Wednesday, June 30, 2010
I am a patient with azoospermia. My wife's reports are perfect with no fertility problems.
We are undergoing TESE- ICSI in a fertility clinic in Bangalore. My wife was superovulated with RECAGAN 100IU which she has been taking for the last 10
days . Today's scan result shows 14 mature follicles . The sizes are:
According to the original plan , we were supposes to take HCG tonight (11th day of the period) and the egg retrival was planned for Wednesday . However, due to non-availability of " TESA Specialist " they are postponing the egg retrival by 3 days and HCG injection by 2 days. We have been asked to continue injection RECAGON 100IU for 2 more days. The doctor gave me harsh reply , saying he can't help this and there is no choice.
I am really worried ! Will this affect our ICSI success chances ? Will it affect my wife's ovaries , because the follicles would have grown even more in 3 more days !
This patient has got a really raw deal. After spending so much time, money and energy, the egg collection is being re-scheduled because the specialist is not available.
This is sad ! This reduces the chances of pregnancy; and also increases the risk of OHSS ( ovarian hyperstimulation syndrome) , because the follicles will get too big !
It's very disappointing that the IVF clinic did not know when the “ TESA specialist “ was coming in advance !
This is why we tell patients that they should always select a full-service clinic which provides all the services themselves and operates around the year and is not dependent upon "visiting specialists" !
Tuesday, June 29, 2010
Monday, June 28, 2010
Whenever an IVF cycle fails, the first question the patient demands an answer to is - Doctor, what went wrong ?
Some doctors get defensive when they hear this question. They feel the patient is challenging their clinical competence, and many will simply refuse to see the patient when the IVF cycle fails. This is adding insult to injury, because they have abandoned the patient in their time of need, simply because they do not feel comfortable answering uncomfortable questions. ( Many of this breed of doctor would rather spend their time doing consultations with new patients, so they can do more IVF cycles !)
Some will blame the patient - either subtly, or otherwise. " The embryos did not implant because you did not rest enough". Some doctors will use this as an opportunity to "run some more tests" to find out " why your body rejected the embryos".
Other doctors blame poor quality eggs and suggest donor eggs; and some will claim that the uterus was not receptive and advise surrogacy ! What often infuriates patients is the fact that none of these "problems" were discussed while the treatment was going on , which means the doctor seems to be "inventing" new problems after the cycle has failed. The same doctor who said "you have beautiful embryos" on the day of transfer is now saying - "your embryos were bad because of poor egg quality" !
In most cases, the truth is often much simpler. Just because the embryos did not implant does not mean anything went wrong - they just did not implant, that's all. The only "deliverable" an IVF clinic can provide are embryos - and once the clinic has made good quality embryos, there's very little anyone can do to determine their future fate after they are transferred into the uterus.
Human reproduction is not an efficient enterprise - and this is true whether you are having sex in your bedroom or whether you are doing an IVF cycle ! Just like couples do not expect to get pregnant every month they have sex ( even if they are completely normal and fertile), it's unrealistic to expect every perfect IVF cycle to result in a baby ! The trouble is that couples do not mind when it takes time in the bedroom - but when it takes time in the clinic , then this hurts !
It's important that doctors teach patients to have realistic expectations of the IVF treatment, before they start the cycle. Good doctors do this routinely - but bad once will often over- promise - and then under-deliver !
Friday, June 25, 2010
Mrs Desai was in tears. She was very depressed and agitated. " Doctor, I have done 4 IVF cycles in 3 different clinics and they have all failed ! What should I do next ? Is there any hope for me at all ?"
I see patients like Mrs Desai every day. I try to help them analyse their problem , so they can find the right solution.
Step No 1 is to use the McKinsey MECE model of exploring all their options - making a list which is mutually exclusive and completely exhaustive. In most cases, this list would include the following options:
- childfree living
- medical treatment ( IVF)
- third party reproduction ( IVF with donor eggs or donor embryos or surrogacy)
Typically, most patients who come to me are willing to consider only the last 2 options.
As I explain to them , for their next IVF cycle, there are only 5 things that they can change -
the eggs ( donor eggs)
the sperm ( donor sperm )
the embryos ( donor embryos)
the uterus ( surrogacy)
If the eggs, sperm and the uterus seem fine, then often the best option is to change the doctor !
Sometimes patients are reluctant to do this. They have invested a lot of time and money and energy in their IVF treatment and they feel that their doctor "knows their case", so it's best to stick with him. Also, many IVF clinics are very good at "holding" on to their patients. They will refuse to give the medical records of the IVF treatment, which means that patients are often clueless as to what has happened in their earlier IVF cycles and and are forced to continue with the old clinic. Also , finding a new doctor is hard work - and patients who have developed a good rapport with their doctor feel they are being disloyal to him by going to another clinic. For others, it's just plain inertia. Better the known devil than the unknown one - and isn't this clinic the best anyway ? So what's the point of going to another doctor ? What value can he add or what can he do differently ?
There are may benefits to changing doctors. For one , the new doctor provide a fresh perspective, and may be able to identify problems the previous doctor has missed. For example, many IVF clinics still do not test ovarian reserve properly, and often fail to diagnosis patients with poor ovarian reserve correctly. Secondly, the new doctor may have special expertise in dealing with your particular problem. Thus, while many IVF clinics do offer PESA and TESE for male factor infertility, the quality of these ancillary services is often poor, because they do not have a full-time embryologist or andrologist on staff. Thirdly, the new doctor can offer options which the earlier clinic was not able to ( for example, vitrification or embryo biopsy). Finally, being able to achieve a pregnancy for a patient who has failed IVF treatment in another clinic is a matter of pride for many IVF doctors, so you are likely to get VIP attention !
