CHR Update

The recent birth of octuplets after in vitro fertilization (IVF), widely commented on in the media, deserves formal comments. The following, therefore, represents CHR's formal position. For more information about the Center for Human Reproduction or about this UPDATE, please email Tom Weidner.



Special UPDATE on the Ethics of Recent CA Octuplets

Definitions

The first rule of medicine is to do no harm. It is for this reason that the prevention of so-called high-order multiple births (triplets or more) has for many years been at the forefront of research in the infertility field.

Practically all forms of fertility treatment convert the natural monofollicular cycle (i.e., a woman releases only one egg at the time of ovulation) into a polifollicular response (i.e., many eggs are released). As a logical consequence, practically all fertility treatments significantly increase the risk of multiple births. With increasing multiples, the length of pregnancy shortens in parallel. In other words, the more multiples, the earlier the pregnancy will be delivered, the higher the risk of prematurity for offspring. With prematurity come significant medical costs and risk for life-long handicaps. Consequently, the world-wide community of fertility specialists defined the reduction of high-order multiple pregnancies many years ago as a principal goal of the specialty.

CHR's Medical Director, Norbert Gleicher, MD, indeed already in the year 2000 published a seminal paper in this area in the prestigious New England Journal of Medicine. Here is some background: Most high-order multiple births are the consequence of ovarian stimulation with fertility drugs, followed by so-called intrauterine inseminations (IUIs). In this process, fertility drugs convert the woman's cycle into a polifollicular ovulation. This means that she releases multiple eggs. How many of these eggs are then fertilized by the partner's semen is to a large degree unpredictable and multiple gestation is unpreventable, as Gleicher and his co-workers demonstrated in their 2000 paper (Gleicher et al.: Reducing the risk of high-order multiple pregnancy after ovarian stimulation with gonadotropins. N Engl J Med 2000;343:2-7).

Demonstrating this fact, the authors, indeed, argued that this inability to control the risk of high-order multiple births with IUIs spoke in favor of an earlier switch from IUIs to IVF, since in IVF, patient and physician decided how many embryos were placed into the uterus and, therefore, controlled the high-order multiple risk to a much larger extent.

When the first news about the California octuplets broke, most fertility experts, ours here at CHR included, were, therefore, convinced that they must be the product of an IUI cycle. The profession was surprised and taken aback when it was revealed that they, indeed, were the consequence of an IVF.

Octuplets after IVF, to the best of our knowledge, have never before been born. This birth, therefore, represents an unprecedented event, which should not be considered typical of IVF practice. They, however, also represent the consequence of conscious decisions by the mother and her physician (who to our knowledge so far has not revealed himself/herself). While in IUIs unusually large numbers of eggs may be fertilized (within the mother's body) simply by chance, in an IVF cycle it requires the conscious decision to transfer a large number of embryos into the uterus to end up with high-order multiple births.

As chances of embryo implantation have improved over the years, we, as a profession, have also learned to "titrate" the number of embryos to prevent high order multiple births. Indeed, the profession's societies, American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproduction (SART) have over the years published explicit (and as the field progressed, changing) guidelines as to how many embryos should be transferred at various ages. Recommended embryo numbers increase as women age because implantation chances per embryo decrease.

ASRM/SART guidelines are sufficiently flexible to allow for consideration of special circumstances but they are explicitly clear that in a young woman (under age 35) only 1-2 embryos should be transferred. Indeed, these guidelines also very clearly mandate that prior history and IVF cycle history be considered in each case whether, within a recommended range, the lower or higher embryo number should be transferred. For example, a young woman with excellent ovarian function, who was going through IVF only because of her husband's poor semen, should probably get the lower number. In contrast, a young woman with poor ovarian function parameters and/or poor quality embryos might very well get the higher number of embryos.

The California Case

Surprisingly little is known about this infamous California octuplets case at time of this writing. It, therefore, is somewhat difficult to comment on many aspects of the case. However, a number of facts deserve discussion; first amongst them the patient's social background.

