Biomedical Ethics

PROPOSAL
Broad Topic:Ethical issues in in vitro fertilization (IVF) for patients who wish to conceive.
Phenomenon of interest:In Vitro Fertilization
Ethical Significance:Fertility procedures are services that provide a patient the opportunity to create or extend his/her family. Fertility specialists and Physician Assistants (PA) are responsible for evaluating each unique case and developing an effective treatment plan. The relationship between a PA and the patient is built upon trust. The patient arrives to the PA in hopes of a successful pregnancy. In return, the PA guides the patient throughout the pregnancy to ensure the health of the mother and the fetus(s). Those who undergo IVF have already made multiple attempts to conceive without success. Therefore, patients undergo many cycles of IVF in the hopes of gestation. Most often, when the patient finally does become pregnant, she wants to keep all her viable embryos. This raises some ethical questions: (a) Should the PA support the patient’s decision to keep the multiple viable embryos? (b) Should the PA limit the patient’s autonomy and decide how many children they have? (c) Should the PA pressure the patient to terminate viable embryos if there are high-order multiple births?
Specific Question:What are the ethical obligations of a Physician Assistant if a patient wants to keep multiple viable embryos after in vitro fertilization (IVF)?

The goal of IVF is to maximize a woman’s chances of gestation due to past unsuccessful attempts. One common method is to implant multiple embryos (about 3) into the uterus. This is a common alternate plan to anticipate at least one successful live birth.

When following the IVF method for pregnancy, the success rate for a live birth is a challenge. The average IVF attempts are 3 to 4 cycles. Couples tend to give up due to physical and psychological burdens. Smith, Tilling, Nelson, and Lawlor (2015) conducted a study to determine the live birth rate per IVF cycle and repeated cycles. For almost a decade, 156,947 UK women were followed to undergo 257,398 IVF cycles in total. The women ranged between 18 to 55 years with the median being 35 years old. Averaging all the women, the live birth rate for the first cycle was 29.5%. The average rate remained above 20% up to the 4th cycle. By the 6th cycle, the cumulative prognosis- adjusted live birth rate was a whopping 65.3%. For women in their early 40s, the firstcycle birth rate was a measly 12.3%. That rose to 31.5% by the 6th cycle. As the number of IVF trials increase, there is over a 65% chance of having a live birth after multiple attempts. Therefore, the study showed that clinicians should notify their patients and consider extending the number of IVF cycles to go beyond only 3 to 4 trials. This would allow the patient to have their best chance to conceive.

The success rate of IVF gestation significantly depends on not only the uterus of the patient, but also the embryo. The quality of embryos varies person-to-person depending on their age, health, and genetic history. Schieve, Peterson, Meikle, Jeng, Daniel, Burnett, and Wilcox (1999) examined the association of the number of embryos transferred during IVF and multiple live birth rates. Unlike Smith et al. (2015), this study only used fresh, non-donor eggs. Fresh and non-donor IVF refers to eggs being removed from the woman, fertilized with sperm, and then the viable embryos are transplanted into the same woman’s uterus. Data collected was from 35,554 women between the ages 20 to 44. In their findings, only 9,873 live births were reported. There was an increase in live birth rates when 2 or more embryos were implanted at a time. With 2 embryos, multiple birth rates ranged 10.8-22.7% (depending on the age of the mother). With 3 embryos, multiple birth rates were 29.4-45.7%. If 5 embryos were transferred in women 40 to 44 years of age, they had a multiple birth rate of about 25%. The research concluded there is an increase in multiple birth rates as the number of embryo transfer increases. However, there is a variation of success in multiple birth rates depending on age. The older the woman, the less chances of multiple births.

According to Thurin, Hausken, Hillensjo, Jablonowska, and Pingborg (2004), IVF has a high risk of premature birth and perinatal death. They researched the chances of multiple births in IVF, specifically in association with the number of embryos transferred at a time. They hypothesized if embryos were transferred one at a time, there would be a reduced rate of multiple births. Some additional common risks of multiple births from IVF are neurological defects, and malformations. In Thurin et al.’s (2004) study, 661 women under 36 years of age had at least two of good quality embryos. At random, 330 women underwent a single, fresh embryo transfer. If there was no live birth, the spare cryopreserved embryo was thawed and then transferred. The remaining 331 women had a double-embryo transfer at a single time. The total rate of live birth was 38.8%1 for the