Have you failed IVF treatment ? Not sure what to do next ? I'll be happy to provide a free second opinion, so you know you are on the right track !
Thursday, June 24, 2010
We have created the world’s first IVF clinic on Second Life. The clinic is now open – please do come and browse around !
- a reception area where you can watch videos about IVF
- a consultation room, where you can do a consultation with a virtual IVF specialist
- an operation theater, where you can watch an egg collection and embryo transfer
- an IVF lab, where you can see how embryos grow
- an andrology lab where you can see how we process sperm for IUI
- a PGD lab, where you can watch how we do an embryo biopsy
- a virtual support group, where you can get counseling and support
Go to Second Life ( www.secondlife.com) and set up a free account.
Use the link below to get to the clinic once you in Second Life
Have fun – and feedback is always welcome !
Wednesday, June 23, 2010
Want to learn
- how to choose the right doctor ?
- how to talk to your doctor
- how to get a second opinion ?
- how to prevent unnecessary surgery ?
- how to take care of yourself in a hospital ?
Tuesday, June 22, 2010
IVF can be a complex process and selecting a doctor can be quite a challenge ! Infertile couples are often frustrated and depressed and most will choose an IVF clinic based on a recommendation by a friend or a referral by a doctor. This is not always the best method and you can end up getting stuck in a poor quality clinic, thus reducing your chances of success. Even worse, many clinics do precious little do educate or inform their patients and patients don't know what questions to ask their doctor.
Also, IVF cycles can fail for many reasons. Sometimes the problem is poor quality eggs - but often it is a poor quality clinic !
Here's the single most important thing you should check, to be sure you are getting good quality treatment.
Insist that your clinic provide you with photos of your embryos ! A good clinic will provide this routinely. This is tangible evidence that they have delivered you with a high quality service - after all, the key output of an IVF clinic is the embryos they produce.
What do bad clinics do ?
- They do not provide photos of your embryos
- They fob you off with specious excuses ( our camera is not working is very popular)
- They just just tell you verbally that the embryos are Grade A
- They "show" you the embryos under the microscope. Unfortunately, for most patients, these just look like blobs - and patients are not sophisticated enough to differentiate between good embryos and bad embryos
Whenever a patient comes to me for a second opinion after a failed IVF cycle , I ask them just one question - show me the photos of your embryos. This allows me to judge objectively how good or bad the IVF lab is - and bad IVF clinics have bad IVF labs !
If you are not sure what good embryos look like, please look at this Visual Atlas of Embryos.
And you can always ask me for a Free Second Opinion !
Monday, June 21, 2010
Sunday, June 20, 2010
IVF patients are always on the lookout for innovations which will improve their chances of success . For example, many IVF patients ask us whether we do IMSI or CAT. These are techniques which have been aggressively promoted in the press, but do not really help the patient at all. I have written about IMSI in an earlier post. Let me discuss CAT ( cumulus-aided transfer) in this post.
IVF doctors have always been frustrated by the fact that though we are quite good at growing embryos in the lab, most of these embryos do not become babies. Embryo implantation is an inefficient process, and trying to ensure that every embryo we transfer becomes a baby is the "holy grail" for all IVF specialists , which is why we use techniques such as blastocyst transfer and laser assisted hatching, to try to facilitate the implantation process .
One logical way to increase success rates is to try to improve lab quality conditions, so that in vitro conditions match in vivo conditions as closely as possible. So what are differences between growing embryos in a plastic dish in the IVF lab and in the human body ?
In the body, the embryo is bathed in nutrients provided by the cells lining the fallopian tube until it reaches the uterus. In the lab, we grow embryos in plastic dishes containing culture medium, which contains a mixture of chemicals which are cleverly designed to support the growth of embryos.
In the past, in order to help embryos to grow in vitro, doctors would add the patient's serum to the culture medium. The hope was that this serum contained ( unidentified) biological growth factors, which would help the embryos to grow well. However, we learned that along with growth factors, the serum also contained embryo-toxic factors, which could actually inhibit the development of the embryo, and we stopped adding serum to the culture medium. Meanwhile, as we learned more about the biochemistry of the early embryo, manufacturers tweaked the chemical composition of the culture medium ( using a mix and match of amino acids ) , so that it because more embryo friendly, and could support the growth of embryos more efficiently.
A lot of research in the early days involved co-culture , and you can find lots of references to this if you do a Medline search for IVF co-culture. Basically, this involved culturing the embryo on a bed of "feeder cells", so that these cells could support the growth of the embryo. Ideally, the feeder cells should be the cells lining the fallopian tube, but these were very difficult to grow, which is why doctors tried using endometrial cells for co-culture; as well cumulus cells ( which were collected from the follicular fluid at the time of egg collection). Using cumulus cells for co-culture is a very simple technique and seems very appealing. This is what was christened CAT or cumulus aided transfer. Unfortunately, the success rates with CAT are no better, which is why the technique never caught on and few IVF clinics now offer this option. After all, every clinic wants to improve their success rates, and if such a simple technique worked, then everyone would use it.
So why don't we ( and the vast majority of IVF clinics all over the world) offer CAT?
