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IVF cycle: Mini-Stim Protocol and Reproductive Physiology

Updated: Nov 16, 2021

Well, I almost had my cycle cancelled. It’s been a whirlwind!

Previously, I had Gonal-f stimulations and no antagonist, so ended up having a peak in endogenous LH. It went from 11 on Sunday to 99 on the Monday.

After seeing these results, my IUI cycle was cancelled (previously cancelled IVF) and it was converted to timed intercourse; No different than what we were doing before. But I learnt that my follicles don’t grow that large before ovulation (around 13mm for a natural ovulation). The diameter of the ovulating follicle will be predictive of the size of the CL post-ovulation. Small ovulating follicle = small CL, less progesterone to carry you through to implantation and ultimately miscarriage. That's basically my dumbed-down version of the science.

This is my second stimulation cycle. We used a mini-stim which is supposed to be better for poor responders and it was combined with Clomid.

Mini-Stim Protocol

Everyone online in the TTC community wants to know what is the best protocol to maximize embryo production. Even in cattle reproductive research, we are always trying to maximize this as well.

So I will just give you an idea of what protocol I used this round.

My prime was with Estrace + Androgel (as previous) and this was stretched slightly so that I could time it with my work schedule. Following about 3 weeks of Estrace + Androgel, I added Provera (compared with Prometrium) for a week. We waited for "day 1" of my menstrual cycle, but essentially, six days after stopping the Estrace, Androgel and Provera I started on Clomid and Saizen (human growth hormone that is supposed to improve egg quality). After 5 days of Clomid and Saizen, I added in Menopur as my gonadotrophin to continue the growth of the follicles. Then I went in for my first ultrasound scan since starting the Estrace. This is when my heart sunk, I was devastated. I cried. I mourned over the loss of those precious follicles, how could I go from 10 to 3 antral follicles??

I still believe that the estrogen (Estrace) over suppressed my ovaries. At least according to this paper, Estrace should be used mid-luteal for a maximum of 10 days. I guess that is also something to think about. Most of the time, they are manipulating the duration of your priming cycle to fit within their own schedule, or mine in this case, and in same cases to ensure that they aren't having to come into the clinic on the weekends for oocyte collection. You also only have so many timeslots in the OR for these procedures!

In my previous stimulation cycle I didn’t have Clomid and I didn’t have an antagonist. Clomid is supposed to suppress the Estrogen signal to the brain which signals the release of LH - that LH peak. Both the REI and primary doctor agreed on this, that I should not break through and ovulate on my own.

So when my primary doctor mentioned that we should cancel, I was choked! They were advising me to cancel my cycle because my LH was too high. They mentioned that we should give me something to suppress the LH, but it should have been started at the beginning of the cycle. Which conflicts with my previous REI who mentioned that you can’t give the antagonist too early as it will suppress them all. How confusing is this?! Not to mention that they keep bringing up this 'empty follicle' issue.

I then spoke with my new REI, they said that Clomid will cause an increase in LH. Clomiphene is a selective estrogen receptor modulator. It essentially tricks the body to not recognize the increase in estrogen that is being produced from the dominant follicle(s). The less estrogen that reaches the brain, the more FSH and LH that ends up being released from the pituitary.

It’s a bit tough living somewhat remotely as there is no REI (reproductive endocrinologist and infertility specialist) near me. Which means I’m getting conflicting information. I will always defer to a specialist, when it comes to veterinary medicine and my own health. This ends up being a lesson in advocating for yourself.

Some of the older research showed clomiphene alone can contribute to poor IVF response, which is why the primary care doctor wanted to cancel.

Essentially, these researchers created a cut off of mean + SD = 20.6; everyone above this level of LH was found to have a poor response for IVF, having lower fertilization, lower cleavage rate and lower pregnancy rate.

Today my value was 25. Yesterday it was 20. So, statistically, based on this one study, it's not looking good.

I will keep you posted on the events, but I really just wanted to plug the cross-over information between human reproductive physiology and cattle reproductive physiology. Physiology is still physiology. Know your form and function and what kind of response are you looking to achieve. Once you know what normal physiology is like, then you can manipulate these with medications.

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