**6. Ethical problems related to frozen surplus embryos from ART and how their untoward situation can be resolved**

As already mentioned, the efficacy of IVF is low. In order to improve this, a large number of embryos are typically produced, usually between 10 and 12, of which 1 or 2 are transferred and the rest frozen. This practice inevitably means that the number of frozen human embryos is gradually increasing.

Knowing what to do with these frozen embryos raises objective bioethical problems. In our view, there are four solutions for these embryos: (a) leave them frozen

indefinitely; (b) use them for biomedical experimentation; (c) thaw them and let them die; and (d) adoption.

Of these four solutions, the most widely employed is the second—using them for biomedical experiments—but this solution clearly poses obvious bioethical problems, since it entails the inevitable destruction of the embryos used.

The solution that presents least ethical problems is the adoption of such embryos by the biological parents, but this is not always possible. What occurs most frequently is the adoption by a couple biologically unrelated to the embryo in question.

The ethics of this type of adoption can be considered from three aspects: (a) from moral philosophy; (b) from secular ethics; and (c) from the point of view of the morality of the monotheistic religions [61].

### **6.1 Frozen embryo adoption in the light of moral philosophy**

They are very few studies that address the moral licitness or illicitness of frozen human embryo adoption in the light of moral philosophy. In our view, this has been addressed in most depth by Antonio Pessina [62].

In his opinion, 'two lines of argument can be raised when evaluating frozen embryo adoption. In the first, it is assumed that human life is an absolute value, immeasurable, and as such is not comparable to any other. In the second, it is recognized that human life is a basic value, because it is a necessary condition to uphold other human goods, but not sufficient to achieve the specific ends of man, which means that the value of human life can be deferred to other values, for example, by giving one's life for another'.

If we accept the first principle, 'there would be no objection to the adoption of frozen embryos; it could even be presented as morally positive and not only licit'. If the second line of argument is accepted, 'the life of the human embryo should be defended only by proportionate, ordinary and morally legitimate means, in this sense the only possibility being to invite the biological mother to have her child's frozen embryo implanted and to carry the pregnancy to term. Other options could be considered disproportionate and extraordinary, which could lead to the violation of other fundamental values related to the dignity of the human person and of human procreation'.

In conclusion, Pessina declares himself morally opposed to frozen embryo adoption.

### **6.2 Frozen embryo adoption from the perspective of secular ethics**

From secular ethics, there does not appear to be any difficulty for frozen embryo adoption. In fact, it is even considered to be a positive solution for these embryos, since, according to it, if the embryos are not used by the parents for reproductive purposes, their adoption is ethically more defensible than any other fate that may be given them. Undertaking a reproductive process to try to have a child born is in their opinion the best solution, since the aim is to help build families, i.e. to help infertile couples to have a child, and also to protect a primary good of the embryo, its life. Consequently, many experts or lay institutions see in frozen embryo adoption an alternative for the fate of such embryos that is ethically better than using them for biomedical research, destroying them or leaving them stored indefinitely [61].

### **6.3 Frozen embryo adoption from the perspective of the monotheistic religions**

In relation to Islam, Sunni Muslims are not in favour of considering third-party gamete donation as morally acceptable nor, by analogy, frozen embryo adoption; however, Shiite Muslims are more agreeable to morally accepting this practice [61].

**201**

*Bioethics of Assisted Reproductive Technology DOI: http://dx.doi.org/10.5772/intechopen.90727*

any form of surrogacy illicit [67].

**7. Human embryo loss in IVF**

baby born, 7.38 embryos were lost.

rogacy [64].

In relation to Judaism, it is difficult to find specific texts that refer to the moral assessment of frozen embryo adoption [61]. There are, however, texts on thirdparty gamete donation [63] so, again by analogy, that assessment could be extrapolated to frozen embryo adoption. In practice, though, most Orthodox rabbis are

Evangelists consider frozen embryo adoption as analogous to gestational sur-

In relation to Catholicism [65], there are two documents in the Magisterium of the Catholic Church that address the issue of embryo adoption: the Instruction *Donum Vitae*, published by the Congregation for the Doctrine of the Faith in 1978 [66], and *Dignitas Personae*, published on 8 September 2008, by the same Congregation [67]*.* The Instruction *Dignitas Personae* is the last document of the Magisterium of the Catholic Church in which the topic of embryo adoption is explicitly addressed*.* Proposals to *use these embryos for research* or *for the treatment of disease* are obviously unacceptable because they treat the embryos as mere 'biological material' and result in their destruction. The proposal that these embryos could be put at the disposal of infertile couples as a *treatment for infertility* is also ethically unacceptable for the same reasons that make artificial heterologous procreation and

