How to become a good IVF patient ?

If you are told that you need IVF to conceive,you naturally tend to spend a lot of time and energy in finding the best IVF doctor.  This is because you know that finding a good IVF doctor will help you in getting the best treatment possible. You want a good IVF doctor who runs a competent clinic; respects you and your needs; will be intelligent enough to tailor the treatment according to your individual requirements ; and is empathetic enough to provide emotional support during your time of distress.

This is quite reasonable, but are you also willing to put in at least half the effort which you took to find a good doctor in becoming a good IVF patient ? Many of us still naively believe that, once we find a good doctor , our responsibility in our treatment gets over , and the doctor will take care of all our needs.  This is not true; getting the best treatment possible and the ease with which you can go through an IVF treatment rests in your hands too. Just like you expect your doctor to be competent, a knowledgeable patient is a good IVF doctor’s delight ! If you learn to be an ideal patient you can reap the best of your doctor and treatment. An ideal patient makes an IVF doctor’s life much easier. Remember, good patients beget good doctors , and vice versa !

How many of you go to watch a movie without reading its review ? If you are willing to do your homework before watching a movie, isn’t it wise to do your homework when undergoing one of the most important and expensive medical treatments you will need  ? It is your responsibility to understand what your treatment is all about , and how it works.  The internet is a boon for patients who want to learn more and there are many authentic websites and blogs written by IVF specialists and IVF patients which will help you to get reliable information. If you become a well-informed patient, you no longer have to be dependent on your doctor for taking treatment decisions; you can work as an intelligent partner with your doctor. This will increase your confidence levels, protect you from medical fraud ( such as unnecessary tests and unproven treatments !) ; and will also act as a shield to protect you against medical errors. If you are a knowledgeable patient your doctor is much more likely to respect you and treat you well. 

Many patients tend to think that they are not intelligent enough to understand medical science. This is why they are afraid to ask their doctor questions, and prefer to bottle these up, thinking that their questions are stupid. . The truth is that you do not need special talents to understand how your body works - you just need to be curious and ask questions. Never be afraid to ask questions; it is the duty of your doctor to explain in terms which you can understand , and clarify all your doubts. When talking to your doctor , make sure that you ask relevant questions , and this can only be achieved if you have done your homework – don’t expect him to spoonfeed you ! When you understand the science behind your treatment , you will be able to understand what your doctor can do for you , and what he cannot. Having realistic expectations of the treatment process  will protect you from emotional breakdown if the cycle fails; and will also safe-guard your doctor from your unreasonable wrath if the treatment does not give the expected result.

Every patient wants her doctor to remember her as a person. You want him to take special interest in your treatment and work extra hard for your success. This can happen only when you work together with your doctor , and show an intelligent interest in what he is doing for you. You should understand that medical science is a rapidly growing field , and there are many different treatment options. When you remain passive, you put all the responsibility on your doctor and he is forced to decide what is best for you. Even though a good doctor works for your best interests, many a time they are biased too ( sometimes without even being aware of their personal prejudices) . They may end up selecting a cookie cutter , generic treatment plan for you, without customizing it to your special circumstances, because this is easier for your doctor , and saves him valuable time. However, this puts you at a risk of receiving sub-optimal treatment. On the other hand, when you understand the niceties of your treatment , you can delight your doctor with your input and ideas, and he is much more likely to understand your needs better. When you contribute to your treatment decisions in an intelligent way, you are more likely to be able to formulate a treatment plan which suits you best – after all, your doctor is not a mind-reader and does not know what your personal preferences are.

A well-informed patient understands that his doctor works for her best interests. If you are totally clueless about your treatment , you will not be able to appreciate what your doctor does for you. It’s only when you appreciate his technical skills and expertise that you will develop respect for him as a professional . Otherwise, you tend to treat him as a person who works for you only because of the money you pay him . A good doctor-patient relationship is important for a good treatment outcome. Like any relationship, a doctor-patient relationship is also a two-way street and it tends to blossom beautifully only when there is mutual trust and respect. A good patient understands this and is ready to do what he can do to make the relationship beneficial for both.

A good IVF patient is patient! She understands that IVF treatment might need more than few attempts to be successful. She doesn’t get disheartened, suspicious and bitter after a single IVF failure. She tends to value and respect her doctor’s advice and act accordingly.  This will help her to remain resilient and carry on with the treatment until she finds success.

In short a good IVF patient has the following characteristics :

•       She has the passion to learn about her treatment 
•       She actively participates in her treatment decisions
•       She respects her doctor and strives hard to maintain a good doctor-patient relationship
•       She engages the doctor by providing inputs
•       She is patient and does not expect that the only acceptable result is a baby !
•       She allows her doctor to earn her trust and follows his advice

Successful IVF treatment needs not only good doctors , but good patients too ! Once you select a competent doctor , you need to work on making yourself competent. This work will pay rich dividends ! The equation is simple - Good IVF doctor plus Good IVF patient = High chances of IVF success !

This I wrote after Dr. Malpani provided me with an outline of what an IVF doctor will expect from his patients. You can read the full article here : http://www.drmalpani.com/good_ivf_patient.htm

Does HLA sharing cause miscarriage ?

I recently heard from one of my friend who is going through IVF to have her child. In the course of her treatment , she went through two pregnancy losses, one at 12 weeks and one at 5 weeks. As usual, a battery of tests were performed on her by her IVF specialist to find out where the fault lay– why did the miscarriage happen ? Of the several tests performed on her, two tests came back positive. She was told her NK cells in uterus are elevated ; and that  her HLA haplotype (what the heck is that?) was very similar to her husband’s. On seeing her results, her doctor told her that it was a waste of time and energy in trying to get pregnant via IVF. He told her that she would never succeed in carrying a baby to term ; and that she needs a surrogate to carry the baby.

