The Risks to the Life and Health of Children Conceived using Assisted Reproductive Technologies by Patrick Carr

The Risks to the Life and Health of Children Conceived using Assisted Reproductive Technologies

The birth of Louise Brown, the first baby to be born as a result of in vitro fertilization, on 25^th July, 1978, had the effect of silencing much of the debate which had raged over this procedure for years while it was being developed. [1] To all appearances, those who had warned of the appalling consequences of tampering with the origin of human life had been proved wrong by the birth of this normal, healthy baby girl. In the quarter century since then, assisted reproductive technology (ART) has grown to become a billion-dollar industry. In the year 2000, over 35,000 births in the United States of America were the result of ART, representing a full 1% of all births. Several recent studies, however, have contributed to a growing body of evidence indicating that the enthusiastic confidence inspired by the birth of Louise Brown was misplaced, and that children born as a result of the various forms of ART may be exposed to a significantly increased risk of suffering from major birth defects.

The increased risk of major birth defects, of course, applies only to those babies who survive to birth. The number of live births represents only 25% of the embryos which are implanted in their mothers’ wombs using the various forms of ART. The other 75% were “unsuccessful attempts”; in other words they died in the course of the treatment. Even this rather poor success rate fails to take account of the many thousands of human embryos which are created every year in order to facilitate these procedures only to be frozen and left indefinitely in a state of suspended animation. At the time of writing there are in excess of 400,000 embryos in this condition in the United States and the figure is rising.

I will attempt in this paper to summarize the various scientific studies that show that babies born as a result of ART suffer from a significantly heightened risk of being afflicted with major birth defects. I will consider too the plight of those embryos which are ‘surplus to requirement’ as well as the broader perils to which all of the embryos involved are exposed. I will then consider the question whether, in the light of the risks to the life and safety of the unborn child, it is morally justifiable to continue with these procedures. This of course prescinds from the question whether generating human life outside the marital act is intrinsically evil, but those who fail to recognise its intrinsic evil may be persuaded to avoid these procedures by the evidence of the risks involved.

The first study [2], carried out in Western Australia, examined children born between 1993 and 1997 and sought to determine whether and to what extent birth defects were more common in children conceived by two methods of assisted reproductive technology – intracytoplasmic sperm injection and in vitro fertilization – than in children conceived naturally. The study was based on those birth defects which were diagnosed by one year of age and which are generally categorized as ‘major’ defects.

Hansen et al. acknowledge that previous studies have not generally suggested that there is an increased risk of major birth defects in children conceived using ART. They point out, however, that much of this earlier research has been subject to various methodological problems such as inadequate sample size and a lack of suitable comparative data. Their study was designed to avoid such problems. Previous studies had also used different criteria to define major birth defects in ART births from the criteria used in the case of natural births. This study takes a random sample of 4,000 naturally conceived births and compares it with the ART births in the same period and area (which numbered 1,138). All births at twenty weeks gestation or later were included as were all pregnancies which were ended by abortion because of fetal abnormality. Internationally recognized criteria were used to classify birth defects as major or minor. The researchers took precautions to ensure that the results were not distorted by an over-reporting of the birth defects affecting ART births, which might result from the fact that these babies might be subject to more thorough surveillance for medical problems.

The study found that infants conceived with artificial reproductive technology were more likely to be delivered by Caesarean section, to have a low birth weight and to be born before term. When multiple births were excluded this increased likelihood was of a significant order. Of the infants conceived by intracytoplasmic sperm injection, 8.6% had a major birth defect diagnosed in their first year. Of those conceived by in vitro fertilization the percentage was similar (9%). Of those who were conceived naturally the incidence of major birth defects diagnosed in the first year was only 4.2%. Overall, the study showed that infants conceived as a result of ART were more than twice as likely to have a major birth defect than naturally conceived infants. Various different analyses of the data produced similar results.

Of the various birth defects diagnosed, those which showed the most marked increase in prevalence among infants conceived as a result of ART were musculo-skeletal disorders (three times more likely) and chromosomal defects (almost four times more likely). Those conceived by in vitro fertilization were also found to have a significantly increased prevalence of cardio-vascular, uro-genital and other defects. The infants conceived by ART were also found to be significantly more likely to have multiple major defects. The overall conclusion of the study was that infants conceived with use of intracytoplasmic sperm injection or in vitro fertilization have twice as high a risk of a major birth defect as naturally conceived infants do.

