The smoke and mirrors behind HLA matching and NK cells activity assay – the “reason” and “cure” for unexplained implantation failure!

I was recently reading a blog post from Dr.Sher.  He discusses immunological implantation dysfunction and claims that it is a common cause of repeated, “unexplained” implantation failure. He says that due to immunological dysfunction the embryo will be destroyed by “malfunctional” NK cells and hence implantation failure ensues. He assures patients that such ruthless “killing” of your precious embryos by “crazy” NK cells can be prevented by some specific therapies.  I was startled to see the way that article is written without any sound scientific basis – a nicely concocted story without any evidence!

The link for that article is here: http://haveababy.com/fertility-information/ivf-authority/unexplained-infertility-and-ivf-failure

Before reading it, you must understand the meaning of two different words which are used frequently in that article – HLA and NK cells. HLA stands for Human Leucocyte Antigen. These are molecules which are present on the surface of almost all the cells of our body and help to protect us against infections.  They are also known as the major histocompatibility complex (MHC) . When our cells are infected by harmful microorganisms, their antigens are loaded on to the cell’s HLA molecules. These HLA molecules then carry the viral or bacterial fragments to the cell’s surface. Once they come to the surface of the cell, they present the microbial fragments to our body’s immune cells called cytotoxic T cells.  Cytotoxic T cells constantly scrutinize our body for foreign antigens (microbial fragments or any other protein which are not normally present in our body). They can recognize these foreign microbial fragments only when they are presented to them by the body’s own  HLA molecules. Once the cytotoxic T cells recognize that a particular cell is infected by a microorganism , it kills the cell , thus protecting our body from harmful microbes. Consider this analogy :  a thief (microbe) enters your home (cell). You need to tell the policemen (cytotocxic T cells) who are on surveillance duty that a thief is in your home. When the thief is not watching, you send one of your servants ( the HLA molecule) with information on a piece of paper (microbial fragment) outside your home , so that the police men gets notified about the thief and can protect you. This is the exact scenario but with a minute difference-our body’s policemen (cytotoxic T cells) destroy (sacrifice) the infected cell to save the nearby healthy cells – they burn the house down to kill the thief !

In order to evade our intelligent immune system some microbes prevent the HLA molecules from carrying the microbial fragments to the surface of the cell. This is analogous to the thief who prevents the servant from going out of the house with the piece of information about the thief. In such circumstances , Natural Killer (NK) cells come to the rescue. When an NK cell recognizes that a particular cell doesn’t express enough MHC molecules on its surface as it should, it just destroys the cell by suspecting a possible invasion. Amazing , right ?

In short,  HLA molecules and NK cells are components of our immune system which help to protect us against microbial invasion and other insults.  If this is so, how they are connected to implantation failure?

Our immune cells attack not only cells that express microbial antigens but all cells that express non-self antigens (proteins that are not normally present in our body). This is why transplanted organs from a non-compatible donor are attacked by our immune system , and this is why they are rejected. A donor is said to be compatible if he/she carries identical HLA molecules as that of the recipient. If the donor’s organ express non-identical HLA molecules , then cytotoxic T cells recognize these foreign HLA molecules and destroy the cells of the donated organ.  This is why HLA is also called Major Histocompatibility (Histo =tissue) Complex (MHC).  It is only after checking the HLA compatibility between the donor and the recipient that organ donations are performed.

If this is the case, how does a fetus which carries half of its genes from its father (and hence different HLA molecules on its cells’ surface) survive the maternal immune system attack? In order to explain this , a hypothesis was proposed: that the uterus is an immunologically privileged site, and for a fetus to be not rejected by the maternal immune system , it has to carry different HLA antigens on its surface , and this helps the maternal immune system to develop tolerance to the fetus. This is exactly the opposite of the organ transplantations scenario , where the donor and recipient’s HLAs should match. As a result , when husband and wife have excessive similarity in their HLA molecules ( a high degree of HLA matching) and suffer from infertility , they are treated with a variety of immune therapies , to try to stop the maternal immune system from rejecting the fetus!

