Why do women undergoing IVF take so many supplements ? And how important
is it to take these supplements during an IVF cycle ? Do these supplements
really help ? Why do so may ART centers prescribe supplements for their
patients before an IVF cycle ? Does this impact their success rates ? There are
lots and lots of questions - and this article is intended to answer some of these
in a rational way.
Why did supplements gain
importance in the field of IVF ?
- Women who are struggling to have a baby are desperate to find a solution for their problem and are ready to try anything which may help to make their dream come true.
- No one can pinpoint why a particular IVF cycle fails – and when there are no simple logical answers for the failure , anecdotal evidence and empirical therapies gain lots of importance in the field of IVF ! Patient pressure and competition among IVF clinics have forced clinicians to give nonfactual solutions to these questions.
- There is always a huge market for snake oil – the human mind is irresistibly attracted towards claims of miracles – especially when you are desperate for a baby!
- When we are spending lots of money for IVF treatment , we want to give it our best shot ! Taking supplements gives us a sense of satisfaction that we are doing our best to maximize the chance of success.
- We all crave simple solutions for our complex problems !
- It is a very interesting topic to discuss with others amidst the IVF struggle.
- We easily fall prey to marketing gimmicks !
- They are easily available over the counter – and people love to self-medicate
What are dietary
supplements?
The Food and Drug
Administration (FDA) defines a dietary supplement to be a product (other than
tobacco) that is intended to supplement the diet that bears or contains one or
more of the following dietary ingredients: a vitamin, a mineral, an herb or
other botanical, an amino acid, a dietary substance for use by man to
supplement the diet by increasing the total daily intake, or a concentrate,
metabolite, constituent, extract, or combination of these ingredients.
Which supplements are used by woman undergoing IVF ?
Following is an incomplete list of supplements which are used by women
who undergo IVF (thanks to Dr.Google !) : Co-enzyme Q10, r-alpha lipoic acid,
Pycogenol, Resveratrol, Melatonin, , Vitamin C, Vitamin E, Selenium, Zinc, Myo-inositol, Cinnamon
extract, Apple cider vinegar, DHEA, Choline, L-arginine / L-ornithine, Prenatal
vitamin, Vitamin D, Vitamin B complex, Folic acid, Biotin, Calcium, Omega 3,
Low-dose Aspirin, Vitex , Royal jelly, Wheat grass, Flax-seed oil, Evening
primrose oil, Nettle leaf and Red raspberry leaf tea, Probiotics,..........the
list goes on and on !
For what purposes are these supplements used ?
- For increasing egg quantity
- For improving egg quality
- For increasing endometrial thickness
- For improving endometrial receptivity
How are the above
mentioned supplements thought to help ?
These supplements fall under the following categories :
- Anti-oxidants (Co-enzyme Q10, r-alpha lipoic acid, Pycogenol, Resveratrol, Melatonin, , Vitamin C, Vitamin E, Selenium, Zinc)
- Insulin sensitizers (Myo-inositol, Cinnamon extract, Apple cider vinegar)
- PCOD mimetic (DHEA)
- Vitamins and minerals (Prenatal vitamin, Vitamin D, Vitamin B complex, Folic acid, Biotin, Calcium)
- Amino acids (L-arginine / L-ornithine)
- Blood thinner ( Low-dose Aspirin)
- Essential fatty acids (Omega 3, Flax-seed oil, Evening primrose oil)
- Miscellaneous (Vitex, Royal jelly, Wheat grass, Nettle leaf and Red raspberry leaf tea, Probiotics etc)
- Traditional ( home ) remedies
Anti-oxidants
Anti-oxidants are believed to help us stay young. Just like iron rusts (
forms iron oxide ) and eventually deteriorates when exposed to oxygen and water,
it is believed that free radicals produced in our body ( naturally and in
response to environmental insults) makes our body “rust” , leading to degenerative
diseases. If anti-oxidants are believed to prevent general ageing, will it not
prevent reproductive ageing too ? This thought might be the reason behind the
use of anti-oxidants in the field of IVF. It is a deeply held belief that free
radicals induce ageing; and by using anti-oxidants which scavenge free
radicals, the ageing process can be reversed. Sadly, even though this is very
tempting and seductive, there is no valid proof to support it. Our body contains
many natural anti-oxidant enzymes which prevent free radical damage. Taking
large amounts of anti-oxidants doesn’t seem to help prevent ageing - and recent
studies have shown that taking certain anti-oxidants could actually increase
the risk of death. Free radicals are
not villains – they also function as key signaling molecules during oocyte
maturation, uterine function and embryo implantation !Using anti-oxidants may
actually impair their role in these vital processes.
