Ivf

Low dose vs High dose stims-what is the best approach for DOR and does it really make a difference?

In the Facebook groups I am an administrator of (the Low AMH, the TTC over 35 and the TTC over 40) not one week passes without someone 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 into contact with (virtually) prefer to exhaust every possibility of using their own eggs.

As I have mentioned it before, and many of you already know first hand, IVF works by narrowing down the chances to finding the better egg. This being said, 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 resulting in negatively affecting their success rates. 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 with IVF, right?

Even more than that, they will have the tendency to give you higher doses then they use for their “fertile” patients, 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 several years ago. Since then, lots of studies have been performed and facts have proven otherwise.

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

I started my IVF adventure in March 2014, on my 40’th anniversary. My RE was one of the most appreciated REs at the American 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 if I may say so, 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-450 if I recall well. My AFC was (and still is to this day, 3 years later) between 9 and 11 on CD3. 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 kick him…

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 forbad me to act like sheep and pushed me into finding out the “truth”, my truth.) He replied contemptuously “Oh, but the antagonist protocol is such a bullshit, I don’t believe in it, I only do 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, on purpose. And I left…

For another famous French clinic, a public one this time. Horrible conditions (you, my American readers won’t understand this but believe me-horrible conditions, lol) fantastic doctor. I was pretty impressed by his CV until he told me “You are in the best hands, I am the best in France, you will NE-VER find another RE better than me in this country”…..ughhhhhhhhhhhhhh…ok………But I stayed…4 IVF (high dose and local anaesthesia only for retrieval) and 1 IUI later, still BFN, not even a chemical. I would like to give him this though: he tried! He changed protocols every cycle. We did Gonal, Pergoveris, Menopur, Puregon. We did testosterone priming (the worst for me, 2 AFC instead of my usual over 9) 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. Whatever he did, I was on 450 FSH and some 150 LH and the best results 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 am willing to leave him and go to London to a clinic I have heard did low dose IF he didn’t accept to do the low dose protocol another RE in NY gave me over the phone, after having sent her 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 that. He therefore prescribed me the usual 450 Puregon and the 150 Menopur the freaking same protocol we had done the previous month. I just couldn’t try to reason him anymore, so I left.

I went back to my obgyn and we did the low dose protocol – IUI, bam, 5 follicles.  It was a huge surprise for both of us. She considered that I respond 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 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, lol) 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 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 managed 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 don’t function ok on high stims. While a gentler approach, a milder stimulation, gives 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, aka “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. One of them is CreateHealth in London who exclusively treats patients with diminished ovarian reserve. There are others too, and if you have come across one, I would ask you to comment with the name and location, in order to help other ladies.

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.

Comparison of IVF Outcomes between Minimal Stimulation and High-Dose Stimulation for Patients with Poor Ovarian Reserve

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

 

Natural IVF cycles may be desirable for women with repeated failures by stimulated IVF cycles

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

SOURCES: http://www.hindawi.com. http://www.ncbi.nlmh.nih.gov

 

Advertisements
Infertility

Supplements-are you taking the good ones?

We know we are born with our ovarian reserve, and the number of our “eggs” can only decrease, from the moment we are born until we completely run out of them, by the time we get to menopause. We also know the quality of our oocytes starts to decrease by the time we reach our thirties, and the chances of ovulating abnormal eggs unable to create normal embryos are higher the older we get. But is there really nothing we can do to improve this egg quality?

The truth is, this a very controversial subject. The efficiency of a treatment, be it a subscription med or a dietary supplement, can only be proven by studies. While medicines benefit from multiple studies, dietary supplements receive far less attention from the part of the medical community. Therefore less studies are performed and easier to say “we don’t know if this supplement really improves oocyte quality, because there are not enough studies out there to confirm it”. Lots of REs though, consider that even if there is not enough proof some supplements help to improve your fertility, they don’t hurt either, so you might as well take them, if only for your peace of mind. And that’s already a great starting point, in my opinion, for having the impression of doing something, instead of just playing the wait and see game, means a lot for an infertility patient. There are some supplements out there who are more spoken about, and who also benefit from some studying. Those are the ones we will discuss today.

