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

 

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Infertility

The CD 3 tests-how important and what do they predict?

If you are familiar with fertility treatments or  if you just had an assessment of your ovarian reserve because you are trying to conceive, the term “3 day tests” rings a bell to you.

Day 3 testing (can also be done and day 2 or 4) consists of bloodwork used to measure hormone levels (FSH, Estrogen, Progesterone, LH) and a scan, meant to measure the number and size of your Antral Follicles. Your AMH level can be measured anytime and if you need to have it measured more than once, it is preferred to do so using the same laboratory, because measurement scales vary for every lab.

E2 (Estrogen) is the main female reproductive hormone, it is being secreted by the ovary and helps to stimulate follicle growth and prepare the lining for implantation, in case conception occurs. The majority of the fertility clinics would want you to have an E2 level under 50 (some under 80) on your day 3. Too high an estrogen level on this day might suggest you have a cyst producing estrogen, in which case stimulation might not be advised. Feeding it stimulation meds, the cyst might not only “eat up” the meds destined for your other normal sized antrals, but also grow and grow until it bursts. A too low estrogen level is not ideal either, suggesting diminished ovarian reserve and possibly  peri/premenopause. Also, very important, when your Estrogen levels are high, the value of the FSH is artificially lowered.

FSH (Follicle-stimulating hormone) as the name tells us, is the hormone that stimulates the ovary to make the eggs grow. Released by the brain, the FSH tends to get higher and higher as we age, and our ovaries struggle more and more to produce an egg. The ideal FSH level is under 10, the lower the better. Some clinics would accept you for fertility treatments with an FSH under 15, but there are tons of studies out there showing success rates diminish seriously as 3 day FSH levels increase. That might explain why older women with high FSH have better chances getting pregnant naturally than with IVF treatments. This being said, if you need help to procreate, there are lots of clinics who offer natural IVF for women with high FSH-meaning no meds, egg retrieval for possibly just one egg, and fertilisation as needed (normal or ICSI, IMSI etc)

LH (Luteinising hormone) helps mature the follicle and eventually, when an LH surge occurs in the end of the follicular phase, helps the release of the mature follicle. The ideal level is under 7 mIU/ml with a ratio LH:FSH of 1:1. An LH much higher than the FSH might be an indication of PCOS (Polycystic Ovary Syndrome).

P4 (Progesterone) should remain low during the follicular phase (under 1ng/ml) and rise after ovulation, as proof the ovary released the egg. The low limit used as indicator for ovulation at 7dpo is 5, but the higher the better. Some women with low progesterone might need progesterone supplementation in order to maintain pregnancy.

AMH (Anti Mullerian Hormone) is a free circulating hormone released by the small antral follicles present in your ovaries, and it is used to assess your ovarian reserve, as in “how many eggs do you still have”. Taken alone, it doesn’t amount for much, and it is far more reliable when discussed in conjunction with the other day 3 levels, and most important, with the day 3 scan. Also, it is important to know that the AMH level has been proven to be artificially lowered by low Vitamin D levels.

Ovarian ultrasound/scan: it is meant to count and measure the antral follicles. The antral follicles are small follicles (between 2-10 mm) found in your ovaries at the beginning of the follicular phase. They are an extremely important and very useful assessment of the way your body might respond to fertility treatments. Each antral contains an immature egg that might develop and ovulate. During natural cycles, the body recruits what is thought to be the best follicle, and makes it grow and eventually ovulate once the Estrogen level is high enough (200-600 E2 level/mature follicle) and the LH surge occurs. In stimulated cycles, all antrals have potential to grow, and even sometimes, some more follicles pop up during stims.

Those are the main tests performed during the day 3 assessment. The list is not exhaustive, though. Depending on your clinic and your health issues, you might have your prolactin and thyroid levels checked, or any other test your doctor might consider appropriate.

Unfortunately, there are some clinics who perform this testing once a year, and consider it available in subsequent cycles. Whether for logistic or financial reasons, this is bad. Hormones fluctuate every God given month, and once you have your period, they are reset and you start the new month with a clean slate. It is possible to have an FSH of 6 in January, and an FSH of 14 the next month, and you surely won’t have the same response to meds during those two months if you are to cycle. Hence the importance of demanding those 3 day tests at the beginning of each and every cycle using stimulation meds, to spare you the heartbreak, the false expectations and yes, the waste of money.

