary and vascular complications like thrombosis in the veins or arteries which could result in heart attacks, stroke or even loss of a limb.

There’s also the risk of an ectopic (tubal) pregnancy, which of course results in the removal of an ovary.

These drugs can cause multiple births, fetal abnormalities and increased risks of perinatal deaths. Again, the media has published lots of photos of boisterous triplets with cheery captions about how fertility drugs have increased the incidence of twins, triplets and quads, and that formerly childless couples are suddenly having to cope with a house full of children.

There’s no doubt that these drugs increase your chances of having anything from twins to quints. In clinical trials with Metrodin, Serono reported multiple births with l7 per cent of pregnancies; with Serophene, l0 per cent were twins, less than l per cent triplets or higher. This percentage increases, depending upon the number of eggs replaced into the woman. A l988 study by the Interim Licensing Authority of all licensed fertility clinics the latest available reported that the overall multiple pregnancy rate for IVF in l988 was 24 per cent; and l9.9 per cent for GIFT. Nevertheless, the multiple pregnancy rate for GIFT increases to 3l.2 per cent when five or more eggs are replaced.

What the media doesn’t tell you is the increased risks your babies will face of being born prematurely or dying. According to a recently published major study by the Medical Research Council working party, which monitored l,58l IVF babies born since l98l, multiple births of all kinds, whether natural or assisted, carry greater risks. Of l,0l5 deliveries, 24 per cent were premature, compared with 6 per cent of all deliveries in England and Wales, and 32 per cent of l,269 babies weighed less than 5 and a half pounds, compared with 7 per cent of the population at large. The IVF babies had a 27.2 per cent perinatal mortality rate per l,000 births, compared with the 9.8 national average.

The working party claims that when allowances were made for the women’s ages and multiple births,this perinatal rate were similar to ordinary perinatal mortality rates, which isn’t very compensatory if they happen to be your babies.

The report also said there was an higher incidence of congenital malformations, such as anencephaly (a defect in the development of the brain and skull, which results in small or missing brain hemispheres). Serono reports that with studies of l803 births following Serophene, 45 infants with birth defects were reported, or 2.5 per cent (compared to a l.83 national rate in England and Wales for l988).

Merrell Down Pharmaceuticals, which manufactures Clomid in the UK, warns in the Data Sheet Compendium: “Although there is no evidence that Clomid has a harmful effect on the human foetus, there is evidence that Clomid has a deleterious effect on rate and rabbit foetuses when given in high doses to the pregnant animal.” In order to avoid taking the drug when you are pregnant, the company suggests that you record your basal body temperature every day that you are undergoing the treatment.

A multiple pregnancy also introduces a Abraham like decision for a mother killing off one or more fetuses so that the others may live. Because of the increased risk in multiple births, particularly for three or more embryos, some centres in the UK and on the continent quietly engage in what is euphemistically described as “embryo reduction” or, even more clinically neutral, “reducing the products of conception”. What this amounts to is “selective termination” of one or more of the healthy embryos in order to decrease the risk of all of them dying through an injection of saline.

Michael Ah-Moy knows of three centres in London, Kings College, the Chelsea Hospital for Women and also the Humana Hospital in Wellington, which handled some cases of fetal reduction, both for abnormalities but also to increase a couple’s chances of delivering a live baby. This dilemma becomes more likely with the higher number of eggs replaced inside the woman’s body.

For this reason, the Interim Licensing Authority recommends that only three and only in extraordinary circumstances, such as advanced maternal age four eggs be replaced. But such figures only apply to licensed units. Unlicensed units may put back as many embryos as they wish, and according to Ah-Moy, as of l990 there were 45 unlicensed units.

Many licensed centres also bend the rules. A Sunday Times article reported that the Monklands hospital in Scotland and the Cameron hospital in Hartlepool, Cleveland, would transfer up to six eggs in GIFT, depending on their quality and the woman’s age.

Naomi Pfeffer blames the practice of suing super ovulation drugs, which she feels aren’t as necessary as heretofore thought. “Women should not be faced with that choice. And what will it be like for a child to know that they’re there because of his sibling’s death. Or growing up knowing you’ve just missed the needle.”