This woman was young, single and already had 6 children at home, at least some (if not all) conceived via IVF. From her medical history one, therefore, can conclude that, with great likelihood she, herself, was not "very infertile." Though we don't know how many prior IVF cycles she underwent in order to conceive her 6 children, a severely infertile woman, at such young age, would not already have 6 children at home.

Considering these facts, and considering above described professional guidelines for numbers of embryos transferred, it will seem quite obvious that this woman should with great likelihood have received a maximum of 2 embryos. With transfer of 2 embryos this kind of a patient would have an excellent pregnancy chance (in our program, of ca. 60%) and approximately one third of these pregnancies would be twins. Indeed, there is actually even a small triplet risk in such a scenario because under very rare circumstances one embryo can split into two and in such a case, even though only two embryos were implanted, a triplet pregnancy may occur. This risk is, however less than 1%.

How then did this woman end up with octuplets? We don't know!

She without doubt received more than 2 embryos. Since rarely all transferred embryos implant, it, indeed, is possible that she received more than 8. It is also possible she received fewer than 8 and some of the transferred embryos split. Whatever number of embryos she was transferred, one thing is clear: she with great likelihood received more than professional guidelines call for and this, of course, raises the question, why?

A Physician's Responsibility

We noted earlier that the first responsibility of any health care provider in any medical field is to do no harm. This, of course, also applies to the infertility field but does so in an even more pronounced and unique way, which this field only shares with our obstetrical colleagues. Like obstetricians, we, for all practical purposes, have more than one patient. The mother, of course, is our paramount patient; however, by hopefully helping her to conceive, we are the responsible party for a 9-months journey that leads to the birth of (at least) one human being. Our responsibility to do no harm, therefore, extends not only to the mother, but also to her offspring. We, therefore, have a very clear responsibility to strive for a healthy pregnancy and a successful delivery at lowest possible risk to mother and offspring.

Our responsibility however, goes even beyond that. Another way of defining our responsibility is to recognize that we strive to make our patients' lives "better" by helping them build families. This means that we need to ask ourselves in each case whether, by fulfilling their requests, we, indeed, will improve their lives.

This, of course, is particularly relevant when it comes to unusual social situations, such as single mothers. The number of single women seeking fertility treatments is very rapidly increasing and represents a significant practice volume here at CHR. A vast majority of such women are well prepared, have carefully considered all the relevant issues of single motherhood, are financially in a position to support a child and have even considered their own premature death and made appropriate arrangements for their offspring in such a case. However, some have not, and being a responsible physician means that we must ask the relevant questions before treatment is given.

This does not represent an old-fashioned patriarchal attitude towards a woman's right towards self determination. In our opinion such an approach simply represents good medicine and part of our responsibility to offer full informed consent before initiating treatment. Patients who have not given thought to all the consequences of their potential medical activities are not in a position to give appropriate informed consent to medical procedures. They, therefore, should not be treated!

Summary and Conclusion

We are very pleased that a majority of the media in this case of the California octuplets very quickly recognized that the traditional, rather romantic, view of high-order multiple births in such cases is completely unwarranted. High-order multiples, and especially at these numbers, have to be seen as the medical catastrophe that they are.

We are looking forward to hearing more form patient and her fertility provider in the hope that there are better explanations for what transpired in this case than we currently can assume. We, however, unfortunately, are not very optimistic that this will be the case, and these California octuplets will, therefore, with great likelihood, become a case of infamy in the otherwise stellar history of IVF.

It is important to remember that over 3 million IVF babies have been born world-wide. The fact that this represents, with great likelihood, the first (and hopefully last) set of octuplets speaks for itself.

- The CHR Staff

CONTACT US

To find out more about the Center for Human Reproduction, or to learn more about any of our infertility solutions, please

contact us.



PREVIOUS UPDATES

We will continue posting periodic UPDATES when there is news to report from CHR. So, continue looking for them! These are exciting times at CHR, and we thank you for your interest in our work.

Last Updated: October 19, 2011