Insulin- sensitizers
Women with PCOD have insulin resistance. Their cells lack the ability to
utilize insulin efficiently. Excess insulin in the body can disrupt hormonal
balance , leading to anovulation. Insulin sensitizers like metformin are proven
to be effective in inducing ovulation and hence helping women with PCOD to get
pregnant. So insulin sensitizers have gained importance in the field of
reproductive biology. Since they induce ovulation and help attain pregnancy in
PCOD women , they are also thought to improve egg quality in normal women as
well. This is why insulin sensitizers have become important as IVF supplements
too.
PCOD mimetic
DHEA come under this category. PCOD women have lots of antral follicles
in their ovaries. DHEA is supposed to increase the number of antral follicles
in the ovary, through an androgen dependant mechanism which is not yet
understood clearly. Taking the PCOD mimetic DHEA is thought to help women to
produce more eggs.
Vitamins, minerals and
amino acids are necessary for the optimal functioning of
the body and hence necessary for the reproductive system too.
It is believed that an anti-coagulant like baby aspirin will help to improve blood circulation to the uterus
and thus can help in the development of a good endometrial lining. By thinning
the blood , they are thought to help embryo implantation too
Essential fatty acids are thought to be necessary for normal hormone production
Other miscellaneous substances (whose mode of action is not known) are
thought to reduce stress, improve mental health, act as a “tonic”, “ flush out
“ toxins, “boost immunity”, and improve general well-being of the body and our
reproductive system as well ! These are just tall fancy sounding claims, which
can never be proven – or disproved !
What are the purported
effects of some of these supplements on the reproductive system?
Pycogenol is a strong anti-oxidant derived from the bark of pine tree ! (When did
humans consume pine tree bark ?) It is also present in peanut skin and grape
seed. It is thought to help with male fertility and there are several other
health claims too. Since it is assumed that free radicals cause damage to eggs
(?) this supplement has gained importance among women who undergo IVF.
Myo-inositol is also called Vitamin B8. It is naturally produced in many of our body
tissues. The best sources are fruits, beans, nuts and grains. Humans generally
consume about a gram of myo-inositol per day. Our kidneys produce 2 grams per
day. There are many functions of it in our body but its positive effect on
reproductive system is due to its action as an insulin-sensitizer. PCOD women
with insulin-resistance are found to be deficient in myo-inositol (perhaps because
they have a defective myo-inositol synthesis pathway). Since myo-inositol plays
a vital role in insulin signaling, it is thought to benefit women with PCOD.
There are studies which claim that it helps women with PCOD by improving their
metabolic parameters and thus by inducing ovulation. So it was also tested as
an IVF supplement and as usual there are some studies which show a positive
effect on IVF outcome - and some which do not. Why should women without PCOD
and/or insulin resistance take myo-inositol as a supplement, when it is
produced naturally in our body and can be obtained easily through our diet ? I
do not think it can help women of old age in improving their egg quality. Women
with poor ovarian reserve and advanced maternal age should be very careful in
taking insulin-sensitizers (including metformin) because use of such substances
can actually reduce their yield of eggs drastically.