There’s also recent evidence in The Lancet (l2 May l990) that embryo reduction may harm those fetuses left behind. “The obstetric outcome after pregnancy reduction in the first trimester is often complicated,” said the report, which cited a case of triplet embryos “reduced” by one. An ultrasound scan revealed that one of the remaining twins had developed an anencephaly like malformation, after which he got the needle, too. The single baby resulting was born healthy and normal at 39 weeks. The same occurred with a quadruplet pregnancy, after “a twin pregnancy was achieved as in the first case”. (Note, again, the strict avoidance of emotive language.) One of the surviving twins also was found to have an anencephaly like malformation, and he got knocked off, after which the only survivor was delivered premature at 32 weeks.

Considering that GIFT and IVF still carry a low success rate (only about 20 per cent) and are only indicated for about 20 per cent of infertile couples, and carry such high risks, anyone faced with a fertility problem should consider it the court of last resort. Furthermore, organizations like Foresight (see box) and the doctors they work with claim that a large number of “unexplained” fertility problems and even blockages or low sperm counts, though to be untreatable, can be resolved if a couple improves their nutritional status and resolves any allergies. Foresight is not the answer to everyone’s problems, but their programme is a lot safer and cheaper as a first investigation when you’ve tried to get pregnant and can’t.

one egg at a go, which they would return Metrodin, which are even more potent than Clomid, produce anywhere from three to 30 eggs at a time.

“It is in stimulating women’s ovaries to produce more eggs that doctors have made one of the major breakthroughs in IVF treatment,” says an Independent leaflet “How to Choose a Test Tube Baby Clinic”, echoing the usual laudatory press view.

Those are the official reasons for using the various therapies. In practice, however, many of the more extreme measures are employed as a matter of course at the first sign that a couple is having a problem, even before the nature of the fertility problem is sorted out and despite the fact that many are known to have a low success rate.

Fertility drugs tend to be handed out indiscriminately by GPs when a couple first report that they’ve been trying without success. Naomi Pfeffer, author of The Experience of Infertility (Virago) and the Greater London Association of Community Health Councils’ leaflet “Infertility Services: A Desperate Case”, says that most women complaining that they haven’t got pregnant are given a fertility drug even before they’ve been investigated. “What’s frightening,” says Ellen Grant, a consultant to preconception care group Foresight and author of The Bitter Pill, “is that consultants are so used to seeing suppressed hormone levels that they are just giving them out like candy.” This is despite the fact that in the view of experienced IVF specialist Michael Ah-Moye, medical director of Holly House Hospital in Essex, Clomid and other drugs “don’t have a very good success rate” other than with those clearcut cases in which the problem is ovulation. Indeed, even the manufacturer of one of the drugs says that it is less effective after three goes and shouldn’t be used indefinitely: “If pregnancy has not been achieved after three ovulatory responses to Serophene, further treatment is not generally recommended.”

Fertility drugs are often given to men with low sperm counts, says Ah-Moye, even though most studies have shown they do very little good. “I rarely give the drug to men unless they insist,” he says.

These fertility drugs are known to have substantial side effects many of which will affect your pregnancy or baby if you do get pregnant while taking them. Although doctors claim the side effects are limited to hot flushes or abdominal discomfort, Swiss based pharmaceutical firm Serono, which has the corner on most fertility drugs, reports in the American drugs bible, The Physician’s Desk Reference, that Serophene also causes blurred vision (for reasons they don’t understand)and ovarian enlargement (in about l4 per cent of patients). This has particular repercussions for patients with endometriosis or ovarian cysts, as it will make the problem worse and possibly permanently affect fertility. Furthermore, says Serono, “maximum enlargement of the ovary. . . does not occur until several days” after discontinuation of the drug.

“With OHSS there is an increased risk of injury to the ovary,” says Serono in the PDR. “Pelvic examination may cause rupture of an ovarian cyst.” If this does occur, surgery may be necessary to remove the ovary and control bleeding.

There’s also the risk of an ectopic (tubal) pregnancy, which can often result in the removal of an ovary.