Among the negative bioethical aspects of IVF, possibly the most significant is

We have attempted to calculate this figure [68] based on previous data from a published article [61]. This study in question evaluated 572 ovarian stimulation cycles that yielded 7213 oocytes, i.e. 12.6 oocytes per cycle. A total of 2252 embryos were produced and 326 live babies were born (226 from fresh embryos and 64 from frozen embryos). Based on these figures, the number of live babies born for every 100 embryos was 14.47; or to put it another way, for every 100 embryos produced, 85.53 embryos were lost, i.e. 6.9 embryos were lost for every live baby born. Another more recent study by the same group [69] analysed 191 ovarian stimulation cycles performed on 53 female donors. The donors were classified into two groups: 28 were highly successful donors, and 23 were classified as standard. The highly successful donor group yielded a total of 2470 oocytes from 130 ovarian stimulation cycles. This produced 779 embryos; 342 were transferred as fresh embryos and 437 were cryopreserved. A total of 125 live babies were born. The standard donor group yielded 1044 oocytes from 61 ovarian stimulation cycles. This produced 336 embryos; 131 embryos were transferred and 205 were cryopreserved. The total number of live babies born was 26. Based on these figures, a total of 1115 embryos were produced and a total of 151 live babies were born. Consequently, the number of live babies born per 100 embryos was 13.54; in other words, the number of embryos lost for every 100 embryos produced was 86.46. Thus, for every live

Accordingly, based on the above data, if approximately 6 or 7 embryos are lost for every child born by IVF, and since 1978, the year in which Louise Brown was born, around 5 million children have been born [20], we can estimate that, so far, around 30 million human lives may have been lost worldwide as a result of the use of IVF [68]. This leads one to say—while admitting that it is a very strong assertion—that IVF is a medical practice that, for the time being, generates more death than life. The natural cycle itself is associated with follicle recruitment followed by dominance and selection, while the nondominant follicles undergo atresia in the same cycle. The

the high number of embryos—human lives—that are lost.

hesitant about the moral licitness of frozen embryo adoption [61].

### *Bioethics of Assisted Reproductive Technology DOI: http://dx.doi.org/10.5772/intechopen.90727*

*Innovations in Assisted Reproduction Technology*

the morality of the monotheistic religions [61].

addressed in most depth by Antonio Pessina [62].

**6.1 Frozen embryo adoption in the light of moral philosophy**

them die; and (d) adoption.

giving one's life for another'.

adoption.

indefinitely; (b) use them for biomedical experimentation; (c) thaw them and let

by the biological parents, but this is not always possible. What occurs most frequently is the adoption by a couple biologically unrelated to the embryo in question. The ethics of this type of adoption can be considered from three aspects: (a) from moral philosophy; (b) from secular ethics; and (c) from the point of view of

Of these four solutions, the most widely employed is the second—using them for biomedical experiments—but this solution clearly poses obvious bioethical problems, since it entails the inevitable destruction of the embryos used.

The solution that presents least ethical problems is the adoption of such embryos

They are very few studies that address the moral licitness or illicitness of frozen human embryo adoption in the light of moral philosophy. In our view, this has been

In his opinion, 'two lines of argument can be raised when evaluating frozen embryo adoption. In the first, it is assumed that human life is an absolute value, immeasurable, and as such is not comparable to any other. In the second, it is recognized that human life is a basic value, because it is a necessary condition to uphold other human goods, but not sufficient to achieve the specific ends of man, which means that the value of human life can be deferred to other values, for example, by

If we accept the first principle, 'there would be no objection to the adoption of frozen embryos; it could even be presented as morally positive and not only licit'. If the second line of argument is accepted, 'the life of the human embryo should be defended only by proportionate, ordinary and morally legitimate means, in this sense the only possibility being to invite the biological mother to have her child's frozen embryo implanted and to carry the pregnancy to term. Other options could be considered disproportionate and extraordinary, which could lead to the violation of other fundamental values related to the dignity of the human person and of human procreation'. In conclusion, Pessina declares himself morally opposed to frozen embryo

From secular ethics, there does not appear to be any difficulty for frozen embryo adoption. In fact, it is even considered to be a positive solution for these embryos, since, according to it, if the embryos are not used by the parents for reproductive purposes, their adoption is ethically more defensible than any other fate that may be given them. Undertaking a reproductive process to try to have a child born is in their opinion the best solution, since the aim is to help build families, i.e. to help infertile couples to have a child, and also to protect a primary good of the embryo, its life. Consequently, many experts or lay institutions see in frozen embryo adoption an alternative for the fate of such embryos that is ethically better than using them for biomedical research, destroying them or leaving them stored indefinitely [61].

