Researchers in a 2021 study compared IVF outcomes in patients who had more than 1 IVF cycle and found that patients who stuck with their original protocol had slightly better outcomes compared to those who switched.
With all the different protocols available, multiple studies have looked at different contexts (PCOS, DOR, BMI, age, ovarian response, etc) and have shown that one protocol may be better suited over another. This kind of information is used to guide the choice of protocol by the physician. But sometimes things don’t go as everyone hopes and for one reason or another the ovarian stimulation protocol may be changed. So is it better to stick with your current protocol, or to try something different? Does it matter which protocol is used?
This is the question that Wald et al. (2021) asked. In their single center, retrospective study they looked at nearly 4500 cycles that had at least two IVF cycles within 12 months. Half of them stuck with their original protocol, and the other half switched to another protocol. Most of the diagnoses were DOR, unexplained infertility, and male factor. The different protocols included:
- E2 priming with antagonist
- Antagonist with or without OCP priming
- Long lupron
- Lupron stop
- Flare (NOT microdose lupron flare, this protocol included an endogenous FSH flare from clomid/letrozole treatment)
They looked at a number of different IVF outcomes, and also at subgroups that had poor fertilization or blastocyst progression during their first cycle.
🔗 Original studies are referenced in this post or within the linked Remembryo posts.
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Eggs retrieved (only the statistically significant changes are shown):
- 1st: Antagonist; 2nd: Antagonist – patients averaged 2.20 more eggs in the 2nd cycle
- 1st: Antagonist; 2nd: Flare – patients averaged 4.60 fewer eggs in the 2nd cycle
- 1st: Antagonist; 2nd: Lupron stop – patients averaged 2.54 fewer eggs in the 2nd cycle
- 1st: Flare; 2nd: Flare – patients averaged 2.14 fewer eggs in the 2nd cycle
- 1st: Flare; 2nd: E2 priming – patients averaged 1.17 more eggs in the 2nd cycle
- 1st: Flare; 2nd: Lupron stop – patients averaged 2.45 more eggs in the 2nd cycle
- 1st: Flare; 2nd: Antagonist – patients averaged 4.60 more eggs in the 2nd cycle
Fertilization rate. There was no improvement in fertilization rates when there was a protocol switch. However, when the protocol stayed the same, the fertilization rate improved only slightly (by 2% – compared to those who switched).
Blastocyst progression. No improvement in the second cycle for those who switched and those who didn’t.
Number of usable blastocysts (that were of acceptable quality for this center). There was no improvement in the number of usable blastocysts when there was a protocol switch. However, when the first and second protocol was the antagonist protocol, there was an increase in the number of usable blastocysts by 1.22 (compared to those who switched).
Euploid rates. No improvement in the second cycle for those who switched and those who didn’t.
Women who had low fertilization in the first cycle (subgroup). No improvement in the second cycle for those who switched and those who didn’t.
Women who had low blastocyst progression rates in the first cycle (subgroup). There was no improvement in blastocyst progression rates when there was a protocol switch. However, when the protocol stayed the same, the blastocyst progression rate improved only slightly (by 3% – compared to those who switched).
Overall, women who repeated the same protocol saw a slight increase in eggs retrieved (2.2 more eggs), fertilization rate (2% increase), and usable embryos (0.2 more). These differences are pretty minor, and based on this data switching protocols doesn’t improve IVF outcomes.
Of course, the big omission here is that they didn’t compare the different patients groups by diagnosis, particularly the DOR group which made up about 40% of their patients. They admit it’s unfortunate that they didn’t have AMH/AFC data so they could see if the DOR diagnosis had an improvement with certain protocols. Depending on your definition of DOR, some evidence shows that different protocols can work better, although it is controversial (Blumenfeld (2020)).
However, as this study is suggesting, it’s possible that the choice of ovarian stimulation protocol isn’t as important as we think. The most important factor might just be having another IVF cycle. Statistics are only meaningful when repeated attempts are made, just like flipping a coin once or twice isn’t enough to guarantee you’ll see heads. By having multiple cycles and “regressing to the mean“, you’re approaching the average as determined by the statistics. In other words, your first cycle may have been just due to bad luck, and people who have had multiple cycles tend to have more consistent results in general.
As a plus, this was mostly a mixed bag of patients (and a lot of them!), which is nice because it gives an idea of what an average person undergoing IVF might expect by changing protocols.
Reference
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About Embryoman
Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.
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