An Overview of the Benefits of SET

With the evolution of new and advanced techniques of in vitro fertilization (IVF) resulting in improved embryo implantation and birth rates, there has been a substantial increase in the rate of multiple births. Largely as a result of this, obstetrical outcomes are poorer following IVF than following spontaneous pregnancy. In fact, multiple births are responsible for a markedly higher risk of prematurity with low or very low birth weight, as well as perinatal death and more frequent lingering neurologic complications and an increased risk of malformations.

Singleton vs. Multiple Gestation Pregnancies

  • When comparing singleton with multiple gestation pregnancies:
  • Twins have 3-times, and triplets a 6-times, greater perinatal mortality rate
  • Twins have 6-times, and triplets an 11-times, greater likelihood of developing cerebral palsy
  • Twins are 50%, and triplets 80%, more likely to be born prematurely
  • Mothers of twins are 3-times, and mothers of triplets 7-times, more likely to experience serious pregnancy-induced complications

SET Benefits

Single-embryo transfer 

(SET) involves the selective transfer of a single embryo to the uterus. The embryo might be fresh, or it may be a frozen embryo from a prior IVF attempt. Recent research has revealed that younger women undergoing IVF who elect to have one or repeated SET’s (over as many cycles as the number of available embryos would allow), can anticipate cumulatively (over several cycles of fresh or frozen SET’s), having a similar number of live-birth deliveries as would be the case for women who have multiple embryos transferred at the same time. The only difference is that pregnancy resulting from a SET would virtually always result in a singleton birth while with the transfer of multiple embryos there is an ever-present risk of multiple births. SET is destined to become the treatment of choice in women under 35 years of age who have good quality embryos available for transfer.

Embryo Selection

Selecting embryos that have the best chance of implanting and propagating a healthy baby is one of the most important remaining challenges in the field of Assisted Reproduction. However, the use of morphologic (microscopic) criteria on day 2-3 post-fertilization as well as conventional preimplantation genetic testing, such as fluorescence in-situ hybridization (FISH), lack both sensitivity and specificity. They are seriously flawed when it comes to identifying those embryos that are most likely to develop into healthy babies (what we refer to as “competent” embryos). Because of this, many IVF physicians still transfer multiple embryos at a time in an attempt to maximize the chance of a successful outcome. Unfortunately, this often results in an unacceptably high rate of multiple gestations with the associated, prematurity-related neonatal complications that often exact devastating short and long-term consequences on the very quality of life after birth.

Ideal Transfer Time

The presumption that it is better to transfer healthy embryos into the uterus sooner rather than later (cleaved on day 2-3 following fertilization, rather than as blastocysts on day 5 or 6), is flawed. In fact, we now know that the vast majority of embryos that fail to develop into blastocysts in the lab are chromosomally abnormal and would not have resulted in a healthy baby anyway. By culturing all embryos to the blastocyst stage, we can effectively weed out many of the non-viable ones. The baby rate per transferred blastocyst is about twice as high as is the transfer of day 2 or day 3 cleaved embryos, at any maternal age. Transferring the most “competent” blastocyst(s) increases the chances of a healthy fetus and normal baby.

It follows that if we could reliably identify and then cryopreserve “freeze” the “competent” embryos without compromising their survival and post-thaw viability, it would be far better for all concerned to conduct SET’s, especially in younger women (under 35 years) who have normal ovarian reserve.

Recent Developments

Three relatively recent developments now make it possible to conduct single embryo transfers in good candidates, with a strong expectation of success. It is especially helpful in couples or single parents looking to have 1 or 2 children, older women, or women with diminished ovarian reserve (DOR) who are considering embryo banking, and for women with alloimmune implantation dysfunction (DQalpha/HLA matching).

  1. New extended embryo culturing methods: The development of advanced extended embryo culture techniques over the last decade makes it possible to successfully grow embryos to the blastocyst stage of development without prejudicing those that are “competent” in the processes.
  2. Ultrarapid embryo freezing (Vitrification): Vitrification is the process used to freeze embryos 600 times faster than conventional (slow) embryo freezing; this keeps ice from forming in the cells and protects the embryo from damage. It allows us to safely bank and store embryos without them being severely damaged by the freeze-thaw process and, at the same time, ensures the same potential to propagate a baby as with freshly transferred embryos.
  3. Reliable full embryo karyotyping using Comprehensive Chromosomal Screening (PGS): It has long been recognized that the numerical chromosomal integrity of the embryo represents the “rate limiting factor” in human reproduction. Those embryos that have more or less than the normal human genome of 46 chromosomes in their cells (i.e., are aneuploid), either will not attach to the uterine wall (failed implantation), attach for a brief period of time and then miscarry, or (albeit infrequently) will result in the birth of a chromosomally abnormal baby (e.g., Down syndrome).

It was against this background that the use of preimplantation genetic screening (PGS) to evaluate embryo chromosomal integrity was contemplated as a method to selectively identify and transfer only those embryos that had all 46 chromosomes intact (i.e., euploid). The test, next generation sequencing (NGS), enables identification of the most “competent” embryos for selective IVF embryo transfer

The Success of SET

The journey of building a family is an arduous one, and deciding upon IVF can be somewhat overwhelming. One of the serious risks associated with IVF is that with the transfer of multiple embryos come the serious risks associated with multiple births. The introduction of technology that makes SET a successful process means there is no longer a need to transfer multiple embryos at one time in order to improve the chance of having a healthy baby.