Empowering Fertility - Ectopic Pregnancy Risk After IVF: How much does the Uterine Environment Matter?

Ectopic Pregnancy Risk After IVF: How much does the Uterine Environment Matter?

Today we welcome Hayley Eichlin, MSN, RNC-NIC to our blog community.  She shares some of the latest evidence on the effect of a fresh vs. frozen embryo transfer cycle on the uterine environment and risk for developing an ectopic pregnancy.

By Hayley Eichlin, MSN, RNC-NIC

An aneurysm, heart attack, a mole with very irregular borders. No matter the specialty, each field of medicine has its set of words that have the power to instill instantaneous fear into those who care for that subspecialty of patients. Often in the field of reproductive endocrinology, those two words are Ectopic Pregnancy. Combine that phrase with any of the following adjectives and you get a lovely mix of phrases that yield varying degrees of panic: suspected, presumed, confirmed. As a newer practitioner in this unique field of healthcare, when I hear hooves I always think zebras—not horses. Meaning that if there’s even an extremely remote possibility that a pregnancy could be ectopic, I’m like a dog with a bone, not letting it go. It is an ectopic pregnancy until proven otherwise.

Why the fuss, you ask? The rupture of a pregnancy outside of the uterus can lead to hemorrhage, loss of fertility, or death. The word ectopic originally comes from the Greek word ‘ektopis’ and translates to “out of place” (MedicineNet, 2013). The Greeks could not be more spot on with this one. An ectopic pregnancy by definition is a pregnancy that implants anywhere outside of the uterus. Trust me when I tell you, that an embryo “gone rogue” has a lot more options for implantation than one might think—the most common being the fallopian tube. 98% of all ectopic pregnancies occur in the fallopian tubes. Gaining a deeper understanding of what factors contribute to ectopic implantation is critical to improving outcomes.

Recently, an article published in Fertility and Sterility examined whether the uterine environment around the time of embryo transfer has any correlation to the risk of subsequent ectopic implantation— and it turns out, it does. Let’s discuss the findings and what is meant by “uterine environment.” Essentially, the authors compared the difference in the uterine lining between patients having fresh embryo transfers and their frozen (thawed) counterparts. Fresh embryo transfers take place after a period of controlled ovarian stimulation using injectable medications with the goal of producing multiple follicles for retrieval. Thus, the hormonal environment of the uterus in this scenario is more “amped up”, so to speak, than it would be if not for the controlled hyperstimulation. In contrast, a frozen embryo transfer takes place without the aforementioned “amped up” hormonal environment. Rather, this type of embryo transfer occurs in a uterus that more accurately mimics what transpires during spontaneous implantation.

Let’s cut to the chase. The results of the study were nothing short of interesting. In women using their own oocytes (eggs), the odds of ectopic pregnancy were found to be 65% lower if they had a frozen embryo transfer in comparison to women who underwent a fresh embryo transfer. That’s undeniably significant. However, in terms of absolute risk, the following statistics might help to put it into perspective. In terms of women undergoing IVF, the estimated overall rate of an ectopic pregnancy occurring is relatively low, at 2-5%; compared to a rate of 1-2% in women with spontaneously occurring pregnancies.

Why the difference between fresh and frozen transfers rates you ask? It appears that the ovarian hyperstimulation that is typical in IVF cycles creates a uterine environment that increases the chance an embryo will fail to implant into the endometrium (where we want it to go!). Suggested explanations for this include the effect that the supraphysiologic hormone levels may have on uterine contractility and/or the receptivity of the uterine lining. It is also possible that the oocyte retrieval procedure that takes place six days prior to a fresh embryo transfer may contribute to ectopic implantation.

Does this mean that we should forgo fresh embryo transfers altogether to avoid any chance of ectopic pregnancies? Definitely not. As with any research, there are many other variables that need to be considered when calculating risk; such as the number of embryos transferred, race, maternal age, and IVF treatment protocols. Also, don’t be fooled into believing that the risk of an ectopic pregnancy is null (absent) in women who opt to undergo a frozen-thawed embryo transfer. All we can conclusively say is that the differences in the uterine environment based on transfer type may play a role in the risk for abnormal or ectopic implantation, and it is something that needs careful consideration. Once we recognize this universally, we can have a greater degree of suspicion for ectopic pregnancies, which may allow providers to intervene earlier to improve maternal outcomes.


Huang, B., Hu, D., Qian, K., Ai, J., Li, Y., Jin, L….Zhang, H.  (2014).  Is Frozen Embryo Transfer Cycle Associated with a Significantly Lower Incidence of Ectopic Pregnancy? An Analysis of More than 30,000 Cycles.  Fertility and Sterility, 102(5), 1345-1349.  doi:http://dx.doi.org/10.1016/j.fertnstert.2014.07.1245

Londra, L., Moreau, C., Strobino, D., Garcia, J., Zacur, H., & Zhao, Y.   (2015).  Ectopic Pregnancy After In Vitro Fertilization: Differences Between Fresh and Frozen-Thawed Cycles.  Fertility and Sterility, 104(1), 110-118.  doi:http://dx.doi.org/10.1016/j.fertnstert.2015.04.009

MedicineNet.  (2013).  Definition of Ectopic Pregnancy.  Retrieved from http://www.medicinenet.com/script/main/art.asp?articlekey=3188

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