DHEA is a PCOD mimetic which is used in laboratory mice to induce PCOD I
took it for 9 months and I did have a high egg yield during IVF. But still I
will be very cautious about the claim that DHEA can do wonders for women who
are running out of eggs. When there are no eggs in their egg bank (ovary) how
could DHEA recruit more eggs ? Some women say that it helped them to produce
more eggs , but for many it does not work.
L-arginine / L-ornithine are non-essential amino acids, which mean that they are synthesized in
our body and we do not need to depend on our diet for procuring them. They are naturally
made in the body and our daily consumption of these amino acids reaches upto
5.5g (even though it is not necessary to take this !). I have no idea how supplementing
this amino acid could help with egg quality or improving blood circulation to
the uterus !
Cinnamon extract, Apple
cider – thought to function as insulin-sensitizers
and hence might benefit women with PCOD !
Melatonin is touted as a strong anti-oxidant. The story of melatonin’s use in
reproductive biology started with its ability to inhibit ovulation. It was even
used in phase III clinical trials to test its effectiveness as contraceptive !
Suddenly now they are talking about its efficacy in improving egg quality when
supplemented during IVF cycles because of its anti-oxidant function ! The
suggested dosage for women who are undergoing IVF is 3 mg / day. Do you know
that this dose is 10 times higher than what our body naturally produces ? Is it wise to take such
an overdose of a vital hormone ?
Co-enzyme Q(10) is another strong antioxidant which occurs naturally in our body. It is
present in abundance in mitochondria. It helps in the production of ATP
molecules which acts as the “energy currency” of our cells. Since egg cell
contains more mitochondria than any other cell type; and ageing egg cells have defective
mitochondrial function (energy production), supplementing with CoQ10 is thought
to be beneficial for women of advanced maternal age . There are many unproven
claims , like aneuploidy prevention, increased egg yield , better egg quality
and so on. CoQ10 is synthesized in our body and can also be also obtained
through our diet. Fish, meat and vegetable oils are all rich sources of CoQ10.
Should we supplement it when undergoing IVF ? It is a very costly supplement –
and it seems to be a shame to waste money on something which has not been
proven to help.
The story of how wheat grass
gained importance as a supplement in order to increase egg yield is amusing. In
1930s, a farmer observed that hens fed with wheat grass yielded 150% more eggs
and the egg quality was much better too !
I wonder whether the quality was determined by the ability of the egg to
give rise to a chicken or by its ability to improve the health of the consumer
! Might be spinach would have done a
better job – don’t you think so ? Spinach contains more nutrients than wheat
grass has ! I bet if the hen is fed with a proteinaceous meal it would have
fared much better ! I am sure the modern poultry industry is successful in
coaxing the hens’ reproductive system to produce better and more eggs than in
1930 - and I wish we women could get
that recipe too! It is a scientifically proven fact that FSH
decreases when you are in love, especially during the first three
months of the relationship. How about a romantic trip with your partner,
where you fall in love all over again and enjoy a secnd honeymoon ?
Instead of spending your valuable money on unproven therapies and
supplements , this is a much better option - even if your FSH level does
not go down , you will have made the best use of your hard-earned money
!
The Royal jelly tale is even more enlightening – if queen bees fed with
royal jelly can produce a large amount of eggs, then why shouldn’t humans
consume it if they want to produce more eggs too ? I wish honey bees never start
thinking - ‘If we eat what humans eat , we will become wise like they are !’.
Poor bees – their hard-work is exploited for our sheer greediness ! Royal jelly
contains royalactin, a protein which is found to give the queen bee its phenomenal
reproductive capacity. I am sure royalactin will be manufactured in tons in the
future - the company which sells it is sure to reap a huge profit !