On closer analysis, it's quite easy to see why CAT does not help. For one thing, in real life, the cumulus cells do not nurture the embryo in vitro. After fertilisation, the cumulus cells disperse, so that the embryo is floating free in the fallopian tube and is not surrounded by cumulus cells in vivo . Also, transferring the cumulus cells along with the embryo into the uterus makes little logical sense because cumulus cells belong in the ovarian follicle - not in the uterus ! In the uterus, the cumulus cells are "foreign" and are unlikely to help in embryo implantation !
Caveat emptor - let the patient beware ! More is not always better - and often established techniques are much better than newer ones !
Saturday, June 19, 2010
The one factor which causes the most stress is having unrealistic expectations . Every patient feels in their heart of hearts that " this is the cycle when it's going to work !" - and I do not think any one would ever start an IVF cycle if they did not feel it was going to work. Unfortunately, the only thing which is in your hands is the process. You can make sure you have a competent and caring doctor; and your doctor can make sure he provides you with high quality medical care. Sadly, no matter how good your prognosis; how good your doctor; and how perfect your IVF cycle, the outcome is always uncertain.
While we are good at growing eggs; making embryos; and then transferring them into the uterus, whether the embryo will become a baby or not is a biological process no one can influence. Implantation still requires a bit of luck ( for lack of a better word !)
This is why, when you can never be sure of the outcome , you should still be able to ensure you have peace of mind you did your best. This is why you need to reframe how you judge the "success" of the IVF cycle. For most people, the answer is easy - did I get pregnant or not ? However, from a medical point of view, this is too simplistic. Was the process performed properly or not is a better yardstick for judging the outcome.
Unfortunately, very few patients have the maturity to prepare for failure when they start an IVF cycle. This is why IVF treatment can be such an emotional roller coaster ride !
" It's got to work ! It's going to work ! I've said my prayers ! Everyone is rooting for me ! I have my lucky charm on ! My period is 1 day late ! I'm feeling some heaviness in my breasts..."
All these mind games just add to your stress levels when the cycle fails - and what's worse, you ( or your loved ones) will then start blaming this stress for the failure. " The cycle failed because you are too tense. If you just relax, I'm sure you'll get pregnant. I know this friend who..."
We find that along with encouraging patients to learn meditation and yoga, offering a guaranteed pregnancy option is very effective in helping them to manage their stress levels. Not only does it signal the fact that we are very confident that we will be able to give them a baby ( after all, I am putting my money where my mouth is !); it also helps them to keep their expectations realistic . When they select this option, they are helping themselves to prepare for possible failure ; and equally importantly, they are making a commitment that they will put in the time and energy needed to help them to reach their final goal.Each failed cycle helps us to tweak our protocol, so we can fine tune it based on your response, until we can finally give you a baby !
Friday, June 18, 2010
We all know that prevention is better than cure, and this is one of the reasons that executive health checkups have become so popular. They promise to help your doctor to pickup medical problems early , so they can be treated more effectively.
Unfortunately, even though the logic is very appealing, the sad truth is that in real life, health checkups are good for hospitals and diagnostic centers, but not for patients ! In fact, most doctors never do a health checkup for themselves , because they know how useless they are !
So what is your doctor not telling you ?
Let's look at why hospitals promote health checkups so aggressively. The checkup is great way of converting well people into patients; and creates a constant stream of customers for the healthcare system.
It's a mathematical certainty that if you run a sufficient number of tests , you are bound to find abnormalities. Once you find an abnormality, then the person is snared into the healthcare system, and the vicious cycle starts.
Abnormality = more tests = more consultations = more treatment - more surgery, often unnecessary
Let's consider a 40 year old asymptomatic woman who goes for a deluxe super-duper health checkup at a local 5-star hospital. Because she has opted for the Platinum scheme, the doctors does a vaginal ultrasound scan to check her uterus. She finds a 4 cm fibroid and then advises the patient to undergo surgery to remove it. Since most patients are ( understandably !) reluctant to undergo surgery, the soft-sell is that this is going to be " minimally invasive" surgery done through a laparoscope, so that there is no cut and this can be done on a day-care basis. Also, the insurance will pick up the tab !
It's very common to do this for ovarian cysts as well. Cysts are very common in women; and most are functional and will resolve on their own. However , the doctor scares the patient into doing surgery, using a number of fear-inducing techniques, such as : it may increase in size; it
may burst; or, it may become cancerous. The sonographer is also a part of this scam, and magnifies the findings by highlighting them and by reporting the size in mm, instead of cm ( a 4 cm cyst is reported as a 40 mm cyst , to make it seem bigger !)
The truth is that you cannot make an asymptomatic patient happier - and if she has no complaints to start with, she most probably does not need any intervention at all ! The right advise would be masterly inactivity. However, few doctors have the maturity to advise this.
In fact, they tell the patient that thanks to this checkup, they have picked up a problem which could have snow-balled in the future. The amazing thing is that patients are happy when an abnormality is picked up ( they can justify the money they spent on the health checkup !). Most patients are very pleased that the problem was spotted before it became a major issue.
The truth is that most of these so-called abnormalities are not really problems at all - they are just incidental red herrings discovered with modern medical technology, which the patient would have happily carried to her grave if she had been unaware of them.
All this overtesting is leading to an epidemic of overtreatment. Is this going to change ?
No - it will just become worse as time goes by. Thanks to better technology , it's becoming easier and cheaper to produce high quality images of practically any nook and corner of the human body. However, better pictures does not equal better clinical outcome. A lot of these images will pickup problems, which are just anatomical variants, but which will be "treated" by over-enthusiastic doctors. There is too much money at stake !
