LEARN INSURANCE

This is a guest post from Carina Freeman, the Fertility Coach.

I think it's time to take the time and share my story. To help you understand why I am passionate about Hold your Hand fertility coaching.

In 1997 I was able to conceive a son with no problems at all. I had no idea what my future would hold. I have always had very severe menstrual cramps. However, I never went to get them checked out because I thought it was "normal." My mom, her sisters, and their mom also had severe cramps. I always wanted more children after my son was born in 1997, but thought maybe it just wasn't my time yet. So, we kept trying for years with no success. This made me feel like less than a woman. Why could I not give my husband a child? After several years, my husband suggested I go to the doctors to have myself checked out. In 2005 I decided to take the 1st step. This step would lead to my documented fertility journey.

My doctor did a "normal" fertility work up (blood work and exam) which came back "unremarkable". At that time he questioned me about my family history and my severe menstrual cramps. From my family history he came up with a possible diagnosis of Endometriosis. This was something I had never heard of. So, I began to research this subject on the internet. My research gave me different answers with m any poss
Still, wanting to bear another child of my own, my physician said IVF would be my best choice. Of course I had to do my own research so I asked several of my MD friends and they all agreed. I read every book that I could find about IVF and realized that would be my best chance to complete my family. A few months later, my husband went to Iraq for his second tour of duty. I felt alone. I felt like no one understood what I was going through. Depression was starting to set in. The "why me" thought was always present and in front of my thinking. What did I do wrong? I felt like less of a woman for not being able to have another child. Living in a military town, it seemed as if EVERYONE around me was pregnant. I couldn't go to the grocery store without seeing a pregnant woman. Why and how can SHE have so many kids, and why not me? The pressure from my mother for a grandd
That was not the change I needed. In fact it left me feeling even more alone. Not even a trained counselor could help me. Since I love to read, I found lots of great books on positive thinking. I learned the art of meditate and the art of training my thinking. I then realized my negative thinking was indeed harmful! That HAD to change! Having negative thinking for so long, it's was VERY hard to change on my own. Luckily, I found a great friend, she was going through infertility too! Together we began to work on our negative thinking, and began to get our minds and bodies ready for this great adventure! It wasn't an easy change, as change rarely ever is. However, now I know it was extremely necessary. We began to work on our diet, while putting our thoughts on a "diet" as well. Finally my husband came home from war. We began to talk about IVF and how we would pay for With a new way of thinking, and feeling confident that IVF would work for us, I began to research different IVF clinics. I came across lots of great US clinics, but one clinic in Europe for IVF caught my attention. Together my friend and I (and our husbands of course)
took a 2 week trip to Europe.

In 2008, after one IVF treatment, I was PREGNANT! I gave birth to perfect babies; a boy and a girl. My friend also got pregnant on her first IVF attempt with twins!
Through out my pregnancy I kept a IVF diary made very public on you-tube. http://www.youtube.com/user/Medicluvstrauma?feature=mhum

My education continues every single day to help you educate you. Dr. Google has good information but is not always the best. With my dedication, knowledge, and compassion to help others, I will be here for you in every aspect!! My way of coaching is like no other. I help bridge the gap between your mental and physical health by helping you find your true self, teaching you how to train your thinking through meditation and other channels, and getting you ready for a successful pregnancy.

Thank you for listening to my story!

Sincerely,

Carina

Throughout my journey there was on online doctor that went above and beyond with the free information he offers. He deserves to be recognized for all he does for the infertility community. Please check out his website and grab the free information he provides. He also provides an infertility cartoon!! Please take a look.

www.ivfindia.com

Thank you so much Dr. Malpani !!

We were a happy carefree couple, enjoying our freedom to do things that we liked, for the first four years of our marriage. And then when we finally thought of starting a family…. It didn’t happen for another year and we were happy childfree couple. Couldn’t figure out initially what can go wrong, but when we decided to do a reality check, we landed up at a neighborhood Obs&G’s clinic. She ran a few preliminary tests which didn’t point to anything in particular, prescribed few medicines for me. Six months later, the same tests were repeated again, and again. And then I was referred to a urologist for surgery for a suspected varicocele. That’s when it dawned upon us that may be we are knocking on the wrong door!

After a couple of months & a million clicks on the net, we decided to go to a specialist. The research on the net had classified us suffering from “unexplained infertility”. We landed up at Dr Malpani’s in search of explanation. Few new tests were prescribed for my wife and same old ones for me. Everything looked normal to the doc, which was a source of confidence that it would happen sooner or later. We were suggested to try IUI at our local gynec for 3 cycles. There was a hint of sadness creeping up after every unsuccessful IUI. Doubts started cropping up… Did we leave it for too late to start the family? We were back to the drawing board. Dr Malpani assured that everything was ok and he suggested IVF and we decided to go ahead. It’s to the clinic’s credit that the entire process is handled so systematically & in such an organized way that it gives you the confidence that every thing possible will be done, without going overboard,
to make it a success. The entire IVF process went as planned by the doctors and bingo…now we have graduated from being TTC couple to 12 weeks pregnant!

A BIG thanks to both Dr Aniruddha & Dr Anjali and their team!

mum.pgs@gmail.com

Many older infertile women are very unsure as to whether they need to do IVF; and if they do need IVF, if they should use their own eggs or to use donor eggs. While they understand with their heads that using donor eggs would maximise their chances of getting pregnant, it's hard for their heart to accept this decision, because most of us want a genetic link with our child !

This is especially true for older women who have regular cycles; grow follicles on ultrasound scans ; or have had a miscarriage in the last 2-3 years. If my cycles are regular and I can get pregnant in my own bedroom, doesn't this prove my eggs are fine ?