COENZYME Q10 – is one of the most important coenzymes. It is a substance made naturally in the body and it plays a critical role in the creation of cellular energy. CoQ10 is found inside the tissue of  organs such as the brain, heart, liver and kidneys (which demand more energy) but  it exists in virtually all our cells and tissues. There are two main forms of this coenzyme, and this creates confusion.

Ubiquinone is the conventional form of CoQ 10. That is what we used to take before 2007, when a better form of CoQ10 was discovered, the Ubiquinol. The problem with Ubiquinone (the basic form of CoQ10) is that your body needs to convert it into Ubiquinol before it can improve the cellular energy your organs need to function at best levels. As we age, the body struggles harder to convert the Ubiquinone in Ubiquinol, hence the recommendation to use directly the Ubiquinol form, for better results.

Ubiquinol is known to be a very strong antioxidant and its main role is to neutralise the free radicals that can harm your cells.

MYO INOSITOL- initially used in PCOS patients and for fighting insulin resistance, this nutrient has become the golden weapon in the infertility battle. It has been proven that, at a dosage of 4 g daily (most studies use this amount as reference) it has improved the ovarian function and number of oocytes retrieved in patients undergoing IVF cycles, and who have previously been considered poor responders.

The following is a link to a 2011 study aiming to evaluate the pregnancy outcome after the administration of myo-inositol combined with melatonin (will talk about it later in this article) in women who failed to conceive in previous IVF cycles, because of low egg quality. The results were crystal clear, everything was better post treatment : number of mature oocytes retrieved, fertilization rate, number of total embryos and number of top quality embryos.

https://www.ncbi.nlm.nih.gov/pubmed/21463230

Here is a more recent study (2015) showing Myo-Inositol supplementation might be beneficial for previous poor responders during IVF cycles.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464995/

MELATONIN is a hormone produced by the pineal gland, and it regulates sleep and wakefulness. Many of its biological effects in humans and animals are produced through activation of melatonin receptors, while others are due to its role as an antioxidant. As a medicine it is used to treat insomnia, and is usually sold over the counter in many countries. The negative effect of the oxidative stress on fertility is no longer a secret. Clinical studies have tried to prove the effect of melatonin as an antioxidant on egg quality. The results of those studies suggest that melatonin supplementation (in conjunction with Myo-Inositol or not) may lead to better pregnancy rates in IVF cycles. Amazingly, not only egg quality was improved in  patients who were administered melatonin during the follicular period, but progesterone levels were also significantly higher in patients who received melatonin during the luteal phase.

Here is a review of several studies with very interesting findings https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209073

The majority of the studies have used 3mg of Melatonin every evening as standard dosage. You will also want to be very careful when taking melatonin during a natural cycle, not to go over the standard dose. It has been proven that taken at high doses (6mg and more) melatonin actually prevents ovulation.

DHEA– naturally existing hormone, the most abundant circulating steroids in humans, that the female body converts into androgens, mainly testosterone. That means DHEA already exists in our bodies, we are producing it, but its levels decrease with age. It is sometimes used as an androgen in hormone replacement therapy for menopause. Lately it has been more and more used particularly during IVF cycles to treat women with DOR (diminished ovarian reserve).

Clinical studies have proven that at a dosage of 75 mg daily for a period of at least 3 months, DHEA increased IVF pregnancy rates, increased antral follicle counts, increased quality and quantity of eggs and embryos, decreased risk of miscarriage and chromosomal abnormalities. DHEA supplementation works by restoring the abnormally low androgen levels in patients with DOR due to advanced maternal age or premature ovarian failure.