In his post , Dr. Sher writes:

“We diagnose alloimmune ID ( immunological dysfunction) by testing the male and female partners for the degree of sharing of genetic markers , known as of as DQa and HLA. A sufficient degree of matching clinches the diagnosis. We also test the embryo recipient for Nka in an attempt to measure the relative severity of the problem. This is because once the NK cells in the uterine lining are activated and the cytokine balance is disrupted, the situation is grave and will remain so (or worsen) unless the NKa cells are medically deactivated (down-regulated) at least 1 week in advance of the embryo(s) reaching the uterus”.

He obviously loves medical jargon , and talks about DQa and HLA, in order to impress patients ( and doctors !) as to how well-informed and erudite he is . DQa is just one sub-class of HLA. HLA is divided into class I and class II. Class I consists of HLA A, B, C and also HLA E, F, G. Class II consists of HLA DQ, DR and DB. Now what is the connection between HLA and NK ( natural killer) cells? How does HLA compatibility between the partners triggers NK cell activity which kills the embryo ?

 I have no clue – and neither does he, but he cloaks his ignorance in a lot of medical gobbledygook.

I need to explain here some scientifically proven facts about HLA expression in the human embryo,  and human NK cells:

Ø  The part of the human embryo which comes in contact with the maternal immune system is its trophoblast cells - more specifically , the external villus trophoblast (EVT).

Ø  These EVTs do not express class II HLA molecules (DR, DQ, DB) at all. They do not express highly antigenic class I HLA molecules (HLA A, HLA B). The EVT cells only express HLA G, E and C.

Ø  You must note that most of the HLA matching between you and your partner is done for HLA A, HLA B, HLA DQ.  Even if there is a high degree of matching between you and your partner for these molecules , this does not have any significance as regards your fertility, because of the simple fact that these molecules are not expressed at all in the cells of your embryos which come in contact with the maternal immune system!

Ø  It was believed (but never proved!) that if partners carry similar HLA molecules, the maternal immune system develop toxic T cells that might destroy the embryo . However, there is no proof that T cells attack human embryo.

The NK cell is another tall tale. I will enlist some facts about human NK cells below:

Ø  There are two types of NK cells: CD56 ^bright+ CD ¹⁶⁺ and CD56 ^dim+ CD¹⁶⁺. CD56 ^bright+ CD ¹⁶⁺ is the cell type predominantly present in the uterus.  This does not have significant cytotoxic activity.CD56 ^dim+ CD¹⁶⁺ is the NK cell type present in peripheral blood and has extensive cytotoxic activity.

Ø  The NK cell activity assay is mostly performed with the NK cells collected from the peripheral blood of infertile women . The NK cells present in peripheral blood do not reflect anything about the NK cell activity in the uterus. In other words, tests performed on peripheral blood NK cells cannot be used to draw conclusions about the uterus NK cells ! This testing is completely flawed.

Ø  NK cells activity assay is performed by measuring its ability to kill K562 cells. K562 cells are cancer cells , and they do not express the HLA molecules (HLA G, E and C.) that are expressed on the human embryo’s extravillous trophoblast. When K562 cells are scientifically manipulated to express HLA E or G, the  NK cells failed to kill the K562 cells!

Ø  When human trophoblast cells are grown in vitro (in laboratory environment) they do not express the same HLA molecules which they express in vivo (in the uterus). Also, even NK cells in vitro do not kill trophoblast cells!

The above scientifically proven facts I have painstakingly collected from the scientific literature emphasize only one thing – HLA compatibility between you and your partner and/or NK cell “malfunction” cannot kill your embryos It is wise to avoid tests used to “diagnose” them and therapies intended to “treat” and “cure” them. I sincerely wish that infertility specialists don’t make the vulnerable and desperate infertile patients’ condition even worse by making a mountain out of a mole hill. When a doctor meets a patient who suffers from unexplained infertility or repeated implantation failure, it is much more honest and humane to say ‘I do not know’ than to sell them false hope. 

