Does taking supplements help IVF patients ?

Practically all women doing IVF are taking supplements of one sort or another ! These are supposed to improve egg yield, egg quality and embryo implantation , thus helping to improve IVF pregnancy rates. I have come across women who take over 10 different supplements daily – and I wonder how they manage to swallow so many different tablets, syrups and capsules in a day ! On second thoughts,  it is not surprising , because the craving for a baby can make a woman move heaven and earth; which means taking umpteen supplements is not such a difficult task to accomplish. I have heard the following questions repeatedly from other women who are undergoing IVF treatment – What supplements are you taking ? Or can you recommend any supplement which can improve egg quality ? Is there any special diet which could help in increasing the chances of IVF success ? I wish I knew a magic supplement or diet which will make our much desired wishes come true ! 

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.

Ref: http://dietarysupplements.nlm.nih.gov/dietary/faq.jsp

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.

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 !

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 !