What matters in an antagonist IVF protocol

on Saturday, June 8, 2013

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.

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