This was a great shock for a woman who was already going through hell in order to have a baby ? Going through IVF is a physically and emotionally draining pursuit. Facing a miscarriage after successful IVF is heart-wrenching. In this situation, how will you react when you are told that there are some killer cells in your uterus which are waiting to devour your precious embryo ? How would you feel when a doctor tells you that you share so much in common with your husband that you cannot carry a baby to term ?Normally, when someone tells you that you have something in common with your partner , you feel happy , but now there is a person telling you that too much sharing means that your joy of having your baby is at stake.

These kinds of diagnoses steal your confidence and the trust you have in your reproductive system and your ability to carry a baby! . They make you miserable,  as you do not know do what to do next. I am sure many of us are completely clueless about what HLA is and what natural killer cells (scary name !) are – I was , even though I am a biologist In fact I  bet that most doctors who perform such complicated tests on you will be unable to explain to you what HLA is ; and how it is connected to miscarriages !If you insist on knowing more, you will be provided with a pamphlet which is full of Greek and Latin.

You wonder if there are any treatment options which will help you to have your baby; and you also start doubting – do I really need to treat this condition - can any of this be true. When you can’t analyze the situation rationally and make a well-informed decision ; and when you have to rely on your doctor for making decisions about your further treatment options (especially when the treatment may cost you an arm and leg , and you are uncertain if the doctor himself understands what is happening) , you are sure to feel handicapped, angry and scared !

This article is intended to explain in simple terms what HLA is all about . Does HLA sharing really cause pregnancy losses ?Do the treatments employed to treat such a diagnosis help patients to carry their baby to term ? Do you really need to treat such a diagnosis ?

Let me start with a little bit of scientific background. Don’t let your eye glaze over – stay with me please – it’s an interesting journey and you’ll enjoy the ride. I’ll try to make it as painless as possible !

   

What is HLA ?

HLA stands for “Human Leucocyte Antigen”. They are a group of proteins which are expressed on the surface of almost all the cells in our body. HLA is also called as Major Histocompatibility Complex (MHC). The genes (stretches of DNA ) which encode for HLA proteins are present in chromosome 6 (we have 46 chromosomes- 23 pairs !).

HLA genes are classified into class I, class II and class III. Class I genes encode for HLA- A, HLA- B and HLA- C proteins. These proteins are present in most cells of our body. Class I region also contains genes which give rise to HLA-E, HLA-F, HLA-G proteins. Class II genes encode HLA-DP, HLA-DQ and HLA-DR proteins. These proteins are present mainly in our immune system cells like B-lymphocytes, macrophages, T-lymphocytes etc. Class III genes encode components of our complement system (a group of proteins which function in our immune system)

We inherit half of our HLA genes from mother and other half from the father. Each person receives one set of HLA genes (HLA haplotype) from either parent.

 

 

 

 

HLA genes are highly variable

The genes that code for HLA proteins are highly variable. Thus, the HLA-A gene is not the same in everyone. They carry minute differences in them , as a result of which they produce proteins which are very different too. The HLA-A gene contains  2,188 variants and these are called alleles of HLA-A. There are 1,571 different varieties of HLA-A protein produced in humans (not all gene variants end up producing a different protein; hence the number of proteins is not equal to the number of gene variants). Each of us carry a pair of HLA-A gene and have only two variants (alleles) of the HLA-A gene. These 2 alleles can be any of the 2,188 variants present. For example if you assign each allele of HLA-A gene with a numerical name from 1-2,188, then I can have HLA-A allele HLA-A* 21 and HLA-A *892 (usually represented like this  : HLA-A*21.892) and my husband might have HLA-A*01 and HLA-A*1076 ( the scientific shorthand for this is HLA-A* 01,1076) This is the same for all other HLA genes as well - HLA-B, HLA-C, HLA-DP, HLA-DQ or HLA-DR. If you understand this , you will be able to make sense of your HLA typing result. 

HLA-A*02, 24

HLA – prefix

A-gene name

02 and 24 – alleles of HLA A (variants of HLA-A gene)

 

What is the function of HLA in human body ?

There are more microbes in this world than humans and there is a constant war going on between them.  Microbes try to attack us all the time and we have to fight them in order to prevent diseases. Just like police searching for thieves, special cells are constantly patrolling our body in search of harmful microbes like bacteria and viruses which can hide within us. If a thief hides within a house,  someone in the house should tell the police that the thief is hiding inside , so the police can trach him down. Likewise, when a microorganism enters and hides in our body , there should be some alerting system which should tell our immune cells ( the cells in our body which fight against microbes and kill them) that a particular cell is infected with a microbe and that they should destroy the microbe or the entire cell , in order to protect the other cells of our body. This is the job of the HLA molecules! HLA proteins help our immune system to identify microbes and thus help to kill them.

 Let’s look at this in more detail. When a cell is infected with a virus, some viruses are killed and broken down into pieces by the infected cell’s machinery . A part of the virus (a protein molecule also called an antigen ) is presented by the HLA class I molecule (which is present on the cell’s surface ) to the cytotoxic T cells of the body’s immune system . The T cell has the power to destroy an infected cell and this is how the immune system can identify which particular cell is infected , allowing the immune system to selectively destroy that cell , along with the invading virus.Similarly, when bacteria enter our body , special cells of our immune system engulf the bacteria, digest them and present the bacterial protein to helper T cells (immune cells which coax other immune cells to produce antibodies which will eventually destroy the bacteria) , with the help of the HLA class II molecule. This means HLA helps in telling our body’s immune system that our body is under attack by microbes, and it helps in recruiting and activating the immune cells to fight this attack . Any microbial protein will be identified by our immune system only when that microbial antigen is presented to the immune cells by the HLA proteins of our own body !This is the reason why HLA genes have so many variants. This large variety of HLA proteins helps in presenting different microbial antigens to the immune cells more effectively. If all humans carried  the same HLA molecules, some new virus or bacteria which cannot be presented effectively to our immune cells would spread quickly and destroy the entire human race ! The more the variety in HLA proteins , the greater the chances that the human race will survive a microbial attack ! There are currently 8,949 HLA gene variants identified in humans ; and this number is rapidly expanding too !