**6.3 Frozen embryo adoption from the perspective of the monotheistic religions**

In relation to Islam, Sunni Muslims are not in favour of considering third-party gamete donation as morally acceptable nor, by analogy, frozen embryo adoption; however, Shiite Muslims are more agreeable to morally accepting this practice [61].

**6.2 Frozen embryo adoption from the perspective of secular ethics**

**200**

In relation to Judaism, it is difficult to find specific texts that refer to the moral assessment of frozen embryo adoption [61]. There are, however, texts on thirdparty gamete donation [63] so, again by analogy, that assessment could be extrapolated to frozen embryo adoption. In practice, though, most Orthodox rabbis are hesitant about the moral licitness of frozen embryo adoption [61].

Evangelists consider frozen embryo adoption as analogous to gestational surrogacy [64].

In relation to Catholicism [65], there are two documents in the Magisterium of the Catholic Church that address the issue of embryo adoption: the Instruction *Donum Vitae*, published by the Congregation for the Doctrine of the Faith in 1978 [66], and *Dignitas Personae*, published on 8 September 2008, by the same Congregation [67]*.* The Instruction *Dignitas Personae* is the last document of the Magisterium of the Catholic Church in which the topic of embryo adoption is explicitly addressed*.* Proposals to *use these embryos for research* or *for the treatment of disease* are obviously unacceptable because they treat the embryos as mere 'biological material' and result in their destruction. The proposal that these embryos could be put at the disposal of infertile couples as a *treatment for infertility* is also ethically unacceptable for the same reasons that make artificial heterologous procreation and any form of surrogacy illicit [67].

## **7. Human embryo loss in IVF**

Among the negative bioethical aspects of IVF, possibly the most significant is the high number of embryos—human lives—that are lost.

We have attempted to calculate this figure [68] based on previous data from a published article [61]. This study in question evaluated 572 ovarian stimulation cycles that yielded 7213 oocytes, i.e. 12.6 oocytes per cycle. A total of 2252 embryos were produced and 326 live babies were born (226 from fresh embryos and 64 from frozen embryos). Based on these figures, the number of live babies born for every 100 embryos was 14.47; or to put it another way, for every 100 embryos produced, 85.53 embryos were lost, i.e. 6.9 embryos were lost for every live baby born.

Another more recent study by the same group [69] analysed 191 ovarian stimulation cycles performed on 53 female donors. The donors were classified into two groups: 28 were highly successful donors, and 23 were classified as standard. The highly successful donor group yielded a total of 2470 oocytes from 130 ovarian stimulation cycles. This produced 779 embryos; 342 were transferred as fresh embryos and 437 were cryopreserved. A total of 125 live babies were born. The standard donor group yielded 1044 oocytes from 61 ovarian stimulation cycles. This produced 336 embryos; 131 embryos were transferred and 205 were cryopreserved. The total number of live babies born was 26. Based on these figures, a total of 1115 embryos were produced and a total of 151 live babies were born. Consequently, the number of live babies born per 100 embryos was 13.54; in other words, the number of embryos lost for every 100 embryos produced was 86.46. Thus, for every live baby born, 7.38 embryos were lost.

Accordingly, based on the above data, if approximately 6 or 7 embryos are lost for every child born by IVF, and since 1978, the year in which Louise Brown was born, around 5 million children have been born [20], we can estimate that, so far, around 30 million human lives may have been lost worldwide as a result of the use of IVF [68]. This leads one to say—while admitting that it is a very strong assertion—that IVF is a medical practice that, for the time being, generates more death than life. The natural cycle itself is associated with follicle recruitment followed by dominance and selection, while the nondominant follicles undergo atresia in the same cycle. The

controlled ovarian stimulation has an advantage of opening the follicular window and rescuing this cohort of follicles who would have undergone atresia if the FSH window was not kept open and multiple follicles salvaged. The current scenario is practical nonavailability of embryos for embryo donation to aspiring couples where female partners are undergoing endometrial preparation for transfer for Donor embryos. Though there are concerns for discarded embryos, the fertility clinics are in practise at a deficiency of embryos that can be transferred. The ethics of embryo transfer should be discussed in a clinically practical rational scenario.