Gynecologists ( who do not specialise in infertility treatment) will often add to this confusion. Because they see 42 year old women who get pregnant in their own bedroom, they fail to understand there is a big difference in the biology of a fertile 42 year old and an infertile 42 year old. They will often "treat" these older women with clomiphene and follicular monitoring - causing them to waste valuable time !

The more sophisticated doctors will get their patient's FSH levels tested - and if these are normal, this will lull them into a false sense of security ! Not only are FSH levels very poor markers of ovarian reserve, they also vary from month to month; and if they are checked without also testing the estradiol ( E2) level at the same time, you may get an apparently normal FSH level, even if the ovarian reserve is very poor. ( A high E2 level can suppress a high FSH level into the normal range, and fool both doctor and patient !)

Unfortunately, most older women do not want to hear bad news. They are often in a state of denial and are not happy to listen to an IVF specialist who tells them that their "eggs are bad" ! They confuse calendar age with ovarian age - and are even more perplexed when they go online and read success stories of older women with high FSH levels who have got pregnant in their own bedroom !

Who should they trust ? Is the IVF doctor pushing IVF because he wants to make more money ?
Or is he providing medically sound advise ? Will you regret not doing IVF ? Or do you have an equally good chance of making a baby in your own bedroom ? And what if the IVF cycle fails ? Then what ?

While it's true that we do have better tests today for checking ovarian reserve, such as the AMH level and the antral follicle count , it's hard to make such an emotionally charged decision based purely on the results of medical tests. How reliable are these tests ? Can the results improve with alternative medicine ? herbal supplements ? acupuncture ?

If you are unsure what to do , and are emotionally detached enough to make a decision based purely on medical testing, then please ask your doctor to do a clomiphene citrate challenge test ( CCT) for you. This is a simple , inexpensive test, which provides very valuable information; and has stood the test of time. When it's hard to make a decision and you are confused, sometimes basing your decision on an objective test result can help you overcome your paralysis and move on with your life !

How does one do this test ?

Day 1 = day the bleeding of the period starts

On Day 3 , you need to do a blood test to measure your levels of FSH,LH,PRL and TSH; and AMH ( anti-mullerian hormone). Do this from a reliable lab please !

Take 100 mg clomiphene citrate from Day 5 - Day 9.

Repeat the blood test for FSH again on Day 10.

If the Day 3 plus Day 10 FSH levels are less than 25, then we can try to do IVF with your own eggs.

If the Day 3 plus Day 10 FSH levels are more than 25, this suggests you have ovarian failure,
and that donor egg IVF would be your best treatment option, if you are willing to consider this. A low AMH level will help to confirm this diagnosis.

If you are not sure how to interpret your results , you can ask me for a free second opinion !

For the older woman, time is now at a premium for you - please don't waste it ! When you are 60 years old and looking back at your life, you should never have any regrets that you left any stone unturned and didn't give yourself the best shot at fertility treatment. Treatment can be expensive, but a baby is priceless !

Taking treatment at a world-class clinic will maximise your chances of success and give you peace of mind you did your best !

Unfortunately, most patients doing IVF treatment are quite clueless about the most important end-result of the IVF cycle - the embryos ! This atlas will help you understand what your eggs and embryos should look like, so you have a better understanding of what happens in the IVF lab !

DAY 0 ( the day of egg collection)

MATURE OOCYTE CUMULUS COMPLEXES

THESE ARE MATURE OOCYTE CUMULUS COMPLEXES, IDENTIFIED IN THE FOLLICULAR FLUID ASPIRATED DURING EGG COLLECTION.

POST MATURE OCCYTE CUMULUS COMPLEX

STRIPPED EGGS
MATURE EGGS :


THIS IS A MATURE EGG (SURROUNDING CUMULUS CELLS HAVE BEEN STRIPPED OFF)

POLAR BODY AT 12 O CLOCK POSITION INDICATES THAT THIS IS A MATURE EGG AT METAPHASE II
STRIPPING IS MANDATORY FOR PERFORMING ICSI ON THEM.
CUMULUS NEED NOT BE STRIPPED FOR CONVENTIONAL IVF.

THIS EGG IS NOT A MATURE EGG. BUT A TINY POLAR BODY WHICH IS PROTRUDING OUT AT 12 O CLOCK POSITION, INDICATES THAT IT WILL SOON BECOME MATURE.

IMMATURE EGGS

Metaphase I egg

We can perform ICSI on Metaphase I eggs. The fertilization rate for Metaphase I eggs is 50 %.


Egg with Germinal Vescicle

THIS EGG HAS A CLEAR GERMINAL VESCICLE IN IT, WHICH INDICATES IT IS AN IMMATURE EGG. WE CANNOT DO ICSI ON THIS EGG. WE CAN USE IVM ( IN VITRO MATURATION) FOR THESE EGGS. AFTER 24 HOURS, SOME OF THEM MAY MATURE AND BECOME M2 ( METAPHASE II) AT WHICH TIME WE CAN DO ICSI FOR THEM

ABNORMAL EGGS


EGG WITH ABNORMAL ZONA EGG WITH ABNORMAL CYTOPLASM.

EGG WITH 2 POLAR BODIES.

POOR QUALITY EGGS

EGGS WITH DARK CENTRAL GRANULATION IN CYTOPLASM.

EGG WITH VACUOLATION IN CYTOPLASM

UNFORTUNATELY, THERE IS NO WAY WE CAN PREDICT THE QUALITY OF EGGS BEFORE WE STRIP THEM.
THIS IS WHY STRIPPING THE EGGS FOR ICSI PROVIDES US WITH VALUABLE INFORMATION ABOUT EGG QUALITY !

DAY 1
DAY 1 EMBRYOS ( ALSO CALLED ZYGOTES) ARE SCORED CONSIDERING

• THE PRESCENCE OF CYTOPLASMIC HALO
• NUCLEAR SIZE AND ALIGNMENT, NUCLEOLI NUMBER AND DISTRIBUTION.

