How many embryos should I transfer?

"How many embryos should I transfer when pursuing IVF?" This is a seemingly easy question but the answer may not be as simple as it seems. With transfer of a single embryo, the risk of multiple pregnancy is reduced. But this may also reduce the take home baby rate. On the other hand if more than one embryo is transferred, the pregnancy rate is increased, but so is the risk of multiple pregnancy.

Several studies have shown that a majority of infertile couples actually desire twins. Twin pregnancy, however, is not as safe as a singleton, but the vast majority of twins will do well. The situation, however, is less favorable with triplets and other high-order multiple pregnancies. These are associated with serious medical complications for both mothers (e.g. high blood pressure, diabetes, increased risk of C-Section) and fetuses (e.g. prematurity, a 47 times higher risk of cerebral palsy) and other social and economic issues. So, the real question is “What is the number (of embryos) that will maximize my chances of getting pregnant with a low chance of high-order multiple pregnancy?” Read on.

This very issue has been hotly debated by infertility specialists the world over. In certain Scandinavian countries, single embryo transfer is the norm. These countries have accepted a relatively low pregnancy rate with the fresh (single) embryo transfer. The extra embryos are cryo-preserved and (if needed) are transferred in a subsequent natural or programmed cycle. The motto seems to be “Transfer as many embryos as you want to but only one at a time”. The reported cumulative pregnancy rate (fresh + cryo-preserved embryo transfer (s)) is actually quite good. This requires patience as the pregnancy rate per (single embryo) transfer is relatively low and it may take several cycles to get pregnant. This could add to the cost of infertility treatment, but that will be a relatively modest expense compared to the cost of raising twins (or triplets). One should note that in Scandinavia, the government usually pays for the entire cycle taking away the financial burden associated with IVF. Other countries have legislation that limits the number of embryos that are transferred to no more than two. This policy, however, if routinely applied, would reduce the success rates in patients with poor prognosis and older patients.

Keeping these issues in mind, Practice Committee of the American Society for Reproduction has published guidelines for the number of embryos to be transferred in IVF cycles (Table 1.). The Practice Committee considers high-order multiple pregnancy (three or more implanted embryos) as an undesirable consequence (outcome) of IVF. Although multifetal pregnancy reduction can be performed to reduce fetal number, the procedure may result in the loss of all fetuses. It also does not completely eliminate the risks associated with multiple pregnancy, and may have adverse psychological consequences. To many patients, multifetal pregnancy reduction is NOT an acceptable option.

Table 1. Recommended limits on the numbers of embryos to transfer (2009)

So what are the characteristics that are associated with a more favorable prognosis?

Independent of age, these are:

1. first cycle of IVF
2. good-quality embryos based on appearance as judged by the embryologist
3. those with excess embryos of sufficient quality to warrant cryopreservation

Cleavage stage embryos are generally seen 2 or 3 days after egg retrieval. When the embryos are cultured on to day-5, they are at a more advanced stage (blastocyst). Only some of the cleavage stage embryos will form blastocysts. Blastocysts are therefore generally considered to have a better implantation potential than day 2 or 3 embryos. The Practice Committee encourages individual programs to generate and use their own data regarding patient characteristics and the number of embryos to be transferred.

Patients with a less favorable prognosis include those that have two or more previous failed fresh IVF cycles, or other factors (e.g. diminished ovarian reserve). As shown in Table 1., in these patients, one additional embryo may be transferred.

Generally, older patients are at low risk for high-order multiple pregnancy. In these patients, a higher number of embryos may be transferred to increase the pregnancy rate. In women ≥ 43 years of age, there are insufficient data to recommend a limit on the number of embryos to transfer.

Currently, we are doing embryo biopsy on day-5 embryos (blastocysts) and cryo-preserving them. The tissue (from the outer cell mass) is sent for chromosomal analysis. We are then doing elective single embryo transfer of a single chromosomal normal (euploid) blastocyst. To date, we have pursued this strategy in more than a handful of patients with pregnancy rates around 70% per transfer. Details to be discussed in a follow up blog.

So, how many embryos should you transfer? The answer varies based on your age and prognosis. I hope this blog has helped you with the answer. To see a Chicago-area fertility specialist who is a strong proponent of elective single embryo transfer, contact us and set up an appointment.