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Frozen Better Than Fresh?

It has been observed for some time that IVF pregnancies are slightly different from those that occur spontaneously. For example, birth weights with IVF are typically around 150 g less on average (not a huge difference, but oddly consistent), the risk of preeclampsia is about 40% higher than in spontaneous conceptions, and the risk of preterm labor, even in singleton pregnancies, is higher than those of spontaneous conceptions. In addition, there is a rare condition called placental abruption in which the placenta “unplugs” from the uterine wall during pregnancy. It is a potentially catastrophic event.  Fortunately it is rare—but slightly less rare with IVF pregnancies.

Data has been accumulating that suggests that these differences between IVF and spontaneous conceptions are not the result of issues with the embryos themselves. Rather, they are caused by the maternal environment that accompanies the ovarian stimulation necessary for efficient IVF. Animal models show that spontaneously conceived embryos that are flushed from the uterus of one animal and placed in the uterus of another animal who has undergone ovarian stimulation show many of the same potential problems, with very similar appearances to the placentas.

During stimulation of the ovaries, in addition to high estrogen levels, there are substances responsible for blood vessel development (such as vascular endothelial growth factors, or VEGF) that are markedly elevated in the same situations. It is believed that substances such as these are responsible for abnormal placental development and even abnormal placental attachment that accompany many IVF pregnancies.

Why We Do Frozen IVF Cycles

It is fascinating that when you compare IVF pregnancy outcomes from fresh embryos versus outcomes using frozen embryos, we see a picture that is much more consistent with spontaneously conceived pregnancies. The increased risks of preeclampsia, preterm labor, low birth weight, and placental abruption are not seen. In our own program, we have noticed for the past five years or more that our pregnancy rates using frozen embryos are actually higher than those using fresh embryos. I’ve always believed that this is because ovarian stimulation results in an endometrium that is abnormal and has been shown in several studies to contain areas that are out of sync with the rest of the uterus. In a controlled endometrial preparation cycle, the uterine lining develops in a more synchronous fashion.

As a result of these observations, some physicians are asking the question, “If we see higher pregnancy rates using frozen embryos, and if we see lower complication rates in the pregnancies when we use frozen embryos, why would anyone choose to do a fresh embryo transfer?”

In our program for the past two years, we have been doing frozen embryo transfers almost exclusively. What we have observed is continued high (and improving) pregnancy rates while we have also reduced the number of embryos transferred (in over half of our cycles, we transferred a single embryo). This, we believe, has improved the outcomes for our patients. We have been able to make this change without further cost increases to our patients and believe this will become the standard of care in the IVF field.

The Process at the Fertility Center

Our current protocol stops all medications after the egg retrieval, while laboratory procedures continue on until the blastocyst stage. All high-quality blastocysts are then frozen through vitrification. The patient will have a menstrual bleed within about 10 days of stopping her stimulation medications. With that menses, she will begin her protocol to prepare the endometrium for transfer. Once the endometrium is adequately thick, we start progesterone and plan for transfer of one or two embryos.

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