 The human immune system detects foreign cells with the help of cell-surface proteins called human leukocyte antigens (HLAs). Each person's cells carry a particular set of HLA molecules — the person's HLA type — which bind fragments of virus or bacterial protein and 'present' them to T cells, the immune cells that recognize and attack infected cells.

HLA is responsible for the immune rejection or immune acceptance of transplanted organs

Every human carries his own set of HLA proteins in his cells, half of which come from the mother and half from the father. If my kidney fails to function , I need a kidney transplant. However, I cannot get a kidney from anybody - I need a kidney donor whose HLA proteins match mine. Foreign (non-self) HLA molecules are readily recognized by my immune cells. Any foreign HLA molecule identified by the immune cells alerts my immune system to mount an attack against that particular tissue or organ,  because anything foreign is considered to be dangerous by our immune system. This is why the same immune system which protects our body from harmful microorganisms also prevents us from getting a potentially life-saving organ donation from a stranger. In order for any transplant (liver, skin, kidney transplant etc) to be successful , the HLA molecules present in the transplant recipient must be similar to the donor. This is why HLA typing is done before any transplantation procedure in order to identify the perfect donor. This is why HLA is also known as Major Histocompatibility (Histo = tissue) complex. Tissue compatibility during transplantation is decided based on HLA.

Since HLA genes are highly variable (remember, there are 8,949 HLA gene variants!) , it is very difficult to find a donor who matches the recipient. Only identical ( monozygotic ) twins have identical HLA proteins in their cells. Your sibling has only a 1 in 4 chance of being an identical HLA match for you. 

How does HLA comes into play in reproductive biology ?

A human fetus receives half of the genes from its mother and half from its father. This means a fetus expresses HLA proteins which are different from its mother ( because 50% of HLA proteins in a fetus come from the father ). If a fetus is not an identical HLA match to its mother , then why doesn’t the mother’s immune system reject the fetus during her pregnancy ? After all, if the son tried to donate a kidney to his mother after birth, there’s a high probability that this would be rejected ! (Remember, HLA mismatch is the strongest predictor of transplant rejection).  

If a HLA mismatched organ is rejected by the recipient’s immune system, then you would quite logically assume that if your husband carries the same HLA molecules as you do, then the chance of your immune system attacking your fetus is less , because the fetus carries the identical HLA molecules you have. But reproductive immunology theory says exactly the opposite !

How is an HLA incompatible fetus carried by the mother ?

A scientist named Wegmann in 1984 proposed a theory called “immunotrophic theory” to explain the paradox of how the maternal immune system accepts a fetus which is not genetically identical to hers. The theory states that recognition of the foreign antigen ( the paternal HLA) by the mother’s immune system is “ good “ for the fetus , because it causes the maternal immune system to produce protective cytokines ( such as G-CSF),which enhance implantation, promote the growth of trophoblastic cells and help in sustaining pregnancy. Reproductive immunologists suggest that recognition of foreign fetal antigens (mainly paternal HLA) by the mother’s immune system is necessary for eliciting a “protective” immune response ( such as the production of protective “blocking antibodies” , which protect the fetus from immune rejection), and this actually helps in the survival and development of fetus.  

If HLA incompatibility between the mother and fetus helps in embryo implantation and growth, then won’t HLA compatibility between mother and fetus lead to harmful pregnancy outcomes ? This is the question which prompted scientists to study the association between HLA sharing between partners and recurrent pregnancy loss.

HLA sharing between partners and fetal loss – what do the scientific studies say ?

This is a highly controversial topic among the scientific community ! One group states that HLA similarity (HLA compatibility) between the mother and fetus disrupts the proper cytokine signals and hence the mother’s immune cells are activated abnormally, leading ultimately to the death of the fetus. (PMID: 7762569 PMID: 8296846 PMID: 8207709 PMID: 1729895 PMID: 3860403 PMID: 10336015 PMID: 1771630 ) 

The other group refutes this hypothesis and argues that their scientific findings do not support the notion that HLA compatibility between mother and fetus (HLA sharing between partners)  can cause recurrent spontaneous abortion. (PMID:2658473 PMID:3477351 PMID:15713211 PMID: 20492598PMID:11530859 PMID:8579756 PMID:1534444 PMID:20605049 PMID: 20566486 PMID: 8839135 PMID: 1358093 PMID: 3245544)

“Everything must be taken into account. If the fact will not fit the theory---let the theory go.”

― Agatha Christie

Studies which support the hypothesis that HLA sharing between partners causes fetal loss have severe limitations in their experimental design

Imagine you want to ascertain whether coffee drinking leads to heart attacks in humans.  You select 100 people who suffered a heart attack and 100 who didn’t. Then you ask how many in the heart attack group drink coffee , and compare this with the number of coffee drinkers in the non-heart attack group. If you find more coffee drinkers in the heart attack group , you conclude that drinking coffee leads to heart attack. This kind of study design ( called a retrospective study) is extremely flawed - 100 people are not enough to study the entire population. If you conduct such a study 10 times , the probability of finding more coffee drinkers in heart attack group simply by chance is 50 %. This means that if 10 scientists conduct such a study, 5 will report that there is an association between coffee drinking and heart attacks and the other 5 will say that there is no association ! This is what exactly happened in studies which are designed to find whether HLA sharing between partners causes pregnancy loss !

A better way to do the study would be to follow  10,000 people who drink coffee ; and 10,000 people who do not drink , to see how many in each group suffer from a heart attack over a period of time. This is called a prospective study – but is much more complex and expensive to perform ! 