1 The single-embryo transfer group includes 8 live births that happened after spontaneous conception between the first, fresh embryo and the second, cryopreserved and thawed cycles.

single-embryo group (27.6% of first, fresh embryo cycle and 16.4%2 of the second, thawed embryo cycle) and 42.9% for the double-embryo transfer group, respectively. The difference was a meager 4.1% between the methods. From the single-embryo transfer group, 38 women did not receive the second treatment because none of their cryopreserved embryos survived after thawing. In addition, 14 others did not continue their second cycle due to multiple reasons from marital problems to severe illnesses. The single-embryo transfer group had only a single pair of twins out of 128 children. The double-transfer group had multiple births of 47 out of the 142 (46 pairs of twins and 1 set of triplets) children. Complications in conception like ectopic pregnancies and spontaneous abortions were insignificant differences between the two methods. The study supports the transfer of a single embryo at a time for IVF because this method results in a significantly reduced rate of multiple gestations and an insignificant 4.1% difference of a lesser chance in pregnancy.

As favorable as it might be to have multiple children at a time for those who have difficulty getting pregnant, there are risks involved. Tang, Chang-xing, Cui, Chang, and Ariet (2005) conducted a population study to determine if multiple birth rates have a greater chance of birth defects than singleton birth rates and what might those birth defects be. The study was conducted using data of 972,694 live births in Florida from 1996 to 2000. The data was from a population-based surveillance system. The control variables were the mother’s race, age, past unsuccessful pregnancies, education, usage of Medicaid, infant’s sex, and number of siblings. It was discovered that 944,967 were singleton births and 27,727 were multiple births. The prevalence of birth defects for

2 The percentage was calculated a total of 177 second, thawed-embryo cycles.

every 10,000 live births was 358.50 and 250.54 from multiple and singleton births, respectively. Taking the control variables into consideration, calculations revealed there was a 46% increased risk of a birth defect when having multiple births than singleton births. Percentage was calculated by the variables mentioned above to have an adjusted relative risk of 1.46 of total birth defects. Difference in absolute risk was not mentioned In fact, for every control variable, multiple births were significantly associated with more birth defects than singleton births. Forty specific birth defects were identified; and 23 of the defects were more common from multiple births. The 5 most common birth defects were: anencephalus, biliary atresia, hydrocephalus without spina bifida, pulmonary valve atresia and stenosis, and bladder exstrophy. The 40 specific birth defects were then classified into 8 major groups: central nervous system, chromosomal, gastrointestinal, genital and urinary, heart, musculoskeletal, oral clefts, and others. There was an increased risk of birth defects from multiple births in 6 out of the 8 classified groups. The research concluded multiple births to have an increased risk of having birth defects than singleton births.

Reproductive autonomy acknowledges a woman to have the ability to decide whether or not to reproduce. With that in mind, she usually decides when, how many, where, and how the birth should be carried out. According to Purdy (2004), women should have reproductive autonomy because they are the ones giving birth and the initial caretaker. However, the two specific factors that impact reproductive autonomy are poverty and belief systems. A main concern with IVF is the high possibility of multiple births. Reduction, to “abort one or more of the fetuses”, helps with the setback of multiple pregnancies. In 1989, later reaffirmed on 1993, hospitals were supportive of triplets being reduced to twins. However, ethical issues concerning abortion came into play when wanting to reduce twins to singletons. These kinds of decisions belong to the women rather than doctors or hospital’s policy. Some women might be persuaded against their wishes and there is speculation of whether sexist bias plays a role because IVF patients are all women. Purdy (2004) believes we need to abandon external factors that influence women’s reproductive choices so they can have a chance for genuine autonomy.

