In Vitro Fertilization and Embryo Transfer:  Tactics Are Being Compared

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Embryo Transfer

If you are considering fertility treatment, then you know the basic options. Hormonal therapies, artificial insemination, and certain other treatments can enable pregnancy with minimal expense in money and time. But when those approaches don’t work, that’s when in vitro fertilization (IVF) comes into play. It can involve donated ova (eggs) or sperm, if necessary, or aspiring parents’ own ova and sperm. For simplicity, we’ll consider the scenario in which the woman’s own ova used to induce pregnancy.

In such cases, the aspiring mother’s ovaries are stimulated to produce ova each month with hormonal therapy. Eggs are retrieved from the stimulated ovaries and fertilized in a laboratory culture dish by combining the eggs manually with sperm from whomever is to be the biological father. Fertilization of an ovum produces a zygote, which soon divides into a 2-cell stage, and then into still more cells. After 2-3 days, the result is said to be in the cleavage stage.

After reaching the cleavage state, specimens can be injected into the aspiring mother’s uterus, allowed to develop further in the lab until day 5-6 when they are called blastocysts, or they can be cryopreserved  –stored at very low temperature for future use. In nature reproductive cycle (which is to say, getting pregnant without IVF), the blastocyst is the stage of an early embryo that implants in the endometrium, the inner lining of the uterus. However, the first strategy for implanting IVF embryos was intrauterine injection at the early cleavage stage, because, early on, researchers did not have the techniques to maintain specimens up to the blastocyst stage in the lab.

Today, they are very good at maintaining the specimens for several days, so embryos can be injected into the uterus in the blastocyst stage. This has brought two questions under study. One question surrounds whether it’s better to inject early cleavage stage, or blastocyst stage embryos. There’s an emerging consensus that that blastocyst injection is a better way to go. One reason for this is that letting the specimens from for a few days in the lab beyond the early cleavage state often reveals defects that can lead to early pregnancy failure. Also, injecting the more developed state specimen primes it to implant in the endometrium at the same gestational age as it would in the natural pregnancy cycle. On the other hand, there’s an idea that using early cleavage specimens gives you more opportunities for a successful implantation, in a sense giving you more bang for the buck.

The other question is whether it’s better to inject embryos that have been cryopreserved and thawed, or “fresh” embryos –fresh meaning just fertilized a few days ago and injected immediately without an intervening cryopreservation period. In the cryopreservation option, cycle after cycle, eggs are harvested from the mother, fertilized via IVF, grown to the early cleavage or blastocyst stage, then put into cold storage. Then a bunch of thawed embryos can be injected all at once.

In the fresh embryo tactic, usually one fresh embryo is injected, along with several thawed embryos, whereas the cryopreservation tactic involves injection of thawed embryos only. The overall picture emerging from the scientific literature is that the cryopreservation approach works better than the fresh embryo approach. Cryopreserved/thawed embryos entail a higher pregnancy success rate and slightly higher birth weights. There may be some advantages to fresh embryos in some mothers, but overall the positives of cryopreservation seem to outweigh the negatives, and this may have to do with improvements to the cryopreservation process. In the past, the only way to preserve embryos was through slow freezing. This produces ice crystals, which may push on, and stretch cells. The newer tactic is called vitrification, the same physical process that produces glass. In vitrification, biological tissues move to very low temperatures and solidify without crystal formation.

The jury is still out on why vitrified embryos do better than fresh embryos, but there is one interesting discovery from recent studies. In older women (those in their late thirties, or forties and beyond), success rates are significantly higher with blastocysts that have been vitrified and thawed. In other words, the older you get, the more you should be thinking about the newer techniques.

David Warmflash
Dr. David Warmflash is a science communicator and physician with a research background in astrobiology and space medicine. He has completed research fellowships at NASA Johnson Space Center, the University of Pennsylvania, and Brandeis University. Since 2002, he has been collaborating with The Planetary Society on experiments helping us to understand the effects of deep space radiation on life forms, and since 2011 has worked nearly full time in medical writing and science journalism. His focus area includes the emergence of new biotechnologies and their impact on biomedicine, public health, and society.

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