Here is one link to two of these studies

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112409/

https://academic.oup.com/humrep/article/25/10/2496/2385689/Addition-of-dehydroepiandrosterone-DHEA-for-poor

ARGININE- is an amino acid that plays an important role in cell division, the healing of wounds, removing ammonia from the body, immune function, and the release of hormones. It can be found in almost all dietary protein : eggs, meat, fish, nuts and supplementation has been proven efficient in improving fertility in both women and men. How does it work ? Arginine is believed to improve blood circulation to the uterus, promote healthy sperm production, improve the production of cervical mucus and increase the libido. There are not many studies focusing on arginine, more research needs to be done, but many fertility specialist recommend this « miracle mollecule » which is already included in most prenatal vitamins anyway.

ROYAL JELLY-Royal Jelly is a strong nutrient produced by young worker bees in the hive. For 2-3 days, these bees are fed only on royal Jelly until they reach maturation and produce enough Royal Jelly to feed the female larva, which develops into Queen Bee. Queen bees are fed their entire life only Royal Jelly while worker bees are feed Royal Jelly for only the first three days of their life. This diet is responsible for making the queen bee 40 to 60 percent larger than a worker bee. There are not many studies on humans, but there some on animals amnd their conclusions suggest Royal jelly might improve fertility. Beware of adverse reactions thouugh : those with allergies to bee products are to avoid this supplement.

FOLIC ACID (Folate, Vitamin B9) is a form of Vitamin B. It is no longer a secret for anyone trying to conceive, that the first supplement you will be recommended by your doctor is going to be the Folic acid. It has been proven for years and years to prevent neural tubes defects and congenital heart defects in newborns, and actually low levels in early pregnancy are believed to be the cause for more than half of babies born with neural tube defects. There are no common side effects, even if taken for long periods of time. Humans can not produce it so it is important to get it from diet (and supplements). Food supplement manufacturers often use the term folate for something different from “pure” folic acid: in chemistry, folate refers to the deprotonated ion, and folic acid to the neutral molecule—which both coexist in water.

There have been lots of studies proving the importance of Folic Acid intake before and during early pregnancy.

Here is one you might want ot read

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218540/

and also the reccommendation of the World Health Organization on this subject

http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/neural_tube_defects.pdf

There are of course, other supplements more or less proven to increase fertility: Vitamin D (previously discussed in the article about the AMH), Vitamin E (used usually during the follicular phase in order to thicken the lining), DHA (not to be confounded with DHEA), Maca, Vitex…and many more.

I tried to focus on the ones who have been more or less medically proven to actually help on improving pregnancy outcomes after administration, during natural or medicated cycles.

Obviously,   not everything is for everyone, and in order to avoid doing more harm it is best to discuss supplements intake with your doctor. In case your doctor is not very pro-supplements, you can always pull out “the study” and show him you did your research. That is what I did, and frankly…it worked 🙂

Sources: NCBI, WHO, OXFORD ACADEMIC

 

Ivf

Priming protocols-what with and who for?

I am going to address a very debated topic and one of huge interest for those who carry the tags DOR or POF and need ovarian stimulation for assisted reproduction.

The way IVF works, we all know the more eggs we make, the better it is. And this because in vitro fertilisation is all about narrowing down the chances to finding the best egg(s). It is a matter of logic because more eggs retrieved will give us more fertilised eggs, hence higher chances of pregnancy. Also, women who respond better to stimulation protocols usually have a better egg quality (PCOS do not enter in this category of better egg quality, we will discuss this later on). Last but not least, “the more eggs the merrier” principle has also financial connotations. With prices so high for stimulation meds, monitoring, retrieval and laboratory, you’re far better off paying thousands and thousands for ten eggs than for one.

While women over 35 and those under 35 but dealing with POF and DOR might be worse responders than the fertile population generally is, lots of protocols have been invented and experienced over the years, some of them with great results and quite encouraging pregnancy rates. One of the approaches is that of using luteal phase adjuvants, hoping to create a better environment for the follicles and preparing the ovaries for the following stimulation cycle.