These drugs may cause multiple births, foetal abnormalities and increased risks of perinatal deaths. Again, the media has published lots of photos of boisterous triplets with cheery captions about how formerly childless couples are suddenly having to cope with a house full of children.

There’s no doubt that these drugs increase your chances of having anything from twins to quins. In clinical trials with Metrodin, Serono reported multiple births with l7 per cent of pregnancies; with Serophene, l0 per cent were twins, less than l per cent triplets or higher. This percentage increases, depending upon the number of eggs replaced into the woman. A l988 study by the Interim Licensing Authority of all licensed fertility clinics the latest available reported that the overall multiple pregnancy rate for IVF in l988 was 24 per cent; and l9.9 per cent for GIFT. Nevertheless, the multiple pregnancy rate for GIFT increases to 3l.2 per cent when five or more eggs are replaced.

The working party claims that when allowances were made for the women’s ages and multiple births, this perinatal rate is similar to ordinary perinatal mortality rates, which isn’t very compensatory if they happen to be your babies.

The report also said there was a higher incidence of congenital malformations, such as anencephaly (a defect in the development of the brain and skull, which results in small or missing brain hemispheres). Serono reports that with studies of l803 births following Serophene, 45 infants with birth defects were reported, or 2.5 per cent (compared to a l.83 national rate in England and Wales for l988).

Merrell Dow Pharmaceuticals, which manufactures Clomid in the UK, warns in the Data Sheet Compendium: “Although there is no evidence that Clomid has a harmful effect on the human foetus, there is evidence that Clomid has a deleterious effect on rat and rabbit foetuses when given in high doses to the pregnant animal.”

A multiple pregnancy also introduces an Abraham like decision for a mother killing off one or more foetuses so that the others may live. Because of the increased risk in multiple births, particularly for three or more embryos, some centres in the UK and on the continent quietly engage in what is euphemistically described as “embryo reduction” or, even more clinically neutral, “reducing the products of conception”. What this amounts to is “selective termination” of one or more of the healthy embryos through an injection of saline in order to decrease the risk of all of them dying.

Michael Ah-Moye knows of three centres which handled some cases of foetal reduction, both for abnormalities but also to increase a couple’s chances of delivering a live baby. This dilemma becomes more likely with the higher number of eggs replaced inside the woman’s body.

Many centres also bend the rules. A Sunday Times article reported that the Monklands hospital in Scotland and the Cameron hospital in Hartlepool, Cleveland, would transfer up to six eggs in GIFT, depending on their quality and the woman’s age.

Naomi Pfeffer blames the practice of using super ovulation drugs, which she feels aren’t necessary in IVF. “Women should not be faced with that choice. And what will it be like for a child to know that he’s there because of his sibling’s death? Or growing up knowing you’ve just missed the needle.”

There’s also recent evidence in The Lancet (l2 May l990) that embryo reduction may harm those foetuses left behind. “The obstetric outcome after pregnancy reduction in the first trimester is often complicated,” said the report, which cited a case of triplet embryos “reduced” by one. An ultrasound scan revealed that one of the remaining twins had developed an anencephaly like malformation, after which he got the needle, too. The single baby resulting was born healthy and normal at 39 weeks.

The same occurred with a quadruplet pregnancy, after “a twin pregnancy was achieved as in the first case”. (Note, again, the strict avoidance of emotive language.)

One of the surviving twins also was found to have an anencephaly like malformation, and he got the chop, after which the only survivor was delivered premature at 32 weeks. Considering that GIFT and IVF still carry a low success rate (only about 20 per cent) are only indicated for about 20 per cent of infertile couples, and carry such high risks, anyone faced with a fertility problem should consider them the court of last resort. Furthermore, organizations like Foresight (see box) and the doctors they work with claim that a large number of “unexplained” fertility problems and even blockages or low sperm counts, thought to be untreatable, can be resolved if a couple improves their nutritional status and resolves any allergies. Foresight is not the answer to everyone’s problems, but their programme is a lot safer as a first investigation when you’ve tried to get pregnant and can’t.