The second study [3] to be considered examined the prevalence of low and very low birth weight in infants conceived with the use of ART. This fact, which had been previously acknowledged, had generally been attributed to the greatly increased frequency of multiple births arising from the use of ART. (It is standard practice to implant multiple embryos to increase the chance of a successful pregnancy.) By 1997 the use of ART accounted for more than 40% of triplets born in the United States. This American study by Schieve et al. sought to determine whether this was the only factor or whether other factors were relevant. The study examined a very large sample of 42,463 infants born in 1996 and 1997 who were conceived by the use of ART and compared them with over 3.3 million infants born in the United States in 1997. Previous studies on this question had been subject to certain problems which Schieve et al. sought to avoid. These earlier studies had failed, for instance, to distinguish among singleton births between those who were conceived singly and those who had been conceived as part of multiple gestations which had subsequently been reduced either spontaneously or by direct abortion. Other problems with previous studies were their limited sample sizes and their failure to consider whether the low birth weight was a direct result of the ART procedures or rather due to the underlying infertility problems which had led to the use of ART.

The study considered a multiplicity of factors which might account for low (less than or equal to 2.5 kilograms) and very low (less than 1.5 kilograms) birth weight, and subjected the data to appropriate analysis to allow for these factors. Such factors included the age of the mother, whether she had previous children, the gestational age at delivery, the type of procedure employed (e.g. whether fresh or frozen embryos were used), and whether the underlying infertility problem was in the father or the mother. In short, any factor which might reasonably be expected to affect the birth weight was considered and taken into account. None of these factors explained the underlying increased risk of low or very low birth rate found in infants conceived as a result of ART.

The study reached the unavoidable conclusion that the increased risk of low or very low birth weight in singleton infants born at term seems to be directly related to the use of ART. One of the specific factors suggested as a possible cause of low birth weight resulting from the use of ART is the use of human menopausal gonadotropin which “has been associated with increases in insulin-like growth factor-binding protein 1; this protein has been linked to intrauterine growth restriction.” [4]. Abnormal levels of other endometrial proteins and structural abnormalities in the placenta have also been found to result from the use of ART. These may also be factors causing growth restriction.

The study found no significant increase in risk of low or very low birth weight in multiple births resulting from ART. Multiple births even from natural conceptions have an increased risk. It was rather in the case of singleton births that the increased risk seemed to be linked directly to the use of ART. The researchers found that more than 3% of low birth weight infants and more than 4% of very low birth weight infants were conceived by the use of ART. This is six times as high as would be expected on the basis of the frequency of the use of these technologies. Most of this disparity is attributable to the higher incidence of multiple births. Nevertheless it is in the increased incidence of low birth weight in singletons that the direct influence of the use of assisted reproductive technologies may be attributed. In these cases the risk to infants conceived by use of such technologies was found to be 2.6 times that of other infants. This is a significant increase in risk.

It is worth noting that low birth weight is not simply an inconsequential feature since such infants are at increased risk of disabilities, both short-term and long-term, including breathing difficulties, developmental problems, and even death.

Other studies have turned up similarly worrying findings. In January of 2003 a report [5] was published which showed that Beckwith-Wiedemann syndrome (BWS) was four to six times as prevalent among children who had been conceived as a result of ART as it was among those conceived naturally. This syndrome can cause the tongue and internal organs to be abnormally large, causing high birth weight. It also increases the risk of certain cancers including Wilm’s tumour, hepatoblastoma, and neuroblastoma. The condition is caused by epigenetic changes – affecting the gene other than in the DNA sequence - causing abnormal genetic imprinting. The same month a small-scale Dutch study [6] was published which suggested a link between ART and the childhood condition retinoblastoma (a malignant tumour affecting the retina). The study indicated that the use of IVF may cause an increased risk of the order of five- to seven-fold. This possible link would seem to merit a larger scale study. Other reports [7] link ART with urological birth defects and Angelman syndrome.

It would seem that there is sufficient evidence at the very least to place the burden of proof on those who advocate these technologies. The accumulation of research pointing to dangerous consequences of the various forms of ART has prompted the Genetics and Public Policy Center at Johns Hopkins University to collaborate with the American Society for Reproductive Medicine and the American Academy of Pediatrics to form a panel of experts to assess the evidence to date. Despite the tendency of the evidence to inculpate ART and the alarming results described above, the reaction of the medical establishment has typically been to downplay the significance of what these studies show. The press release issued by the Office of Communications and Public Affairs of the Johns Hopkins Medical Institutions concerning the BWS study expresses the opinion of the researchers that “the results should stimulate further investigation, not change parents’ decisions.” [8] Dr. Arnold Strauss, Chief of Paediatrics at Vanderbilt University Medical Center in Nashville (who is one of the panel of experts who will be reviewing the evidence on this question) is quoted as describing it as “really a question of subtlety and small differences.” [9] In a commentary in The Lancet on the Dutch study, Dr. David BenEzra, of the Hadassah Hebrew University Hospital in Jerusalem, while recognizing the need for further research and an open debate on the findings, concludes with his concern “to minimize potential harmful effects of unfounded and potentially misleading information.” [10] The predominant concern seems to be to avoid alarming potential customers.