Please read these articles for detailed info on this subject: 

http://myselfishgenes.blogspot.de/2013/03/does-hla-sharing-cause-miscarriage.html

http://myselfishgenes.blogspot.de/2014/07/tests-for-nk-cells-and-cures-for.html

What can I do differently after a failed IVF cycle to increase my chances of success ?

This post is for you Anu (thanks for the kind suggestion!) and for all my blog readers! I will be very happy if you could ask me more questions. Remember, every of your questions and doubts will help others who are in a similar situation too !

"Manju, what did you do differently this cycle ? You have undergone 7 embryo transfers without success, so what helped you to succeed this time ?" This is the question I am asked most frequently now-a-days.  I wonder how people came to the conclusion that doing something different helps in achieving success ! Here are my answers.

1. Can you tell us something about your medical history ?

My reason for doing IVF is tubal factor infertility. At the age of 29 I was diagnosed with a hydrosalpinx in the left tube and I had to remove it. My right tube is present but non-functional due to adhesions. I started my IVF journey at the age of 29. I learned that women with tubal factor infertility have very good chance of IVF success and now I am 35 years old and pregnant with embryos that were created from eggs extracted from my ovaries when I was 33 years old ! I expected my IVF journey to be short but I it took almost 6 years to get pregnant and carry it past the first trimester !

2. Is there any problem with you other than non-functional fallopian tube ?

I was diagnosed with PCOD and I am insulin resistant (this tendency run’s in my dad’s family!). I have been on metformin 1500mg from the age of 25. While on metformin , I had regular periods. Many different tests were done on me during my IVF attempts and after my miscarriage. The following “abnormalities” were found :

• Compound heterozygous MTFHR mutation – I started taking 5 mg folic acid because of this diagnosis.

• I was tested for HLA compatibility with my DH. They found 2 or more HLA loci compatible with my husband. This test was done immediately after my m/c. I didn’t have much knowledge then. I thought let them do whatever is needed so that I will have my baby. My RE in Germany asked me to undergo paternal lymphocyte immunotherapy to help my embryos implant and prevent further m/c. I didn’t even understand the principle behind the therapy then. I asked my RE but he had no clue either ! The therapy was performed like this : they isolated lymphocytes from my husband’s blood, injected them under my skin and monitored my blood after 1 month to see whether I had developed antibodies against his HLA ! They said “you have to get pregnant within a year, otherwise the antibody titer falls and you have to repeat this therapy again”. This therapy was done in 2009. I never conceived in my further attempts. I really started to panic whether this therapy did any irreversible harm to me and then I started to explore what this therapy really means. Then Dr. Malpani asked me whether I could write about it. During that time I learned a lot about HLA matching and about the “mindless” therapy I underwent for no good reason. My current pregnancy shows that HLA matching between husband and wife has nothing to do with successful embryo implantation or early pregnancy loss ! Please read : http://myselfishgenes.blogspot.de/search?q=HLA

•  I have PAI 4g/4g mutation. The literature says PAI 4g/4g mutation predisposes me to insulin resistance. Another information I now know about this is, this mutation carriers may have increased risk for HELLP syndrome.

3. What kind of therapies were suggested by your REs ?

As mentioned already , I underwent paternal lymphocyte immunotherapy in Germany 4 years ago without it helping at all! My RE in Germany firmly believed that giving me heparin will help. I asked Dr. Malpani about it once and he said it was unproven and not necessary. I was so comfortable with Dr. Malpani’s conservative approach. He never wanted to experiment on me with any therapy which had no evidence to back it. His confidence made me very confident too. He believes firmly that embryo quality matters the most and that is what is my current pregnancy shows. I never again thought about using heparin – after all , I don’t have any problems with blood clotting. I did not even use baby aspirin this successful cycle.