Vitamin D is the new age wonder vitamin
! Since the facility to test vitamin D levels in serum is widely available today,
almost everyone is screened for their
vitamin D levels, irrespective of their sun exposure status and age. The pity
is that there are no proper studies to suggest what vitamin D concentration in
serum is normal for a particular group of people. Even worse, a lack of this
vitamin has been linked to every disease in the world - and use of this vitamin
has been shown to prevent practically all the diseases under the sun. So why
should reproductive biology leave this ‘miracle’ vitamin unused ? Vitamin D was
shown to increase AMH level, the hormone which is a marker for ovarian reserve
. Hence it is widely believed that taking Vitamin D will improve ovarian
reserve – a claim which can never be true (you will realize this if you
understand the relationship between AMH and antral follicle count ( AFC) )! If
you have a high AFC , your AMH levels will be high but a substance which
increases AMH level will not increase your AFC (actually it can do the
opposite) ! A study in Fertility and Sterility journal in 2012 concluded that “A novel relationship
is reported between circulating 25OH-D and AMH in women aged ≥40 years,
suggesting that 25OH-D deficiency might
be associated with lower ovarian reserve in late-reproductive-aged women”
– I wonder how a reputed journal in reproductive biology has allowed the
publication of such a speculative conclusion which is totally misleading !
There are contradictory publications which state that repleting vitamin D
levels increases IVF success rates; and another which states that a high
vitamin D concentration in follicular fluid can decrease IVF success (crazy
experiments and crazy findings !). A recent study also suggests that people
with less vitamin D levels live longer (PMID:
23128285) !
Fifteen minutes of exposure to sun for three days every week is enough
to satisfy your body’s vitamin D requirement. Vitamin D was found to regulate
3000 different genes (not only AMH!) in our body – which means it is wise not
to take an overdose of this vitamin when there are controversial research
findings. If you are healthy and have good sun exposure I do not think
supplementing this vitamin will help you in anyway - if you do not believe me
think about your ancestors who never supplemented their diet with vitamin D and
had a healthy reproductive life . I live in a country where the chance of
exposure to sun is very low in winter (we have short summers too) and many
people living here never take vitamin D supplements nor do they test their
serum levels - and they are very healthy and fertile !
Are there any supplements
which every woman undergoing IVF should take ?
Yes ! Every woman who is trying to conceive should take folic acid. It
is a supplement which is proven to prevent neural tube defects in the developing
fetus. Folic acid prevents 70 % of neural tube defects. So make sure you take
400 µg of folic acid atleast 3 months before starting your IVF treatment. Women
with a mutation in their MTFHR gene need 5 mg folic acid in order to protect
their fetus against neural tube defects. Women who have had a child with NTD
and women who themselves have NTDs are also advised to take 5 mg folic acid
daily. Myo-inositol was able to prevent folate-resistant NTDs in mice but in
humans whether this is true is not known. Women who had child with NTD even
after consuming enough folates could try taking a myo-inositol supplement too.
Can lack of a particular
nutrient hinder my chances of conception ?
For answering this question , there is no need for complicated research
findings. Just look at the women around you ! I come from a developing country
in which there are so many women who live below the poverty line. Many survive
on just rice or wheat. They can't afford meat, fresh fruits or vegetables on a
daily basis. Do you think that their
families are any smaller ? Since they are poor and illiterate, they are married
at a young age (this is the most important reason for their high fertility
potential !) They are extremely successful in expanding their family - actually
most have a bunch of children (some even have 10-12 children and many are
successful in producing babies late into their reproductive age !) due to their
lack of knowledge about contraception! If
nutrients play such a pivotal role in conception , these women who live below
the poverty line would never have any offspring ! After seeing them I am
tempted to conclude that excess nutrients and lack of physical work might play
a role in accelerating reproductive ageing ! It is a well-established fact that
calorie restriction protects the reproductive system in mice from ageing !
Supplements don't cause
any harm, do they ?