• PRESCENCE OF CYTOPLASMIC HALO

PICTURE A – HALO POSITIVE ZYGOTE PICTURE B – HALO NEGATIVE ZYGOTE

2) NUCLEOLI NUMBER AND DISTRIBUTION

ZYGOTES ARE SCORED ACCORDING TO THE Z-SCORING SYSTEM.

• PICTURE A IS Z1 ZYGOTE WITH EQUAL NUMBER OF NUCLEOLI, ALIGNED AT THE PRONUCLEAR JUNCTION.
• PICTURE B IS A Z2 ZYGOTE WITH EQUAL NUMBER OF NUCLEOLI, SCATTERED IN THE TWO NUCLEI.
• PICTURE C IS A Z3 ZYGOTE WITH UNEQUAL NUMBER (DIFFERENCE OF MORE THAN 2 NUCLEUS) AND / OR SIZES OF NUCLEOLI.
• PICTURE D IS A Z4 ZYGOTE WITH SEPERATED PRONUCLEI AND UNEQUAL NUMBER OF NUCLEOLI SCATTERED IN THE TWO NUCLEI.

NORMAL ZYGOTE


Z1 EMBRYO

POOR QUALITY ZYGOTE

Z3 EMBRYO

ABNORMAL ZYGOTES

ZYGOTE WITH 3 PRONUCLEI

ZYGOTE WITH 2 PRONUCLEI WITHOUT NUCLEOLI

ZYGOTE WITH 1 PRONUCLEUS

We deal with a number of difficult patients who have failed multiple IVF cycles elsewhere. Many of these are poor ovarian responders and a common question is - How many follicles do you need to go ahead with the treatment ? Is there a number in your clinic below which you will cancel the cycle ?

These patients suffer from a lot of anxiety and apprehension during the superovulation, because they know they are not likely to grow many eggs. They have already had many of their cycles cancelled in the past - and this can be quite a cruel thing to do , because these are eggs which they have produced with a lot of effort ! Their eggs are precious - and represent their best chance of their having a baby with their own genes. This is why when the doctor cancels the cycle because they have not produced enough eggs, their heart breaks.

From the doctor's point of view, cancelling the cycle seems to be a very rational thing to do . Why make the patient spend so much money when the chances of success are so slim ?

What they forget is that the patient knew prior to starting the cycle that the chances of success were slim, so that the fact that she has grown few eggs has not really changed anything. If she's prepared to take that slim chance it can be cruel to deprive her of it

It's especially cruel when the real reason doctors cancel the cycle is because of "clinic policy" - because they do not want to mess up their success rate statistics !

These are challenging patients, and during superovulation, the major worry is - Will we reach the stage of egg colleection ?

Many doctors will cancel cycles if there are less than 4 follicles, because poor responders have a lower success rate and they do not want to harm their clinic IVF succcess rate. These are league table games clinics play, where they weed out the difficult patients to artificially elevate their published succcess rate figures.

We need just one follicle to go ahead, as long as the patient has realistic expectations and understands that there are still many more hurdles to be crossed after egg collection: there may be no egg; or the egg maybe immature; or it may not fertilise. We can be aggressive and are happy to do our best to help the patient to have a baby, but sometimes biology can be cruel !

With this approach , our patients have peace of mind they did their best ; that they explored all possible medical options and did not leave any stone unturned. With this approach, it's often easier for them to move on to Plan B ( adoption or donor eggs) because they know they've given it their best shot.

The outcome is always uncertain, and I do not want them to regret the fact that they did not try. We do our best to work with our patients - even if this brings down our success rates.

Donor Embryos: Biologically , embryo adoption is exactly the same as a traditional adoption , in that the child and the parents have no genetic linkage. However , here the resemblance ends. Whereas with traditional adoption it is a child who is adopted after birth, in embryo adoption the infertile couple adopts an embryo before pregnancy.

However , the sad tragedy is that there are just not enough babies available for adoption. Not only is the demand for adopting babies increasing day by day as infertility becomes more prevalent , the supply of unwanted babies being put up for adoption by the mother has become drastically reduced.

It is ironic that while the technology of contraception and abortion has reduced the availability of adoptable children, assisted reproductive technology now offers a new option to infertile couples. This is the option of embryo adoption.

There are many advantages to embryo adoption. There is no waiting list; and the infertile woman gets to experience the pleasure of pregnancy and birth. This obviously enhances bonding between the infertile couple and the child. Another major advantage is that there is no social stigmata involved ; and the couple does not need to get permission from family members or disapproving in-laws. Also , since these embryos are usually of high quality, the success rates are better than 50% per cycle. The only disadvantage is that the treatment can be quite expensive.

We see many patients who have failed multiple IVF treatment cycles in other clinics. Most of them are quite depressed and frustrated. They are not sure whether it's worth trying another IVF cycle with us, or whether they should explore alternative options .

The key question in their mind is - What can you do differently from the other IVF clinics ? What makes you better ?

I enjoy treating these patients . For one, they are a challenge, and if our treatment works where other clinics have failed, this is a feather in our cap ( doctors can be very competitive !)

Also, because they have done IVF earlier, they understand the basics of the treatment, so I can have an intelligent conversation with them and explain what we are going to differently. Because we are a full-service clinic, we can offer additional options which other clinics may not be able to.

These patients can be quite emotionally labile, but because we offer a lot of hand holding in our clinic, along with plenty of personalised support, we can help them to cope quite effectively.

Because we are very transparent in our approach and make it a point to educate patients and actively involve them in their treatment, most patients are appreciative of our approach because it's a refreshing contrast from what they have experienced in other clinics.