SYNTHESIS

In reference to the research articles, IVF is the go-to-method when a woman is having difficulty conceiving. After multiple, failed attempts, women are compelled to do whatever they can to increase their chances in pregnancy. The high success rate of IVF is because of the transfer of multiple embryos at a time to influence a high chance at implantation and then growth. This option however can have a negative effect if in place of just one child; there can be multiple births. In addition, during parturition, the mother can have difficulty giving birth and the fetus(s) can even have certain birth defects. Schieve et al. (1999) is in favor of multiple trials and Smith et al. (2015) wants to increase in the number of embryos transferred at a time. This would be the ultimate way to not only increase the chance of pregnancy, but even multiple births all at one time to avoid any future miscarriages. Thurin et al. (2004) however, is not supportive of transferring more than one embryo at a time because of the increase in chance of multiple birth rates. Because of the high multiple birth rates, Tang et al. (2005) was able to make note of over 40 birth defects. According to Purdy (2004), it does not matter how many children a woman wants to have. The pregnant woman has the right to her reproductive autonomy to decide what she wants to do. All this research brings forth the ethical dilemma of what should a clinician, specifically a Physician Assistant (PA) do concerning a patient who is interested in keeping multiple viable embryos after IVF?

PROPOSED ANSWER and ARGUMENTS

Given the challenges a woman has to face to conceive, she would naturally want to keep all or most of her viable embryos just in case she is not able to have more children in the future. In addition, IVF procedures are not the most affordable method to do repeatedly. Therefore, the more embryos implanted, the greater the chance for a woman to have a successful pregnancy on the first try. It is understandable why a PA would be opposed to multiple viable embryos. There is a high possibility of birth defects and/or even complications during delivery. To avoid these difficulties, a PA might want to express paternalism and coerce the mother to have only one child at a time. However, this is not a decision for a PA to make. Based on the principles of reproductive autonomy and beneficence, patients should be allowed to keep their multiple viable embryos up to a limit where beneficence can still be achieved.

According to Yeo (2010, p.91), autonomy is “…the right to make independent decisions concerning one’s own life and well-being”. This means, in the case of IVF, a woman has the ability to make independent decisions specifically concerning her reproductive autonomy.

Autonomy can be broken down into four additional connotations: free action, effective deliberation, authenticity, and moral reflection. Free action is the “liberty” to do whatever one pleases. Effective deliberation is to distinguish how capable a person is to make a “rational decision”. Authenticity is how close a person is to their day-to-day personality and decision-making capacity (pp. 92-95). Decision–making capacity is the mental ability to make an informed decision. To make a decision, the patient is mindful of the options and is able to appreciate the potential outcomes of each decision (pp. 97). Expanding on authenticity, moral reflection is the thought process of the decisions that were made in reference to one’s true self (pp. 95). In summary, the general description of autonomy is a careful deliberation by someone based on rationality and the true representation of their character and moral values.

A more specific branch of autonomy is reproductive autonomy. Reproductive autonomy applies to women who are pregnant, not interested in becoming pregnant, trying to become pregnant, or have at some point already been pregnant. According to Purdy (2005), reproductive anatomy is, “…the power to decide when, if at all, to have children; also, many—but not all—of the choices relevant to reproduction.” However, factors like poverty and anti-autonomic religious beliefs make it difficult for women to take control of their reproductive decisions.

The IVF procedure increases the opportunity to conceive for women who have difficulty getting pregnant. According to the research of Schieve et al. (1999), the clear reason for excessive IVF success rates is because multiple embryos are transferred at a time. The more embryos transferred, the greater the chance of multiple birth rates. In reference to Smith et al. (2015), when 3 embryos are transferred, a healthy woman under the age of 40 has about a 50% chance of a multiple birth rate. Also, because of factors like age and health status, IVF is not always success in the first try. So it is recommended for women to keep trying IVF trials even after 3 to 4 failed attempts. As the number of attempts of IVF trials increase, there is over a 65% chance of having a live birth. Research and data evidently support the success rate of IVF when multiple viable embryos are implanted.

PAs provide high quality, patient-centered care. They respect a considerable amount of patient autonomy when diagnosing and treating a patient. This being said, a woman undergoes IVF when conventional methods have not proven to be successful. The entire reason for IVF is to increase her chance of pregnancy. She is able to deliberate the risk of multiple births as well as birth defects; but that is exactly what she is there for. Her reproductive autonomy allows her to decide how to proceed with her pregnancy and how many children she wants to give birth to.

Therefore, the PA should respect a woman’s reproductive autonomy and allow her to decide how many embryos she would like to have implanted; which would allow to her to have the greatest chance in a successful pregnancy.

