High estrogen at transfer may be responsible for some poor obstetrical outcomes

February 27, 2013Carole 2 Comments »

IVF practitioners have long recognized that extremely high estrogen levels from ovarian stimulation cycles can result in a syndrome called ovarian hyperstimulation syndrome or (OHSS) which, if severe, can cause serious complications. Rarely, OHSS has caused patient deaths. In these high E2 cycles, the resulting embryos are often frozen and transferred in a later cycle when the symptoms of OHSS have resolved to avoid escalation of OHSS symptoms with pregnancy.

In an earlier post, “Freeze all” IVF with later FET may increase your pregnancy rate, I talked about research showing that frozen embryo transfer cycles often achieve better pregnancy rates than fresh cycles. The reason for these better outcomes may be because we have optimized cryopreservation with vitrification (so freeze damage is negligible) and the preparation for transfer works to optimize the endometrium for implantation.

We also know that IVF babies, even singleton birth babies, tend to have a lower birth weight than naturally conceived babies and their mothers are more likely to have some obstetrical issues (eg. pre-eclampsia, a disorder of abnormal placental development). This finding was surprising and largely unexplained. Two recent papers may provide a hormonal explanation for why these obstetrical problems persist for some IVF babies.

The article “Peak serum estradiol level during controlled ovarian hyperstimulation is associated with increased risk of small for gestational age and preeclampsia in singleton pregnancies after in vitro fertilization” demonstrated that patients with a high E2 (defined as greater than 3,450 pg/ml at time of hCG) were more likely to have low-birth weight babies and and suffer from pre-eclampsia than women with lower E2 levels.

The  second article ” Elective cryopreservation of all embryos with subequent cryothaw embryo transfer in patients at risk for obarian hyperstimulation symndrome reduces the risk for ovarian hyperstimulation syndrome- a preliminary study“demonstrated that patients with high E2 levels at hCG trigger who chose to freeze all their embryos and delay transfer were less likely to have  problems with pre-eclampsia and low birth-weight babies than women who proceeded with fresh transfer even with high E2 levels.

Dr. Anthony Imudia, an instructor in Obstetrics, Gynecology and Reproductive Biology at Harvard Medical School and author on both of these studies, describes their clinical approach in a recent Science Daily article, “Our center takes a very individualized and conservative approach to ovarian stimulation, so fewer than 10 percent of our patients had extremely high estrogen levels of greater than 3,450 pg/mL. 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. 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.”

Non-human primate research has shown that E2 plays an essential role for normal development of arteries in the early placenta. In humans, we know that estrogen levels are relatively low (below 200 pg/ml) in natural cycles before transfer, so we might expect that 15 fold elevations in E2 may dysregulate the normal process of placenta formation. More research is necessary to understand exactly how E2 regulates placental development in pregnant women and why high E2 levels are problematic, but it seems clear that low estrogen at the time of transfer is preferable for best patient outcomes.


© 2013, Carole. All rights reserved.

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