What has our experience with these patients been ?

While it's true that success rates do tend do drop in women who have had failed IVF cycles, this is not always true, and there are some refreshing exceptions !

Thus, many patients have taken treatment at sub-standard clinics. Their quality of care has been so poor, that for all practical purposes, all they have done is throw their money away. Doing an IVF cycle for them properly ( the way it should be done !) helps many of them to get
pregnant !

Similarly, some patients with PCOD have been very poorly managed in other clinics. Many doctors are so scared of OHSS, that they end up mistiming the HCG injection, as a result of which they get few eggs and poor quality embryos. We have extensive experience in doing IVF for PCOD patients, and our pregnancy rates are better than 45% per cycle for PCOD patients.
You can read more about this at www.drmalpani.com/pcod.htm !

Patients with male factor infertility are also often poorly managed in many IVF clinics. This is especially true for patients who need TESE and PESA. Because we do these procedures ourselves , we can use fresh sperm, giving us a much higher success rate ( unlike other clinics which have to depend upon an outside andrologist and therefore often have to use frozen testicular sperm which has a much lower success rate )

The other group of patients who are very fulfilling to treat are those with poor ovarian reserve. Because we are willing to use alternative medicine; supplements; and aggressive superovulation, we can often achieve a pregnancy in these patients ( whom other clinics shun because they are considered to be heartsink patients !)

Another interesting trend has been that most clinics in the West use gentle stimulation these days, because they want to transfer only a single embryo. While this works well for women with a good ovarian reserve, it's not the best approach for women with poor ovarian reserve. For these women, because we can superovulate more aggressively, we can often find the one good egg they have in their ovaries, and help this to become a baby !

One of my patients recently asked me - Which protocol is better for IVF - the Letrozole Antagonist Protocol vs the Estrogen Priming Protocol ?

( In passing, I'd like to point out how impressive it is that patients are so well informed about medical minutiae ! Most gynecologists are quite unaware of all these finer details !)

Actually, the principles of any superovulation protocol for IVF are extremely simple. Superovulation forms the heart of modern IVF. We use medications to help you grow more eggs. Every month you start to grow about 30-40 follicles, but in a natural cycle, most of these undergo atresia (die), so that only one matures every month, in the normal course of events. With the help of medications, we are able to rescue follicles which would otherwise have died, so that we can help you to grow many mature eggs in one cycle.

Since follicles grow in response to the hormone FSH ( follicle stimulating hormone), this is the most important medication we use for IVF. This comes in many different forms . The traditional medicine has been urinary gonadotropin ( menotropin or human menopausal gonadotropin). Brand names include Menogon and Repronex ). This has been the work-horse of IVF for many years and is still the most cost effective medication available !

The gonadotropins now come in many new ( and much more expensive !) flavours, including the recombinant ( rec) gonadotropins, which are produced in vitro in a bioreactor. These are the rec-FSH and rec-LH preparations, and brand names include Gonal-F and Follistim. All these are very similar as far as their clinical activity goes , though the recombinant drugs are much more expensive ( and are therefore promoted much more actively, even though they are no better !)

We can also use tablets such as letrozole to help you grow more eggs. These act by boosting the prodction of your own gonadotropins, thus helping you to grow more eggs.These are much gentler and much less expensive , and are very useful for the minimal stimulation IVF programs.

So if all we need to make you produce more eggs is to superovulate you with medications, why is this such a big deal ?

Remember that we also also need to prevent the eggs from bursting on their own. We need to time egg collection in an IVF cycle very precisely. We want to collect mature eggs before the follicles rupture. We cannot afford to go in too early ( or we will get only immature eggs); and neither can we wait too late ( or the follicles will rupture and we will lose the eggs).

Since we know that spontaneous follicular rupture is triggered off by an endogenous LH surge which is initiated by the pituitary gland, the drugs we traditionally use to prevent this spontaneous follicular rupture are the GnRH agonists. Brand names include Lupron and Buserelin ; and these switch off your pituitary gland, preventing it from producing any LH. However, they take a long time to act and need to be given for at least 10 days in order to be effective. These were administered as either a long protocol ( from Day 21 of the earlier cycle; or a short protocol ( starting from Day 1 of the cycle).

The newer generation of drugs which allow us to equally effectively prevent the spontaneous LH surge are GnRH antagonists, such as Ovurelix and Cetrotide. These act much more quickly, which means they can be started from Day 7 onwards, which means you need to take fewer shots ! However, these are much more expensive , as compared to the GnRH agonists, and are no better than them as regards their clinical efficacy.

In reality, pretty much any protocol works well for patients with good ovarian reserve, so there's not much to pick and choose between them, and most clinics get good results with whichever protocol they are comfortable with.

However, some patients can be quite tricky. These include patients with PCOD, who have a high risk of getting OHSS. They need much gentler superovulation, and closer monitoring.

The really difficult patients are the ones with poor ovarian reserve. They have fewer eggs left in their ovaries, which means they respond poorly to the standard superovulation protocols.

It is for these patients that doctors have developed newer protocols, in the hope that we will be able to coax these ovaries to produce more eggs !

A lot of the emphasis is on precycle preparation. The hypothesis is that if we treat patients prior to starting their IVF cycle with estrogens ( the estrogen priming protocol) or androgens ( such as DHEA) , they will produce more eggs because more follicles will be recruited when we start the superovulation . Many doctors will also use supplements like wheatgerm , Vit D3 and CoQ 10; as well as alternative medicine ( yoga and acupuncture) to boost ovarian response.

So much for the basics . However, I find many IVF doctors seem to deliberately complicate matters . They love coining fancy new names for their "new" protocols ( which are actually very similar to each other in reality !)

