A Little More About Normal Ovulation

Here is a question someone asked about the timing of hCG. It’s a good starting point for this blog.

“I am 40 and just had a failed first IVF cycle that resulted in all immature eggs (7 retrieved) after only 5 days of stims (follistim/menopur + ganirelix days 4 & 5) before the hCG shot.
The doctors were very surprised that by day 5 I had 7 follies 12 - 19 (more <10) and they said I had to trigger, my final E2 was only around 700. I had a good hCG level after the trigger.

I have never heard of anyone only stimming for 5 days. I am curious what your experience has been with people who are fast responders and what you recommend in terms of changing protocols? Do you believe that follicle size alone determines egg maturity or can a short follicular phase be a problem even with larger follicles?”

Figuring out the right time is not that difficult, but there are a few important factors that must be taken into consideration. We need to first start with a brief review of what happens in the natural menstrual cycle, then it will be easier to understand how the IVF cycle works. There are 3 important elements: the growing follicle’s schedule, estrogen levels, and the size of the follicle at ovulation.

Just a reminder: the follicle is the fluid-filled cyst that houses the egg. Each follicle has one egg. We can't see the egg on ultrasound because it's microscopic. But we can see the follicle.

The Growing Follicle’s Schedule: By the 2-3rd day of bleeding, the previous month’s follicle has disappeared and the new one, which has already been chosen, has not started to grow much. On ultrasound you may see it, but you may also see other small ones that look the same. It’s the FSH coming from the pituitary gland (the pituitary will be a blog to come) which causes the little follicle to start and continue to grow.

As the next week goes by, the chosen (or dominant) follicle gets bigger and bigger, until it ovulates somewhere usually between days 11 and 20, most often close to day 14. It’s pretty rare to ovulate before day 11, but not so rare to ovulate later. The day of ovulation is related when the follicle starts to grow, and the cycle length gives us a hint as to when this was. It takes about 2 weeks for the follicle to grow from tiny to big. That means for a 28 day cycle, the follicle grows till ovulation, usually day 14.

What if the cycles are, say, 35 days? Well it still takes the 2 weeks to grow, it just starts later. So for a 35 day cycle the early follicle sleeps for about a week, then wakes up and starts growing day 7 and ovulates day 21. We don’t know what causes these differences.

What if the cycle is 24 days? In this case the follicle probably takes less than 2 weeks to grow, so 2 weeks is not mandatory. Again, the reason for these differences are unknown.


Estrogen Levels: As the follicle grows, it makes more and more estrogen, so the blood levels of estrogen rise each day. The estrogen is not coming from the egg, it comes from the tons of little ovarian cells (the granulosa cells) that surround the egg. The estrogen is probably not important for the egg, but one of estrogen’s very important jobs is to thicken up the lining of the uterus.

Estrogen’s second job is to cause the ovulation. The pituitary gland is constantly monitoring the estrogen levels, and when they get high enough, the pituitary dumps out LH (this is what your home ovulation kit reads) and this is what causes the egg to pop out.

There is not an exact estrogen level that causes the ovulation. Most of the time it’s anywhere from 150 to 350. Why there is a difference we do not know, it may be that there are other unknown hormones that work with the estrogen to get the job done.

Follicle Size: The size of the follicle is important too. Most ovulations occur with a follicle that is 20-25 mm(about one inch), but 16 mm is close to the bare minimum and 30 mm is close to the top size.

Next time we will talk about the timing of ovulation in an IVF cycle.

Thanks for reading,

Dr. Licciardi