So far we have considered only the plight of those embryos who are implanted in the wombs of the women who are to carry them to birth (who may not be their biological mothers). There is, however, another group of human subjects whose predicament is worthy of attention. In the course of performing the ART procedures large numbers of human embryos are fertilized in laboratories, many of whom will never be implanted in a womb and allowed the precarious possibility of growing and being born. ART makes possible a variety of unprecedented, and indeed hitherto unimaginable, situations. Never before has it been possible to share a womb with a sibling who is not your twin (or triplet etc.) in the proper sense, or indeed with a complete stranger who is quite unrelated. The most baleful situation, however, which ART has made possible and all too common is that of the human embryo who is fertilized in a petri dish, is surplus to present requirements and is frozen against the chance that he may some day be wanted (or used for research or to provide ‘spare parts’). It is believed by those who practice ART that the length of time that an embryo remains frozen does not affect its chances of successfully implanting once it is thawed, [11] so in theory these embryos could be kept in suspended animation indefinitely. It was not without reason that the French geneticist, Jerome Lejeune, described these embryos as being held captive in concentration cans. [12] The process of freezing these embryos involves first their dehydration and the replacement of their natural fluids with a chemical. The purpose of this chemical is to avoid the formation of intracellular ice. [13] In effect what happens to this tiny human person is that each cell in his body is separated (by the cryoprotectant chemical) from the rest. Remarkably, some embryos survive this procedure, which would certainly kill them if they were any older. [14]

If the embryos in question are human persons, and I hold that they must be[15], it seems clear that the process of freezing them (which involves effectively atomizing them), holding them captive for an indeterminate time and then thawing them is a grotesque violation of their bodily and personal integrity. Those who practice these techniques generally regard the embryos which they manipulate as raw material, or at best, products which they are free to treat as they please with impunity. The practice of pre-implantation genetic diagnosis, which involves the removal of one cell from the embryo for analysis (a form of ‘quality control’) is a clear indication of the way in which these embryos are regarded as products, rather than tiny human persons.

There are many strong arguments for the case that using assisted reproductive technologies is something that one ought not to do which are outside the scope of the present paper. [16] Our concern here is specifically with the increased risk to which the child who is to be born as a result of these technologies is exposed. The question is whether, if these technologies were otherwise unobjectionable, could one morally expose the child to be born to the significantly increased risk of death or disability involved. It seems that one could since, in this purely hypothetical situation, there would be no moral difference between a couple who sought to conceive using these technologies and a couple who sought to conceive naturally but who knew that they carried an hereditary disease that their child might suffer from. In this latter case the couple would have just cause to avoid getting pregnant by practicing periodic abstinence, but if they chose to conceive, the good of the life of the child to be born would still be a great good, even if his life were burdened by an inherited disability. [17] However, the child who suffers as a result of the use of ART suffers precisely as a result of the means used to generate him, whereas a naturally conceived child with an inherited disability suffers not as a result of the means used to generate him (the marital act), but, as it were, from nature.

However, this hypothesis is based on the assumption that there is no other reason not to use ART. As there are, in fact, a number of compelling reasons not to do this, the increased risk to which the child would be exposed, while not in itself a sufficient reason, constitutes an additional reason. In conjunction with the other reasons why one ought not to conceive a child other than through the marital act, the significant risk to which that child would be exposed, which I hope this paper has demonstrated, would add further to the fundamental injustice which is done to such a child, and would make the question subject to the same moral norms which prohibit proxy consent for non-therapeutic experimentation on others where they would be exposed to significant risk.

Byrd, William, ‘Cryopreservation, Thawing, and Transfer of Human Embryos’ in Seminars in Reproductive Medicine, 20 (1), Feb. 2002, 37-43

Hansen, Michèle, Kurincuk, Jennifer J., Bower, Carol, & Webb, Sandra, ‘The Risk of Major Birth Defects After Intracytoplasmic Sperm Injection and In Vitro Fertilization’ in The New England Journal of Medicine, 2002 Vol. 346, 725-30.