Why do they do this ? I think there are 2 reasons. If you use long complex technical names, this helps to put patients in their place . If you make it complex, patients don't ask too many questions because they are out of their depth, and they respect you even more because you are the expert who has mastered all these esoteric medical details !

Doctors also have a fascination for anything which is new . Doctors like to innovate - and it's fun to design and do something new !

Finally, it's a clever marketing ploy, because it helps to attract patients who have failed IVF cycles elsewhere. Patients who have failed IVF are desperate to do something different ( and preferably something new !)

Just remember that new is not always better - and please try to understand the principles behind the treatment, so you do not get taken for a ride !

Everyone loves advising infertile couples ! ( After all, if they've had a baby in their bedroom and proven their fertility , this makes them fertility experts, right ? )

The commonest advise is - Just relax ! Do not stress - do not take any tension ! This advise is even more pronounced during an IVF treatment cycle. If you want your IVF to succeed and the embryos to stick, you've got to "go with the flow" and not stress out. If you get too stressed out, your uterus will reject the embryos and they will not implant !

This is very unhelpful advise ! Of course there's a lot of stress in an IVF cycle - after all, no one wants to come to Dr Malpani to have a baby ! All my IVF patients are stressed out - and even the hyper ones do get pregnant ! It's true that patients need to learn constructive ways of dealing with this stress but to pretend that there's no tension involved is just being unrealistic.

The worry is that this kind of advise leads to blaming the victim. " You did not get pregnant because you were too stressed out ! Your IVF cycle failed ( what a cruel word) because you did do not relax enough !" This is hogwash. Don't forget that even a woman who gets raped ( whose stress levels must be through the roof) can get pregnant !

IVF patients understand the importance of optimism. However, many of them are very scared of getting their hopes up . They have been let down too many times in the past so far; and they are worried that if they become too optimistic, the crash down to reality will be much more painful if the cycle fails. This is why many patients keep their expectations low - so that they are better able to cope with failure .

Personally, I find a balanced approach the best option.

I request my patients to remember the Serenity Prayer -
God grant me the serenity to accept the things I cannot change;
the courage to change the things I can;
and the wisdom to know the difference.

Having a Plan B ready even before starting the IVF cycle can help you better cope with the IVF emotional roller coaster ride !

My patient was at her wit's end and was sobbing her heart out. I have done 5 IVF cycles all over the world, Dr Malpani - and they've all failed. What do I do next ?

This is always a complex question - and there's no easy answer. You need to be analytical and logical, so we know what to do next. The trick is not to waste time looking for problems, but rather to focus on solutions which will allow us to bypass the problems !

We need to ask ourselves - what have we learned from these failures ? What can we do differently the next time ? What can we change to increase the chances of success ?


If you do need to change something, remember that there are only 5 things we can change in any IVF treatment

1. The IVF treatment protocol
2. The clinic
3. The sperm
4. The eggs
5. The uterus

Let's think through this process logically , so we can prepare a plan of action for the next cycle.
This is a very useful framework, which helps you to analyse the failure; learn from it; and then move on !

First, I need to emphasise that sometimes there's really no need to change anything at all. Not every IVF cycle is going to result in a baby, even it it's text book perfect. Sometimes, all you need is to be patient - and a little bit of luck !

But what if 3 cycles have failed ? Then what ? Let's look at what we can change, step by step.

1. The IVF Treatment protocol. While the IVF treatment protocol is pretty standard, every woman's body is different, and every patient responds differently to IVF medication ! Each cycle teaches us how your body responds to superovulation - and a lot of the art of IVF and the skill of a good IVF doctor consists of superovulating you with just the right dose of medications, to get you to produce an optimal number of high quality eggs. While most young patients with normal ovarian reserve grow well in response to a standard protocol, patients with poor ovarian reserve and those with PCOD need a lot of extra attention and closer monitoring. We may need to use additional alternative medicine supplements such as DHEA for these patients; while others may need higher doses of HMG. Some of this is trial and error - and you must keep careful records and learn from each cycle , until we can customise the perfect protocol for you !

2. The clinic. If you find your doctor is very rigid and is not willing to make any changes inspite of repeated failures, then it's a good idea to get a second opinion, to confirm you are on the right track. Getting a fresh brain to look at the problem can be very helpful and can offer new insights ! While the basics of IVF are the same all over the world, there is a great deal of difference in the quality of the services IVF clinics provide - and it's a good idea to keep an open mind and explore alternatives if you feel your present clinic is stuck in a rut; or refuses to do anything different. This is especially true if your doctor batches patients; does IVF on a part-time basis; refuses to share medical information with you; or does not provide you with photos of your embryos ! A word of warning here - doctor shopping is not usually a smart thing to do - and if you have a competent doctor with whom you have a good relationship, then it's best to preserve this, and ask him to offer additional options to you, rather than to establish a new relationship with a new doctor. However, when you do go from one IVF clinic to another, you are quite likely to get VIP care, because IVF doctors are quite competitive, and it's often a matter of pride for them to get a patient pregnant when the earlier IVF doctor has failed to do so !

3. The sperm. If you have failed fertilisation in an IVF cycle, then you need to do ICSI in your next cycle. This will ensure fertilisation and is a simple and effective solution ! Using ICSI allows us to work with practically any man's sperm, no matter how low the count or poor the motility and morphology . I do not believe DNA fragmentation affects success rates if ICSI is being used if the embryologist is competent ; and I believe that if we have poor quality embryos after ICSI even in men with severe oligoasthenospermia, the problem is usually because of the egg or the lab, and not because of the sperm. ( I know that many clinics will blame the poor sperm quality when they get poor quality embryos after ICSI. This is rubbish - it's usually just a poor quality lab which is to blame ! However, men with a low sperm count have low self-esteem - and they are quite willing to accept this flawed conclusion - and use donor sperm for the next cycle ! ) . It's possible that in a very very few men who have persistently poor embryos after ICSI, it could be the poor quality sperm which are responsible. The only way to prove this is by split crossover testing ( fertilising the wife's eggs with donor sperm; and fertilising donor eggs with the husband's sperm, and then comparing the embryo quality ), but as you can imagine, this can be very hard to do in real life !

