Not Looking Good!

My endometrium after 48h of G-CSF infusion remains the same at 6.5 mm. It looks trilaminar. I was very disappointed and I am a bundle of negative emotions yesterday. Now I feel it is OK. I beleive everything happens for a reason and hopefully for the good. I will have the next ultrasound on tuesday. Dr.Anjali increased my estrogen dosage from 16 mg to 40 mg. So hopefully we see some improvement by tuesday. If not, I have to decide whether to cancel the cycle, wait for some more time or to go ahead and transfer. My intuition says do an embryo transfer whatever it is! There are studies which did not find any difference in pregnancy rates between thin and thick endometrium. There are studies which talk about the importance of thick endometrium. It will be a a hard decission to take but my heart will break if I have to return with an empty uterus. I do believe that if my embryos are competent enough they will be ok with a thin bedding too ;) Here is the blog post of Dr.Liccardi regarding thin and thick endometrium http://infertilityblog.blogspot.in/2008/08/endometrium-part-iii.html

Thin Endometrium –a side-effect of calorie restriction and fat loss?

Vaginal ultrasound showing a thin endometrium

I always had great endometrial lining during all my IVF cycles (greater than 8mm, mostly between 10-12 mm). In FET cycle too there was no problem. So, what went wrong this time? Even though I can just speculate, I know deep within me that my speculation is right. I have lost lots of weight during the past 5 months. I was insulin resistant before. I had a HOMA IR (a measure of insulin resistance) of 4.1. There is no standard value for HOMA-IR. The current studies consider that HOMA-IR < 2 is normal, HOMA-IR ≥ 2 is pathological, with HOMA-IR > 4 reflecting the pre-diabetic stage. My fasting insulin was 17uUnits/ml (although a fasting insulin of 5-25uUnits/ml is considered normal, anything above 10uUnits/ml is not so good. People with fasting insulin of less than 5uUnits/ml are found to live longer). I have a family history of diabetes in my dad’s side. I was diagnosed with PCOD at the age of 25 and I am on metformin (1500mg) for a long time. I stopped metformin for the past year because of gastrointestinal problem. After stopping metformin my BMI was 26.2. I was overweight. Lack of implantation in my previous ART cycle made me to ponder what can be done to improve my chance of conceiving. The only sore point I had is my weight and perhaps insulin resistance because of it. My blood glucose was normal. I also became aware of the fact that calorie restriction has a positive impact on egg quality. This made me to think seriously about removing the excess weight. My boss is an endocrinologist. I used to discuss with him about the weight issue and ask him whether carbohydrate rich meals are the culprit. He used to say-eat anything, but eat less. I started a very strict calorie restriction diet and jogging. I limited my calories to 800-1000 for the first 2 weeks. I achieved this by intermittent fasting. To my surprise my fat deposits around my waist started to melt. After two weeks I upped my calories to 1200-1500 calories. I avoided sugar, sweets and carbohydrate rich foods. I avoided rice as much as I can. I took only 300 calories per meal. I started metformin 1000mg. I stopped non-vegetarian all together and I am not planning to eat it anymore during my lifetime :). Within 5 months my weight dropped from 68 kg to 61 kg. The best point is I lost all the excess fat. For the first time I had a flat stomach. My energy levels improved. I can skip a meal easily without any trouble. I attribute it to my lowered insulin levels. In short I felt great. Received mixed comments from friends. Some are worried. They said I have lost the charm. But my DH is happy. He said I looked better now. I am happy too :)