In a future article I will bring to your attention a list of supplements with great effects on your fertility, and the links to the medical studies that attest it.

 

 

Infertility

Low AMH- the villain, but how bad indeed?

A rather recent discovery (1990’s) the Anti-Mullerian hormone has become the bad guy of fertility assessments. Lots of medical articles about it on the web, but in normal non medical language, what is the AMH, where does it come from, why is it low (if it is low), can we make it grow, and most importantly: how big a role does it play in our fertility?

We, females, are born with a certain ovarian reserve, i.e a certain number of eggs. We are born with them and we grow old with them, ovulating more ore less one egg every month, ever since we start having our period and until we get menopaused, unless we are pregnant, on birth control or having anovulatory cycles.

This means our eggs age as we age, which is not fair, but hey…what is fair when it comes to women and their womanhood, compared to men? (don’t get me started…)

It has been discovered that the shell of our eggs produce this hormone, the AMH, and it circulates in the blood, where it can be tested any day of the month, unlike the other fertility assessment tests known as Day 3 tests, that we will talk about later. We know AMH can fluctuate, but not by much, and that different labs can produce very different results, which is why it is essential to have this test done in the same lab, if you need to have it tested several times.

AMH being the reflection of our ovarian reserve, it is natural it decreases with age, as our ovarian reserve is depleted. Therefore, women over 40 are expected to have lower AMH levels. Fertility wise, a low AMH is considered to be under 1 ng/ml. This being said, pregnancies are known to occur even when AMH is undetectable. We all know someone who knows someone who, in their early or mid-forties thought to have reached menopause, only to discover the menopause was in fact a baby 🙂 So basically, every woman in her late 30’s and early to mid 40′ who getting pregnant, gets pregnant despite low AMH levels (we might safely assume that practically every woman of this age has low (er) AMH levels, cause that is the way things are)

And we get to the burning question: is low amh REALLY linked to infertility? Does having low AMH mean we cannot get pregnant? The answer is NO.

More and more reputable reproductive endocrinologists worldwide admit lately that AMH is actually too new to be able to give an accurate image all by itself. That while it can give us an idea of how a woman might respond to fertility treatments (in case she ends up needing them, that is) AMH doesn’t mean much when taken separately. Instead, a better view on the female fertility is given by the AMH level corroborated with the Day 3 Tests and the Antral Follicle Count.

One thing is clear and most experts agree on it: AMH has to do with egg quantity, not quality. Therefore, while you may produce less eggs for IVF in case IVF is what you need to get pregnant, they can still be of decent quality, depending on your age. Or, better yet, if you do not have any reason to do IVF, and so you are not interested in the number of eggs, you can relax, low AMH doesn’t mean your eggs are not good anymore. Again, depending on your age.

When we find out our AMH is on the low end, the first question that comes to mind is “can I make it grow”? Well, no you can’t, not really. Since AMH is a reflection of the quantity of eggs we have left, it is just logical that not being able to increase the egg reserve, it is impossible to “grow” the reflection of it in your blood stream.

But there might be a catch here. It has been discovered that Vitamin D, one of the vitamins with crucial role in conception (and not only) might influence our AMH levels. If your Vitamin D level is low, this may artificially lower your AMH levels. Once you get proper supplementation of Vitamin D and your vitamin D levels get back into the normal range, you may have the surprise to discover your AMH level is higher. Which again, doesn’t actually mean your AMH has “grown” but just that it has been brought back to its place.

Studies show that humans do lack Vitamin D as a general rule, and more than that, there is also a matter of proper absorption when it comes to vitamin D. Here is a good read that might bring a scientific view on the matter

https://www.ncbi.nlm.nih.gov/pubmed/22508713

How much Vitamin D is needed? Read here to find out:

http://www.health.harvard.edu/blog/vitamin-d-whats-right-level-2016121910893

And last but not least: when you are told your AMH is “low”, what exactly does “low” mean? We shan’t forget that AMH has different values for different ages, and what is low for a 25 year old, might be perfect for a 38 year old. Here is a chart explaining it clearly

amh-levels-and-age

Sources: Harvard Health Publications/The National Center for Biotechnology Information

 

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 🙂