4. How many IVF cycles have you done and where ?

I have done 6 IVFs and 3 FETs (9 embryo transfers altogether). The last FET was a success and I am currently 11 weeks pregnant with twins. I have done 5 IVFs and one FET in Germany without success (although I conceived in my 2nd IVF , that pregnancy was short lived !). I did my 6th IVF with Dr. Malpani of Malpani infertility clinic. You can see all my IVF cycle details (dosage of medicines, how many eggs retrieved, how many embryos were obtained and how many were transferred to the uterus ) in this post : http://myselfishgenes.blogspot.in/2012/05/my-ivf-journey-timeline.html. You can also read about a more detailed description of how I ended up with more eggs in my 6th IVF in this post : http://myselfishgenes.blogspot.in/2012/08/from-3-eggs-at-age-of-29-to-24-eggs-at.html

In my 6th IVF cycle with Dr. Malpani, I got more eggs than all my other 5 IVF cycles combined. Dr. Malpani allowed me to tweak the protocol in the beginning a bit , but I do not think that could be the sole reason for a high egg yield. I took 75 mg DHEA for 8 months (as per Dr. Malpani’s recommendation) before my 6th IVF and I also stopped metformin which I was taking for years. I also didn’t use Gonal F (a recombinant form of FSH which is a highly purified form) during my 6th IVF. I used a much cheaper version of FSH called Menopur ( a crude form of FSH preparation which is isolated from the urine of menopausal women). Might be a combination of everything or just the increased dosage of FSH which Dr. Malpani started me on from day 1 of cycle worked its magic and I got 24 eggs in that cycle. I am sure Dr. Anjali’s egg retrieval skills played a major role too.

5. What kind of transfer was your successful cycle – was it a fresh embryo transfer or frozen embryo transfer ?

I got 24 eggs in my 6th IVF. 3 good embryos were transferred during that cycle (fresh transfer) and 7 embryos which were of good quality were frozen. Out of 7, 2 were blastocysts and 5 were 8-celled day 3 embryos.

My fresh transfer was not successful. I had a great endometrial lining during that cycle. It was around 10mm, trilaminar. The next was a FET where we transferred 2 frozen blastocyst stage embryos. Again no pregnancy was established- the embryos failed to implant. We thought my poor endometrial lining (only 6.5 mm) was to be blamed for this failure (I used G-CSF for this cycle as uterine infusion to help my endometrium grow but it was of no use, my endometrium didn't respond well to G-CSF as expected).

I got a BFP with my recent FET during which my endometrial linig was only 6.7 mm. We transferred 3 8-celled embryos which were graded excellent. The remaining two 8-cell embryos ( out of the 5 frozen ) were grown to blastocyst and were refrozen again. Out of the three transferred two implanted and I have completed 11 weeks as of 28.8.2013 - and so far so good !

Remember, FETs are much more successful than fresh transfers now-a-days ! So find a clinic which uses vitrification for embryo freezing ! Please read this post for more info : http://myselfishgenes.blogspot.de/2012/12/in-past-standard-was-transfer-best.html

6. So what did you do differently this time ?

To be very honest, I didn’t do anything differently.

Many things went wrong this cycle. I had a poor endometrial lining again. It was only 6.7mm at the time of transfer ! I took 4 progynova (estrogen, 2 mg each) from day 1 of my menstrual cycle until day 21. Usually I ovulate at around day 21 so I thought why not give my lining a bit more time to grow. Since my endometrium was thin I just continued taking 4 progynovas until day 21. But the lining didn’t increase its thickness beyond 6.7 mm. I didn’t use lupron this cycle to suppress my pituitary. We actually thought lupron use might have caused poor endometrial growth but later we found that lupron was not the culprit (omitting lupron didn’t make any difference in my endometrial response to progynova). Since I didn’t use lupron this successful FET, at around day 7 of taking progynova I had an early LH surge (which indicates ovulation !), my LH at that point was 22 IU/l. But my progesterone was within pre-ovulatory range at that point and I didn’t have any follicles in my ovaries ripe enough for ovulation. Hence there was no chance for ovulation. So we continued with the cycle. Just 5 days before transfer I ended up with severe pain in my stomach (perhaps amoebiasis due to eating in restaurants in Mumbai !), so I ended up taking metrogyl 400 mg twice a day and I stopped it just the day before embryo transfer !