Everything sounds good, right? Then, where lays the problem? Calorie restriction is good. It was found to prevent aging in experimental animals. It also delayed egg cell aging and extended fertility in experimental mice. Metformin is a calorie restriction mimetic too. It can also improve egg quality (both by preventing egg cell aging and by decreasing insulin levels). I do not think short time calorie restriction will have any effect on egg quality in humans. If calorie restriction is started in 20s it might extend fertility into your 40s. The same is true with metformin usage. Long term metformin intake can preserve egg quality via preventing genetic defect accumulation, while short term intake can increase egg quality by decreasing insulin levels. It was found that exercise and weight loss is much effective than metformin in decreasing insulin levels. So bringing down your weight at any point of your lifetime will have positive effect on your overall health by decreasing insulin, glucose and harmful triglyceride levels. This will keep your hormones balanced which is necessary for optimal fertility. As a result egg quality (not genetic but physiological parameters) and  endometrial health improves. Consider calorie restriction if you are suffering with infertility due to overweight and PCOD (high insulin!).  Reduce your weight through calorie restriction and proper exercise. Continue exercise regimen and increase your calorie intake for maintaining the appropriate weight. BUT never do calorie restriction when you are on fertility medicines, if you are underwieght or when you are trying to conceive.  Never be on very restricted calories (less than 1500 calories) when you are trying to conceive. This is the mistake I did this cycle. Even after starting fertility medicines (progynova) I continued with fewer calories. Lesser calories actually signal your body to go into the survival mode (during which only minimal bodily functions are maintained). Reproduction is an extremely energy consuming process. Once your body senses that you do not have enough calorie supply (as in times of food scarcity) it switches on mechanisms which  prevents energy expenditure. It tries to switch off high energy demanding functions like reproduction. In short all the anabolic activities which require high energy are switched off and catabolic processes which produce energy are switched on. Since I took less calories my estrous cycle is severely affected leading to poor endometrial development. My body in short doesn’t want to get ready for performing reproductive function.

I got this information from a website:

Reproduction: Feeding the reproductive cycle

Energy metabolism is known to affect reproductive cycles, acting as an evolutionary oversight to ensure that reproduction occurs only in favorable nutritional conditions. A recent study characterizes a mechanism through which the liver integrates metabolic responses to control ovulation (Cell Metab. 13, 205–214).

Investigating the link between estrogen and food consumption in mice, Sara Della Torre and colleagues found that caloric restriction decreased hepatic estrogen receptor-α (ER-α) activation in the liver and arrested estrous cycle progression. Interestingly, amino acid supplementation was sufficient to rescue mice from this metabolic block of the estrous cycle.

The authors found that ER-α activation led to increased hepatic expression of insulin growth factor–like-1 (IGF-1) and increased the amount of circulating IGF-1. Increased IGF-1 expression was required for E2-induced proliferation of uterine lumen epithelial cells and for estrous cycle progression in vivo.

The findings highlight a crucial role of hepatic ER-α as an integrator of metabolic and reproductive functions. The exact mechanisms by which IGF-1 and E2 promote progression of the estrous cycle remain to be determined, but this study might provide insights into infertility conditions, especially those linked to metabolic dysfunction. 

On the other hand there must be a connection between fat reserve and estrogen function. It is known that estrogen is stored in fat reserves. I have read that people who are obese are prone to estrogen sensitive breast cancers. Overweight people are also more prone to endometrial cancer. You need healthy fat reserves for your estrogen to function properly. Dr.Malpani sent me the Frisch hypothesis paper which talks about the connection between body weight and onset of menarche.

In short I learned a lesson which is invaluable. Do not change your diet or exercise regimen extremely during IVF or FET cycles.  Do not loose weight especially fat reserves when undergoing fertility treatment. Increase your intake of healthy fats. Do not restrict calories. The above said are very important for proper functioning of your reproductive harmones which intrun is important for your treatment success.

Another interesting information to ponder : In certain regions of south India, daughter-in-law who enters husband's home for the first time, after marriage, is given cow's colostrum. Perhaps a nice way of preparing her to carry their generation :) Milk is know to increase IGF-1 levels. When I say this I do not want to make IGF-1 master of all reproductive functions, just a note because I am talking about IGF-1 in this post. Our ancestors do have lots of wisdom :)

Stupid me ! Dr said –don’t beat yourself up! He asked me to read ‘Shoulda, Woulda, Coulda’ :). I will try not to regret. Hopefully G-CSF works and perhaps everything happened for my good :) Otherwise I will not have had a chance to use G-CSF which is supposed to increase pregnancy rates atleast in a couple of studies :)

Mumbai - through my eyes!