Also, remember that if an "abnormality" is detected, it requires a very courageous doctor to advise against treating it with surgery ! In reality, it's s much easier for the doctor to advise surgery and "fix" the problem. After all, if he does the surgery, no one will object ( whether the surgery was needed or not is never discussed). Find a problem - fix the problem, is a common knee jerk response. It's also much more profitable for him !
However , if he advises against surgery and the problem worsens over time ( as it will in a very small minority of patients), the patient is quite likely to sue the doctor for not taking care of it when it was first pointed out ! Even good doctors will advise surgery to protect themselves, even when they know in their heart of hearts that this surgery is not in the patient's best interests !
Thursday, June 17, 2010
Traditionally, Indian patients were passive and were quite happy to leave all medical decisions to the doctor . However , times have changed, and internet positive patients are hungry for information and want to work in partnership with their doctor. This is a huge challenge – and a great opportunity as
well . We feel patients are the largest untapped healthcare resource and that Information Therapy is Powerful Medicine !
In partnership with the Patient Information Forum, UK, HELP is organizing The Empowered Patient Conference. Our keynote speaker will be Mr Mark Duman, President of PiF.
Information Therapy can help patients (and health insurance companies !) save money on medical care by
1. Promoting SelfCare and helping them to do as much for themselves as they can
2. Helping them with Evidence-Based Guidelines , so that they can ask for the right medical treatment that they need – no more and no less
3. Helping them with Veto Power, so they can say No to medical care they don’t need, thus preventing overtesting and unnecessary surgery .
Information Therapy is good for doctors and hospitals as well, as patients who are well-informed have realistic expectations of their treatment. They are much more likely to have a good medical outcome and much less likely to sue.
How can we all work together – doctors, patients, hospitals, health insurance companies and IT companies , to ensure that patients are at the heart of everything we do in healthcare ?
If you are interested in participating, please send an email to me at email@example.com !
A vaginal ultrasound scan has now become a routine part of the work of an infertile woman, because it provide so much useful information. Unfortunately, many IVF specialists misuse this simple technique.
I have seen patients who have been advised donor eggs by IVF doctors, because their "ovaries looked small" on the vaginal scan done at the time of the consultation . Even worse, is the fact that some doctors advise surrogacy because " the uterine lining is thin".
They do not bother to provide any documentation of their scans - or to explain options and alternatives to their patients. Most patients are quite easily initimidated; and since the IVF doctor is seen to be the "court of last resort", many follow the doctor's advise blindly or get disheartened and give up.In fact, some clueless patients are very impressed by how skillful the doctor must be, that he ( or she) could come to the correct diagnosis so quickly - a diagnosis which had eluded all their earlier doctors ( because it is wrong !)
Wednesday, June 16, 2010
I seem to be seeing an epidemic of tuberculosis ( TB ) these days ! Practically all Indian patients who come to me have been treated with anti TB drugs ! Most gynecologists now routinely test the
endometrium ( uterine lining) for TB using a new generation of fancy ( and very expensive !) tests such as PCR ( polymerase chain reaction) . In the past, the only test available for making a diagnosis of TB was by growing the TB bacillus in the laboratory; or by finding tubercles on histological examination. However, both these methods are quite insensitive.
This is why PCR was introduced with great hope. This test amplifies a specific segment of DNA and labs believed that finding DNA sequences unique to the tubercle bacillus in the endometrial tissue would help to make a unequivocal diagnosis of TB infection. Unfortunately, this test has proven to be unreliable because it is too sensitive and can pick up even minute quantities of DNA, leading to many false positives. Because it is very expensive, it has not been validated in the fertile population, and in some labs, over 50% of the samples sent to them test positive for PCR for TB ! This obviously means the test is unreliable, but doctors continue doing it, without understanding its limitations and pitfalls – and patients are unnecessarily subjected to the trauma of 9 months of useless treatment !
Here's one simple reason why I feel the test is unreliable. When the tubercle bacillus reaches the genital tract ( from the lungs) , it first attacks the fallopian tubes and then later damages the endometrium . This means that whenever the endometrium is TB PCR positive, tissue from the fallopian tube should also be PCR positive. However, for many patients whose endometrium is positive, the fallopian tube is negative !
The other group of tests which is very popularly misused to make the diagnosis of TB are the blood tests which test for the presence of antiTB antibodies – both IgG and IgM. Firstly, remember that these tests are not picking up the presence of the TB bacillus – they are only testing for the presence of antibodies ( produced by the immune system to protect the body !) against the TB bacillus. As most Indians have been exposed to the TB bacillus, it is hardly surprising that many have the presence of antiTB antibodies, and often test positive. Doctors often believe that this is proof of TB infection, and promptly start treatment ! Similarly, the Mantoux skin test also tests merely for the presence of immunity against TB – and can be similarly misinterpreted.
In summary, the diagnosis of TB of the genital tract remains notoriously difficult to make. Most patients are misdiagnosed as having TB when in fact they don’t, and many are treated for no good rhyme or reason !If your gynecologist diagnoses you as having genital TB based on these unreliable tests, then please do NOT start anti-TB medicines. Please insist on getting a second opinion from a physician, preferably once who is a TB specialist !
The truth is that no one really knows how to interpret these results - but no doctor will admit to this fact. What does a positive test mean ? Nothing ! I am sure if a controlled study is done , a lot of fertile women will also turn out to have positive tests for TB ! ( Actually, this would be an easy study to do ! Fertile women who are scheduled for a laparoscopic tubal ligation could have their endometrial biopsy done at the same time and this could be sent for testing for TB. It is my prediction that over 50% of these samples will turn out to be positive ! I'd love to be proven wrong !)