So with a lining of 6.7 mm, a premature LH surge and taking massive doses of metrogyl (actually this wouldn’t have had any ill effects anyway !) we carried on with embryo transfer. Dr. Malpani was not so happy that I decided to transfer my precious embryos to my poor lining but he was happy to let me decide. I always told him “Dr, I have the best lining in the whole world”.

7. What went right this cycle ?

Lot of things :)

• I believed in what I did. My poor endometrium (as per so many scientific publications !) did not deter my spirit. I didn’t waste my time thinking that something is wrong with my endometrial lining and I didn’t do anything to improve it. I didn’t take massive amounts of estrogen nor did I take baby aspirin or any other blood thinners. No Viagra too :) After thinking a lot, I came to the following conclusion - My endometrium grew very well during all my fresh IVF cycles (10-12mm). This clearly showed that I had no underlying problem (fibroids, adhesion, infection etc) with my uterus. I confirmed it with a hysteroscopy which took just 5 minutes. The doctor who did hysteroscopy concluded that I had a small uterus but there was nothing to worry about – after all there will be lots of biological variations in the size and shape of uterus ! Since my endometrium grew well in fresh cycles (where enormous estrogen is present in the body) any end-organ damage is ruled out. During FET my estrogen levels (on progynova) rose to about 200pg/ml and this is in the normal range for an ovulatory cycle (200-300 pg/ml). With that amount of estrogen in my body, my endometrium could only grow upto 6.7 mm. I thought well and good, that might be my body’s natural response. I see so many women in infertility forums worrying about their lining thickness and trying so many different therapies to increase the thickness. From my experience I would say, If you do not have any underlying problem in your uterus , then do not worry about the lining thickness. The receptivity of the lining is what matters the most, and a thin lining can be receptive. What matters most is your embryo quality. If endometrial lining is that important for embryo implantation how come ectopic and extra-uterine pregnancies occur ?

• I had wonderful people around me who made me so comfortable during embryo transfer. Dr. Sai’s gift to me did magic to my confidence level ! I suggest every IVF clinic give their patients some cute gifts before ET to boost their morale (how much does a gift cost when compared to the huge amount they charge :)

•  I was so relaxed and was ready to face whatever comes my way. I always have plan B, C, D etc

•  I believed in the competency of embryologist and my Dr - I trusted them !

• My embryos looked so beautiful-thanks to the embryo creating skills of Dr. Sai !

• My loved one’s prayed for me. My mom sent me to the ET room like a warrior, she applied some holy ash on my forehead ( and my DHs’ as well for extra god luck) . I did feel like going to a war front :) The love I felt in her gesture and HER prayers, the sacrifices she made (removed her hair, gave up eating sweets and pickles – the things which she likes most !) did play a major role in achieving this BFP.

8. Manju, did you take any supplement ?

I personally don’t believe in taking supplements to improve endometrial lining or its receptivity. So I didn’t take anything at all. All I took was 5 mg folic acid, 500 mg metformin (I am insulin resistant !), 4 progynovas and uterogestan ( progesterone) as instructed by my Dr and that is it. Please read : http://myselfishgenes.blogspot.de/2013/01/does-taking-supplements-help-ivf.html

9. How about bed rest ? Did you restrict your activities ?

I was on my feet 5 minutes after ET . I went back to hotel room, had my dinner and slept. From the next day onwards I took it easy, meaning, I didn’t engage in any strenuous activity. I went out for shopping, walked to a nearby restaurant to have my lunch, roamed with my mom and husband in the evenings. No bed rest at all ! Please do not torture yourself by lying down in bed for 3 or 4 days-it doesn’t help. It can harm your physical and mental well-being. Please read : http://myselfishgenes.blogspot.de/2013/02/will-embryos-fall-out-after-embryo.html

10. Can I fly immediately after ET ?

Yes, you can. But I stayed in Mumbai for 5 days after ET. The sole reason was to spend time with my mom. I get a chance to see her only when I come to India . She lives with my old granddad , and takes care of him, so it is not possible for her to visit me in Germany. I was not able to take holidays because I needed holidays for my treatment. I was so happy to be with her and my DH those 5 days. They both treated me like a queen :) (few joys of being infertile !)