One and the Only!

Serene

Look at the young one! Sometimes I can't close my eyes in the most comfortable bedding! Lucky fellow!

Blue sky and calm sea! Serene, isn't it?

Another perfect example of serenity! Totally unaffected by the heavy traffic around :)

Gateway of India

Marine Drive

I am constructing my home! :)

I was watching this crow trying to pick up a big twig. Suddenly another crow came, took away the twig which this crow had in its mouth by force and flew away :) I wish the second crow is its partner who just lent a helping hand and not a thief :) Have a happy home and lots of chicks. No home is perfect without youngones!

Mount Mary Church, Bandra

Candles shaped like babies, hands, feet etc. I did buy and keep a baby boy and a baby girl candle figure (twins are great!) at Mother Mary's feet. I will do anything which can bring a sense of happiness to my mom and DH :) If you ask do I believe such prayers ? - I donno! But when I stood in front of Mother Mary my mind is serene and happy.

Update on endometrial ultrasound and G-CSF

I had a vaginal ultrasound yesterday to check for my uterus lining. Not so good news again! After 2 days of 16 mg estrogen (8 progynova tabs) my lining has grown from 6 mm to 6.7 mm. Dr. Malpani suggested that I should have neukine infused into my uterus. Neukine or Filgrastim is nothing but Recombinant Human Granulocyte Colony Stimulating Factor. It is sold under the brand name Neupogen in USA. It is a drug or a cytokine actually sold to prevent decrease in neutrophil count during chemotherapy which causes myelosupression. Decrease in neutrophil counts is called neutropenia and it is accompanied by fever. It causes the patient more prone to infections. Recombinant G-CSF causes a dose-dependent increase in circulating neutrophil counts thus preventing spurious infections in patients receiving myelosuppressive chemotherapy. What does G-CSF has to do with endometrial growth? Please visit this Center For Human Reproduction link for further information. Here is the blog post of Dr.Malpani regarding thin endometrium and the use of G-CSF to improve it.

So today I received an infusion of Neukine inside my uterus. Keeping my legs in that evil stirrup is uncomfortable. Dr.Malpani eased my tension by chatting with me. Still no signs of high estrogen in my body but I wish my endometrium responds well to Neukine giving me a nice, plump lining where my embies can snuggle in and start establishing contacts with me. Mumbai is great, I am very happy today. I will update about my Mumbai adventures soon.
Somemore interesting reads on G-CSF:
http://badplumbing.kurvy.com/2010/12/g-csf-the-last-frontier.html
http://clinicaltrials.gov/ct2/show/NCT01202656

In Bombay for FET

We came to Mumbai two days back. A heavy downpour welcomed us! Every time I enter India, for a day or two, a kind of depression sets in instead of happiness. I feel as if I am waking up from a pleasant dream. The reality slaps me hard. I live outside India for 7 years. The country where I live now is clean, sparsely populated, rich and comfortable. The first thing that makes me vexatious when I reach India is the dirty environment. Mumbai is the financial capital of India, and no need to say how densely populated it is. The dust, unruly traffic, dirt and poverty made me wonder why there is so much discrepancy between two countries. I saw a family of three; husband with torn clothes, wife with the dirtiest saree you can ever imagine and a newborn lying nearby them - all three are resting inside a shed of tarpaulin, on an elevated mound, which is found in between two parallel roads! I could clearly read the worry on their faces. They must have been living in platform and the heavy rain made them to panic. When I saw it, how much I wished I could just go back to Germany and imagine that life is hunky-dory everywhere! If you accuse me of being selfish – I AM. I am selfish to the core. I need the comfort which Germany gives me. I need the clean environment. I need the calm working atmosphere and I badly need the money for our baby-making journey. I am helpless, truly helpless. Every time I come to India my conscience kills me. I feel guilty for being comfortable, for being self-sufficient moneywise, for living in a clean environment, for attempting to create a costly baby when many road-side children are living in the footpath. Wait; do not judge India by what you read just now. This is just one half of the story. When I see such extreme poverty on one side, I also see supreme richness too. Costly cars, branded clothes, dining in five star hotels and lavish spending-this is also the way of life for many in India. Why is Indian society too unbalanced? Are these the result of evil caste system which we created long back?  

