Repeated IVF Failure: What Do We Know In 2013
Repeated in-vitro-fertilization (IVF) failure is perplexing for patients as well as the infertility team providing care. In spite of repeated placement of what appear to be healthy embryos, ongoing pregnancy does not occur. These patients usually have had extensive evaluations that include careful evaluation of the uterine cavity, genetic testing of both parents, testing for clotting disorders (thrombophilias) in the woman, comprehensive endocrine assessment, and evaluation of the male. With the availability of pre-implantation genetic screening in recent years, we have learned that many normal appearing embryos are in fact genetically abnormal. The story has been further complicated by the finding that the original technology (PCR) being used to determine embryo genetics is flawed, yielding both false negative and false positive results. Recent reports have demonstrated that these inaccurate results may be minimized by changing the day that the embryo is biopsied from the 3rd to the 5th day of embryonic development. Erroneous results may be further minimized by applying more accurate technology such as quantitative polymerase reaction (qPCR), array comparative genomic hybridization (aCGH), or single nucleotide polymorphism (SNP).
Depending upon the woman’s age, 50-90% of all embryos produced may be genetically abnormal. In recent years conventional wisdom has been that when couples experience repeated IVF failures, the explanation is that they are producing a large percentage of genetically abnormal embryos that have no chance for successful implantation and live birth. Until recently, there have been no well conducted studies in which the best available technology (qPCR, or SNP) has been applied at the appropriate stage of embryonic development (blastocyst). An abstract presented at the conjoined meeting of the American Society of Reproductive Medicine and the International Federation of Fertility Societies in Boston, October 16, 2013 sought to investigate this conventional wisdom.
The study looked at couples with repeated implantation failure (RIF) and couples with recurrent miscarriage (RM). Embryos were biopsied at the blastocyst stage and only embryos that were genetically normal were transferred. Interestingly, in the repeated IVF failure group (RIF), the clinical pregnancy rate was 42.1%. Among the patients with recurrent miscarriage (RM), the clinical pregnancy rate was 84.5%. These results suggest that there are significant factors other than genetics that are responsible for repeated IVF failure, possibly flaws in the receptivity of the uterine lining or a flaw in the interaction of the embryo with the endometrium. The high clinical pregnancy rate noted in the recurrent miscarriage group suggests that when a couple is able to achieve pregnancy followed by repeated early pregnancy loss, the underlying cause is often an embryonic genetic abnormality. In the case of recurrent IVF failure, factors other than genetic abnormalities of the embryo are operative. Identification of these factors will enable us to more effectively treat these patients. While we await additional research, one potential clinical approach might be to utilize a gestational carrier.
Source: Katz-Jaffe, M.G., Surrey, E., Minjarez, D. Gustofson, R.L., Stevens, J., Schoolcraft, W.B. Can the transfer of euploid blastocysts in a frozen embryo transfer overcome repeated IVF failure? Abstract presented Boston, Oct 16, 2013 conjoined meeting of IFSS/ASRM.