What's the result of all this testing ? A lot of unnecessary expense; and even worse , this leads to 9 months of unnecessary treatment with toxic drugs with unpleasant side effects. As a result of this waste of time, patients get fed up and frustrated. Sadly, most gynecologists are pretty clueless about what these results means - and it's much easier to "do something" ( prescribe antiTB medicines) rather than explain to the patients that nothing needs to be done !
Tuesday, June 15, 2010
Here's a short list of features which can help you identify a poor quality IVF clinic
1. Clinics which depend upon outside embryologists to do their procedures for them. IVF is a demanding process and your embryos need the full-time loving care and devotion of an experienced embryologist. A full-time embryologist spends a lot of time honing his skills and optimising the conditions in his IVF lab to ensure high pregnancy rates. This is not something a "visiting embryologist" can do. Thus, these clinics will very rarely freeze spare embryos , and your supernumerary embryos are usually discarded - or donated ( without your content or permission) to another patient.
2. Clinics run by over-busy doctors who travel a lot and are not available in one location. This is a problem for many reasons. These doctors are so busy shuttling from clinic to clinic, that they simply cannot provide the needed care and attention to their patients. While this may not be an issue for many young patients ( who are good ovarian responders), this can be a major problem for patients with poor ovarian reserve or those who develop OHSS. Another problem is that these clinics will often treat patients in batches. This means they will group all their patients together, and do about 10-15 egg collections in one day ! While this works fine for young women this not a good option for difficult patients ! After all, when you have 25 women cycling at one time, how can you possibly ensure that all 25 women will grow eggs at exactly the same time so that they are allready for an egg pickup on the same day ? When there are too many patients , care gets regimented and fragmented, and there is more scope for errors.
3. Clinics with too many assistants. Because there aren't too many good IVF clinics, the good clinics are all very busy. To maximise their patient through-put and revenue, the senior doctor employs assistants. This means that often the history is taken by a junior - and patients rarely get a chance to bare their soul or establish a rapport with the senior doctor. As the treatment progresses, most of the instructions are relayed to the patient by a nurse or an assistant. Once you've paid your fees and signed up for the IVF treatment, you rarely get a chance to see the senior doctor again !
4. Clinics which do not provide medical documentation or records. This is a major problem because IVF clinics want to "hang on" to their patients. They are worried that their patients may desert them or go to another doctor, which is why they treat the patient's medical records as their personal property - and refuse to give even a copy to the patient. A good clinic should routinely give you a treatment summary as well as photos of your embryos - and if they do not, then you should be very concerned !
Monday, June 14, 2010
Image via WikipediaMany women with blocked tubes go in for IVF treatment . Some of them have a hydrosalpinx, in which the blocked tube is filled with fluid. It has now become standard advise to remove the hydrosalpinx or to clip the blocked tube prior to IVF. This needs to be done by performing an operative laparoscopy ; and this procedure is supposed to improve IVF pregnancy rates ( because the hydrosalpinx fluid is toxic and can prevent the embryos from implanting.)
Most gynecologists are happy to advise this surgery before referring the patient for IVF, because this is an additional surgical procedure for which they can charge the patient. In reality, however, this unnecessary surgery can actually end up causing harm.
For one, it leads to overtreatment. In many IVF clinics, all blocked tubes are surgically removed prior to IVF, even if the hydrosapinx is very small ! This has never been proven to be of any benefit ( the original study only selected patients with a large hydrosalpinx) , but sadly patients are not well informed enough to ask questions and most are quite happy to sign on the dotted line. However , as is true of all surgical procedures, even this "minimally invasive surgery" carries a risk. This surgery can impair ovarian blood flow and reduce ovarian reserve.
In reality, there is a much easier way of ensuring that the hydrosalpinx fluid will not affect the embryos when they are being transferred . At the time of egg collection, the hydrosalpinx can be aspirated under vaginal ultrasound guidance. This means that when the embryos are being transferred into the uterus 3-5 days later, there is no toxic fluid in the hydrosalpinx to harm the embryos . This is a simple, zero-cost, non-surgical solution which ensures that the hydrosalpinx fluid will not affect embryo implantation or IVF success rates !
Sunday, June 13, 2010
Both IVF ( in vitro fertilisation) and ICSI ( intracytoplasmic sperm injection) are types of assisted reproductive techniques, but patients still get confused between the two. Which do we select and when and why ?
The technique which was first developed was IVF . ICSI is a modification of the basic IVF technique. From the patient's point of view, everything remains the same, as regards superovulation, scans, monitoring, egg collection and embryo transfer. The only difference is what happens in the lab. In IVF, we allow the sperm to fertilise the eggs on their own. In ICSI, we give the sperm a piggy-back ride into the egg with the help of a micromanipulator.
For male factor infertility ( men with very low sperm counts or those with azoospermia) , ICSI is the only option, so there's no question of choosing between the two
However, for men with normal sperm counts, is IVF better ? or is ICSI better ?
The answer is - both are equally good, as long as the sperm fertilise the egg. This is because the embryo implantation rate for both IVF and ICSI is the same. As long as we have an embryo, whether the embryo is formed as a result of IVF or ICSI does not affect success rates at all
Some clinics believe that doing ICSI can harm the egg ( because we are mechanically introducing a sperm in the egg). However, this is not true - and with a skilled embryologist, the egg damage rates after ICSI are less than 2%
What about the risk of injecting an abnormal sperm in ICSI ? Theoretically, some doctors believe that IVF will ensure that only the healthy " best" sperm will fertilise the egg, whereas with ICSI if the embryologist selects an abnormal sperm, the embryo will be abnormal. However, years of experiences with millions of ICSI cycles has proven this is not a valid concern in practise.