Do not form an opinion about me from what you read in the previous paragraph. I am not trying to project myself as a simple person with great social responsibility. I am a very normal and self-cantered woman. All the above said guilty feelings usually vanish from me in 24 hours. I get used to the way of life in India. I do walk past the hungry, homeless road-side children and enter into a mega shopping area to satisfy my shopping spree. My guilty feeling vanes away day by day until it becomes negligible. I indulge myself in all normal worldly pleasures ignoring the sufferings around me! Sometimes I wish I was non-existent or I wish I had the power to change every misery around me. But at the age of 34 I have learned that life is not fair. If I have to remain sane and serene I should surrender to the fact that life is unfair. As a human, I am trying my best to be compassionate and kind to my fellow beings. I try to lend a helping hand to the needy whenever I can. I also try to keep in mind the serenity prayer which Dr.Malpani taught me:

God, grant me the serenity

To accept the things I cannot change,

Courage to change the things I can,

And wisdom to know the difference.

This serenity prayer was written by the theologian Reinhold Niebuhr.

So coming back to the original story - we are doing a FET. We have 7 embryos left from my last ICSI cycle (5 day 3 embies and 2 blasties). I am happy to see Dr.Malpani and his team. Dr, understood that I am the anonymous person who leaves crazy comments (sometimes good ones too!) in his blog. All his staffs are very friendly as usual. Dr.Anajli Malpani is  cute and pleasant as always.

I took 6 mg progynova for 12 days and had a vaginal ultrasound on 11.6.2012 to check my lining. Dr.Malpani was not so happy about my endometrial thickness. My lining was only 6 mm. He increased my progynova dosage to 16 mg. I am going for an ultrasound today. I wish my lining has grown at least a mm by now. I have no EWCM even after taking such a massive dose of progynova. Does it mean anything? I do not know. I am worried and I started to write this blog post to calm my anxiety. I will update after today's scan what actually is the next course of action, and I would also like to speculate in my next post why I ended up with a thin lining!

Female foeticide - Why are we so obsessed about the foetus 'Right to Life' than our underprivileged womankind well-being?

My native is a village in south India. Our neighbourhood is occupied by people who belong to a particular caste. Their job (of those particular caste men) in olden times is thieving! Somehow ancient society came to term with the fact that theft is their means of survival and income (it is because theft with some kind acceptance from the society prevented those people from committing horrendous crime!). People belonging to that caste used to steal cattles from neighbouring village and the stolen cattles were retrieved back by giving money or grains to the people who stole them. They are very aggressive people (even now!). Women in their community are treated like cattles. The passion to have a boy child is extremely high among those people. The wish to have a particular sex baby is not wrong but they do this at the expense their girl child’s welfare. Girl children are taken for granted. They deprive them of proper nutrition and education.

In front of my house there lived a woman who had two girl children. She went on to have two more girl child but they were killed as soon as they were born. The fifth girl child survived few years because it is a belief that fifth child brings luck to the family! But when that fifth girl child became ill it was not given proper medical care and was allowed to die. A doctor started a private practise near my home. He came to know of all these happenings and he took the woman when she was pregnant again for a scan to know the sex of the baby (of course illegal!). But his stand is at least the baby can be aborted (if it is a girl) so that no cruel murder will take place. I really appreciate him. Fortunately the baby is a boy and the particular family were happy because their dream of having a boy child came true. To end the story the boy when he was around 15 years ran away from home and their dreams that the boy child will take care of them when they become old is shattered! The first two girl children are married at the tender age of 15 or so and the vicious cycle continues again. I am very young at that time to understand and think seriously about all these things. But I used to hear all these stories. That particular woman’s husband poured hot oil over her head when she is frying some snacks (because of a fight!). She used to sell those snacks to sustain her family. That is the plight of women living in such bad socio-economic conditions!