About 3 % of women suffer from recurrent spontaneous abortion (RSA). RSA is defined as 3 or more miscarriages that occur before 20 weeks of gestation. Scientists who studied the association between HLA sharing and fetal loss, studied couples who had had RSA ; and compared their degree of HLA sharing with normal fertile couples who had had no pregnancy losses. If they found more HLA sharing between partners in the RSA group , they concluded that RSA is caused because of HLA sharing ! Because the sample size used for the studies is very small , they have severe limitations in their design, which is why you should take their results with a generous pinch of salt. Keep in mind that they are many other genes which are involved in a baby’s development , and defects in these can cause miscarriage too. The studies conducted didn’t ( and can’t!) take into account all these confounding factors. 

So, if there are studies which both support and refute the hypothesis , how do I interpret the scientific data ?

 

“In questions of science, the authority of a thousand is not worth the humble reasoning of a single individual.”

― Galileo Galilei

Here is where we should use our common sense ! We have so many inbreeding communities in the real world. Endogamy (practice of marrying within a specific ethnic group, class, or social group) is still common in many cultures and ethnic groups (Middle East, Assyrians, Jews, Yazidi Kurds, Muslims, Knanaya Christians, Hindus). If a population is inbred , then there is a high chance that partners share their HLA haplotype. Do such inbred communities suffer from RSA and infertility ? For example, India has several communities where inbreeding ( marriage between uncle and niece ; and marriage between first cousins)  is very common.  This study (PMID: 11874619) conducted on an Indian community which practices consanguineous marriages failed to identify any overall adverse effect of inbreeding on fertility. The results of many such studies showed that consanguineous couples actually had more children ! In India, marriages with first cousins ( who have a 1 in 16 chance of being HLA identical ) have been practiced for centuries in many communities ; and these communities have flourished. If such marriages affected human reproduction adversely, the communities would have stopped following practices which were harmful.

Some more interesting information about HLA

When HLA testing is performed in the lab on you and your partner, they mostly check for compatibility between HLA-A, HLA-B, HLA-C, HLA-DQ etc. Do you know that these HLAs are not even expressed in the trophoblastic cells that come in contact with the mother’s immune system ? The only HLA type that is expressed on trophoblast cells is HLA-G ! Doesn’t this simple truth tell us many things ?

Should I consider paternal lymphocyte immunization therapy for “treating” the HLA sharing between me and my partner ?

 

If your doctor has suggested you this therapy, ask for the mode of action of this therapy and possible adverse events – most probably he will not know because the scientific community doesn’t know too !

Paternal lymphocyte immunotherapy has been used for treating RSA patients. It was hypothesized (one of the many existing hypothesis!) that the inability to build protective antibodies against fetal HLA (because of HLA similarity between mother and fetus as a result of the HLA sharing between the parents ) led to overactive NK cells and other immune cells , which killed the embryo and led to fetal loss. These antibodies are produced in a normal pregnancy, where they control and regulate the overactive NK cells , and protect the pregnancy from attack by them.

In Lymphocyte Immunization Therapy (LIT) your partner’s lymphocytes are isolated from his blood and injected under your skin , so that you can mount an effective immune response against the MHC molecules which his lymphocytes carry. The immune cells which are produced in your body against the MHC molecules are thought to protect the pregnancy.

These publication (PMID: 16625529) (PMID: 22349103) states that such unproven therapies do not provide any significant beneficial effect than placebo. 

There are also studies which show that paternal lymphocyte therapy can cause adverse effect to mother and fetus !(PMID: 21062364 PMID: 1453393 PMID: 10708244)

After comparing the evidence for and against the concept of HLA sharing and recurrent spontaneous abortion , I am convinced that the diagnosis of HLA sharing between partners , and the paternal lymphocyte therapy which is used as “treatment” has little scientific validity ! It appears to be more of a pseudoscience than a proven scientific theory to be taken too seriously.

Should I undergo therapy for HLA sharing ?

If you suffer from recurrent abortions and do not know what to do next , you may be desperate enough to try every possible therapy under the sun before giving up . You maybe willing to be an experimental guinea pig, since there is very little modern medicine can offer in the form of treatment for this distressing disorder. You may be willing to undergo unproven therapies , and this is quite understandable.  Even if you do decide to do so, please understand that such therapies have only anecdotal success stories , and are not a magical cure for your condition ! Over 50% of women who have had 3 or more miscarriages eventually achieve a successful pregnancy without any medical intervention, with the help of TLC – “tender loving care” ! Remember, “ HLA sharing between partners causes miscarriage” is a theory which not has not been proven. Please question your doctor if he pressurizes you to undergo treatment which is unproven and whose safety is not tested properly. 

I wish doctors would stop demoralizing infertile women with scary unproven theories and therapies !

“Just because an idea is true doesn't mean it can be proved. And just because an idea can be proved doesn't mean it's true.”

― Jonah Lehrer

Does going through IVF cause premature menopause ?

Many women worry that going through IVF will deplete their ovarian reserve , as a result of which they will run out of eggs , reduce their long-term fertility, and reach the menopause earlier. Logically, this makes sense  ! We all know that women are born with a certain number of eggs ; and that their ovaries do not produce any new eggs after birth. If the doctor stimulates the ovaries to grow lots of eggs during the IVF treatment by giving hormonal injections, won’t this mean that there’ll be fewer eggs left in the ovaries after the IVF treatment – especially if they are doing many IVF cycles ? When going through IVF , the doctor harvests several eggs at the time of egg retrieval by stimulating the ovaries with hormones (FSH or a combination of FSH and LH). A woman with a menstrual cycle length of 28 days ovulates only 12 eggs per year. But women going through IVF produce 15 or more eggs at a time. Doesn’t  this mean that IVF depletes the egg reserve faster than usual and can lead to earlier menopause ?