4. The eggs. When you remember that the egg is a thousand times bigger than the sperm; and that the energy for cell division during embryo cleavage comes from the mitochondria in the egg's cytoplasm, it's hardly surprising that the vast majority of time embryos fail to implant is because of "egg problems". The problem is that it's very hard to make this diagnosis, as eggs are just spherical blobs, and we simply do not have the technology to assess egg quality or egg function. However, if there is a problem with embryo quality in a good IVF lab, 9 times out of 10 the problem is because of the eggs. While it's sometimes possible to correct this problem in the next cycle by using various measures to optimise egg quality ( such as DHEA or a more aggressive superovulation procotol), most of the time the most effective solution is to use donor eggs. This option has a very high success rate - but it can be quite hard for some women to accept - especially those who are young and have a good ovarian response, with a normal AMH level and a normal antral follicle count. It can be hard for them to come to terms with the possibility that their eggs may be flawed - and the idea of using foreign genetic material can be unpalatable to many women ( and their partners).

5. The uterus. Surrogacy has become very popular recently because of the disproportionate amount of media attention it attracts, and many women feel that the best medical solution for them after many failed IVF cycles is surrogacy. After all, the fact that the embryos are not implanting means the uterus must be " defective" , so doesn't it make sense to use a fertile woman's uterus as an incubator for 9 months ? However, the truth is that surrogacy is an expensive and complex treatment option, which is best reserved for women without a uterus. Research shows that the reason for failed implantation is much more likely to be genetically abnormal embryos ( because of poor quality eggs), rather than a uterine problem. However, because it's very profitable to offer surrogacy , many IVF doctors are keen to push their patients towards this option . For a woman who has failed 5 IVF cycles and is fed up and frustrated, surrogacy does seem to be a very attractive option - no hassles with the dreaded 2 week wait - someone else can do all the hard work ! However, the success rate for surrogacy for these women is very poor, because it's not their uterus which was the problem ; which means that using another woman's normal uterus is not going to help at all !

I remind patients who have failed IVF to remember the Serenity Prayer -
God grant me the serenity to accept the things I cannot change;
the courage to change the things I can;
and the wisdom to know the difference. Outcomes are always uncertain, but if you take well-informed decisions on a logical basis, you will have peace of mind you did your best !

The failure of an IVF cycle always causes major heartburn. The next question is - Why did the IVF cycle fail ? What should I do next ? Did I get good quality medical care ? Or should I change my doctor ?

This is always a hard question to answer, because even if the quality of medical care provided is excellent, the IVF cycle can still fail. How is the patient to judge the quality of technical competence of the IVF clinic ? Did the cycle fail because the clinic was bad ? Or was it just bad luck ? You cannot rely on a doctor's bed side manner to judge his clinical skills - you need more tangible evidence - but what should you be looking for ?

Fortunately, the answer is very easy - you should ask for photos of your embryos ! The core competence of a good IVF clinic is to produce high quality embryos. Of course, whether these embryos will implant and become babies after they are transferred is not something which any doctor can control - but the quality of the embryos is a tangible end point which can easily be measured and compared.

I feel every patient should ask their IVF clinic for photos of their embryos - and most good IVF clinics will routinely provide these to their patients, even without being asked. Good clinics are proud of their skills - and are happy to show off the embryos they make in the IVF lab to their patients !

If your doctor refuses to give you a photo of your embryos, you should worry a lot ! What does he have to hide ? And why ?

And if you need help in making sense of your embryo quality, please email your embryo photos to me, and I'll be happy to help !

HOW I IMPROVED MY VITRIFICATION TECHNIQUE !

SAIPRASAD GUNDETI, SENIOR EMBRYOLOGIST, MALPANI INFERTILITY CLINIC PVT. LTD.

Vitrification involves freezing the embryo about 600 times faster than ever before. This ultrarapid process is so fast that it literally allows no time for intracellular ice to form. As a result, vitrification avoids trauma to the embryo.
In conventional (slow) freezing, 20-30% of embryos do not survive the freeze-thaw, and those that do survive have less than half the likelihood of generating a pregnancy as do fresh embryos. In contrast, vitrified embryos have a better than 95% freeze-thaw survival rate, and a pregnancy generating potential that is comparable to fresh embryos.
Vitrification is now regarded as potential alternative to conventional (slow)freezing.

Major advantages of Vitrifiction over Slow freezing are :

• Its prevents ice crystal formation within the cells, which can damage the embryo.
• It eliminates use of expensive freezing unit(required for slow freezing).
• High survival rate post thaw.
• High pregnancy rate following transfer of thawed vitrified embryos.

At Malpani infertility clinic, we have been using vitrification for a number of years to cryopreserve both embryos and eggs. When it comes to embryo cryopreservation, we freeze all stages of embryos i.e. Day 1, Day 2, Day 3, Day 5 and Day 6.

Steep Learning Curve :

To avoid embryo exposure to high concentrations of toxic cryoprotectants for extended periods, vitrification protocols generally require that embryos remain in the vitrification solution for a fixed time. This can be difficult, especially since vitrification technique have an extensive learning curve before the technique is mastered. Even with practice, one may not be able to quickly pick up embryos and vitrify within the time required.

Therefore it's critical that we determine the length of time the embryos can safely reside in vitrification solution, so that we don't overexpose embryos to toxic cryoprotectants, which can kill them or lead to very poor post thaw survival.