I told my dad once ‘how horrible that woman is, she killed her babies as soon as they are born!’ My dad said, ‘You do not know about their social condition. Those women have no rights to take any decision. Even if she has decided to kill her babies, you must think about the situation which made a mother behave like that. The situation of female child in that particular community is not so good. They have to undergo all sorts of child abuse. When a mother feels that her child should not undergo the sufferings she has endured perhaps she decides to end the baby’s life at the very beginning. They do not have the money to afford many children and she cannot also avoid her in-law's or her husband’s pestering of having a boy child. If this has to change our society has to change. Our government has to implement programmes which will provide them job and education. Until the root cause of the problem like dowry, poverty and illiteracy is not cured these kind of female infanticide will continue to happen in our country’. He also said that ‘instead of curbing the root cause of the problem our government is trying to implement control measures which will lead ultimately to such happenings’. My dad was a judicial officer! I am angry with my dad for supporting that woman. I am angry at him for his inability to do anything. I thought ‘as a judge why can’t he put them behind bars'. Now I realize what he said is true.

When women from affluent socio-economic conditions sit in their comfort zone and talk about female foeticide I get angry. Actually what do they know? They should come out and move with those women to know what is actually happening (for sure they can’t even survive a single day in those conditions!). They should realise how horrifying the living condition of such women are! What kind of life those girl children are leading (filled with negligence, lack of education, lack of nutrition and sexual abuse)! People who fight against female foeticide talk about the foetus ‘right to life’. They never seem to care about what happens when the foetus really becomes a human with the ability to feel pain and emotions! As a woman struggling to have a baby I cannot support any form of killing (Baby, baby everywhere (even people abort or kill too!) but still I am unable to get one to shower my love :( ) But in case if I end up with multiple pregnancy and if I am advised to do selective abortion for the benefit of one foetus I will definitely go for it in order to give at least one of my offspring the best chance of survival. Am I a murderer then? So if parents do so in order to balance the family (having a boy and a girl) or to give their offspring the best economic condition by aborting an unwanted baby, is it wrong? Should we just be selfish to protect our species (we kill animals for recreation, for eating, we even kill chimpanzees and gorillas which are capable of learning languages and have emotions like us!, nobody cares about their pain or emotionsas much as we care for a human foetus which do not feel any pain or emotions.) and propagate our genes as much as possible and be careless once they come into the world and leave them with the attitude ‘let the best survive’, ‘let natural selection do its job!’. Until we are not able to change the living conditions of such women and girl children we have no rights to talk or comment about what they are doing with the foetus (or even the infant!) they create!


If our government implement laws to prevent female foeticide then people from poor socio-economic background try killing the infants after birth and if the law threatens them again they will just vanish leaving the girl child in dustbins. Why is our society so afraid of girl child? The answer is simple-dowry, poverty and illiteracy. Until these issues are addressed properly there is no point in creating laws to protect the female foetuses. Is PNDT successful in preventing female foeticide? Definitely not! It has only lead to gruesome murders (infanticide) and to the act of abandoning the girl child. What will happen if PNDT act is withdrawn? Women living in poor socio-economic conditions will benefit from it. They do not have to carry a baby all nine months only to kill or abandon them. The girl child who comes into this world unwelcomed need not have to face negligence, physical and emotional violence. If unwanted teenage pregnancies could be aborted for the benefit of the concerned female why can’t we provide that right to a couple (especially to a woman who is already facing a hell lot of socio-economic problems, in-law’s and husband’s torture) who want to complete their family with a girl or a boy?