Let’s look at the facts.

The ovaries are a pair of organs situated in the pelvic region of women, one on each side. They act as the reservoir for our eggs. Eggs are the cells which carry half of the information (genetic blue print) necessary for creating a baby. Such precious egg cells are stored, nourished and protected within specialized structures in ovaries called follicles.  A female foetus at around 18-22 weeks of gestation contains about 2,000, 000 follicles in its ovaries and each follicle contains one egg. At the time of birth, a girl has only about 3,00,000 egg left in her ovaries – she’s lost over 80% of her eggs even before being born ! The remaining follicles continue to get depleted during her life time ; and when there are only about 1000 follicles left, she reaches menopause . A woman normally ovulates only about  400 eggs during her lifetime , releasing one mature egg each month , from the time of attaining puberty until reaching menopause. An ovary contains several immature follicles (and hence several eggs!) but not all these follicles will become mature enough to release a functional egg. More than 99.99 % of the follicles (and hence the eggs) are simply lost , without serving their biological purpose.  Human reproduction is remarkably inefficient !

During each menstrual cycle , several ovarian follicles start growing in response to the FSH secreted by the pituitary gland. Of these recruited follicles , only one follicle grows to maturity , and this is called the dominant follicle.  It carries the mature egg which will be released during ovulation. The other follicles which fail to reach maturity are lost . They die, and this natural process is called atresia. During IVF treatment our body is supplied with high amounts of FSH (several folds higher than our body naturally produces), in the form of injections. This high amount of FSH helps to rescue more of the follicles which are recruited during that particular menstrual cycle. This is the reason why IVF specialists are able to harvest several eggs during an IVF treatment. This is also the reason why IVF treatment will not deplete your ovarian ( egg) reserve ! The follicles (  and the eggs inside them) which would normally have died during that particular menstrual cycle are being rescued during an IVF cycle. This is why an IVF treatment will not cause you to go through menopause earlier. This is true even if you do many IVF cycles !

However, do remember that many infertile women are at increased risk for having poor ovarian reserve and reaching menopause early , whether they do IVF or not ! This maybe because they have endometriosis, or because they have undergone laparoscopic surgery.  If they reach menopause earlier than expected after having taken IVF treatment , they are quite naturally going to blame the IVF treatment for this – whereas the reality is that they would have reached the menopause early anyway,  even if they had not done IVF !

Adopt, don't shop !

This is a guest post from one of my blog reader. We infertile couples, often come across people, who look at us as if we are sinners when we say we are undergoing IVF treatment to have our baby. Their arguement is "why don't you just adopt, there are so many children without home?". They think adoption is a nicer thing to do instead of spending so much money to have a baby. Some even think doing IVF is against God's wish. This is a comment I received on my article " So, why don't you just adopt a baby ? " I thought this comment by the reader is very honest and explains the problem which is inherent in an adoption proocess. I wish everyone finds this useful too ! Remember, we are not shopping for a baby, we are fighting  for our right to have a baby !

 A good post and certainly pertinent to anyone experiencing infertility. I've actually been "looked down upon" by quite a few people for wanting to pursue IVF. And of course, the critics are either completely uninterested in ever having children or have a litter of babies themselves. What bugs me the most is that they seem to think that it's the job of the infertile to save the troubled children of the world. Granted, that is a noble endeavor, but why is it any more MY duty than those who are fertile?

Most people don't know how immensely complicated (and expensive!) adoption is. In some cases, it's even cheaper to succeed at IVF than adoption. And even after you've shelled out tens of thousands of dollars, there still is no guarantee that everything will go smoothly. Some of my acquaintences tried to adopt abroad and their child got stuck in limbo in a state nursing facility for 2 years after birth. Believe me, if adopting were as simple as taking a stroll to the local catholic monestary to pick up a child, I'd be a father many times already!

But if its one thing that troubles me least about adoption it's the genetic difference. I always saw something romantic about choosing to love a child, rather than being coerced into the relationship by Darwinian destiny. What DOES bother me is that, when you adopt, everyone seems to want to get their talons in your child one way or another. In the United States, domestic adoption is a seller's market, which means adoptions are "open." In other words, the "birth parents" stay in regular contact with THEIR children and sap away the joys of parenthood while the adopting parents shoulder all of the burden. If it's one thing I simply couldn't handle, it would be some stranger visiting at Christmas, telling my child how much he/she takes after THEM.

Even if you adopt from abroad, there is this accepted truth in society that somehow your child is not entirely your child. That some essential part of them remains in the place that they were born. That you must pay some kind of homage to the "culture" from which their soul has apparently sprung forth. And its this social perception of adoption that strikes me most painfully: that even though you put in 100 percent of the love that any other parent would, the adopted child can only really be half yours, in the end.

In the United States, our television channels are littered with shows about adopted children going off to reunite with their "birth" parents. That they simply felt lacking until they were able to become one with with their "birth family" again. All the while the adoptive parents are expected to stand back and smile. The adoptive parent is expected to share the thing that parents of biological children are NEVER expected to share. It may sound selfish, but I could never share my children in this way. It would break my heart.

And so I think that's what pushes me toward IVF most.

Do IVF drugs increase the risk of cancer ?

Infertile women go through lot of emotional turmoil, and to add insult to injury, there are lots of misconception regarding the use of fertility drugs. Some link fertility drugs with gynaecological cancers; while others even believe that children born out of fertility treatment carry an increased risk for developing certain kind of cancers. What is the truth ? 

It’s easy to understand why women would have this belief – it sounds quite logical ! We know that breast cancer is a hormonally dependent tumour; and that estrogen levels are high during IVF treatment. Also, a lot of hormonal injections are given during an IVF cycle , in order to help the women grow lots of eggs. If the hormonal stimulation helps them produce a lot of eggs, it’s quite reasonable to conclude that this ovarian overactivity may increase the risk of developing ovarian cancer later on as well ! Husbands are understandably scared about the impact of these drugs on their wives, and don’t want to risk her heath in their quest for a baby.  

