I will never ever carry a baby

I need a surrogate. This is the only thought running in my mind after I lost my children. It was dark and cold in Germany. I was longing for the warmth of a little one.  All my post-pregnancy hormonal fluctuations made coping even more difficult. I was in tears and full of fear.  All I needed is a baby as quick as possible!

Immediately after losing our twins we decided to go back to India. I had my own fears about shifting to India but my hubby (Rajender) was very adamant. Rajender’s coping mechanism was very different than that of mine. He needed to keep quiet and be within himself. For me, I needed to talk all my fears to someone; I needed words, comforting words. Although few thoughtful friends dropped in some time, everyone had to look after their life too. I am very thankful for the ones who came with their little ones. Those were the times of solace for both of us, a little oasis in the horrible desert we were in. There are friends who never came. I understood them too. Many are even afraid to face us, didn’t know what to tell us. But the truth is, when someone is going through difficult time in their life, the best thing you can do is to spend some time with them. Your time and comforting words are the best gift you can give someone during such times.

As time went on, I saw the truth in Rajender’s words; staying back in Germany will only make the situation worse. We needed the warmth of sun. We needed our parents so badly. In India, the situation for our parents was not any better. They wanted to see us, wanted to keep us within their wings.  I would say, Rajender took the most appropriate decision and I followed him.

The only idea that was brewing in my mind is to use a surrogate. Not only that, I was so greedy and unreasonable too. You will understand that when I explain what I actually wanted. I was constantly pestering Rajender for surrogacy. I told him, if I get pregnant again and if I have to lose the baby, I will no more survive. I never intended these words as blackmail; it’s the way I felt. He tried a lot to make me see the situation in a better way. He asked me, in your quest for your baby, will you exploit another woman. I told him, I am not exploiting anyone, I am going to give money which they need and I will have my little one. He looked at me eye to eye and asked, ‘what is the guarantee that you will have a baby with surrogate?  What will we do if the surrogate loses her life in the process, although it is unlikely, there is no assurance that it will not happen.  If something like that happens how will we be able live with such a huge guilt?’ I was shocked. All I can do is to cry. But this didn’t deter my spirit of pursuing surrogacy. I saw so many blogs where surrogacy gave the couples their much needed baby. I was so adamant and crying every day. I had only one more soul who could help me decide – my Dr! I asked Dr. Malpani’s opinion. All he said was to wait until the grieving period ends. He said, ‘whatever you decide now may not be correct. I never tell anyone what to do.  It is your life and only you have to decide’. I had no mood to listen to his wise words; all I needed was a path in front of my eye, the path to a baby so that I can remain peaceful. At last seeing my pain and agony, Rajender told me: ‘Manju, you are the one who has to carry the baby. If I can carry the baby I would do so happily. I will leave the decision in your hands. Whatever you decide I will support you. If you think surrogacy is the best option for you let us pursue that’. I should have been happy with those words, right? But unfortunately not!  I wanted from Rajender one more thing too; I told him that I will never ever do ovarian stimulation again. I have no strength to go through that roller coaster. If the remaining two frozen embies do not stick to surrogate’s womb then we will opt for donor eggs. He was shocked beyond belief. He said, why you think so far. First let us transfer the two embies, and then let us decide. But, the adamant, greedy person within me was not satisfied. Rajender didn’t yield to my unreasonable demand. He told me clearly that, if those two embies do not stick, we will adopt. I am not against adoption; all I wanted is a baby to spend my time with when my maternal instincts are high. But I thought, if not my genes, why not I have at least Rajender’s genes in my child – I know how animal instinct rules us but I perceived the power of it!

                            ....... A new beginning, will update whenever possible :)

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

How to cope with a failed IVF cycle ?

Question:

 Dear Manju,

 

I dont know where to begin. 

 

With great hope and faith I approached Dr. Malpani for donor egg ivf. As per schedule they retrived 12 eggs from the donor and 10 fertilised and out of these 9 were A grade embryos. My endo thickness on 10th day was 12 mm and on Day 14 they did the ET. 

 

During ET they transferred 3 good embryos- one morulla, one 10 cells and one 8 cells compacting. After two days we returned back home. After ET progynova and suppository continued. On day 7 of post ET I noticed little spotting. I thought it was implantation bleeding. But then next 2 days it continued and turned to pink/redish discharge. I asked the Dr. and he suggested me to double the dosage of progynova and suppository. But still the bleeding continued and on 11 day I started to wear pad ( Sorry for my language). I emailed to Dr and he suggested me to do the Hcg next day i.e., 12th day and it came -ve. (Today)

 

 I am upset and frustrated now. Dont know which path to take. I am not able to decide what to do now. I dont know what went wrong. Dr Sai, Ali and Dr. Malpani including me and my husband were very happy about the embryos. Dr. Anjali said " your endo thickness is good. why you are not getting pregnant. You should get pregnant this time" 

 

I dont know what went wrong? 

 Sorry I cannot continue.. 

 

Answer:

I feel your pain. I have gone through this pain for more than 7 times now and the most recent ordeal I went through is horrible. If I can be strong, you can be too. I agree it pains, just cry your heart out. This pain will subside. Take your time. Tomorrow will not be like today and one month later it will be much better ((((((( hugs)))))), lots and lots of. I wish I could be nearby you to hold your hands during this difficult time.