It is important to understand that the FDA is not responsible for
ensuring the safety of dietary supplements available in the market – and it
does not check their efficacy too . This
means that there is no certainty that the claims of the manufacturers are true -
and their safety is not guaranteed either . Remember that too much of a good
thing can be bad. Certain vitamins when
taken in excess are toxic (especially fat-soluble vitamins like vitamin A and
D). Studies have shown that taking some
vitamins in excess actually increases the risk of death ! Do you know that
excess Vitamin B6 can cause permanent nerve damage ? Even the CoQ10 story is
very confusing. There are studies which show that CoQ10 can function as a
pro-oxidant (a substance which can increase free radical levels) too. A study
in the Journal of Science showed that C. elegans (a worm which is used to study
many of the evolutionarily conserved signaling pathways which are similar in
humans too !) fed with coenzyme Q deficient diet lived 60 % longer - and the
worms looked younger too (PMID:
11778046) ! A calorie restricted diet ( which is shown to preserve
reproductive function in mice well into their old age ) also decreases their CoQ10
levels ! (Should older women really take CoQ10 ?) Do you know that a Finnish
study conducted for 8 years in smokers showed that smokers who supplemented their
diet with anti-oxidants vitamin E and beta-carotene paradoxically had increased
mortality (PMID:8127329)
? The field of supplements is not entirely black-and-white, and there are many
grey areas left. Hence it is wise not to overdo anything when you do not know
what effect they have on your reproductive system. When you get a particular
nutrient through your diet how could taking them in excess helps ? Remember,
more is not always better !
Patients end up wasting a lot of time and money consuming ineffective supplements such as Fertilaid, just because they are marketed very slickly ! They spend a lot of money on marketing and posting patient testimonials on bulletin boards and forums , and because patients are so desperate, it's easy to take them for a ride.
Patients end up wasting a lot of time and money consuming ineffective supplements such as Fertilaid, just because they are marketed very slickly ! They spend a lot of money on marketing and posting patient testimonials on bulletin boards and forums , and because patients are so desperate, it's easy to take them for a ride.
I am taking only herbal
supplements and hence I can’t suffer any side-effects !
It is a very illogical on our part to assume that the so-called ‘herbal’
supplements are safe. The word ‘natural’ in supplements doesn't mean they are harmless
! . Even worse , many herbal supplements
contain alkaloids or heavy metal contaminants which can cause serious damage to
your vital organs. Some herbal supplements can interact with the medications
you are taking and make them ineffective . Are you aware that even grape fruit
juice can interfere with medications you are taking and can cause
life-threatening complications ? So please do not think that everything which
is marketed as herbal or everything which occurs naturally is OK to take
without a second thought, especially when there is no proof for the tall claims
their manufacturers make !
What about the IVF
preparation kits which are available in the market ?
Many online websites are cropping-up which are trying to exploit our
desperation to have a baby . I received a mail from one of my friends who
enquired about the IVF preparation kit which the following website sells - http://natural-fertility-info.com/. I looked at
their website and was very impressed as to how cleverly they have designed it
to sell their products ! They gave very
good scientific explanations for all the problems infertile women face - and
they then also gave pseudoscientific solutions for the same !
Can supplements make my
eggs younger or help my embryo to implant ?
Our ovary is like an egg bank where the eggs are stored for years. As
women age , their eggs in their ovary age too ! Ageing affects the genetic
quality of the egg; and the quantity of eggs available in the ovary declines
too. Unfortunately, we do not know the exact mechanism behind such changes , and
hence we do not know how to prevent it ! I wish there was a supplement which could
make me and my eggs younger too !
What about supplements for improving sperm count and motility ?
The simple answer is - nothing works ! However, because this is not an answer which patients want to hear, they consume thousands of dollars worth of cleverly named supplements,to "boost" their sperm count and motility. They usually stop after they fail to see results in a few months - but this wasted therapeutic trial damages their confidence - and their bank balance !
What about supplements for improving sperm count and motility ?