Indeed, multiple births have more risks compared to singleton births. After adjusting control variable, the prevalence of birth defects in multiple births is 46% greater than singleton births (Tang, et al, 2005). For that reason, it is understandable if a PA has qualms of supporting a patient to have more than one viable embryo at a time. Such a high likelihood of risk does not support the principle of beneficence. Beneficence is to encourage “someone else’s good or welfare” (Yeo, 1996, p.103) Ultimately, beneficence means to “do good”. While the risks are accurate, supporting the reproductive autonomy of a patient who wants to keep multiple viable embryos after IVF is not completely against beneficence. Tang et al. (2005) notes, “Some studies found contradictory conclusions that total congenital malformations were not significantly more frequent in twins.” They are also informed that, consistent to other studies, there was a low incidence of deformities in twins because of the lower risk of congenital hip dislocations. In addition, multiple births also had a lower risk of pyloric stenosis. That being said, not all multiple births have the possibility of doing harm. Yes, multiple births have a greater chance of birth defects, but the numbers show they are not extraordinarily dangerous for twins and triplets.

The responsibility of a PA, like any other clinician, is to always do good for the patient. This is especially in regards to the patient’s autonomy. If the PA decides to support the patient to have multiple births, there is a great deal of beneficence to be appreciated. Statistically speaking, the risks of conceiving quadruplets and quintuplets are far worse than triplets or twins. Therefore, the request of the patient can still be completed without the PA having to worry about doing harm to the patient. Supporting the patient to have twins or triplets will be highly beneficent because not only does it respect the patient’s autonomy, the PA is remarkably fulfilling his/her duty in helping the patient have a viable birth. Thurin et al. (2004) had an outcome where if two embryos were transferred, there was a 4.5% greater chance of having a viable birth than transferring only one embryo at a time. The goal of an IVF procedure is to have a viable birth. Patient’s who most commonly undergo IVF are woman who are having difficulty achieving pregnancy and then a viable birth. It is most beneficent if the PA can deliver exactly that, and sometimes even more to the patient when multiple births are involved. There is also an essential factor about the psychosocial aspect of the PA-patient relationship. By respecting the patient’s desire to keep multiple viable embryos, the PA can ensure the patent’s mental composure during this most fragile and difficult moment in their lives.

Therefore, it is most beneficent if the PA supports the decision of the patient if they are interested in keeping multiple viable embryos that can lead to twins or triplets. Not only does this respect the patient’s autonomy, but also the beneficence of the mother, as well as the soon-to-be born child(ren). In conclusion, the patient should be supported in her decision if she chooses to keep multiple viable embryos to protect her reproductive autonomy. Although risk factors can be involved if the number of embryos is excessive, beneficence can also be achieved if the PA is able to persuade the patient into having a maximum of 2 to 3 children per cycle.

 

REFERENCES:

Purdy. “Women’s reproductive autonomy: medicalisation and beyond.” Journal of Medical Ethics 32 (n.d.): 287-91. Web. 06 Dec. 2016.

Schieve, L.A., Peterson, H.B., Meikle, S.F., Jeng, G., Danel, I., Burnett, N. Wilcox, L.S. “Live-Birth Rates and Multiple-Birth Risk Using In Vitro Fertilization.” JAMA 282.19 (1999): 1832. JAMA. Web. 04 Dec. 2016.

Smith, A.D., Tillig, K., Nelson, S., Lawlor, D.A. “Live-Birth Rate Associated With Repeat In Vitro Fertilization Treatment Cycles.” JAMA 2662nd ser. 314.24 (2015): 2652- 662. Web. 04 Dec. 2016.

Tang, Y., Ma, C.,Wei Cui, Chang, V., Ariet, M., Morse, S.B., Resnick, M.B., Roth,J. “The Risk of Birth Defects in Multiple Births: A Population-Based Study.” PubMed10.01 (2005): 75-81. Web. 05 Dec. 2016.

Thurin, A., Hausken, J., Hillensjö, T., Jablonowska, B., Pinborg, A., Strandell, A., Bergh, C. “Elective Single-Embryo Transfer versus Double-Embryo Transfer in in Vitro Fertilization.” The New England Journal of Medicine 23.351 (2004): 2392-402. Web. 04 Dec. 2016.

Yeo, Michael Terrance, and Anne Moorhouse. Concepts and Cases in Nursing Ethics. (pp. 103) Peterborough, Ont., Canada: Broadview, 1996. Print.

Yeo, Michael. Concepts and Cases in Nursing Ethics. (pp. 92-95, 97) Peterborough, Ont.: Broadview, 2010. Print.