It has been a little more than 25 years since the first baby was born in England following in vitro fertilization. In that quarter of a century, there have been dramatic advances in Assisted Reproductive Treatments (ART), with over one million healthy babies being born worldwide from these procedures. The applications and indications for these procedures, as well as the advances in different techniques, equipment and medications have been significant.
Throughout the past 25 years, this field has had to grapple with ethical and legal issues, which sometimes have not kept pace with scientific advances. Issues such as cloning, stem cell research, posthumous reproduction and genetic engineering, are a few of the areas where legislative intervention has been, and still is, necessary.
One of the big issues in our field remains the incidence of multiple pregnancies, and the problems associated with these outcomes. In particular, pre-term labor and prematurity are important issues, which may have devastating consequences. The good news is that new advances in the measurement of molecular markers of embryo competency can enable physicians to identify those embryos most likely to yield a pregnancy and in so doing, feel comfortable transferring fewer embryos. This, in turn, will decrease the incidence of multiple pregnancies, which are directly related to the number of embryos transferred back to the uterus.
In this day and age, with all of the options available to patients, there should be no couple who cannot have a family, be it with their own biological child, adoption or third party reproduction. Regrettably, these treatments are still not covered by many insurance companies, due in large part to the fact that they do not consider infertility a disease. They also have legitimate concerns about the incidence of high order multiple pregnancies and the consequences thereof, especially the incidence of prematurity and risks of cerebral palsy associated with this problem. This situation sometimes places significant burdens on those who need to avail themselves of these treatments.
Some of the newer advances in the field include the following:
Pre-Implantation Genetic Diagnosis (PGD)
In this procedure, a cell (blastomere) is removed from an 8 cell (3-day-old embryo) and analyzed for its chromosomal make-up. Presently only nine of the possible 23 chromosomes are able to be analyzed. This research is advancing quickly, and with the knowledge available from the Human Genome Project, it is likely that within the relatively foreseeable future, it will be possible to test all 23 chromosomes. The greatest application of PGD lies in the detection of single gene defects (e.g. cystic fibrosis, sickle cell disease, etc.), where carriers of these conditions can be evaluated, probes developed and the removed blastomere tested to determine whether the defective genes are present or not. If affected, those embryos are not transferred. Besides the fact that not all chromosomes can be tested, the techniques are difficult and if performed by those not proficient in them, this can cause irreparable damage to the embryos.
Embryo Marker Expression Test (EMET)
In contrast with PGD, this test is performed in a completely non-invasive manner by removing a small amount of the fluid surrounding 2- and 3-day-old embryos, and testing this fluid for molecular markers. One such marker is soluble HLA-G. This marker has been shown to be strongly correlated with the implantation potential of the embryo. It is imperative that embryos are cultured singly in dishes in the lab. When they test positive for these markers, fewer, high quality embryos can be selected for transfer, thereby maintaining acceptable pregnancy rates, yet significantly reducing the incidence of high order multiple pregnancies. It is likely that in the near future, additional molecular markers of embryo competency and embryo health will be identified, which will open all kinds of possibilities for research and therapeutics in this field.
Immunology
A recognition and understanding that immune tolerance is pivotal for successful reproduction has been an important development in recent years. Higher levels of so-called Natural Killer Cells and various cytokines can destroy early embryos after implantation. Immune modulation therapy using IVIG has been demonstrated to reduce the levels of these cells thereby making growth of early implanted embryos more likely to occur. When coupled with steroid therapy and anti-coagulation treatment, couples who suffered from repetitive miscarriages and repeat IVF failures are now able to successfully reproduce.
Third Party Reproduction
Egg donation and Gestational Surrogacy are now frequently performed. These options have evolved considerably over the past decade and enjoy very high success rates (50-75 percent range). Unfortunately, the laws vary considerably in different parts of the country and world. There are significant psychological issues when performing these treatments and counseling is often an integral part of the process. Furthermore they are quite costly, however these options have opened up enormous possibilities for successful reproduction in couples who can benefit from them.
Oocyte (Egg) Freezing
It is well known that reproduction declines significantly as a function of age, declining after age 30 and dramatically after age 40. When perfected, egg freezing will likely result in a paradigm shift in how young women prioritize their lives. It may reach the point where, upon entry into college, a young woman will have eggs frozen to “place the biological clock” on hold, so to speak. She will then pursue career objectives and return several years later with her partner to reproduce from the eggs which would have been frozen years before. One of the important obstacles of this procedure has been damage to the chromosome spindle upon freeze/thaw of the oocyte. It is important at this time that young women are not given false expectations about the likelihood of successful reproduction taking place from frozen oocytes. It is likely that these techniques will be perfected in the near future, but they are not yet at that place. There have been over 100 healthy babies born as a result of egg freezing to date and the research in this area is very active.
Sex Selection
New advances in methods to separate sperm into X-bearing (girls) and Y-bearing (boys) fractions have shown some promise. The techniques are not yet perfected and possibly will never reach 100 percent perfection. With these possibilities of family balancing come some ethical dilemmas, which must be kept in mind. These involve appropriation of funding resources, societal sex ratio imbalances and moral considerations. These techniques do hold promise for those affected with sex-linked disorders where it is possible to obtain embryos of a particular sex.
Secondary Infertility
Secondary infertility affecting those who have previously reproduced successfully is often very frustrating. It is frequently related to age and a decline in egg quality as a function of age. The good news is that the vast majority of those affected will be able to successfully reproduce if they are willing to accept treatments such as egg donation.
Infertility affects approximately 15 percent of all couples trying to conceive. Unfortunately only a small percentage of those who need treatment, actually receive treatment. Ignorance of available treatment options, embarrassment and lack of affordability are the most frequently cited reasons for this disparity. In this day and age, there should be no couple who remains childless if they are willing to overcome personal obstacles which may be in their way.
Today, fortunately, we have a lot more reliable and accurate methods than counting with a pen and a paper calendar.
