Jumping the Gun: Progesterone Levels Before Oocyte Retrieval and IVF Success

While every IVF clinic does things a bit differently, there is broad consensus that the two core components of “monitoring” response to medication during an IVF cycle include:

1. Blood estradiol
2. Follicle growth as measured by transvaginal ultrasound

That said, there are multiple reasonable approaches to IVF; some clinics also like to check other hormones, such as FSH, LH, and progesterone at certain times during the IVF stimulation.

Three recent studies (links below) highlight growing evidence supporting the importance of checking progesterone during an IVF cycle, particularly in the latter part of the cycle (after 6 or 7 days of medication). Progesterone is the hormone that causes the uterine lining to become receptive to pregnancy (“pro-” i.e. supporting, “gest” i.e. gestation/pregnancy). In normal physiology, progesterone is produced mainly by the corpus luteum, the structure resulting from the follicle after the egg has been released. By definition, therefore, progesterone action is timed by nature to kick in after ovulation, when a conceptus may be looking for a place to implant.

In an IVF cycle, however, due to the growth of multiple follicles (rather than just one, as nature would have it), progesterone levels sometimes start to rise prematurely – before ovulation, and even before the oocyte retrieval is performed. Early exposure to elevated progesterone levels is theorized by some to have detrimental effects on an embryo’s ability to implant. In other words, even the slight increase in progesterone levels caused by the IVF stimulation may throw off the synchronicity of the embryo and the lining enough to decrease chances of pregnancy.

There have been multiple studies aiming to address this subject in the past 10-20 years, and the results have been inconsistent. Many of these have been small studies using different cutoffs for what is considered an “elevated” progesterone level. Two of the studies cited below are amongst the largest ones that demonstrate a link between elevated progesterone and decreased chances of IVF success. The third, and perhaps most intriguing, takes this idea of “progesterone timing” even further and looks at the duration of progesterone elevation in addition to the amount. Taken together, I believe these studies warrant serious consideration when there is evidence of a premature progesterone rise prior to egg retrieval in an IVF cycle. While no studies address the question of what is the best plan of action in this situation, one logical option would be to forgo a fresh embryo transfer in order to allow the lining to “recover,” and plan for a frozen-thaw cycle with a healthy, well-timed lining 1-2 months later. 

1. Subtle progesterone rise on the day of human chorionic gonadotropin administration is associated with lower live birth rates in women undergoing assisted reproductive technology: a retrospective study with 2,555 fresh embryo transfers.
2. Premature progesterone rise negatively correlated with live birth rate in IVF cycles with GnRH agonist: an analysis of 2,566 cycles.
3. The duration of pre-ovulatory serum progesterone elevation before hCG administration affects the outcome of IVF/ICSI cycles.