### **8. Use of preimplantation genetic diagnosis in IVF: ethical assessment**

PGD is a laboratory method especially directed to the genetic study of embryos before they are transferred and, therefore, before implantation in the uterus. The aim of this procedure is to determine if the embryos have a genetic or chromosomal abnormality, or if they are carriers of a genetic risk factor of disease, especially in those couples in which at least one of the partners presents a high risk of having a genetic condition that they could transmit to their offspring [70]. Another common indication in the field of assisted reproduction is aneuploidy screening to ensure the implantation of euploid embryos [70]. Similarly, PGD is currently and increasingly often being used to try to prevent diseases that can appear in adulthood [71]. In general, it may be said that PGD is used in IVF to improve its efficacy.

The technique essentially involves in vitro culture of the embryos to be examined, so that when these reach an adequate number of cells, a single cell can then be extracted for study.

There different biopsy methods are used for PGD at present [72]. The most common is the biopsy of one or two blastomeres on Day 3 of embryonic development, during the screening or cell segmentation phase. However, the ESHRE recommends extracting six or more cells in the embryos [72, 73], because more cells can be biopsied in this phase with less risk of damaging the embryo [72].

As regards its use for improving IVF outcomes, this seems controversial, since many authors obtain positive outcomes using it, while others have been unable to detect such an improvement. Furthermore, Mastenbroek concludes that, not only does it fail to improve IVF outcomes, but it lowers the LBR in women of advanced maternal age, with no beneficial effects in the rest of the women [74].

When assessing this practice bioethically, the main difficulties are: (1) that it treats the human embryo as experimental material, objectifying it, which is absolutely incompatible with its intrinsic dignity, and (2) practising embryo selection for health reasons is a clearly eugenic practice.

Nevertheless, there are authors who not only are not opposed to the use of PGD, but also encourage its use, due to the benefit that it may bring for children by trying to prevent them from being born with a genetic or chromosomal disease or who have the risk of having one of these diseases in the future. In fact, some even advocate the positive duty of parents to use PGD when they consider that its use may be beneficial for their children [75, 76].

To circumvent the ethical difficulties of the use of PGD, and to maintain its hypothetical advantages, it has been proposed to analyse one of the two polar bodies of the oocyte, to thus determine whether said oocyte is a carrier of its mother's disease before the zygote is formed. In this way, only the healthy eggs would be fertilised [72, 77, 78], although this technique has the limitation that it could only be used in women.

**203**

*Bioethics of Assisted Reproductive Technology DOI: http://dx.doi.org/10.5772/intechopen.90727*

**9.1 Good of the child**

**9.2 Good of the donors**

genetic relationship [81].

**9.4 Good of society**

**9.3 Good of the assisted reproduction clinics**

since gametes from older donors are usually of lower quality.

preimplantation diagnosis of genetic disorders [80].

embryo development. However, the study of gene expression of these cell layers could be the basis of a non-invasive method for predicting oocyte quality, serving as a biomarker for selecting oocytes and embryos, as an alternative to the use of PGD [79]. Another alternative constitutes trophectoderm biopsy in human blastocysts, where extraembryonic material can be obtained by this technique for

**9. Ethical problems arising from donor gametes in IVF, especially the right to privacy of donors and of children to know their parents**

and (d) to establish whether even the good of society should be ensured.

From a bioethical point of view, in our opinion, there are a number of issues with respect to whether the donation of gametes, both eggs and sperm, should be anonymous or not. We consider these four the most important: (a) to know whether the good of the child should prevail in the overall assessment of the process, as we believe it should; (b) to determine whether the privacy of the donors should be ensured; (c) to assess whether the interests of assisted reproduction clinics should be safeguarded;

With regard to children, it seems obvious that they have the right to know their biological origin, i.e. to know who their parents are. This is not only for emotional reasons, which must also be considered, but mainly for medical ones, since it cannot be ruled out that it may be necessary during the child's life to know who his parents are, if he has a genetic disease that needs to be identified, in order to be diagnosed and treated.