Kolibianakis, E.M., Zikopoulos, K., & Devroey, P., ‘Implantation Potential and Clinical Impact of Cryopreservation – A Review’ in Placenta 24, Suppl. 2, Oct. 2003, S27-S33

May, William E., Catholic Bioethics and the Gift of Human Life (Huntington, IN, 2000)

Schieve, Laura A., Meikle, Susan F., Ferre, Cynthia, Peterson, Herbert B., Jeng, Gary, & Wilcox, Lynne S., ‘Low and Very Low Birth Weight in Infants Conceived with the use of Assisted Reproductive Technology’ in The New England Journal of Medicine, 2002 Vol. 346, 731-737.

Selick, C.E., Hofmann, G.E., Albano, C., Horowitz, G.M., Copperman, A.B., Garrisi, G.J., & Navot, D., ‘Embryo quality and pregnancy potential of fresh compared with frozen embryos--is freezing detrimental to high quality embryos?’ in Human Reproduction 10 (2) Feb. 1995, 392-5

Tonti-Filippini, Nicholas, ‘The Embryo Rescue Debate: Impregnating Women, Ectogenesis, and Restoration from Suspended Animation’ in The National Catholic Bioethics Quarterly 3.1 (Spring 2003) 111-38

1. Some of the issues involved are considered by Paul Ramsey in Fabricated Man: The Ethics of Genetic Control (Yale, 1970)

2. Hansen, Michèle, Kurincuk, Jennifer J., Bower, Carol, & Webb, Sandra, ‘The Risk of Major Birth Defects After Intracytoplasmic Sperm Injection and In Vitro Fertilization’ in The New England Journal of Medicine, 2002 Vol. 346, 725-30.

3. Schieve, Laura A., Meikle, Susan F., Ferre, Cynthia, Peterson, Herbert B., Jeng, Gary, & Wilcox, Lynne S., ‘Low and Very Low Birth Weight in Infants Conceived with the use of Assisted Reproductive Technology’ in The New England Journal of Medicine, 2002 Vol. 346, 731-737.

5. DeBaun, Michael R., Niemitz, Emily L., & Feinberg, Andrew P., ‘Association of In Vitro Fertilization with Beckwith-Wiedemann Syndrome and Epigenetic Alterations of LIT1 and H19’ in Am. J. Hum. Genet. 72 (2003) 156-60

6. Moll, Annette C., Imhof, Saskia M., Cruysberg, Johannes R.M., Schouten-van Meeteren, Antoinette Y.N., Boers, Maarten, & van Leeuwen, Flora E., ‘Incidence of retinablastoma in children born after in-vitro fertilization’ in The Lancet 361 (2003) 309-10

7. Cox, Gerald F., Bürger, Joachim, Lip, Va, Mau, Ulrike A., Sperling, Karl, Wu, Bai-Lin, & Horsthemke, Bernhard, ‘Intracytoplasmic Sperm Injection May Increase the Risk of Imprinting Defects’ in Am. J. Hum. Genet. 71 (2002) 162-4

10. Editorial and Review, in The Lancet, 361 (25^th January, 2003)

11. e.g. Kolibianakis, E.M., Zikopoulos, K., & Devroey, P., ‘Implantation Potential and Clinical Impact of Cryopreservation – A Review’ in Placenta 24, Suppl. 2, Oct. 2003, S27-S33

12. Lejeune, Jerome, The Concentration Can (San Francisco, 1992)

13. Byrd, William, ‘Cryopreservation, Thawing, and Transfer of Human Embryos’ in Seminars in Reproductive Medicine, 20 (1), Feb. 2002, 37-43

14. A good account of the predicament of these frozen embryos is given by Nicholas Tonti-Filippini in his article ‘The Embryo Rescue Debate: Impregnating Women, Ectogenesis, and Restoration from Suspended Animation’ in The National Catholic Bioethics Quarterly 3.1 (Spring 2003) 111-38

15. For the reasons for holding that most people’s lives begin at conception, see May, William E., Catholic Bioethics and the Gift of Human Life (Huntington, 2000) 156-70

17. While the demonstrable risk of major birth defects would appear to be an argument against the use of ART which could be useful in persuading someone whose moral vision was obscured to the validity of the other reasons, it should be borne in mind that to such a person this argument would seem to make it morally imperative that a couple who carried an hereditary disorder should not have children.