Please remember that being infertile is itself a significant risk factor for developing certain kind of gynaecological cancers. For example, women who were never pregnant have a higher risk of developing breast cancer. This is because both pregnancy and breast feeding reduces a woman’s exposure to the estrogen hormone produced by her ovaries, which stimulates the growth of the cells lining the mammary glands in the breast. Pregnancy and breast feeding also mature these breast cells into milk-producing cells , and these mature cells are refractory to the transforming effect of hormones. Women who had a full-term pregnancy also have a lower risk of ovarian and endometrial cancers – the higher the number of full-term pregnancies , the lesser is their risk of developing these kinds of gynaecological cancers. You can read more about this at http://www.cancer.gov/cancertopics/factsheet/Risk/reproductive-history. 

What do the data show ? To assess whether the risk of cancer after doing IVF increases or not is an extremely complex task , because there are so many other variables which have to be taken into account . Simple examples include: an individual’s life style, family history of cancer and their exposure to carcinogens, all of which are likely to confound the results . This is why these studies are very hard to conduct. One such recent study involving 9175 Finnish women showed that the general risk of cancer or the risk of hormone-related cancer was not increased by IVF (PMID:22343550). Another study in Lancet examined the incidence of breast and ovarian cancer in 10,358 women referred for IVF between 1978 and 1992. They concluded that ovarian stimulation during IVF does not increase a woman’s risk of breast cancer. They also found that there was no significant increase in ovarian cancer after ovarian stimulation for IVF. On the other hand, they concluded that women with unexplained infertility had an increased risk of ovarian cancer ! (PMID:7475593).

 

This is good news. Remember that IVF hormonal injections are natural hormones, which get excreted promptly from your body, and do not linger on to cause mischief later on. Over 2 million IVF babies have been born worldwide over the last 30 years, and we have not seen an increased prevalence of breast or ovarian cancer, so this is very reassuring. Going through IVF will not increase your chance of having cancer at a later age. Infertile women should try to ensure they have a healthy lifestyle , because infertility by itself is a significant risk factor for certain forms of gynaecological cancers – but this is simple common sense advise , and you don’t need a doctor to tell you this !

Will embryo(s) fall out after embryo transfer ?

A fear which is wide-spread among IVF patients is – will my embryo fall out if I stand up or walk around after the embryo transfer ? This is quite a reasonable worry – after all, if the embryos are transferred through the uterus through the cervix, then why can’t they come out through the same route?  However, if you understand the anatomy of the uterus , these doubts will vanish and you will fell much more confident and comfortable during your 2ww.

Women imagine that when the doctor puts the embryos inside the uterus, they are deposited inside a space within the uterus in which the microscopic embryos can roll freely!  They believe that if they rest, the embryos will settle down and stick to the wall of the cavity. After all, when you stick two pages together with glue, don’t you leave them undisturbed for some time to allow the glue to set ? They are worried that if they walk about, the embryos will be disturbed from their resting place , and may fall out of the cavity.

In reality, the uterus is a muscular organ , about the size of your fist. When people hear the word ‘uterine cavity’, they imagine that there is a real cavity within the uterus ( like a cave, perhaps) , but this is not true. The cavity we talk about is not a true cavity , but just a potential cavity . The walls of the uterus are in contact with each other – after all, there cannot be any empty areas inside the
body ! For example, press your palms together. There is no real space between them , since your palms are touching each other. What happens when you insert a small ball in between your palms ? The ball has created a space for itself ! In the same way , a uterus which doesn’t have an embryo inside it carries only a potential space. Only when the embryo grows in size will this space enlarge. Do you know that at 5 weeks of gestation your embryo is just the size of a sesame seed ? Imagine what will happen if you keep a seed between your pressed palms and move your hands in whatever way you might wish to ? There is no way the seed will be dislodged  - it is safe , snug and secure in its resting place. This is exactly what happens to your embryos inside your uterus !  Nothing you do can dislodge an embryo – NOTHING (even jumping or running) ! If the embryo is healthy and if your endometrial layer is receptive , the embryo will stick to the wall and bury itself inside the lining (just like a seed does , when planted in fertile soil). External physical activity cannot influence this natural biological process which occurs in utero.

A lot women refuse to go to the bathroom for a few hours after the embryo transfer, because they are scared that if they pee, their embryo will fall out of the uterus. They just end up making themselves completely miserable – and I worry that an overdistended bladder can actually cause uterine contractions needlessly ! Others are scared that if they cough or sneeze after the transfer, they will ruin their chances of success. Please do not obsess – remember that nature has designed the body with enough intelligence, that you don’t need to worry at all !

After the transfer, the uterus can contract (for example , during an orgasm, which often occurs while sleeping during  the 2ww ), but the progesterone produced during the luteal phase will prevent these uterine contractions from dislodging the embryo. Intercourse and orgasm cannot cause any harm after the transfer – after all, fertile couples do have sexual intercourse during the 2ww, and they get pregnant all the time.

After an embryo transfer , bed rest is absolutely unnecessary. I have heard from women who have been forced to spend 2 weeks in bed after the embryo transfer – and many of them have done so because of their doctor’s orders ! ( I think the reason some doctors continue to give this outdated advise is a clever way of subtly blaming the patient if the cycle fails ! “ You didn’t get pregnant even though I did such a good job with your IVF treatment , because you did not rest properly “ is their subliminal message) . Even a couple of days in bed can do you harm , physically and emotionally. Bed rest may increase body aches and back pain , and makes your physically uncomfortable.  Resting may actually reduce uterine blood flow by reducing pelvic circulation. Bed rest creates havoc  with your mental well-being as well ! When you lie down in bed all the time and have nothing to do, your mind will start to play all sorts of games with you. The end result is an unhealthy obsession with your body’s symptoms and signs – and this often causes panic , which does not help after a stressful IVF cycle.  The bed rest, rather than resting your mind, often causes more stress !