N, hope and faith can't help much with IVF success. You must have realistic expectations about IVF. Do you think women of younger age conceive in their first attempt (either in bedroom or during IVF)? Science of IVF is not fool proof. There are so many variables which needs to be perfect for implantation to occur and many of which are not in anyone's hand. The embryos must be good enough, your endometrium should be receptive (thickness of an endometrium doesn't say how receptive it is!), the ET has to be perfect and after transfer your embryos should grow and attach. It is just like a probability game. Since you are using donor eggs your chance of success was brighter and still is. When doing IVF, please give 3 tries – with the same clinic, provided you are confident about their competency and most importantly their ability to create good embryos. 60 % women conceive within 3 IVF cycles. The remaining 40 percent need more attempts and some never conceive - no one can pinpoint the reason! 

N, I am sorry that everyone's positive words have raised your hopes too high. Just because the embryologist says you have good embryos and just because your doctor says you have good endometrium, it doesn't mean you have 100 percent chance of success. Every IVF cycle gives you only 40 - 50 percent success even if everything looks perfect. I am sorry, really sorry I didn't know that you didn't expect a failure. Otherwise I would have warned you before.

I agree that the amount of money spent and the efforts made and the dreams you had will make coping difficult. All I can say is - do not give up! It is our ill fate that we have to undergo so much financial, emotional and physical pain to get a baby. All that we have in our hands is to make this journey as pleasant as possible. There is something to learn, there is something to expect for, there is something to be happy about, there is something to be proud of (who will be able to tolerate such a suffering!) even during this difficult journey. Use it to grow spiritually, enjoy your time with your husband, use this time to make your relationship stronger, develop more love for your life, and see everything with curiosity and amazement - this suffering then becomes somewhat pleasant. Never think a baby is the ultimate happiness. There are many ways to have a little one still, do not give up until you have exhausted all your options. Never fall into depression, take care of your life, never let your happiness slip out of your hands in your quest to have a baby. All will be well! 

I hope my words will help you, lessen your pain a bit.

Reply:

 

Dear Manju,

Thank you so much for your response and advice...I truly appreciate it. I especially like what you had to say about there being no mistakes in life, only lessons.

" All that we have in our hands is to make this journey as pleasant as possible. There is something to learn, there is something to expect for, there is something to be happy about, there is something to be proud of ( who will be able to tolerate such a suffering! ) even during this difficult journey."

I have never heard that before and I just love it. I am feeling much better now. I will stay in touch and let you know what we decide to do....probably going to take a break and then we'll see about it in June. It's tough to think about doing it all again....but I just need to remain strong and we will get through this.

Thanks and God bless you.

How long to wait between IVF cycles ?

It depends on your physical, financial and emotional comfort. Some women find it difficult to do back-to-back IVF cycles while some women do not want to wait in between IVF cycles. Sometimes, due to ovarian hyperstimulation you might end up with cysts in your ovaries. In such cases your doctor will want you to wait until the cysts regress before starting another IVF cycle. If you have frozen embryos, you can do the cycle back to back, if you so desire. Whether you do your IVF cycles back-to-back or whether you wait , is a very personal decision. It will not affect the outcome of the IVF cycle. Your age also plays an important role in determining how long to wait between IVF cycles. As a woman ages,  her fertility declines, and hence it is wise not to wait too long before proceeding with another IVF cycle.

Why did my eggs fail to fertilize ? (complete fertilization failure)

This is another heart-breaking situation which some couples face when they go through IVF. You are very anxious to know the day after egg collection as to how many of your eggs have fertilizedand how many embryos you have ! But there are some rare instances where none of your  eggs fertilises and you are left with no embryos to transfer. The reasons for complete fertilization failure include :

•  Lab error - technical problems in the embryology lab , such as infection in the culture medium or an incubator malfunction can cause this

• Sperm problems  –  Sometimes even normal looking sperms can fail to fertilize the eggs.  This kind of fertilization failure due to functionally incompetent sperm can be prevented by using ICSI (a technique where a sperm is directly injected into egg , thus facilitating fertilization).  If ICSI fail to solve the problem then the issue lies most probably with the egg and not with the sperm.  This is because once the sperm enters the egg , the further events that take place are controlled by the egg’s machinery , and not by the sperm’s !
• Egg problems

What do you do when faced with such a situation ? This is a medical emergency !

• Ask the embryologist whether there was a lab problem. However, even if there was, it’s quite likely that the lab is not going to be completely honest about this. If only your eggs failed to fertilize on the particular day,  while the eggs of the other patients fertilised normally, the chances of a lab error are low.
• Ask the embryologist to do rescue ICSI. Here the embryologist injects a sperm into the unfertilized egg . While the success rate is low, this can help to salvage the cycle; and will also prove that the problem was with the sperm and not with the egg
• Try again in another clinic – this gives you a better chance of pinpointing where the problem lies!

Read more at : http://blog.drmalpani.com/2010/10/failed-fertilisation-after-ivf.html