This is the 13th in a series of answers to common questions about failed IVF.

Virtually everyone recognizes that pregnancy with multiples (especially triplets or greater) is associated with a high incidence of premature delivery that has serious consequences for the babies, who are not adequately prepared at that stage to face life outside of the womb. Complications such as cerebral palsy, ocular defects, respiratory distress syndrome, and necrotizing enterocolitis are but a few examples of conditions which can either lead to perinatal death or seriously compromise the quality of life after birth. In addition, multiple pregnancies increase the incidence of pregnancy-induced complications such as hypertension, preeclampsia, placenta previa and post partum hemorrhage, all of which significantly increase risk to the mother’s health.

Most IVF patients recognize that the more embryos transferred, the greater the likelihood of a multiple pregnancy with its incumbent risks. However, to many such patients, the increased chance of an IVF pregnancy trumps their concern of pregnancy related complications. They often believe that in the final analysis, medical technology can protect them from the perinatal and long term risks associated with multiple pregnancies. To make matters worse, some IVF doctors tend to encourage the transfer of multiple embryos in the hope and belief that this will increase their IVF pregnancy rates. This symbiotic inclination can lead to the type of travesty we recently saw with the “Octomom” case.

Without exception, each patient undergoing IVF ponders how many embryos should be transferred. This is not always a simple deliberation because the decision must take into account a number of factors including:

1. Embryo quality
2. Stage of development at the time of embryo transfer
3. Age of the egg provider
4. Patient preference

Embryo quality: Microscopic grading of embryos allows us to identify the characteristics of embryo development and then express these in terms of the likelihood to propagate a pregnancy. Many grading systems exist. The one we use at SIRM is known as Graduated Embryo Scoring (GES). Here we allot scores to several developmental characteristics at various stages of embryo development and express this as a percentage, approximately 72 hours following fertilization. A GES of greater than 70% suggests a greater likelihood of a successful IVF pregnancy following transfer, while a score of less than 70 suggests that healthy implantation is unlikely. We have also observed that high GES scoring embryos are the ones that are most likely to develop into blastocysts.

It is important to recognize however, that the morphologic appearance of the embryo does not always correlate with its chromosomal integrity – and that it is the latter that really matters. Embryos that have an irregular numerical chromosomal component (aneuploidy) will usually not implant. Those that do are generally lost as a chemical pregnancy or as a miscarriage in the first trimester. The only way to assess true embryo “competence” (i.e., the ability, upon transfer into the uterus, to propagate a normal baby) is through full embryo karyotyping, which is currently achieved using a technique known as Comparative Genomic Hybridization (CGH).

Since it is almost always the chromosomal integrity of the egg rather than the sperm that determines subsequent embryo “competence,” we can predict this through the performance of CGH on the egg or subsequently on the day-3 embryo. When this is done, the embryo needs to be frozen and stored (cryobanked) for subsequent dispensation as soon as CGH results become available a few weeks later.

Stage of development at the time of embryo transfer: Embryos that fail to attain the 6-9 cell stage of development within 72 hours of fertilization and those that exceed that level of cleavage are either growing too fast or too slowly. Such embryos are the ones that are most likely to be aneuploid and thus “incompetent.” Additionally, embryos that fail to reach the expanded blastocyst stage of development within 6 days of fertilization are with few exceptions aneuploid, and thus not worth being transferred to the uterus. It follows that there is little advantage in transferring embryos that have not proven themselves by having first attained the blastocyst stage. Those that say that an embryo might be better off in the uterus than in the incubator and therefore, the sooner an embryo is transferred the better, are misguided in my opinion.

Therefore, by challenging embryos to grow to the blastocyst stage, fewer embryos need be transferred at a time, thus reducing the risk of multiple pregnancies. It is also true that when a woman only produces one or two embryos by day 3 post-fertilization, there is generally no advantage (in terms of achieving a pregnancy) to delaying embryo transfer until the blastocyst stage. The only benefit in doing so would be for the purpose of trying to assess embryo competence, because many “incompetent” embryos would fail to survive that far along.

Finally, all CGH embryo testing requires that embryos be taken to the blastocyst stage. At SIRM, the transfer of a CGH-normal embryo to a receptive uterus (one that is free of anatomical, biochemical or immunologic impediments) will result in a viable pregnancy about 70% of the time. Therefore, there is a big difference in transferring non-CGH tested versus CGH tested embryos. In the case of the former, the number of embryos transferred should be influenced by the woman’s age, while in the case of the latter, it is rarely justifiable to transfer more than 2 CGH-normal blastocysts at a time.

Age of the egg provider: The incidence of egg aneuploidy increases with a woman’s age. Under age 35, about 2 in 5 eggs (40%) are chromosomally normal. At age 40, about 1 in 6-8 (12-17%) and by the mid 40’s less than 1 in 10 (microscopic grade of the embryos selected for transfer. On the other hand, a CGH-normal embryo should have about the same chance of propagating a normal baby regardless of the age of the egg provider. Accordingly, no more than 2 CGH-normal blastocysts should be transferred.

Patient preference: While it is the doctor’s responsibility to advise patients of all of the factors that could influence IVF outcome, especially the number of embryos recommended to be transferred, in the final analysis it is up to the patient to make an informed decision.