BIRTH CONTROL – By far the most used approach before a medicated cycle. Its main purpose is to give your ovaries a rest, and give them the chance to start the next cycle with a clean slate. Useful for reducing cysts, it also comes, unfortunately, with a bad side effect: the dreaded suppression. BC pretreatment in IVF protocols establishes an estrogenic environment and increases sex hormone-binding globulin levels while decreasing follicular androgen levels. But by putting the ovaries to sleep the risk is they might not wake up well enough… Sometimes, we end up with a lower antral follicle number, and we are facing the need of stimulating for a longer period of time, and with higher doses of stims, which might in turn, affect egg quality for older patients.

Here is a very interesting study, where  even young egg donors have experienced lower AMH levels and lower numbers of oocytes after being put on birth control.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637242/

If in the case of a young donor, having  5 eggs retrieved  instead of 10 might not make much of a difference, because donors are chosen to be young and healthy, therefore having a great egg quality, things are quite different with us, older women, where quality as well as quantity might be a problem.

TESTOSTERONE PRIMING- Relatively new,  and controversial. If you listen to Dr Sher, a very famous and respected Reproduction Endocrinologist, you should run away from testosterone exposure, especially if you are not very young anymore. If you listen to me, LOL, my biggest failure of a cycle was the one I primed with testosterone gel. While I usually would have an antral follicle count of 9-10, one week of testosterone gel reduced my AFC to a whopping 2 (two), and thats what I got until the end of stims, when I told my RE there is no way I am going to waste an IVF cycle on two eggs, and converted to IUI. Even he himself later admitted that testosterone priming was a mistake in my case (I was 41 at the time, this might have been a reason) and he is known to be a very stubborn and proud one…And it was no coincidence: all the other cycles I ever did (and we are talking 12 with full protocol, my afc was never under 8)

This being said, there are many studies out there who scientifically prove testosterone priming works for many low responders. If you read this analysis of several studies (https://http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4061182/) you will see the mean age of the patients was 36-37, so there….probably that’s the key, being younger is better for testosterone priming. I personally guess there is no way of knowing until you try.

Oh, and most important: I grew no beard during the treatment, neither did I engage in violent exchanges with people in pubs 😛

ESTROGEN PRIMING– It avoids the suppressive effect of BCP on the ovaries. In addition, the use of estrogen during the pretreatment cycle prevents premature recruitment of follicles that can reduce the number of follicles available for stimulation. Studies have shown that this protocol allows more gradual and coordinated growth of follicles resulting in improvement of embryo quality and quantity. For me this has been the only way I could avoid the growth of the horrible LEAD follicle, the scarecrow of IVF…I personally took estrace pills, but patches are used with the same success.

You might want to read this study https://www.ncbi.nlm.nih.gov/m/pubmed/22160464/ and also this analysis of several studies https://www.ncbi.nlm.nih.gov/pubmed/23887073

I believe it is essential to have a doctor you really trust. I, for one, could not trust any doctor who insults my intelligence by imagining that in this age and time I have no ways of gathering enough information as to educate myself on matters concerning my health and my life. Would this auto-education give me a medical degree? Obviously not! And I do not pretend it does. What it does give me, is at least basic knowledge, so useful in understanding where I stand, and if the direction I am heading to is the good one. It gave me the power of standing up and saying NO, when I knew for a fact that the approach I was suggested would be wrong for me (I wish I knew what I know now, when I was suggested the testosterone priming…) It gave me the power to fight me RE for the estrogen priming protocol, that as an anecdote he himself invented, but not so much used afterwards, for fear of oversupression. I fought him and he gave in, and later admitted I was right. It also gave me the power to say NO to him for yet another high dose stimulation protocol, and when he wouldn’t give in and would insist low dose is “counterproductive” for low responders (sic!) I would say bye to him, and find another RE who was willing to try on me my estrogen priming low dose protocol. And we got 8 eggs, instead of my usual 2-3.

