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Study: Freeze-Only Transfers Outperform Fresh Transfers

¹ Why is this so? It may have something to do with the delicate “dance” between the embryo and the lining of the uterus (endometrium).

Reproductive synchrony. For implantation to be successful, this embryo-endometrial dance must be well choreographed. The embryo must bring the right complement of chromosomes to its “dance partner,” and the endometrium must establish an environment that’s welcoming for the embryo. A receptive endometrium depends upon endometrial gene expression as well as responses to hormones throughout different phases of the menstrual cycle.

IVF impacts on implantation. How might in vitro fertilization (IVF) affect this process? Injections of reproductive hormones stimulate the growth of multiple eggs, which we retrieve and fertilize in the laboratory. We can then transfer the resulting embryos a few days later as a fresh transfer or freeze the embryos and transfer them during a normal hormonal cycle at a later date.

Ten years ago, researchers found that ovarian stimulation conducted for IVF alters gene expression in the endometrium, possibly lowering rates of implantation.² Could it also be possible that premature elevation of progesterone in the follicular phase of IVF lowered chances of implantation? If so, would it make sense to wait and allow hormones to resume more hospitable levels for implantation? And would separating the steps of ovarian stimulation, egg retrieval, and embryo procedures from the embryo transfer itself help overcome impediments like these?

Fresh-frozen face-off. Although not directly testing these hypotheses, a recent retrospective study began to explore these questions, as well as the influence of maternal age on outcomes. Using blastocyst-stage embryos only, the researchers compared 1,455 cycles of freeze-only transfers with 1,455 cycles of fresh transfers—closely matched for patient and cycle characteristics—to see the differences in implantation rates and ongoing pregnancy rates (OPR). (These ongoing pregnancies were defined as pregnancies lasting long enough for care to be transferred to an obstetric practice.) The study did not report on live birth data.

Freeze-only transfers included patients with premature progesterone elevation or ovarian hyperstimulation as well as patients who had simply preferred frozen transfers.

In addition to overall implantation rates and OPR, the researchers further analyzed their data based on age (younger than 35 or 35 and older) and progesterone levels on the day the women received human chorionic gonadotropin (hCG) injections.

Study results. These were their findings:

• OPR was 52.0 percent for freeze-only transfers and 45.3 percent for fresh transfers.
• In women with higher progesterone levels at the time of egg retrieval, the OPR was higher in patients of both age groups who underwent freeze-only transfers. The difference was greater in patients who were older than 35.
• Regardless of age, the OPR did not differ between the freeze-only and fresh transfers in women with low progesterone at the time of egg retrieval.
• Freeze-only cycles benefited women with increased maternal age—regardless of progesterone levels.^1,3

The researchers concluded that the freeze-only group had a higher OPR, especially when compared with fresh transfers where progesterone was high on the day of the hCG trigger and possibly for women who were older.

More frozen-only transfers? In the past, embryo freezing was mainly used for surplus embryos, after transferring a fresh embryo. However, with the advent of more effective technology such as vitrification, some specialists—including physicians at Pacific Fertility Center (PFC)—have begun using it as an alternative to fresh transfers. We routinely perform freeze-only embryo transfers because 90 percent of our patients undergo comprehensive chromosome screening (CCS) of their embryos, which requires freezing the embryos until test results come back.

Results from this study seem to validate the hypothesis that implantation is more successful when we more closely mimic the physiologic processes of a natural cycle—and it may help explain why our success rates at PFC have been high.

Sources

1. Wang A et al. Fertil Steril. 2017;108(2):254–261.e4.
2. Martinez-Conejero JA et al. Reprod Biomed Online.2007;15:45–50.
3. Science Daily: “Elective freezing of IVF embryos linked to higher pregnancy rates in some cases.” Available at: https://www.sciencedaily.com/releases/2017/08/170801103838.htm Accessed 11-15-17.

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