11. What was your thyroid level pre-pregnancy ?

I was diagnosed with sub-clinical hypothyroidism (TSH 5.5) few years back. So I am on thyroxine. I do not have TPO antibodies. I tried hard in the beginning to keep my TSH around 1, as it was said that a TSH of close to 1 is ideal for achieving a pregnancy. I took 75 mcg of eltroxin and my TSH was around 1.3 or so but I felt like crap. I felt too hot, got frequent cramps in my leg and lost weight. After sometime I gave up worrying about the numbers on the papers and tried to concentrate on my body. I took 50 mcg and my TSH was around 3.5. I felt good. I had no symptoms of hypo or hyperthyroidism. So I maintained my dosage of 50 mcg. Last week during my visit to gynecologist (at around 10 weeks of pregnancy) they checked my TSH again and it was 0.88 to my surprise. As hCG hormone increases TSH levels tend to fall. Such increase in thyroid function is normal during pregnancy I learned. If you have thyroid autoantibodies it is wise to regulate your levels before getting pregnant but please listen to your body rather than obsess about the values on the lab report. Maintain a dosage which is comfortable for you and do not try to bring your TSH too low if you are not comfortable with this . A large scale study didn’t show any association between sub-clinical hypothyroidism, chance of conception or miscarriage. Women with TPO antibodies are prone to increase in their TSH (due to declining thyroid function) during pregnancy. So please check your TSH during pregnancy and adjust your dosage accordingly. Remember, severe hypothyroidism has to be treated as it can lead to abortions and premature deliveries.

12. Is there any advice you can offer me to increase our chance of IVF success ?

Yes, for sure !

• Select a competent clinic. Go to the best IVF clinic available nearby. It does make a lot of difference.

• Learn a lot about the IVF procedure. Opt for information therapy before IVF therapy.

• Ask your clinic to show you your embryos. Educate yourself about how your embryos should look according to their age. Do not say I trust my doctor so I do not have to look at my embryos. There is a old saying “ Believe in God but lock your car”. Be wise and protect yourself from fraudulent activities which exist in the field of IVF. If someone cheats us once, they are fools . If they cheat us twice, we are. Please read : http://myselfishgenes.blogspot.de/2012/10/what-can-i-do-if-my-ivf-doctor-does-not.html

• Demand a copy of your medical records.

• Do not think IVF is a single attempt process. The younger you are and the more the eggs you produce , the more likely you are to succeed. So have patience and be persistent in your attempts. Be flexible and open to different treatment options (like donor eggs, donor sperms etc)

• Do not doubt your uterus, in most cases the culprit is the egg quality ! Please read : http://myselfishgenes.blogspot.de/2012/12/why-did-my-ivf-cycle-fail.html

• Trust the doctor you selected, appreciate them for the work they do for you, be friendly with the hospital staff. If you treat them only as workers you will fail to get their warmth and compassion when you need it the most !

• Please do not undergo any unproven therapies like IVIG, LYMPHOCYTE IMMUNOTHERAPY, USE OF STEROIDS, BLOOD THINNERS (if you are not diagnosed with clotting problems) which are not scientific established when undergoing IVF. IVF is a game of probability. If you are young and lucky enough you will find success soon. Otherwise it might take a few more attempts. I recently received a mail from an infertility specialist who conceived in her 17th attempt. An IVF failure doesn’t mean something is wrong with your body and you need to “correct” something. Human reproduction is a remarkably inefficient process. A normal, fertile couple needs on an average 12 months to conceive. If they don’t conceive in their bedroom in 4 months, they do not go to the doctor and ask him to “correct” something in their body- you don’t have to either!

