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Reducing Complications in IVF Pregnancies

Two studies published in the June 2012 and January 2013 issues of the journal Fertility and Sterility confirm that high estrogen levels at the time of IVF embryo transfer increase the risk of low birth weight and preeclampsia. This study was specific to single-birth IVF pregnancies.

For IVF to be successful, patients use fertility drugs to induce the development of several follicles, which contain eggs. “In a natural cycle, we count on development of one follicle, and that follicle is what produces estrogen to prepare the uterus for implantation,” says Dr. Anthony Imudia, a Senior Fellow at Massachusetts General Hospital Fertility Center, and lead author of both papers. “Each developing follicle produces 200 to 400 micrograms of estrogen. In IVF, where we want at least 10 follicles to develop, we are increasing the level of estrogen produced.”

Prior to ovulation, the eggs are retrieved and fertilized, and in most cycles the developing embryos are transferred in what is referred to a “fresh” embryo transfer. It was determined that freezing the embryos and transferring them in a later cycle, when hormone levels are not elevated, greatly reduces the risk of low birth weight and eliminates preeclampsia.

The study published in 2012 June found that in almost 300 IVF pregnancies that resulted in the birth of a single infant, women whose estrogen levels right before egg retrieval were highest had significantly greater incidence of preeclampsia and of delivering small infants.
In the recent study, the researchers examined how a protocol for mothers at risk of ovarian hyperstimulation syndrome (OHSS) would affect risks associated with extremely high estrogen levels. They compared the outcomes of 20 patients who chose to have their embryos frozen and transferred later with those of 32 patients with very high estrogen levels pre-retrieval who chose fresh embryo transfer.
In the patients who froze their embryos, 10 percent of the infants were small for their gestational age, compared with 35 percent of the infants from fresh embryo transfer.
Almost 22 percent of patients experienced preeclampsia after fresh embryo transfer, but there was no preeclampsia in the group that froze and transferred the embryos in a later cycle.
"If other centers validate our findings by following the same approach and achieving similar outcomes, we would recommend that each patient's hormonal dosage be adjusted to try and keep her estrogen levels below 3,000 pg/mL," Imudia says. "If the estrogen level exceeds this threshold, the patient could be counseled regarding freezing all embryos for transfer in subsequent cycles, when her hormone levels are closer to that of a natural cycle."


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