Another main argument put forward by the social activists is, if female foeticide continues the ratio of female to male will dwindle. They insist that if it happens then violence against women will be more as males in our society will start fighting for the woman and try to own them. Females will be considered like a property. I do not think so, my view is a bit different. If the number of females available for marriage decreases, naturally the value of woman goes up in the marriage market which will ultimately lead to the eradication of dowry or the entire dowry system will be reversed (like a male has to offer dowry inorder to marry a woman).Why shouldn’t we let it happen? Let human's face the consequence of their deeds. Nature is so powerful and for sure it will bring back the balance in the human ecosystem.


Think it in this way-if you find a small baby and a young doctor getting drowned and if you have the chance to save only one of them who will you save? Saving a doctor is far more beneficial for the society isn’t it? Now think of a woman who is already tormented by our social system and her unborn foetus which cannot recognize pain and does not posses any emotions? Whose well-being will you consider first? If you still do not understand just consider the fact that the pitiful woman is once upon a time a foetus. Does it make sense now if you cannot take out the foetus inhibition from your brain? Let us first consider the happiness of our womankind who is in flesh and blood. Let us work towards their betterment and then we can think about the foetuses. Our society is simply not yet ready to consider the foetus ‘Right to Life’ when our fellow adult women are struggling for their ‘Right to Dignity’. My dad used to advise me when I use my emotions to judge a situation, ' Manju, be rational. In life there are only very few situations which demands you to decide with your heart (emotional thinking) and 99.9% of the time it is better to use your brain (rational thinking)'. I think this topic is also one such thing where your emotions should take a back seat.

Let me know what you think. All sorts of criticism are most welcome!

What does scientific research say about improving oocyte/egg quality?

Oocyte quality is the most important determinant of IVF success. As a result of aging more chromosomal and spindle abnormalities accumulate in oocytes leading to increased incidence of infertility, foetal loss and birth defects like trisomy 21 or Down syndrome. Eggs obtained from younger women carry less genetic abnormalities and hence have higher chance of implanting and becoming a healthy baby. This is evident by the fact that women even after their menopause are able to get pregnant and carry the baby to term using donor eggs obtained from younger women.

When a woman undergoing IVF faces repeated failure, naturally the issue of egg quality crops up in the mind of infertility specialist and the patient. Unfortunately even after dramatic improvement in ART techniques, there is no sure way of saying whether an egg is competent enough (without genetic abnormalities) to produce an embryo which will subsequently implant and produce a baby. Although embryologists are able to select good embryos by observing their morphology under the microscope it doesn’t guarantee that the embryos are without abnormalities. A beautiful looking embryo of an older woman has more chance of being genetically defective than that of a younger woman. 

As a result older women as well as younger women who undergo repeated IVF failures are desperately searching for ways which would increase their egg quality and give them their most wanted wish-a baby! Infertility bulletin boards are filled with women who are determined to find a cure for their bad quality eggs. DHEA, metformin, melatonin, myo-inositol, wheat grass, anti-oxidants, fish oil, co-enzyme Q10, vitamins, especially vitamin D and other nutritional supplements are now-a-days extensively used by women to improve egg quality. Some of these substances used have scientific proof but some not. Selling supplements to improve egg quality is growing into a huge market as many businessmen are trying to make cash of our desperate situation. This led me to screen the scientific literature to find out what does science say really! Most of the experiments concerning oocyte quality are conducted in mice as it is difficult to do such experiments in humans for a number of reasons. 

Anti-oxidants

Oxidative stress contributes to somatic aging and it is also implicated in reproductive aging. So experiments were done to see whether using anti-oxidants improve egg quality and reproductive parameters. The researchers supplemented mice with pharmacological doses of vitamin C and E (both are well-known antioxidants) during their early or late life. They found that administration of oral anti-oxidants counteracted the negative effects of female aging on oocyte number and quality (PMID: 11835584). Good news right! Please do not rush to the pharmacy. Their research finding is not yet complete! Even though they found a positive effect of these supplements on the oocyte level they also found that oral administration of pharmacological doses of vitamin C and E reduced reproductive fitness and impaired ovarian and uterine function of female mice. They also said that the antioxidant diet decreased the frequency of litters, litter size, total number of offspring born and survival of male pups to weaning (PMID:12054212). Shocking or? A very recent publication suggested that, when mice are given low concentration of N-acetyl-L-cysteine the quality of fertilized oocytes and early embryo development improved. It also improved the quality of oocytes in older mice (PMID: 22357770). 

