Added ethical difficulty, the damage inflicted on the embryo, which will be subjected to various freezing/thawing processes, resulting in many of them having to be discarded in the proces….

Introduction

In its July 2014 edition, the journal Fertility and Sterility published three studies that analysed the different circumstances that affect the complicated process of obtaining embryos and their use in in-vitro fertilisation (IVF) cycles.

They analysed the ovarian stimulation procedures used to obtain oocytes for subsequent fertilisation in the laboratory, and the advantage of transferring the embryos obtained in the same cycle in which they were obtained, or freezing embryos them by different methods and transferring them in subsequent cycles.

In view of the findings of these studies, it seems that the likelihood of success for achieving a pregnancy varies according to whether one or other method is used. The neonate’s health can also be affected by the IVF method selected, all factors that pose not only a clinical but also an ethical dilemma.

Ovarian stimulation

The first step in the IVF process consists of obtaining oocytes, either from the future mother or from a donor, for subsequent fertilisation in the laboratory.

The need to work with several of these to increase the probability of success in the assisted fertilisation process requires stimulation of multiple ovulation in the woman, by administering drugs such as clomiphene. These treatments not only cause the proliferation of several ovarian follicles, in which many oocytes will mature (the objective pursued), but they will activate a series of changes that will influence the subsequent implantation process, compromising its success. They also have potentially serious side effects, such as thromboembolic disorders, some types of cancers and even death. These changes are, basically, elevated estrogen levels and increases in the plasma progesterone concentration during the super-ovulation. These will cause changes in the endometrial receptivity, the expression of certain genes involved in the progression of the implantation process and pregnancy, and in vascular endothelial growth factor (VEGF)-mediated vascular proliferation of the endometrium, altering the period in which the endometrium will be receptive to implantation of the blastocyst. Likewise, a relationship has also been described between the progesterone levels and the establishment of a maternal-foetal immune tolerant environment, which will be critical for the progression of the implantation process and the pregnancy, in which multiple factors are involved. The natural killer (NK) cells have a notable role here, secreting interleukin-15, which converts them into uterine NK cells; these in turn secrete VEGF, cytokines and leukaemia inhibitory factor (LIF). The number of these uterine NK cells is significantly reduced in the case of women undergoing ovarian stimulation treatment compared to levels in normal cycles.

Studies in mice have also shown that there are epigenetic changes in the embryo itself that will remain after birth, as a result of the ovarian hyper-stimulation.

Some of these studies suggest that performing the embryo transfer in a later cycle (after the one in which the oocytes were obtained following stimulation) may increase the possibilities of success in achieving a pregnancy, thus making it necessary to cryopreserve the embryo, an outcome that poses new dilemmas.

Freezing Embryos – cryopreservation

If the fresh embryo is not transferred after its creation in the laboratory, it must be frozen for subsequent use. There are basically two freezing techniques that are currently used: slow freezing and vitrification, or ultra-rapid freezing. The first has been used since 1984, and in 1990 the first child was born from an embryo that had been vitrified and thawed. The differences between both methods lie, as well as in the rate at which the freezing/thawing cycles occur, in the concentrations of the Cryoprotective Agents (CPAs) used, which are lower in the slow methods; these act as drying agents, at both intra- and extracellular level.

Although freezing embryos – cryopreservation, allows embryo transfer a posteriori, it also has the major disadvantage of causing abnormalities in the frozen embryos, which can compromise their subsequent viability. Various studies have examined the viability of these embryos, in an attempt to establish selection criteria after they have been thawed, to increase the chances of success in their subsequent transfer and implantation in the uterus. Some of the studies have stated that embryos in which at least half of the blastomeres are intact after thawing should be considered viable.

Microscopic examination of the embryo after thawing is the screening method used to determine those that will or will not be transferred. We understand that embryos that have been thawed and discarded are definitively eliminated, which is extremely important from an ethical point of view.

This embryo selection after cryopreservation and thawing appears to increase the success rates as regards the number of full-term pregnancies achieved per embryo transferred, but it reduces the number of embryos available (many are discarded) and prolongs the IVF process, making it more expensive.

Nevertheless, some studies have suggested that freezing of all embryos obtained could be indicated, instead of trying to transfer fresh ones. They argue that the endometrium is more receptive in women who have not undergone ovarian stimulation treatment in the same menstrual cycle in which the embryo transfer is performed, children born from embryos transferred after cryopreservation with respect to those from fresh cycles have better health, and there is a greater increase in the transfer success rates of cryopreserved embryos with respect to fresh embryos. Unlike previously, today both methods are equally successful.

Ethical assessmentFreezing embryos present objetives ethic problems due to the process used

The production of embryos in the laboratory, outside the natural setting where this should take place, already presents ethical difficulties. These are worsened if more embryos are produced that can be expected to transfer. Surplus embryos will be frozen for later transfer (or not), or to be used for other purposes, such as for obtaining stem cells.

However, this advocated cryopreservation has an added difficulty, namely the damage inflicted on the embryo, which will be subjected to various freezing/thawing processes, resulting in many of them having to be discarded in the process.

If we recognise, as science very clearly confirms, that each of these embryos is an individual of the human species, it seems that treating these embryos as simple cell clusters that can be tested, selected and discarded, is an attack on their dignity, against which the voices of well-founded ethics should be raised up, the ethics that respects life and seeks its good.

 

julio-tudela

 

Julio Tudela Cuenca

Bioethics Observatory

UCV