Moreover, this policy is in accordance with the first major document developed

In relation to donors, there is a trend towards suppressing anonymity in gamete donation, which may be a negative factor for donors. This is because, if the parentchild relationship can be established, it could lead to parental obligations for the donors that they may not want to assume. This is especially so if we also take into account that there are websites specialising in genetic matters that can match people who were born through gamete donation, so it can be determined if they have a

There is no doubt that suppressing anonymity in gamete donation can dramatically reduce the number of donors who attend those clinics, as has already happened in the United Kingdom, which is undoubtedly an added difficulty for these practices. In addition, it is also possible that if anonymity is suppressed, it will particularly affect younger donors, which could be detrimental to IVF procedures,

One risk of anonymous donation is that a donor can make a donation repeatedly and in different places, in the absence of real control over the process. This could

by the United Nations in 1989, on the 'Rights of the Child', which, in Article 7, defines that one of those rights is the right of the child to know his or her parents.

It is also known that the oocyte is surrounded by several cell layers and that those layers play a key role in its normal function, ovulation, fertilisation and

*Bioethics of Assisted Reproductive Technology DOI: http://dx.doi.org/10.5772/intechopen.90727*

*Innovations in Assisted Reproduction Technology*

controlled ovarian stimulation has an advantage of opening the follicular window and rescuing this cohort of follicles who would have undergone atresia if the FSH window was not kept open and multiple follicles salvaged. The current scenario is practical nonavailability of embryos for embryo donation to aspiring couples where female partners are undergoing endometrial preparation for transfer for Donor embryos. Though there are concerns for discarded embryos, the fertility clinics are in practise at a deficiency of embryos that can be transferred. The ethics of embryo

**8. Use of preimplantation genetic diagnosis in IVF: ethical assessment**

PGD is a laboratory method especially directed to the genetic study of embryos before they are transferred and, therefore, before implantation in the uterus. The aim of this procedure is to determine if the embryos have a genetic or chromosomal abnormality, or if they are carriers of a genetic risk factor of disease, especially in those couples in which at least one of the partners presents a high risk of having a genetic condition that they could transmit to their offspring [70]. Another common indication in the field of assisted reproduction is aneuploidy screening to ensure the implantation of euploid embryos [70]. Similarly, PGD is currently and increasingly often being used to try to prevent diseases that can appear in adulthood [71]. In

The technique essentially involves in vitro culture of the embryos to be examined, so that when these reach an adequate number of cells, a single cell can then be

There different biopsy methods are used for PGD at present [72]. The most common is the biopsy of one or two blastomeres on Day 3 of embryonic development, during the screening or cell segmentation phase. However, the ESHRE recommends extracting six or more cells in the embryos [72, 73], because more cells can be

As regards its use for improving IVF outcomes, this seems controversial, since many authors obtain positive outcomes using it, while others have been unable to detect such an improvement. Furthermore, Mastenbroek concludes that, not only does it fail to improve IVF outcomes, but it lowers the LBR in women of advanced

When assessing this practice bioethically, the main difficulties are: (1) that it treats the human embryo as experimental material, objectifying it, which is absolutely incompatible with its intrinsic dignity, and (2) practising embryo selection

Nevertheless, there are authors who not only are not opposed to the use of PGD, but also encourage its use, due to the benefit that it may bring for children by trying to prevent them from being born with a genetic or chromosomal disease or who have the risk of having one of these diseases in the future. In fact, some even advocate the positive duty of parents to use PGD when they consider that its use

To circumvent the ethical difficulties of the use of PGD, and to maintain its hypothetical advantages, it has been proposed to analyse one of the two polar bodies of the oocyte, to thus determine whether said oocyte is a carrier of its mother's disease before the zygote is formed. In this way, only the healthy eggs would be fertilised [72, 77, 78], although this technique has the limitation that it could only be

It is also known that the oocyte is surrounded by several cell layers and that those layers play a key role in its normal function, ovulation, fertilisation and

transfer should be discussed in a clinically practical rational scenario.

general, it may be said that PGD is used in IVF to improve its efficacy.

biopsied in this phase with less risk of damaging the embryo [72].

maternal age, with no beneficial effects in the rest of the women [74].

for health reasons is a clearly eugenic practice.

may be beneficial for their children [75, 76].

**202**

used in women.

extracted for study.

embryo development. However, the study of gene expression of these cell layers could be the basis of a non-invasive method for predicting oocyte quality, serving as a biomarker for selecting oocytes and embryos, as an alternative to the use of PGD [79]. Another alternative constitutes trophectoderm biopsy in human blastocysts, where extraembryonic material can be obtained by this technique for preimplantation diagnosis of genetic disorders [80].