Now the question is how seriously we should take these experiments? First we should keep in mind that these experiments are performed in mice. The next thing to remember is ‘nothing equals a good diet’. Do you feel that you are not able to eat enough vegetables and fruits a day? Is your medical condition preventing you from getting appropriate amounts of nutrition from your diet? Supplementing with a good vitamin pill is a nice thing to do. Otherwise the best way is to add colour to your life by eating different coloured vegetables and fruits. Remember darker their colour more is the anti-oxidant content in them. 

DHEA

I am sure most of you will be aware of DHEA. If you google you will find lots of information about DHEA. Please visit CHR (Center for Human Reproduction) website for further details. DHEA was found to increase oocyte production (PMID: 16169414). The mechanism behind it is not so clear. DHEA is used in mice to induce PCOS phenotype in previously normal ovaries (PMID: 16514202). DHEA supplementation was also shown to decrease embryo aneuploidy (genetic defects) (PMID: 21067609). 

I have seen women who swear on DHEA for their IVF success. Many women even achieved natural pregnancies after taking DHEA. Will DHEA work for me? It might work. It worked for many but we should not also forget that it didn’t work for so many others. I am not trying to be negative, just trying to be cautiously optimistic. Try to monitor your thyroid levels and insulin levels when on DHEA (as it is found to affect both either in a positive or negative manner). Please remember that it is a steroid hormone and it is wise to be safe than sorry! 

Melatonin and Myo-inositol

Melatonin is a hormone produced in our body and it regulates circadiac rhythm. It has very powerful anti-oxidant properties and is found to protect nuclear and mitochondrial DNA (hence less genetic abnormalities) (PMID: 16217125). A recent publication concluded that melatonin is likely to improve oocyte and embryo quality in women undergoing IVF or ICSI but they found no statistical significance between the treated and non-treated group (PMID: 21770829). Melatonin was found to significantly improve thyroid function, reduce gonodotrophin levels, and in some women it helped in the re-acquisition of normal menstrual cycle. Furthermore, an abrogation of menopause-related depression, amelioration of hot-flashes and improvement of quality and duration of sleep has been reported. Myo-inositol is involved in several aspects of human reproduction. Elevated concentrations of myo-inositol in human follicular fluids appear to play a positive role in follicular maturity and also act as a marker for good quality oocytes. (I got this information from clinical trials.gov identifier: NCT01115127)

Should I try it?

Why not? Both melatonin and myo-inositol are naturally synthesized in our body and supplementing them won’t be a bad idea (but please read about the side-effects of melatonin supplementation). But better way is to optimize your health and get sound sleep.

Vitamin D

A search for vitamin D and oocyte quality did not give any appropriate pubmed result. I am sure many publications will come in the future on this topic. But searching for vitamin D and fertility gave some interesting information. Human sperms express vitamin D. Serum concentration of vitamin D is positively associated with sperm motility (PMID: 21427118). It is also found to regulate a large number of genes in reproductive tissue (PMID: 22047005). Animal data show that low vitamin D status is connected with impaired fertility, endometriosis and polycystic ovary syndrome (PMID: 10232622). 

Are you living in a country where winter is harsh and there is very less sunlight? It is advisable to take vitamin D supplements. There is lot of contradictions regarding safe vitamin D dosage. According to the new guidelines the tolerable upper limit is 4000 IU for ages 9 and above. Vitamin D at very high doses is found to cause calcification of soft tissues including brain tissue and several other complications. Published cases of toxicity, for which serum levels and dose are known, all involve intake of ≥ 40000 IU (1000 mcg) per day (search in google for Vitamin D Council for further information).

