Size of follicles at trigger: is bigger always better?

You responded pretty well to your stimulation protocol for IUI or IVF and you are approaching the finish line.

Your ovaries are growing a certain number of follicles (the more the merrier for IVF, under 5, usually, for IUI) and you are anxiously waiting for the liberating trigger shot.

Be it a urinary-derived hCG like Novarel or Pregnyl, a recombinant hCG like Ovidrel, or an agonist such as Lupron or Decapeptyl, the trigger shot will provoke a surge of LH which will add a final touch to your follicles and will help them burst.

If choosing the right protocol for the right patient is a work of art, please know that timing the trigger shot is not less important!

Trigger too early and your oocytes will be immature. Trigger too late and it may be…too late.

How do we decide when to trigger? Is follicle size the only indicator? Or are there other aspects we should consider?

As the follicles grow in size during the follicular phase of your cycle they start putting out estrogen, which in turn thickens your endometrial lining, preparing it for implantation, in case conception occurs. In natural cycles, when only one dominant follicle is being recruited, the pituitary gland will release the LH surge that will start ovulation based on the level of estrogen your follicle is releasing. To put it in simpler words: your brain doesn’t know what size your follicle is, so it will rely on your detected estrogen level.

This is why Reproductive Endocrinologists prefer to check your estrogen levels during stims, and not rely solely on your follicle sizes when triggering you.

When a follicle is mature enough, it usually puts out between 200-400 ng/ml estrogen.

Studies show us that if the total estrogen level does not impact IVF outcome, the serum estradiol per mature follicle is extremely important.

How does that translate into plain English? Basically, you may have a total estrogen level of 450 at trigger, for two mature follicles and have success, and fail with a total estrogen level of 2000 for 20 follicles.

One question that occurs obsessively on infertility groups and forums is “what size should my follicles be at trigger?”

The truth is no one can answer this question for you. For some women, follicular maturity occurs when lead follicles have sizes between 15 and 18 mm, for others when follicles are well over 20 mm. Hence the importance of having the serum estradiol level tested before trigger, and doing the math.

Last but not least, different protocols may impact the size of follicles.

It has been demonstrated that in Clomid and Letrozole IUI cycles, higher pregnancy rates were achieved when the lead follicles were in the 23 to 28 mm range.

What happens if estradiol levels are not tested before trigger, and we end up with immature follicles? In case of IUI not much can be done to save the situation. The released egg has to meet the sperm on its own and be “fertilizable”. If it is immature, fertilization most likely won’t occur.

In case of IVF the situation is a little bit different. There are clinics that practice the "In Vitro” oocyte maturation. This technique, initially used for patients with PCOS and patients who had severe Ovarian Hyperstimulation in their previous IVF treatments, is now being used for many other reasons: oocyte maturation problems, poor responders, rescuing IVF cycles, older patients. The treatment is not considered to be a conventional one, it is only used as an alternative, and again, not every fertility clinic has the means to do it.

What happens when we trigger too late? The term “over mature”/ “post-mature” oocyte does come up often in patient/doctor conversations but the truth is it is not well explained in medical literature. The proven risks of triggering too late are premature ovulation, despite the administration of an antagonist to prevent an LH surge, premature raise in progesterone levels impacting endometrial quality and therefore implantation in case of fresh transfer, and also ovarian hyperstimulation in the case of women with normal ovarian reserve or PCOS.

You may be the lucky winner of an amazing clinic that triggers you at the most perfect moment. But in case you've happened to hear the phrase "your follicles were immature on egg retrieval" too often, maybe you should talk triggering options together with your doctor, just to make sure you've got all your bases covered.