It is important to emphasise that the risk of birth defects is not increased after ICSI. It is true that azoospermia men with Y chromosomal microdeletions who do ICSI will have sons who also have the same microdeletion. However, the children of men with normal chromosomes who are born after doing ICSI will also have normal chromosomes . The procedure of ICSI by itself will not cause genetic problems !
Even though the success rates with IVF are as good as with ICSI, we prefer doing ICSI in our clinic, even when the sperm are normal. This is for two reasons.
In ICSI , we need to denude the oocytes before doing the ICSI. This allows us to assess the oocyte quality much more closely - and we think this is important for older women and women with poor ovarian reserve, because this allows us to assess egg quality.
The other reason is that the major disadvantage of IVF over ICSI ( in men with normal sperm) is that in some patients for whom we do IVF, we will have total failure of fertilisation . This can be a big blow, because this is totally unexpected. Even though the sperm count and motility are completely normal, the sperm are not capable of fertilising the eggs, and we only find this out after doing IVF. If there are no embryos, then the chances of achieving a pregnancy are zero - and this means the patient has to start another fresh cycle, in which we have to do ICSI to ensure fertilisation. Doing ICSI for all patients routinely helps to prevent this heart-breaking problem.
Saturday, June 12, 2010
Mrs. Bhatt had very poor ovarian reserve. Her AMH level was 0.3 ng/ml and she had reached the oopause . We advised her to use donor eggs but she was quite certain she wanted to have a baby with her own eggs. We explained to her that her prognosis was bleak, but she was determined, and requested us to do our best to help her to have a baby with her own eggs.
We superovulated her aggressively using a letrozole – antagon protocol, with 750 IU of HMG daily. She had a very poor ovarian response as expected, and grew only one follicle. We advised her to cancel the cycle, but she was very keen on getting pregnant and requested us to proceed with the treatment. Dr. Anjali did the egg collection and retrieved one oocycte cumulus complex from the follicle after flushing it multiple times. When I stripped the oocyte, it unfortunately turned out to be immature – it was a germinal vesicle stage egg.
We decided to keep the egg for In vitro Maturation ( IVM) .The egg matured exactly after 20 hours. I performed ICSI on that egg. It fertilized and we transferred the embryo back into the uterus on day 2. It was a gorgeous 4-Cell Embryo.
Even though we got only one embryo, the patient was very happy that at least we had helped her to reach this stage. She had been mentally prepared to get zero eggs and zero embryos, so this was quite a positive development from her point of view. Thanks to the technique of In vitro Maturation, they got a beautiful embryo to transfer.
We kept our fingers crossed – and 14 days after the transfer, she was on top of the moon when the HCG result was positive, confirming that she was pregnant ! Her pregnancy is now progressing well !
So what is in vitro maturation ? and how do we do it ?
In vitro maturation, as the name suggests, refers to the process of maturing immature oocytes outside human ovaries, in the IVF lab.
Applications of In vitro maturationof oocytes :
- Oocyte donors, to preserve their eggs in egg bank.
- Fertility preservation for women with cancer who are undergoing gonadotoxic chemotherapy.
- Fertility preservation for young women without partners needing IVF treatment.
- Poor responders to ovarian stimulation.
- Patients with lots of immature eggs after egg collection.
- Patients with PCOS syndrome, leading to retrieval of lots of immature eggs, after being hyperstimulated.
Mature Oocyte Immature oocytes
In vitro Maturation medium is now commercially available.
At our centre we use "SAGE In vitro Maturation medium”
It is not a ready to use medium. One has to prepare it.
Maturation media is usually supplemented with recombinant FSH and hCG.
The protocol for preparation of In vitro maturation medium is as follows :
Solution A = 1 ml IVF culture medium
Solution B = We use Menogon ( HMG). This powder contains a mixture of 75 IU
FSH and 75 IU LH. Dissolve this in 1 ml of IVF culture medium (A).
Solution C = 1 ml of Fresh Oocyte Maturation Medium in a test tube.
Solution D = Add 10 ul Solution B into Solution C
Solution D is now prepared Oocyte Maturation Medium.
In Vitro Maturation of Oocytes :
In Vitro Maturation on cumulus-enclosed oocytes :
- Done on oocytes retrieved from small sized follicles.
- Done on oocytes with apparently compact cumulus complexes
Immature oocyte cumulus complex
- Immediately after retrieval, cumulus-enclosed immature oocytes are placed in a specialized IVM medium for 24–48 hours.
- Generally germinal vesicle–stage oocytes that matured within 30 hours of culture are developmentally more competent than are oocytes necessitating longer time to mature.
- After IVM, mature oocytes are transferred to traditional IVF media for insemination and embryo culture.
- Insemination of IVM-Mature oocytes can be done by either Conventional IVF technique or ICSI. ICSI has been our preferred method as oocytes are frequently denuded of granulosa cells for evaluation of maturational status. ICSI has been used to increase the chances of fertilization whether or not a male factor has been detected.
In Vitro Maturation on Stripped oocytes :
- Done on Germinal Vesicle stage oocytes (confirmed after denuding them of the surrounding cumulus cells)
- All Germinal Vesicle Stage oocytes are kept in Specialized IVM medium for 24-48 hours.