In summary are you living in a country where you get ample sunlight? Then just roam around with no sunscreen and expose your skin to sun’s rays. Exposure to sun rays for 10 minutes will help your body synthesize 10,000 IU of vitamin D. You can do this without the fear of vitamin D toxicity because your skin has a built in mechanism to prevent vitamin D toxicity. Take vitamin D supplements if you live in a country where there are very less sunny days and monitor your serum vitamin D levels at appropriate intervals. 

Diet or calorie restriction

This section is the most interesting part of this article. I found a very high quality publication on this topic and this is means it is more reliable. Calorie restriction in the absence of malnutrition is found to slow down the aging process and extend lifespan. If calorie restriction can slow down the aging process of somatic cells does it has the ability to slow down oocyte aging too? The research says YES. Recently a publication in PNAS, which is a reputed, high-ranked journal, showed that calorie restriction showed striking beneficial effects on chromosomal, spindle and mitochondrial dynamics in mature oocytes of adult female mice at ages normally associated with poor reproductive parameters. The study said that calorie restriction vastly improved fertility in aged animals. When initiated during adulthood calorie restriction significantly extended reproductive lifespan and increased the survival rate of offsprings conceived by aging females. This study clearly states that old age induced oocyte aneuploidy and spindle defects can be safely circumvented using calorie restriction (PMID:21730149). The study is well-designed and very promising. Rhesus monkey maintained on calorie restriction diet into advanced age showed the same health benefits as in mice.

Should I start a calorie restricted diet?

Why not? But you should also remember that this study is done in mice. Sometimes animal studies cannot be translated to humans. Please remember to take a good nutritional supplement (especially folic acid) when you are on a calorie restricted diet. Our ancestors are wise enough to starve themselves (do a fast) atleast once a week. Calorie restriction comes with an added benefit, who wouldn’t love to look younger than their real age!!!

Metformin

Metformin is a calorie restriction mimetic. It induces a dietary restriction like state (PMID: 20090912). It extends life span and is considered to be an anti-aging drug. It possesses anti-tumour properties. It activates genes which are induced during calorie restriction. So if calorie restriction preserves oocyte quality metformin can also do it! Hyperinsulinemic conditions are detrimental for oocyte quality. Metformin reduces insulin levels by decreasing insulin resistance and hence increases the egg quality of women suffering with PCOD.

Should I start metformin?

Are you diagnosed with PCOD? Do you have insulin resistance? Are you having poor egg quality because of PCOD? Metformin is for you. Do you have diminished ovarian reserve? Are you struggling to produce enough eggs? Then metformin is not for you. Metformin is known to reduce antral follicle count and when you are undergoing IVF number of eggs collected matters too!

Does lowering FSH and increasing AMH help me if I have poor egg quality?

FSH and AMH help to determine our ovarian reserve (egg quantity) and not egg quality (

PMID:

 21133869), (

PMID:

2073613). But as you age both egg quantity and egg quality starts to decrease simultaneously. This does not mean that egg quantity and quality are related. I think egg quantity and quality are two different events which has no connection to each other. This can be substantiated by the fact that younger women with diminished ovarian reserve are more likely to get pregnant and carry the baby to term even though they produce less amount of eggs during IVF stimulation (

PMID:

21602123). On the other hand older women with low ovarian reserve are less likely to conceive. So both FSH and AMH should be just looked as markers for poor ovarian reserve and nothing more. This can be understood if the actual modes of action of these two hormones are studied in detail. Egg quality is something to do with our genetic machinery which has no connection to these two hormones. Decreasing FSH or increasing AMH is also less likely to increase follicle numbers. Actually increasing AMH artificially can bring down your antral follicle count. 

These are some of the important scientific information which every woman undergoing multiple IVFs should understand. I wish this will reduce their tension about what supplements to take and what not to take, what is realistic and what is not. But at the end if you think taking certain supplements (because your friend took a supplement and fell pregnant miraculously!) increases your confidence level go ahead and take it, provided it should be from a reliable pharmaceutical company. You should also know for sure that the particular supplement does not have any negative side-effects that will compromise your health. Good luck for every woman who is searching frantically for that single good egg which will make their dream come true!