How difficult is it to master the technique?

Vitrification technique is a difficult art to master:

1. Due to high concentrations of cryoprotectants, vitrification medium is very viscous. High viscocity makes it very difficult to handle embryos, while they are in the medium. Needs lot of practice in order to get efficient.
2. One needs to be quick while handling embryos in vitrification medium, as long exposure of embryos to cryoprotectants can kill embryos or lead to poor survival rate post thaw.
3. Loading embryos onto cryolock is the most difficult part. It requires lot of practice. Improper loading can also affect the survival rate.
4. Thawing procedure (called Vitrification Warming) is as important as the Freezing. Improper thawing may lead to poor survival. So one needs to thaw embryos carefully in order to ensure good survival of embryos.

How do I vitrify your embryos and eggs?

VITRIFICATION FREEZING

We use Quinn's Vitrification Medium at our centre for freezing Embryos and Eggs.
Quinn's Vitrification Medium contains 2 media, "Equilibration Medium" and "Vitrification Medium"

Equilibration Medium contains Base Medium(Hepes buffered Medium) + 7.5 % ethylene glycol + 7.5 % DMSO (Dymethyle sulfoxide) + 20 % Protein supplement

Vitrification Medium contains Base Medium(Hepes buffered Medium) + 7.5 % ethylene glycol + 7.5 % DMSO (Dymethyle sulfoxide) + 0.5 M Sucrose + 20 % Protein supplement

Preparation of Vitrification Dish :

Place 1 drop of 0.1 ml of "Equilibration Medium" and 4 drops each of 0.05 ml of "Vitrification Medium" as shown in the figure.

The entire Freezing procedure is performed at room temperature.

We need to leave the Petri dish in the workstation for 15 min, for the medium to recover to room temperature.

Equilibration

• Place embryos or eggs to vitrify in equilibration medium. (This will be number of embryos or eggs that will be placed on 1 cryolock). We don't put more than 3 embryos or eggs on 1 cryolock.
• Once embryos or eggs are placed in Equilibration Medium, they spontaneously begin to shrink . This is when the intracellular water comes out.

Picture of shrunken embryo, after placing it in the equilibration drop.

• The shrunken embryo or egg will gradually recover back to its original size. This takes approximately 7 to 8 minutes. This may be less or more than 7 to 8 minutes in some embryos and eggs.

Vitrification

• Once the embryo or Egg recovers back to its original Size, its ready to be vitrified. I generally vitrify the embryo or egg once it recovers to about 80% of its original size.
• Pick up the embryo or eggs from equilibration drop with a flexipet and place them in the 1st drop of vitrification medium.
• Once the embryo or egg is placed in the vitrification drop, it again starts shrinking. Keep the embryo or egg in the 1st vitrification drop for 10 sec. This is basically to get rid of Equilibration medium, which is carried along with the flexipet while transferring them from equilibration medium.
• While the embryo/egg is in the first drop of vitrification medium for 10 sec, rinse the flexipet by pipetting the vitrificaition medium to get rid of equilibration medium.
• After 10 sec, pick up the embryos/eggs from the 1st vitrification drop and transfer them to series of 3 drops of vitrification medium one after other.
• Quickly load the embryos onto cryolock with very little medium. Make sure to gently remove excess medium in case a bigger drop is made on the cryolock.
• immediately plunge the cryolock in Liquid Nitrogen. Now the embryos are vitrified.
• Slowly put the cap to the cryolock, while it is immersed in the liquid nitrogen.
• Put all the cryolocks in one visitube.
• Put the visitube into canister.

Vitrification Warming (thawing)

Quinn's vitrification warming medium contains 3 media, "Thawing Solution", "Dilution Solution" and "Washing Solution"

Thawing Solution (TS) contains Base media (Hepes buffered medium) + 1M Sucrose + 20% protein supplement.

Dilution Solution (DS) contains Base media (Hepes buffered medium) + 0.5M Sucrose + 20% protein supplement.

Dilution Solution (DS) contains Base media (Hepes buffered medium) + 20% protein supplement.

Preparation of dishes :

• Place a drop of 0.2 ml of Thawing solution (TS) in one dish as shown in the figure.
• Keep the dish for warming at 37 deg. C on a warming plate for about 15 min.
• Place 1 drop of 0.1 ml of Dilution Solution (DS) and 2 drops each of 0.2 ml of Washing solution in another dish as shown in the figure.
• Keep the dish at room temperature.

0.2 ml of Thawing Solution at 37 deg. C.

• Identify the cryolock (embryos we want to thaw) and put in the box containing Liquid Nitrogen.
• Remove the cap of cryolock, while it is immersed in Liquid nitrogen.
• Quickly submerge the cryolock tip into thawing solution under stereomicroscope view.
• The embryo will automatically dispel.
• Leave the dish at 37 deg. C for 1 minute.
• After 1 min, carefully collect the embryos from the thawing solution to Dilution Solution at room temperature making sure carrying forward minimal amount of thawing solution along with the embryos.
• After 3 min. pick up the embryos and transfer them to 1st washing solution. The embryos will recover back to its original size approx after 2 min.
• After 3 min. transfer the embryos to second washing solution.
• after 3 min transfer the embryos to culture dish.
• Incubate the embryos for 2 hours before transferring them to patient's uterus.

What mistakes can a beginner do while vitrifying, that can lead to a poor survival rate?

Preparation of vitrification dish

Mistake :

Placing only 1 drop of vitrification medium, trying to cut down on the amount of medium consumed.

Reasons :

• Using only 1 drop of Vitrification medium doesn't allow us to get rid of Equilibration medium before actually vitrifying the embryo/egg.
• The Equilibration Medium is not very effective when it comes to cryoprotecting , as compared to Vitrification Medium.