- After IVM, Mature ( metaphase II) oocytes are transferred to traditional IVF Medium for ICSI.
Germinal Vesicle Stage oocyte. The germinal vesicle is the clear vacuole within the cytoplasm.
Photo of the egg after IVM. It has now become mature ( metaphase II – MII) . You can see that the germinal vesicle has dissolved and the polar body can be seen at 12 o'clock.
IVM is not a panacea for all problems – and not all immature eggs will mature in vitro using this technique. However, it does allow us an additional option, and can be very helpful when treating poor ovarian responders !
Friday, June 11, 2010
She now wanted me to do another insemination for her. When I advised her that it was time to consider IVF, she got upset. - Why do I need IVF when all my test results are normal, doctor? Can't we just do another IUI cycle please?
This is typical of many patients I see. They change multiple doctors, but each new doctor ends up doing exactly the same thing the previous doctor did. When I ask why they give permission for their third laparoscopy, the typical answer is, - My new doctor did not trust the previous doctors reports and needed to see for himself. - Hope springs eternal in the human breast, but patients get so fed-up and frustrated going through the same cycle month after month that by the time they come to my clinic, they are ready to give up.
As an infertility specialist, I find the saddest stories are those of patients who failed to get pregnant because they did not get the right medical care. Being infertile is bad enough, but having a problem that is not treated correctly is even worse. Instead of wasting her time and money on repeated laparoscopies and IUI, it would have been much more cost effective for her to have moved on to IVF.
What can you do make sure you don't get sub-optimal care? Here are the common mistakes I have seen infertile patients often make, and you need to learn to guard against these.
-We'll Take Care of it Later
Since infertility is never an urgent problem, many couples keep on putting-off seeking medical attention. There is always something more pressing, and who likes going to a doctor anyway? Many will refuse to go, because they'd rather not acknowledge there might be a fertility problem.
- Refusal to Consider Alternative Treatment Options
This is a common mind-block, especially among men. Many of them believe that treatment is unnatural or artificial, and they would rather have a baby who was conceived in the bedroom. It's better to be aware of all your options up front, and to explore these systematically, rather than try a hit-and-miss approach.
- Getting Fed-up and Giving Up
Infertility is likely to be one of the first major life crises you will encounter, when you have to confront your biological frailty. Moreover, it's a problem that will not go away by throwing money at it, since the technology is still not perfect. How well you cope with this adversity will depend largely on your adversity quotient, and your need to develop coping skills. Joining a support group can be a very valuable source of emotional strength.
- Not Doing Their Homework
The most important tool in your arsenal is information. Knowledge is power, and this is especially true for infertility treatment, which is potentially open-ended, expensive, and has an uncertain outcome. Don't minimize the problem or take an ostrich-in-the sand attitude and hope that it will go away. If you are well informed, you will be able to make your own decisions for yourself, to suit your own life plan and personality. There are no right answers in this field, only whats right for you. Trust your own heart.
- Not Getting a Second Opinion
While it's an excellent idea to trust your doctor, this should not be left to blind faith. It's always worthwhile to get a second opinion from an infertility specialist, to make sure you are on the right track. It's even better to get an opinion from a specialist who is not going to be treating you; this is much more likely to free of bias. You can get a free second opinion from me online !
- Losing Control
Patients who have unrealistic expectations from their treatment go through highs and lows that they find difficult to cope with. You need to have a plan of action, in which you hope for the best, but prepare for the worst. Don't think of any treatment on a single cycle basis. You have to learn (the hard way, unfortunately) to accept that nature is not very efficient at making babies!
- Let's Try Something New This Time
Some patients want to try every new wrinkle every time they read a report in the newspaper. Remember that newspaper reports are deceptive and often give a one-sided view that emphasizes the successes. It's hard to trust media hype. Don't act as a guinea pig - let the technology mature. If it's really good, it will be even better in another two years. Many fads come and go, and not all of them are truly helpful for patients (though they often help some doctors rake in quick bucks because its the latest thing to be doing!).
- Repeating the Same Treatment Again and Again
As a rule of thumb, if a treatment has not worked in four cycles, you have reached the point of diminishing returns, and the treatment is not likely to be right for you. It's possible the next stage of treatment may be more expensive, but just because the right treatment is expensive is no reason to do the wrong treatment just because it is cheap!
Do these mistakes sound familiar? Have you made any of them? Don't kick yourself - put it down to a learning experience (you are now wiser!) and move on. Everyone is allowed to make one mistake once - just don't repeat it twice!
-Of all sad words of tongue or pen, the saddest are these: " It might have been! " While the final outcome of treatment is always unpredictable, you should have peace of mind that you did your best. Take the path of least regret and 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.
Quality Control (QC) and Quality Assurance (QA) in the IVF laboratory plays an important role in the success of any IVF program.
The role of QC procedures in the IVF laboratory is to fine tune existing protocols in order to more effectively help infertile patients in their quest to have a healthy baby. The three most important physical conditions in the IVF laboratory that can be controlled are the temperature, pH and osmolality of the IVF culture medium. Laboratories are required to document and monitor these physical conditions regularly as part of their ongoing QC/QA programs. Monitoring and documentation of temperatures inside incubators, refrigerators and freezers is an integral part of routine day to day QC in the IVF laboratory.
Quality Control of Laboratory Equipments :
CO2 Incubators :
Variation in pH and temperature affects the embryo quality and thereby pregnancy rate. Therefore proper maintenance of CO2 incubator is very critical.
