Fresh or Frozen: Which Embryos Should Be Transferred?
The IVF world is approaching a great fork in the road. Since the first IVF baby was born thirty-six years ago, there have been a number of such branch points along the way, including the means of stimulating follicles, egg retrieval techniques, culture media types, to ICSI or not to ICSI, as well as optimal egg- and embryo- freezing techniques. Although most of the past three plus decades have brought progressive small, iterative changes to the assisted reproductive technologies, certain turning points are momentous and dramatically change the course of IVF throughout the world. The fork in the road just ahead is whether embryos should be transferred to the uterus in the fresh IVF cycle or in a subsequent frozen-thawed (FET) cycle. Stated differently: Should we freeze all embryos and eliminate fresh embryo transfers?
The thinking behind freezing all embryos with a future FET cycle is that the embryos are returned to a “more normal” or more physiologic uterine environment. That is, the embryos are transferred into an endometrium that has not been exposed to large amounts of gonadotropins – stimulating hormones such as Follistim, Gonal-F and Menopur. The rationale has been that such an FET cycle may result in better pregnancy rates and decrease risks such as low birth weight and prematurity. Indeed, a review of a compilation of studies published in 2012 revealed that FET pregnancies, when compared to fresh-transfer pregnancies, had significantly decreased risks of preterm birth, small for gestational age fetuses, low birth weight, perinatal mortality, placental abruption and placenta previa. The risks for congenital abnormalities and some other risks did not differ significantly. (1) With respect to FET transfers, there was an increased risk for large for gestational age fetuses as well as cesarean section. In fact, various clinical reports have verified better implantation rates and pregnancy rates with FET over fresh-transfer cycles.
Certainly, freezing all unavailable embryos makes sense to decrease the risks of ovarian hyperstimulation syndrome (OHSS), and to allow for preimplantation genetic diagnostic screening or diagnosis. In the context of a rising progesterone level prior to egg retrieval, freezing all embryos is also a common practice.
There has been a clear and rather sharp turn toward more FET cycles during the last eight years in theU.S.and, although promising, it is too early to prescribe “freeze all” cycles for all patients even at a given IVF center. Treatment must be individualized and based upon clinical parameters as well as emerging clinical studies. (Translation: We should slow down and consult our navigation system as we approach the fork in the road!)
1. Maheshwari A, et al. Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of frozen thawed versus fresh embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril 2012;98:368-77.