Sharing some insight about estradiol levels.
Estradiol: What It Is and What It Tells Us.
The level of estradiol is measured in almost every blood sample taken during the monitoring of almost every type of assisted pregnancy. It is arguably the most informative of the three tests. Because of this, we will spend more time and space on estradiol. Don't worry-- the other two won't be nearly as long.
Estradiol is a hormone that stimulates the lining of the uterus, causing the lining to grow, and to make itself ready for embryo arrival. (This is not estradiol's only function, but for us, it's the important one). Estradiol is tied into pregnancy by it's method of production: oocytes (eggs) contain follicles. These developing follicles contain 'granulosa cells'. These granulosa cells synthesize the estradiol and release it into the blood circulation.
This means that more follicles produce more estradiol. This helps measure how many follicles are actively developing. The longer they continue to develop, the longer the estradiol level continues. As they develop, the level continues to rise. This rise can further indicate that the oocyte within the follicles is reaching its maturity.
An example of the use of estradiol level is when it is measured during down-regulation cycles. In down-regulation we expect low levels of estradiol: below 30pg/ml. If levels are not this low, this suggests that the ovaries are not yet suppressed, and that the down-regulation should continue a little longer, until they actually are suppressed.
Estradiol And Ultrasound Scans
Blood estradiol is also used in combination with ultrasound scans. Taken together they help indicate how (and if) the ovaries are responding to stimulation. Is there a response? Is it adequate? Is it excessive? To tell us this, the blood level has to be viewed in relation to the stage of pregnancy and the day in the cycle in which the level is being taken.
For example, a level of 1500 pg/ml on day eleven might be considered acceptable in a stimulated cycle, as reflecting the presence of a reasonable number of mature follicles. However, if this level were present on day eight, it would be considered unacceptably high. It would almost certainly reflect the presence of an excess of follicles. At this stage (day eight) they would still be Immature ones. Their quantity, however, would suggest that continued stimulation would carry an unacceptable risk of developing OHSS-- ovarian hyperstimulation syndrome.
Don't Expect Easy Comparison
Before we continue, one important point: levels of estradiol are not the same from person to person. They cannot simply be compared from one to another. People vary-- everyone is slightly different, and everyone responds to a different degree. Some more so than others. A level that is dangerously high in one person-- or dangerously low in a second-- might be normal and healthy for a third. This is why blood levels can't just simply be compared. It's also why blood levels can't always be interpreted with complete certainty in the first cycles. Without prior cycles to 'calibrate' the levels, the meaning of a level can only be determined as to what it usually means-- what it 'probably', or perhaps even 'almost certainly' means.
Despite individual variation, estradiol level does provide very useful information.
A Rough Rule-of-Thumb for Good Estradiol Levels.
Exact figures are not possible. As a rough guide, however, a level in the range of 150 to 500 pg/ml is generally considered reasonable for the eighth day of a stimulated cycle. An approximate doubling of this level every 48 hours is considered promising, as a sign of continued good follicle development.
When the Estradiol Level Stays Flat or Begins to Fall.
Occasionally, the level of estradiol fails to rise during a cycle, or even falls. If this happens it strongly suggests that the follicles are not responding appropriately, and that the oocytes within will not be of good quality. Under these circumstances our advice is almost invariably to cancel the cycle, because a change in stimulation protocol may yield more oocytes-- and healthier ones-- in a later attempt.
Low Estradiol Not Always a Problem
A more common situation is when the level is low in the early part of the cycle. The choice then is to either carry on with the same amount of stimulation, to increase the amount of stimulation, or to cancel the cycle. This decision has to be based on a number of factors. These include:
the previous response to stimulation chronological age how low the level is
the ultrasound appearance of the ovaries is there a pressing need to ensure that an optimal number of oocytes are obtained, as in the case for couples with male factor infertility?
How It All Comes Together with Estradiol.
It should be clear from all of the above that estradiol levels do not tell the entire story by themselves. One level leads us to advise a couple to cancel. The same level in another couple leads us to suggest continuing.
We've already discussed levels that are low. When levels are high, we have the same choice: change the stimulation (reduce it), or cancel the cycle. The criteria to consider are the same as for low levels. The one additional factor is that with high levels we also think carefully about OHSS (ovarian hyper-stimulation syndrome). When assessing the risk of OHSS we look to previous cycles, if there are any. Any suggestions from these cycles of OHSS problems would quite definitely weigh heavily towards cancelling the cycle.
When the decision is to proceed, levels of estradiol continue to be monitored. If they continue to exceed acceptable levels, even with reduction in stimulation, we might reassess the cycle, and once again advise cancelling. If however they do return to normal levels, then the cycle will continue.
What is the limit of acceptable estradiol level? Acceptable levels vary-- it's not possible to give a definite, absolute number. However, any level of 4000 pg/ml or above does require careful consideration. Levels that are much in excess of this usually do lead to cancellation, though not always.
What about the lower limit? This too involves many factors. However, if the estradiol level has not reached a minimum of 600pg/L (**** beth-- should this be per liter, or per ml?***), then our usual policy is to discontinue the cycle. In practice we usually don't proceed unless the ultrasound shows three or more mature follicles. Since estradiol levels and the total number of follicles are related (as discussed in the beginning of this essay), this by itself eliminates most of the possibility for levels at or below this lower limit. Three or more mature follicles will, under most circumstances, secrete enough estradiol by themselves to give a level in excess of this minimum.
Do bear in mind that the above are only a rough, rule-of-thumb guides, however. They can and do vary depending on individual circumstance.
Luteinizing Hormone, or "LH": What Is It and What Does It Do?
Before the introduction and widespread use of drugs such as Lupron, assessment of luteinizing hormone was at least as important, if not
more important, than estradiol levels. It remains an important test for anyone undergoing any cycle where Lupron or Synarel (GnRH agonist) is not being used. This is because, without Lupron, an early unwanted LH surge may occur.
LH Surges (note: the next entry implies that an LH surge is desirable, and necessary. This entry implies that it isn't. How do the two reconcile? is early=bad, but near end=necessary?)
A surge in the level of LH may cause undesirable changes in egg quality, or cause early egg release. Both of these decrease the chance of pregnancy. Regimens such as Clomid, Clomid/Pergonal cycles, or "straight" Pergonal, Metrodin or Humegon cycles all must include urine LH testing (for instance, Ovuquick, or ClearPlan Easy). If a sudden rise in the level of LH is detected (often termed "an LH surge"), this indicates that the process leading to ovulation and release of the oocyte has begun. It is this process that is blocked, in the vast majority of cases, by the use of Lupron. Unfortunately, there is no way of knowing when a rise in the level of LH actually begins, except for testing blood or urine every three to four hours. This makes it virtually impossible to accurately time egg retrieval. This timing is necessary to be certain that the oocytes are mature. Because of this problem, the cycle is usually canceled if an LH surge is detected.
