Sunday, June 9, 2013

What matters in an antagonist IVF protocol

There have been many, many studies conducted to optimize the IVF protocol. I looked at some of the questions that seemed relevant to my situation, and this blogpost discusses what I found.

Fairly conclusive: Stimulation  with a lower dose (150 IU follistim/day) may be a good idea
  • Study 1: The proportion of chromosomally normal embryos was higher in patients subjected to a mild stimulation (150 IU/day, antagonist started when lead follicle reached 14 mm) than in those subjected to a convention stimulation (long term downregulation with agonist, 225 IU FSH/day).
  • Study 2: Another group (which compared 225 IU vs. 150 IU, with both groups receiving agonists) reported a similar finding, and also observed that the fertilization rate was higher.   
Note: As expected, the low stimulation dose elicited fewer eggs, with a greater frequency of cycle cancellation. But here is the striking part: the total number of chromosmally normal embryos was similar between the two groups.  So basically, stimming with a higher dose puts your body through the wringer
for no real advantage and even a possible disadvantage in that it may decrease the quality of the embryos you produce and make you go through the emotional and financial turmoil of more embryo transfers and possibly pregnancy losses, while not affecting the live birth rate.

No real difference evident:  Comparison of Follistim and Menagon

  • Study 1: Study in women of advanced reproductive age: Comparison of Follistim and menagon on aneuploidy rates:  follistim is slightly better, but this difference did not reach statistical significance. The clinical pregnancy rate was significantly increased in the Follistim Group

Mixed findings: Agonist vs. Antagonist

  • Study 1: The agonist protocol produces more embryos, but is associated with a lower clinical pregnancy rate.
  • Study 2: No difference in the clinical pregnancy rate observed, but the antagonist protocol conclusively reduces the risk of OHS.

Conclusive: The antagonist dose can be reduced

  • Study 1: Giving the antagonist (0.25 mg/day) daily or every other day does not appear to make a difference.
  • Study 2: Doses of 0.25 mg/day (standard) or a 0.125 mg/day dose of the antagonist elicited similar results in IVF

Difficult to figure out: The best time to start giving the antagonist

The choices are Day 1-4 (with the FSH), Day 6, or individualized (when the lead follicle reaches 14 mm).

  • Study 1: A study comparing the day 6 and the individualized protocols found that the individualized one worked better (generated more oozytes, while requiring a lower amount of FSH) 
  • Study 2: No difference seen between Day 1 start and a day 6 start.
  • Study 3: A day 4 start was better than a day 6 start. 

 Difficult to figure out: To supplement or not with LH?

  • Study 1: A analysis of a large number of clinical trials examining the effect of LH supplementation in an antagonist protocol showed a benefit (increase in pregnancy/live birth rate) only in the poor responder/pregnancy loss group.

So--- based on all that, all I know is that a low dose FSH regimen is a good idea, and I should not get greedy and increase this, because quantity (growing follicles seen on the ultrasound) is not what matters, it is the quality of what is recovered in the end. Additionally, I could take the antagonist every other day without it making a difference.

Where I am in the dark about: When should I start the antagonist? Should I take any additional LH? In other words, am I a poor responder, who may benefit from a little, but not a lot of it?

Here are my choices....

Protocol choice 1
Start Follistim (150 IU/day) CD2 onwards
Start antagonist (0.25 mg every other day) on the day when the lead follicle hits 14 mm.
Trigger 10,000 units HCG
Pros: super easy on me, only 1 injection/day for a while.
Cons: A higher LH level early on may be detrimental.

Protocol Choice 2
Start Follistim  (150 IU/day) CD2 onwards
Start antagonist (0.25 mg every other day) CD2 onwards
Trigger 10,000 units HCG
Pros: Not so many injections
Cons: A total lack of LH early on may be detrimental.

Protocol Choice 3
Start Follistim (150 IU/day), CD2 onwards
Start antagonist (0.25 mg every day) CD2 or 3 onwards
Low dose Luveris (37.5 IU/day) CD4 onwards
Trigger 10,000 units HCG
Pros: Everything is very controlled; you cut off LH almost completely and supplement with a measured small quantity every day. This has shown to do no harm, and there is the slight chance it will help.
Cons: Luveris is expensive. Many more injections required.  Plus, it comes in an ampoule form containing 75 IU, which means I'd either waste half an ampoule, or have to take 1 injection every 2 days.

If anybody can wade through this knowledge dump and offer any feedback after, please do. Please, please, please, share your own experiences with regard to any of the points discussed in here: FSH dose, Antagonist dose and regimen, and the choice of adding back LH.


  1. While I do not understand the science, I wish you all the best.

  2. Dear Jay,

    Nice to know that you are starting your IVF cycle again. Since you had the problem of asynchronous follicle growth, I would avoid antagonist protocol if I were you ! Don't you think long lupron protocol or something similar will help you to grow follicles synchronoulsy ? I will tell you what gave me synchronous follicle growth and good egg yield. I was on BCP (birth control pill) to regulate my cycle (just took for 9 days !) . Three days before stopping BCP, I started lupron. I continued lupron thereafter and started stimulation from day 1. This is the cycle I had the best egg yield and had the maximum number of embryos. But what worked for me need not have to work for you too ! In the protocol I mentioned above, your natural FSH will be suppressed by BCP, and when you overlap BCP with lupron for few days there will be a flare effect (lupron triggers a spurt of FSH release !) which will jump start your antral follicles perhaps synchronously ! (AFCs are the ones which respond to FSH). Jay, I read Dr. Sher's post on overlapping BCP and lupron and ended up with a protocol like what I mentioned above :) Do not ask me what kind of protocol is that and what is its name :) I do not know. It is not a long lupron though ! Good Luck ! Hope it is of some help to you.

  3. Thanks Manju. Its a valid point you bring up, I think synchronization and the number of oocytes would be improved with an antagonist protocol, but I don't think a lack of synchronization was the main reason my IVF failed. I had 6 "synchronized" eggs with no pregnancy.

    So everything I'm doing here is designed

    1) to improve the quality of the eggs, not the quantity of the yield. You could end up with 15 eggs and no clinical pregnancy..or with 1 egg and a pregnancy.

    2)be as kind to my system as possible. The antagonist protocol is definitely easier than the long agonist protocol.

    There are trials which show that the long agonist and the antagonist protocols offer no real advantage over the other now with respect to the success rate, and there was one which showed that the antagonist had a mild advantage in terms of the pregnancy rate.

    However, the differences are so mild that its always hard to say. Nonetheless, 2 things are clear: a huge dose of stims and a high amount of LH early in the cycle may not be a good idea, and that is what I'm trying to avoid.

  4. For anybody reading this discussion afterwards: While I was not aiming for synchronization, there turned out to be fabulous synchronization (9 follicles were synced up in the left ovary and around 7-8 in the right ovary) with the antagonist protocol.

    Interestingly, the 2 ovaries themselves were not very well synced, with the left responding faster than the right. Interestingly, the right caught up in the end, after I added a little LH 2 days before trigger, and we got 19 eggs, 16 mature, 15 fertilized, 8 blasts.

  5. Jay, your blog has been a godsend for me. You're so kind to share your accumulated wisdom.
    I currently have one IVF behind me and am preparing for a second. I can't tell you how often I stop by here to get advice.

    Many thanks!

  6. You are welcome Elizabeth; thanks for your comment; it has nudged me into adding something I've been meaning to add for a while :) Best of luck with your next cycle...I remember very well how scary this time is.