I don’t know if it is my journalistic background, or maybe just me being a stubborn Aries, but I am a strong believer in the “Knowledge is power” part, as much as it might sound  like a cliche.

Apparently you believe so too, or else you wouldn’t be here, trying to find out more ❤

Sources: NCBI

 

Infertility, Ivf

How many eggs are not enough?

There has been a question asked very often on IVF with DOR pages: how many eggs are needed for ivf and what is the inferior limit?
One of the big paradoxes of this DOR/IVF thing is this one: most of the RE’s recommend DOR/POF patients to hurry and do IVF cause “they are running out of time (and eggs)”
The RE’s also say that for IVF to be successful, the more eggs, the better.
We all know (personal experience mostly) that DOR/POF patients have anything BUT many eggs.
So how do you marry DOR and IVF with the “many eggs needed” approach?
Well, you don’t!
Unfortunately medically assisted procreation has become more and more of a business lately.
What started out as a genuine desire to help infertile couples procreate, turned into the rush for the golden egg in the eyes of fertility clinics that are being more and more numerous, some offering bargain packages that would make Walmart and Costco green with envy.
Patients are put on birth control so that they all fit in the same batch, they all have their periods and stimulation schedules coordinated
It has turned into a huge business bringing millions and millions in for clinics
Do we as patients benefit in the end?
Sometimes we do, and when we get to hold our miracle babies we would forget all the bad and focus on our success
But what happens with the ones that don’t fit?
Clinics mostly focus on success rates, cause that’s what brings in the cash. And more patients.
Therefore they cherish the convenient patient the most: and that would be the youngish couple with male fertility issues, the patient with bad or no tubes, the pcos patient…
And what about us? The DOR, the POF, the over 40 patient?
We can’t be put on birth control cause it’s suppressive, we don’t fit in batches cause our periods are irregular, our FSH is high, our response to meds is under average and we certainly don’t raise the success rates of any clinic with our 2-3 eggs retrieved…
Heck, some clinics don’t even let us get to their door, we are being served the donor egg speech over the phone and told that an AFC of less than 4 is Grandma style so… bye Felicia…
And that’s why I am focusing on empowering women to stand up for their rights and ask for what they truly deserve: a tailored made medical approach.
When you buy shoes, you don’t go in a shoe shop that sells only size 7 shoes, cause you might be wearing a 5, an 8 or even a 10!
You won’t buy size 7 shoes if you’re wearing a 9, right? You pay for them, you might as well get some shoes that fit you well!
Do you pay the RE?! Oh hell yes!
Do you have to accept whatever the RE serves you, without the right to ask for something else, or to go somewhere else to someone who cares to work for and with you!?
No way!
That’s why I encourage ladies in my FB groups to keep up looking for THE good RE, the one who is less interested by the stats, and more interested in giving them what they need and want.
There are doctors like this out there, ladies!
Some of us have been lucky to have found them, although more often than not, not from the first try 🙂
There are the doctors who don’t choose their patients based on the number of eggs they produce.
The ones that give DOR a chance.
The ones that are not afraid of low stims and natural IVF, the ones that retrieve two eggs, or maybe just one, without adding frustration upon frustration on a woman already having to deal with the disappointment of not being able to get pregnant in the first place.
So to answer the question: what is the inferior limit for ivf and how many eggs do we have to have?
Well … certainly 15 eggs have a better chance of success than 1 egg only, it’s a matter of numbers and of narrowing down the chances to the best one.
But that doesn’t mean that 1 egg shouldn’t get the opportunity of a chance!
Of course that with one egg chances are about the same as with iui, but let’s not forget iui is not always an option, and for couples who absolutely need ivf, one egg should be given just about the same credit as more eggs.
We should all be given our chance, and the right to follow our dreams 🙂