Frozen Embryo Transfer in IVF--As Good as Fresh?

Fresh Versus Frozen Embryo Transfer

In vitro fertilization (IVF) has three prerequisites for successful implantation: a healthy embryo; a properly built, receptive endometrium; and adequate synchronization. To obtain several oocytes/embryos, controlled ovarian stimulation is applied, and in contrast to a natural cycle, this causes steroid hormones to rise to supraphysiologic levels. This can induce accelerated endometrial changes, premature luteinization, and altered gene expression.^[1,2] These undesired effects also can hinder implantation.

Decades of research have focused on methods to identify the embryo with the highest implantation potential.^[3] Only very recently have the benefits of alternative methods of embryo transfer (eg, freezing all with delayed transfer) been assessed.^[4] A recent meta-analysis^[5] compared clinical outcomes with fresh versus frozen embryo transfer (as part of a freeze-all cycle strategy) in women with different degrees of ovarian response.

Data from 5265 patients who took part in eight randomized controlled trials of IVF were included in the meta-analysis. The investigators compared the outcomes of fresh embryo versus first frozen embryo transfer in normal and high ovarian responders.

The number of oocytes and metaphase II oocytes retrieved were comparable among normal and high responders. The number of fertilized oocytes was similar after fresh and frozen embryo transfer cycles in high responders, but in normal responders, fewer oocytes were retrieved from frozen embryo transfer cycles.

The probability of clinical pregnancy after fresh versus frozen embryo transfer was the same for normal and high responders. In high responders only, the probability of a live birth was significantly higher with frozen embryo transfer. Miscarriage rates after frozen embryo transfer were significantly lower in high responders compared with normal responders.

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The extra embryos created during IVF can be cryopreserved and stored for later use. With the now widely used vitrification technology, close to 100% survival can be achieved and the success of a frozen embryo transfer cycle compares favorably with fresh cycle transfer.^[6] Cryopreservation is offered for several indications. Before chemo- or radiation therapy, cryopreservation can be offered to cancer patients, and it's an effective tool in avoiding ovarian hyperstimulation. Cryopreservation is used pending the results of genetic testing of the embryos or for purposes of patient convenience and scheduling. In some fertility clinics, cryopreservation is offered routinely and fresh transfers are no longer an option. The frozen embryo transfer method minimizes the nontrivial impact of the supraphysiologic steroid levels induced by ovarian stimulation.

In fact, this meta-analysis found a benefit with elective cryopreservation and frozen embryo transfer in high responders, who are most likely to be affected by rising hormone levels during ovarian stimulation.

The time has not yet come to move entirely to the "freeze all with subsequent frozen embryo transfer" approach. The evidence, however, does suggest that we shouldn't be afraid of canceling a fresh transfer when necessary. This is particularly true for high responders, in whom the frozen embryo transfer can enhance both safety and clinical outcomes.

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