The ‘right’ dose of FSH for an IVF cycle?

In retrospect, it is easy to say that your specialist selected the ‘right” dose for your IVF cycle if you are pregnant . However, as you should be aware, the majority of woman who have an embryo transferred will not be pregnant in that cycle. 30-40% success is pretty standard in women under 38 years. After that first cycle, many women will be fortunate in having frozen embryos from that fresh cycle. But ultimately 60% of women, who start the IVF Journey, will need a second fresh cycle in continuing that Journey.  At that point it is important that your specialist reviews the previous cycle. They should be looking at your response to the FSH dose they originally chose.  

Before we discuss the decision making for the second cycle, let’s go through the process a specialist should go through when they decide the type of drugs and the dosage for the first cycle. Most of us are aiming in an ideal world of getting between 10-12 eggs. Such numbers should virtually guarantee one or two blastocysts (day5 embyros). Nature produces a number of “dud” eggs that will either not fertilise or not grow on to Day 5. In choosing the dose we don’t want overstimulate cos that can lead to Ovarian Hyperstimulation Syndrome and hospitalization. And while there are more eggs, their quality may be affected. Nor do we want to under stimulate since it reduces the odds of even achieving an embryo to transfer. 

The factors that should be taken into account are 

1.       Woman’s age 

In general as a women gets older, her ovaries reaction to FSH drugs declines. This is mainly due to reduced egg numbers. 

2.       Antimullerian Hormone Level (AMH) 

This protein is made by the immature follicles that will become mature in time. Its level is a very good predictor of the reaction of the ovaries to FSH stimulation- the higher the levels the more eggs we can expect. 

3.       Maternal weight 

Probably because of the leakage of FSH drug into the adipose tissue, women over 90 kg generally need higher medication doses. 

So the specialist should use these parameters to estimate the best dose. On top of these specific things, experienced specialists will have a gut feeling based on hundreds/thousands of previous cycles that they have managed.  

There are clinics who believe low doses are better whatever these three parameters are indicating. Their rationale is 1. It avoids any risk of overstimulation and 2. Th eggs are alleged to be better quality cos it is “more natural”. There is no evidence to support this view. It does lead to more cancelled cycles or cycles where there are no embryos. It does mean lots of repeat cycles which might be good for the doctors involved. 

I use the following table 

AGE <30 yrs 30-35 yrs 35-40 yrs 40+ yrs 
FSH dose/day 100 150 200 300 
AMH  
>20 (minus 25 IU) 75 125 175 275 
<5 (plus 50IU) 150 200 300 400 
WEIGHT 
>95kg (plus 50IU) 150 200 275 375 
< 50 (minus 25IU) 75 125 175 275 

Despite this approach, I get surprises since there is clearly more to the sensitivity of the ovaries than these variables.  

So let’s go back to the situation of an unsuccessful first fresh cycle. In arranging the next cycle, the specialist should review all aspects of the cycle.  

  1. Was the response to medication appropriate in term of the rate of growth of the follicles 
  2. Did they grow at the normal rate? 
  3. Was the length of stimulation to get to the trigger day longer than average? 
  4. How many good sized follicles were there? 
  5. Are we sure all medications were taken at the correct times? 
  6. Once the trigger was given, did egg collection occur between 36-38 hours later? 
  7. How many eggs were retrieved? 
  8. How many were mature (if undergoing ICSI)? 
  9. How many fertilized? 
  10. How many grew on? If they didn’t, which day did they fail? 
  11. Was the embryo transfer straightforward? 

Having asked these questions, the specialist should reassess the management of the unsuccessful cycle. 

Generally they would vary the dose if the egg numbers were different to the expected 10-15eggs. This would mean increasing the dose if low numbers or reducing the dose in high numbers. However from cycle to cycle women vary in their ovarian response. A Melbourne study did give the same dose in three consecutive cycles and the number of eggs varied up and down by as much as 50 %. So changing the dose may not necessarily improve the yield. However I do believe tailoring the dose once we have seen a cycle, is worthwhile. 

The other change that specialists often make in subsequent cycles is the type of FSH medication. In Australia the commonest used preparation is Gonal F. Why? Because it has been around the longest time. There are, however, a number of other options of just FSH like substances 

Puregon 

Benfola 

Elonva 

Recoville 

All these have slightly differing biochemical structures and are made in differing ways. But randomized controlled trials suggest that over large groups of patients there is no differences in success.  

There are also drugs that combine FSH with chemicals which have an additive action of LH. 

Menopur 

Progoveris 

Their main indication is if you have low LH levels during that last cycle. Some LH is important for good growth of follicles. These preparations may be helpful in those cases. 

 Your doctor may make the judgement to change medication brand and type for many reasons – the ease of the pen use, their anecdotal experience in the past or even how nice and helpful that the pharmaceutical reps are.  

We justify a change after an unsuccessful cycle , since for you as an individual, one drug MIGHT be better than another. 

The most important aspect of your care is that your specialist has the expertise and knowledge to be able to assess your previous cycle(s) and modify the treatment to maximise your chances of success. It is not as simple as following a recipe book!