Solution :

• Use 4 drops of vitrification medium.
• Serially transfer embryos/eggs through the series of these 4 drops of vitrification medium. This allows us to get rid of the equilibration medium effectively.
• This will definitely ensure better survival rate.

Equilibration

Mistake :

• Keeping the embryos in Equilibration medium for a short period of period before transferring them to Vitrificaition medium.
• This happens when we rely on fixed time period for each medium.

Reasons :

• Once the embryo/egg is placed in Equilibration medium, it will shrink spontaneously and slowly recover back to its original size. The recovery period varies for different embryos.
• When we rely on fixed time period for e.g. 5 min in Equilibration medium, it may not be enough for the embryo/egg to recover to its original size.
• If we transfer the embryo/egg to vitrification medium before it recovers back to its original size, it doesn't vitrify properly, which leads to extremely poor survival rate post thaw.

Solution :

• Rather than relying on a fixed time, it's best to individualise the time, based on the shrinkage and recovery of each individual embryo/egg , to ensure better vitrification.
• The embryo/egg can take approximately 7 to 8 min. to recover back to its original size.
• In some embryos it can be less or more than 7 to 8 min.

Vitrification :

Mistake :

• Making a large drop of vitrification medium along with embryo/egg while loading it on cryolock.

Reasons :

• A large volume of vitrification medium on cryolock will not allow proper vitrification of the embryo/egg.
• If the embryo is not vitrified properly, it leads to poor survival.

Solution :

• Make a flat small droplet of vitrification medium.
• Even if the drop is large, get rid of the excess medium by aspirating it gently.
• An embryo placed in a minimal amount of vitrification medium on cryolock vitrifies perfectly.

Many IVF doctors in India travel extensively. They have many clinics all over the city ( and in some cases, all over the country). Naive patients get impressed by such doctors - wow - he is so busy and so much in demand that he needs to travel all over the place. In fact, some doctors even go to Dubai and Africa ! While this seems very impressive, in reality this means that the quality of care they provide to their patients leaves a lot to be desired. Let me explain.

The personal goal for these doctors seems to be to maximise the number of patients they treat, so they can maximise their throughput and their revenue. While it's very good for an IVF clinic to be busy, it's also important that the quality of care provided to their patients not be compromised in the quest for quantity !

How do these doctors manage to do IVF in so many locations ? They usually do so by batching groups of patients together, so they treat lots of patients within 1-2 days. After they finish one batch of patients at one site , they then move on to the next site ! While it's medically quite feasible to program IVF cycles, the truth is that ensuring that all patients grow eggs at exactly the same time so that they will all mature on the same day for egg retrieval is simply not possible. The doctor is forced to cut corners for some patients because he's trying to force a square peg into a round hole - and this is especially harmful for older patients ( with poor ovarian reserve); challenging patients ( who have failed many IVF cycles in the past) ; or patients with PCOD ( who may end up hyperstimulating), because it's not possible to individualise their superovulation protocol. Such a rigid travel schedule means the doctor cannot afford to be flexible or cater properly to the "outliers".

So what happens to these patients ? They fail to get pregnant - and unfortunately they are not sophisticated enough to realise that the failure is not because there is a problem with them, but rather because they are not good candidates for "programmed" IVF ! They need a more focussed clinic which can spend the time and energy needed to optimise their chances. However, doctors who are focussed on the bottom line are really not very interested in treating these challenging patients. They would rather treat lots of young patients and improve their turnover, rather than take pride in getting the difficult patients pregnant !

The other major problem with this kind of itinerant IVF is that it's not possible to develop a relationship with your IVF doctor. In fact, you may not even see the IVF specialist for more than a few minutes, because this "big-shot, big-name" doctor may just breeze in, do the embryo transfer, and then breeze out ! If you have questions, you will never know whom to get the answers from, because all the juniors are uncoordinated and cannot make decisions, because they do not have the expertise or the experience to do so !

Now there's nothing wrong with this McDonald approach - after all, it seems to work well for these doctors ! This is because in each batch, the young patients who are good ovarian responders , will get pregnant ( though the success rate will not be as high as it could be in a full-service IVF clinic). But this approach is obviously not right for all patients ! If you've failed an IVF cycle; or have poor ovarian reserve; or need TESE or have PCOD, then you should rather select a clinic which provides all its services all the time in one location !

This is why all the world's leading IVF clinic all operate from a single location. They understand that IVF is a very labour intensive process, which needs close monitoring and extensive tweaking to optimise outcomes for their patients. Good doctors would rather focus on each individual patient, and are confident that if they are good, patients will come to them, rather that their having to go to other cities to find more patients to treat !

If you need a second IVF cycle, and if your IVF doctor is not present in the clinic all the time, you should be very worried about the quality of the care you will get ! If you want to maximise your chances of getting pregnant, send me your medical details by filling in the free second opinion form at www.drmalpani.com/malpaniform.htm and I'll be happy to help !

Malpani Infertility Clinic have just launched India's first free phone service to educate infertile couples about infertility.

This innovative IVR ( interactive voice response) service called FertilityFactsFoneLine, powered by BolTell, walks patients through their treatment options, and helps to dispel many myths and misconceptions.

Best of all, it's free !

Try it out by dialling 08042658370 !

A long-term study following 1,000 families with children born using IVF between 1994 and 2002 in the UK and US has shown the importance of parenting in the outcome of a child's behaviour.

In the study, which investigated the mental wellbeing of both the parents and children, some of the children were biologically related to their parents, while others were unrelated and conceived using either donor sperm or eggs, or both. This gave the researchers a unique opportunity to compare the role of nature (genes) and nurture (the environment) in the development of a child's behaviour.

This is why patients who use donor gametes for IVF after counselling and forethought are usually very happy with their kids !