Low dose or high dose stims for DOR? Does it make a difference?

Not one week passes without someone in my Facebook group complaining a high dose stimulation cycle failed her and she was directed towards donor eggs.

Obviously, it comes a time in the fertile life of every woman, when her eggs will no longer be good. And when the body really can't deliver anymore, the science can't do much about it. But until this happens, the vast majority of women I come in contact with (virtually) prefer to exhaust every possibility of using their own eggs.

You probably know it already, IVF works by narrowing down the chances to finding the better egg. The more eggs you produce, the better chances you have for success. This is why some clinics turn off clients with low AMH and diminished ovarian reserve, for fear this clients won't be able to respond well enough to treatments, to produce enough eggs to ensure a positive outcome. This in turn, will result in negatively affecting their success rates, and you wasting money.

Those clinics will probably serve you the donor egg speech even without considering treating you.

There are of course other clinics, the majority of them actually, who really believe they can do well, and take you in. They treat you just like they treat their "fertile"patients (let us not forget for a moment that IVF was initially conceived to overcome male fertility issues and tubal problems) and therefore they try to make you produce as many eggs as possible, cause the more eggs the merrier the IVF, right?

Even more than that, they will put you on higher doses because they know your DOR makes your ovaries pretty lazy, and they believe higher doses of stims compensate for your ovaries' lack of reactivity. This was indeed the approach until a few years ago. Since then, lots of studies have been performed and science has come to other conclusions.

What I am going to tell you next, is my own personal experience.

I started my IVF adventure in March 2014, on my 40th anniversary.

My RE was one of the most appreciated REs at an amazing hospital in Paris, and I just loved his calm and poise, and the patience with which he answered all our questions. All my tests were perfect, except for my AMH who came back at 0.5 only to throw me into a black despair. Little did I know about AMH  back then, or that I shouldn't pay too much attention to it. I had gotten pregnant precisely 10 months ago, naturally, like I always did, on the first month trying. Unfortunately and very unfairly, I lost our little boy at 16 weeks because of an incompetent cervix, that I later corrected through surgery in USA.

My RE told me the same story most of your REs tell you: your AMH is low, we have to be pretty agressive in order to make the most of these ovaries of yours. He started me on an agonist, a French kind of Lupron, and high doses of Gonal F. My AFC was between 9 and 11 on CD3. Not stellar, but not bad for my age either. As the days went by and my retrieval approached, I could see my follicles disappearing: 11 became 8, then 6, then 4...eventually that cycle we got 3 eggs.

To say I was disappointed would be a huge understatement. We converted to IUI and when I asked him what the heckity heck happened, he shrugged and told me morosely: "Your AMH is 0.5, what did you expect?" Yeah, I wanted to scream...

But I didn't, and when I got a BFN, I went to see him again, and I asked him how did he prefer to proceed for the next cycle? Should we try an antagonist protocol? You see, in the meantime I had discovered fertility groups, I started to read studies, articles, and educate myself. My journalistic self didn't allow me to follow blindly and pushed me towards finding out the "truth", my truth.

He told me "Oh, but the antagonist protocol is not ok for you, I don't believe in it, I prefer this protocol and it works so well for my patients".

I knew then it was time for us to part...I don't believe in making the same mistake twice, especially not on purpose. And I left. For another famous French clinic, a public one this time.

Horrible conditions, famous doctor. 4 IVFs (high dose and only local anaesthesia for retrieval) and 1 IUI later, still BFN. Not even one chemical, not that I would have wanted one!

I would like to give him this, though: he tried! He changed protocols every cycle. We did Gonal F, Pergoveris, Menopur, Puregon. We did testosterone priming (the worst for me, 2 AFC instead of my usual over 9)we did estrogen priming (he was the first RE to ever use this protocol, he invented it).

We did everything! The only thing we didn't do was low dose, though. Whatever he did, I was on 450 FSH and some 150 LH and the best result I ever got with him were 3 lousy eggs, with a 100% fertilisation rate, giving me 3 lousy embryos.