- We measure the CO2 percentage and temperature of incubator daily to ensure stability of pH and temperature.
- A Log book is maintained for proper documentation.
- Regular Cleaning and decontamination of incubator is done.
- Water in incubator pan ( to maintain humidity) is changed regularly
- A Sperm survival test is done before every batch to ensure proper functioning of incubator.
- We have an Annual maintenance contract with the supplier for regular servicing.
- Back up Power supply is mandatory.
Laminar Flow workstation :
- Daily cleaning of surface.
- Regular servicing, cleaning of HEPA filter.
- Ensuring the HEPA filter is working properly by testing the density of the particulate matter in the air
Micromanipulator and Stereozoom Microscope :
- Regular cleaning.
- Daily measurement of temperature of stage warmer.
Pressure Modules (Air purifier) :
- Regular servicing.
- Regular cleaning of HEPA filter.
Quality control of Culture medium and disposables :
- Documentation of shelf life and batch number is maintained.
- Stock keeping with reorder level is maintained to avoid shortage.
- Proper maintenance of refrigerator i.e. cleaning and regular temperature measurement for storage of culture medium.
Sterile Culture Conditions :
To ensure that your embryos are happy in the IVF lab, we need to ensure optimal culture conditions .
These include :
- IVF Lab cleanliness :
= Daily Cleaning of IVF lab with proper disinfectant is mandatory.
= The disinfectant should be non-toxic and odourless. We use diluted H2O2 to do so. Alcohol-based solutions can be embryo toxic and should not be used.
- CO2 Incubator Cleanliness :
Regular Cleaning and disinfection of CO2 Incubator should be performed.
- Aseptic precautions while handling Gametes and embryos :
= One should wash his hands properly before handling the dishes containing embryos.
= Gloves should be worn, while preparing dishes and handling culture medium
Correct handling and identification of patients and their gametes and embryos
Written procedures should be present describing the various phases of IVF techniques. Rules concerning the correct handling and identification of gametes and embryo samples should be established by a system of checks and, where needed, double-checks.
- All material obtained from the patients, i.e. tubes with follicular fluid containing eggs and containers containing sperm, should bear the names of the treated couple.
- At our centre, when the husband collects a semen sample for an IVF procedure, Semen Freeze or Semen Analysis, the nurse charge will ask the patient to write his full name on a piece of paper, to avoid any spelling mistakes and the same name will be written on semen collection jar. The Jar is labeled with husband's name and cap of jar is labeled with his wife's name.
- Once the sample is collected and it arrives in the lab along with your file, the name on the jar is cross checked with one on the file. We analyse the sample and transfer the sample to sterile centrifuge tube, which is labeled with his name. The cap is also labeled.
- The sperms will be processed while they are in this tube and will remain in this tube till we use them for IVF procedure.
- The culture dishes required for your IVF Procedure are prepared in advance. All the dishes are labeled with your name. The shelf of the incubator in which your dishes are kept is also labeled.
- At our centre, when the husband collects a semen sample for an IVF procedure, Semen Freeze or Semen Analysis, the nurse charge will ask the patient to write his full name on a piece of paper, to avoid any spelling mistakes and the same name will be written on semen collection jar. The Jar is labeled with husband's name and cap of jar is labeled with his wife's name.
- Verification of patients' identity should be performed at critical steps: before egg collection, at semen recovery and embryo transfer procedures.
- At our centre, the nurse and OT staff cross check your file before taking you inside the OT for procedure.
- The nurse informs Dr. Anjali and me about your being taken into the OT.
- For embryo transfer, the nurse stands as witness, while I load you embryos into the catheter.
- I confirm your name audibly with Dr. Malpani, before handing over the catheter loaded with your embryos to her.
- Double checks need to be considered at critical procedures such as : insemination of oocytes, replacement of embryos, embryo freezing and thawing.
Handling of oocytes and spermatozoa
The laboratory procedures regarding the handling of gametes for assisted should be easy, simple and effective and must be performed in a laminar flow hood equipped with stages and heating blocks pre-warmed at 37°C. Disposable items used in the laboratory procedures for culturing eggs and embryos should be of tissue culture grade.
- Aseptic technique should be used at all times.
- Appropriate measures should be taken to ensure that oocytes and embryos are maintained at 37°C during handling/observation using stage warmers or other systems.
- Tissue culture grade disposables should be used for handling gametes.
- Pipetting devices (pasteurs, drawn pipettes, tips etc.) used for procedures should be disposed of immediately after use.
- Simultaneous treatment of more than one patient should never be done in the same working place.
The purpose of the protective measures is also to ensure aseptic conditions for gamete and embryos :
- Use of non-toxic (non-powdered) gloves and masks.
- Use of vertical laminar-flow benches.
- Use of mechanical pipetting devices.
- Use of disposable material; after usage, it must be discarded immediately in the proper waste containers. Potential infectious materials must be disposed of in a manner that protects laboratory workers and maintenance, service, and housekeeping staff from exposure to infectious materials in the course of their work.
- Needles and other sharps should be handled with extreme caution and discarded in special containers. The Pasteur pipettes and broken glassware should be discarded in special containers.
Quality Control using evaluation of results :
At our centre, we evaluate results on a regular basis. The following factors are regularly evaluated:
- Fertilization rates
- Embryo Quality
- Pregnancy rates
- Multiple pregnancy rates
- Implantation rates
- Survival rate for frozen embryos