Please do not restrict your normal day-to-day activities after an embryo transfer.  Use your common sense, and do not do any strenuous activity which might cause you to blame yourself if your cycle fails ! And what happens if your mother in law enforces house arrest ? Remember that she has been brainwashed , and is following well-meaning but misguided advise, based on centuries of myths and misconceptions about bed rest and pregnancy. She is not trying to harass you – she is just trying to help you to have a baby , based on her personal ( but flawed) world view ! Please don’t rock the boat by flatly refusing to listen to her – just give her this article to read , so she understands why bed rest does not help!  And if she is still unconvinced, please share this with her - Bed rest has not been scientifically proven to improve pregnancy rate after embryo transfer(PMID: 19590224). 

Embryo Transfer

The process of embryo transfer

The day when our in-vitro embryos return back to us (to their mama !) is one of the most exciting moments of an IVF cycle. We forget the struggles we went through when we are admiring our microscopic babies under the microscope. Embryo transfer is one of the rate-limiting steps in an IVF cycle and plays a pivotal role in determining IVF success. Since the invention of IVF, major developments have been made in ovarian stimulation protocols; the way oocytes are collected ; and in the IVF lab; but the embryo transfer method remains largely unchanged. Embryo transfer done badly by an inexperienced doctor can change the fate of an IVF cycle –there is a vital intangible “physician factor” involved in determining the outcome of an IVF cycle! When different individuals perform embryo transfer within the same ART programme , the pregnancy rate of each doctor varies widely. This shows the importance of the embryo transfer technique and how it determines IVF outcome. It is estimated that 30% of IVF cycles fail because of shortcomings in this crucial procedure. What actually happens during an embryo transfer ? Is it an easy procedure ? Will it be painful ? Can my embryos fall out of my uterus after the transfer ? As usual there are many questions: come let us find the answers together.

What is an Embryo Transfer ?

Transferring one or more embryos into the uterine cavity of the recipient is called embryo transfer (ET).  It is the final and crucial step of an IVF process. The embryos in the IVF lab are grown usually until day 3 or day 5 in an incubator in a petri dish. The qualities of embryos are graded by inspection under a microscope. The top quality embryo(s) are returned back to the uterus , where they belong ! Even though more than 90% of patients who undergo IVF reach the embryo transfer stage , only a small percentage of them actually get pregnant. Unfortunately, not all the embryos which are transferred to the uterus become deeply desired babies !

How is an embryo transfer performed ?

During ET, the doctor puts you in the undignified lithotomy position in the operation room, and inspects your cervix with the help of a speculum . The sticky cervical mucus is cleared away using a moist cotton swab carefully. Then the cervix is washed with a sterile fluid. The best embryos are then loaded into the transfer catheter ( a long thin hollow soft sterile plastic tube) by the embryologist in the adjoining IVF lab . He does this under the microscope, and sucks up the embryos into the catheter by applying negative pressure with the help of a 1 ml syringe.  He brings the loaded catheter to your doctor , who performs the ET slowly by inserting the catheter into the uterine cavity through the cervix;  and then expelling its contents ( which consist of the embryos floating in a microscopic drop of culture medium)  by gently pushing the barrel of the syringe. This deposits the embryos into the cavity of your uterus. This method of transferring embryo(s) to the uterus is called transcervical  (through the cervix) embryo transfer. After transferring the embryos , the doctor hands over the catheter to the embryologist , who then examines it immediately under the microscope, to see whether there are any embryo(s) retained in the catheter. If this is the case, the retained embryo(s) are transferred back again to the recipient. An embryo transfer procedure is normally painless, and takes only few minutes to perform. You do not need anesthesia for this procedure. Most embryo transfers are easy but some embryo transfers can be difficult too ! Normally your husband is allowed to stay with you during the ET procedure , in order to hold your hand and provide you with emotional support , so that you remain stress-free and relaxed. 

Are there any variations in the transcervical embryo transfer method ?

Transcervical embryo transfer is performed in two ways – without ultrasound guidance (traditional ‘clinical touch’ method) and with ultrasound guidance. 

In the traditional ‘clinical touch’ method , the catheter is positioned blindly in the “desired position” ( about 1 to 2 cm away from the uterine fundus), by relying on the clinician’s tactile senses. In other words the ‘clinical touch’ embryo transfer method relies on the experience of the person who transfers the embryo ! During ultrasound-guided embryo transfer, the clinician is able to find the appropriate position for placing the catheter and releasing the embryos using the ultrasound scan image. During ultrasound-guided embryo transfer , you need to have a full bladder , so that the uterus can be viewed clearly ! It does create a lot of discomfort for the patient because the embryo transfer procedure can cause pressure on the already full urinary bladder ! The uterus should not be disturbed during the transfer in order to avoid uterine contractions – if the uterus contracts,  there is a danger of the embryo being expelled from the cavity.

Is ultrasound-guided embryo transfer better than ‘clinical touch’ method ?

As usual , this is a hotly debated topic. There are studies which reported that ultrasound-guided embryo transfer significantly enhanced embryo implantation rates ; and there are studies which found no difference if the ET was done by an experienced clinician in the absence of ultrasound guidance. This is a decision which is best made by your doctor , based on what works best for him ! For junior doctors, an ultrasound guided transfer seems better, as they learn how to master this procedure.

What are trial transfers or mock embryo transfer?