Please read : http://myselfishgenes.blogspot.de/2012/07/my-advise-for-someone-starting-their.html

13. Can you provide me with an IVF checklist – what kind of tests are a must before an IVF cycle ?

• Check your anti-muellerian harmone (AMH) and antral follicle count (AFC) to test your ovarian reserve.

• Check your Thyroid stimulating hormone (TSH). If it is not within the normal range please see an endocrinologist to further asses the reason for thyroid dysfunction.

• If you are diagnosed with PCOD and have high BMI, check your fasting insulin. If the fasting insulin is high, life-style changes along with metformin use will give you a better chance for IVF success. Metformin use during the first 12 weeks of pregnancy was shown to reduce miscarriage rate in PCOD women.

• Check your blood sugar to make sure you don’t have diabetes. This test becomes very important if diabetes runs in your family.

•  Hysteroscopy to check your uterus if any abnormality was detected using ultrasound images.

14. What did your infertility experience teach you ?

I will never consider my infertility experience as ill-fate. Infertility taught me many good things, introduced many wonderful people in my life, and made me knowledgeable. I have an infertility blog (thanks to Dr. Malpani !) now which helps many people and all the writing I did and the knowledge I gained because of that made me very confident. The confidence thus obtained and emotional protection it gave me is also one of the reasons for my success.

The lessons I learned :

• Never believe in unproven therapies that exist in the field of IVF and waste your time, energy and money.

• IVF is a game of probability, you may need few attempts before finding success. If you do not find success soon, It doesn’t mean your body is defective.

• There are only three main components important for IVF success : good embryo, efficient embryo transfer and a uterus without any defects. Your embryo quality is decided by two factors : your age and your clinic’s competency in producing good embryos and to some extent the quality of sperm (perhaps a 10%). Embryo transfer (please read : http://myselfishgenes.blogspot.de/2013/02/embryo-transfer.html) depends on two factors again : the ease with which your uterus can be accessed and your doctor’s skill. Your uterine cavity must be free from adhesions, scar tissues and certain type of fibroids which might interfere with embryo implantation.

• The competency of your IVF clinic matters a lot ! Always asses your clinic’s competency by how your embryo looks. Please, please do see your embryos before transfer and demand pictures of your embryos.

• Patience and persistence during times of infertility provides rich dividends. 

• Helping others is the best way of helping yourself.

• Find good emotional support.

• Have healthy hopes and weed out unhealthy expectations.

• Infertility struggle doesn’t end when you get a positive BFP. The real struggle starts then and doesn’t end until you have your baby. Even if you get a positive BFP be cautiously optimistic. I was totally heart-broken with my m/c after my 2nd IVF attempt – I wish someone could have warned be about the possibility of m/c. 1 in 4 pregnancies end too early and the risk of m/c increases as your age increases.

• Enjoy the journey !

15. I do not have enough money to do IVF, IVF is too costly for me – what should I do ?

This is a tough question and a question which breaks my heart all the time. I will try to suggest some possibilities :

• If you are ready to donate half of your eggs to women who are in need of egg donation , then you are entitled for free IVF in some clinic. Please do find out if this is feasible. But for egg donation you must be within 30 years of age.

• Some clinics offer a money-back guarantee programme. You have to pay for 3-4 cycles and if your IVF is not successful, they then repay 100% of your treatment costs . This gives you some financial security . You can check out an example of such a program at http://www.drmalpani.com/guaranteedpregnancy.htm. Not everyone qualifies for this programme, and age matters , so enquire about this option in your clinic.

•  Bargain – there is nothing wrong in bargaining with your IVF doctor. Doctors are humans too and if you could give a valid reason and show proof that your income is low , many doctors might help you. I know in Dr. Malpani’s clinic they do free cycles for people who couldn’t afford IVF. But again if you are healthy and young the chances are more that your doctor is willing to help you.

• The most important solution is to fight for the rights of infertile couples. We need to pressure the government to pass rules which ensure that IVF treatment is covered by medical insurance. It will take a lot of effort and lots of people to achieve this.