One day, I went to see him and I told him I was willing to go to London to a clinic I have heard of where they did low dose for their DOR patients. Unless he accepted to try the low dose protocol another RE in NY gave me over the phone, after having studied all my medical records.

He said "sure, sure, we will do whatever you want, just know that this protocol is counterproductive and you will never get more eggs than what you got so far".

He therefore prescribed me the usual 450 Puregon and the 150 Menopur we had done the previous month. I just didn't have the force to try to reason him anymore, so I left.

I went to my Obgyn and we tried the low dose protocol, in view of an IUI. And bam, 5 follicles!  It was a huge surprise for both of us. She considered that I responded too well and in case I wanted to do another cycle (that IUI cycle was still BFN) I would be better off doing IVF.

She spoke to my first RE and she asked him would he accept performing IVF with my own protocol next time? He said yes! We did it in April and we got....8 eggs. 6 fertilised, 4 embryos, 3 were pretty poor quality and were transferred on day 3, and one was kept growing but it arrested later that day.

BFN yet again. But my actual (and ex first RE) changed the tune. He was so super amazed by the wonders this low dose protocol did for me, that he wrote it down. Where he once told me my AMH was so low I had nothing to hope for, now he is very optimistic we can make this work and it is worth trying despite me being 43 now. He put me on Myo-Inositol (I am also taking Ubiquinol, Vitamin D, Folic Acid, Zinc and L Arginine) and he wants me to try again in September, to see if over 3 months of supplements intake manage to positively impact the quality of my embryos. Which is exactly what we will do.

This journey, as well as the experiences of so many of you out there who did much better on low dose (or even natural IVF cycles) made me think of a comparison between cars.

Take a Lamborghini and a Fiat 500. Both brand new. The Lamborghini can go up to 200 miles per hour, The Fiat only to 120 per hour. If you push the pedal of the Lamborghini you can definitely make it ride up to 200 miles per hour, and she will.

But there is no point pushing the pedal of the Fiat to try and make it ride at 200 miles per hour too. She won't be able to. Because all she can do is 120. And forcing her to go to 200 won't actually make her go to 200. But what can happen is she can break.

It's the same for us. Pushing huge doses of stims into ovaries able to produce a certain quantity of eggs  won't necessarily make them produce more eggs. Hence the bad response we hear about all the time. More often than not, DOR patients see their ovaries block and not function ok on high stims. While a gentler approach, a milder stimulation, may give them better results.

This has not been discovered only by us, patients, but it has become a trend lately in the medical world. Studies have been performed that have proven mild stimulation and in some cases even natural IVF (that is no stims at all, just one egg retrieved) work better for DOR patients, the "bad responders". Some REs will tell you live pregnancy rates are low for natural and low dose IVF - and they are, when you compare them to the high rates of normal responders. But when you compare them to the results bad responders have after failing cycles on high doses, you will find that something is still better than  nothing.

There are more and more clinics offering this low dose approach.

Whatever protocol you and your RE choose, just keep in mind that IVF is really trial and error. It is pretty rare for an IVF patient to be successful on the first cycle, and this is even truer in the case of  poor responders.

Therefore, if your first IVF cycle fails, do not despair.

Chances are you will have learned a lesson and you will know what and how to do better next time.

And know that unless you try, you cannot really know how you will respond, either to low doses or high doses.

The most important thing is to have the luck to come across a doctor who knows DOR, who is familiar with both approaches not only the aggressive one, and who is willing to work with and for you, to get you the best outcome. And that would be a baby :)

Meanwhile, you might want to take a look at these recent studies, giving hope to us, poor responders who might want to use the milder approach versus the aggressive one.

Sources

https://www.hindawi.com/journals/ijrmed/2014/581451/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582079/

www.hindawi.com. www.ncbi.nlmh.nih.gov