The simple answer is - nothing works ! However, because this is not an answer which patients want to hear, they consume thousands of dollars worth of cleverly named supplements,to "boost" their sperm count and motility. They usually stop after they fail to see results in a few months - but this wasted therapeutic trial damages their confidence - and their bank balance !
If supplements don’t
help, then why do doctors prescribe them ?
Most take the approach – if supplements do not cause harm, then why not
let patients take them ? Most doctors are happy to humor their patients – and
will prescribe supplements to keep their patients happy – and not because they
think they are useful. Most doctors are quite clueless about the role of
supplements, because these have never been scientifically studied properly .
They are quite happy to get on to the supplement bandwagon , primarily because
of the pressure on them to “do something” ! The danger is that taking these
supplements creates false hopes – and this is an unkind thing to do . Not only
are they expensive, when they do not work, patients lose confidence in
themselves – and in their doctor. In reality, most patients do not even bother
to ask their doctor for advice on supplements. For one thing, they are scared
their doctor may disapprove , because these are not “mainstream medicine”. For
another, since these supplements are
easily available online, they are quite happy to buy them on their own, without
having to bother their doctor. Patients get easily swayed by the anecdotal
success story of a patient who took a supplement and then promptly had a baby
in 4 weeks ! They have no way of checking the failure rate of these supplements
.
Should I take supplements
?
When all is said and done, if taking supplements helps in giving you peace
of mind that you are doing your best to make the IVF cycle a success, go ahead
and take it. But before taking them , analyze critically what you might need , depending
on your specific condition. If you have PCOD with insulin resistance , try an insulin
sensitizer. (But remember, insulin-sensitizers can never replace a sensible
diet and a good exercise regimen in controlling PCOD). If you are a women with
poor ovarian reserve try using DHEA. Women of advanced maternal age can try taking
anti-oxidants. A multivitamin tablet is always a safe option – the extra
vitamins will just make you produce expensive colorful urine ! But it is definitely
not advisable to take a cocktail of supplements ( a mixture of powerful
anti-oxidants, insulin sensitizers and so on )
at a time. Respect your body and have faith in its ability to handle
things. Having a fertility problem doesn’t mean that your body has lost all its
ability to produce, absorb or utilize nutrients. Reproductive ageing doesn’t
mean your body is sick. If a particular supplement can be synthesized by your
body or you can obtain it through proper diet, please do not take them – you never
know how your body will react to too much of good thing ! To bolster their
claims, many supplement manufacturers provide “scientific evidence” that when we
get old , a particular nutrient declines in our body - and they trick us into believing that it is this decline which is the reason for
ageing. Hence they suggest that we buy their supplement, to increase our levels
of that nutrient, the hope being that this will reverse the ageing. We need to learn to be critical and not get
fooled – perhaps the level of the
nutrient in our body declines as we age because our requirement for that
particular nutrient decreases ! The wisdom of our body senses this , and
decreases its level in order to protect us from unknown insults which could happen
as a result of nutrient excess ! Using supplements is like dying your hair - you
get the satisfaction that you look younger , but the truth is you cannot reverse
ageing - you can’t fool your cells. If you are suffering from a particular disorder
(PCOD, diabetes etc) or do not have a proper diet , please talk to your doctor
to determine which supplement might help when undergoing IVF. Never
underestimate the power of healthy eating habits and proper exercise regimen ;
it will definitely help your reproductive system to fare much better than any
other supplement could !
The most important supplements as per my understanding when undergoing
IVF are vitamin L (lots of love and pampering from your dear ones !), Vitamin H
(Hope!), Vitamin P (Patience and Persistence !) and Vitamin K (Knowledge about
the IVF process!). Nothing can beat these supplements in providing proper
mental balance and support (and this will increase your physical well-being
too). Never obsess about other ‘miraculous’ supplements (when there are no trials
with sufficient power to substantiate the claims) – they are not worth it !