Trial transfers or dummy transfers are performed before the actual embryo transfer. They can be done just before the ET ; or during the ovum pick-up ; or prior to the start of the IVF cycle. During a trial transfer the doctor inserts an empty catheter into the uterine cavity , to find the easiest passage to the cavity; and to measure the length of the uterus and the cervical canal (uteri and cervixes come in many different shapes and sizes !) This allows him to measure how deep he has to insert the catheter , so that he can place the embryo at the appropriate position inside the uterus , without disturbing the fundus. Most embryo transfers can be performed easily , but there are some women where the doctor finds it technically difficult to negotiate the catheter through the cervix. In such a situation , their cervix has to be dilated to widen the cervical canal , so that the embryo transfer catheter passes easily through the cervix. There are women where the doctor needs to use a tenaculum to straighten the uterine axis (remember that the cervical canal and uterus are at an angle to each other) and sometimes the uterus is so tilted that the passage of the catheter from the internal opening of the cervical canal into the uterus is difficult. Sometimes pulling on the tenaculum alone cannot do the job , especially if the uterus is acutely angulated in relation to the cervical canal. Then it maybe necessary to curve the catheter, so it conforms to the curve of the uterus. In these patients, using specially designed catheter sets allows the doctor more freedom in gently guiding the catheter through the cervix.

What factors play a role in affecting embryo transfer results ?

The embryo transfer should be smooth and trauma-free. Many studies have shown that the pregnancy rate after embryo transfer is better if it is performed by an experienced physician, as compared to a newbie. 

1.      Placement of the embryo

Placing the embryo 2 cm from the uterine fundus (the upper rounded extremity of the uterus , above the openings of the fallopian tubes) helps in enhancing embryo implantation. This is the region which is thought to possess maximum implantation capacity.

2.      Uterus contraction

When the cervix is handled roughly or if the catheter touches the uterine fundus , the uterus can contract. This can expel the embryos from the uterine cavity into the fallopian tubes or cervical canal, and compromising IVF success.

3.      Cervical mucus

Carefully removing the cervical mucus without causing trauma to the cervix improves IVF outcome. The cervical mucus can plug the catheter tip , thus preventing the deposition of the embryo in the uterus. It can also be a source of introducing bacterial contamination into the otherwise sterile uterine cavity.

4.      Catheter choice

Soft catheters have a better IVF outcome because they avoid trauma to the uterine wall.

5.      After the doctor has done the transfer, the embryologist checks it under the microscope. The presence of blood in the catheter suggests that the transfer was technically difficult – and this may reduce pregnancy rates.

6.      Trapped embryos

 Sometimes the embryos remain trapped with the catheter, even  through the doctor has plunged the barrel of the syringe completely. When the embryologist identifies the trapped embryos in his petri dish, he simple reloads them again into a new catheter, and the doctor can then re-transfer them . This does not seem to affect pregnancy rates. 

Why are some embryo transfers difficult to perform ?
 Some embryo transfers are difficult to perform because of the following problems in patients :

1.      Cervical stenosis ( narrowing) or anatomical distortion of the cervical canal and uterus

2.      Acute utero-cervical angulations

If a physician has several years of experience in doing IVF, then most embryo transfers are like a cakewalk. But in some women , the embryo transfer can become an arduous adventure because of the difficulty encountered in traversing the cervix. This is commoner in women of Indian and African origin , where pelvic inflammatory disease (PID) and cervical infections are more prevalent. There can also be anatomical distortion of the cervical canal and uterus because of previous surgery.  These conditions might lead to a traumatic embryo transfer (there might be bleeding , and the patient many experience pain) ; or the embryo transfer cannot be performed at all. The presence of an acute curvature between uterus and cervical canal (utero-cervical angulation) can also make the embryo transfer hard to perform.

How to avoid difficult embryo transfers ?

Performing mock transfers before the actual embryo transfer helps in identifying the problem beforehand , and can help the doctor to take precautionary measure. For example patients with cervical stenosis can undergo a process called cervical dilation to widen the cervical canal. This might help in the atraumatic passage of the ET catheter into the uterine cavity.

But there are some patients in which transcervical embryo transfer becomes impossible ! In such rare cases , there are other techniques which could be used to transfer the embryo to the uterus.

What are the methods which bypass the transcervical route for embryo transfer ?

1.      Transmyometrial embryo transfer

2.      ZIFT

 Transmyometrial embryo transfer

In this method , using a special Towako set, two needles (one inside of the other) are passed through the vagina into the uterus wall , under ultrasound guidance, until the needle tip reaches the edge of the endometrial lining. The inner needle is then removed and a thin catheter is inserted inside the outer needle, which carries the embryo into the cavity. The embryos are then released in the endometrium. But the success rate with such embryo transfers are less when compared to transcervical embryo transfers.

 ZIFT

ZIFT stands for zygote intrafallopian transfer. During ZIFT , cleavage stage embryos are transferred into the fallopian tubes , instead of the uterus , using laparoscopy. ZIFT is a very good option for women who cannot have a transcervical embryo transfer, but who have at least one normal fallopian tube. Since cleavage stage embryos belong to the fallopian tube and not to the uterus , ZIFT has a higher pregnancy rate than conventional ET. 

 Most clinics are not able to offer the option of doing a ZIFT , because of the lack of surgical skills and anesthesia facilities. If your embryo transfers are difficult, then find a clinic which offers this option !

e-SET (elective Single Embryo Transfer) 

Elective single embryo transfer (e-SET) is becoming popular for women who are young and have good ovarian reserve. While transferring multiple embryos improves the pregnancy rate, it also increases the risk of multiple gestation. Children who are a result of multiple pregnancies have an increased risk of health problems, because of the increased risk of preterm delivery and low birth weight . With the advent of better embryo selection strategies such as comprehensive chromosome screening (CCS) , single embryo transfer may become the norm in the future !

Some FAQs about embryo transfer : http://myselfishgenes.blogspot.de/2013/05/some-faqs-about-embryo-trasnfer.html