Empirical therapy in IVF - good , bad and ugly

Doctors are very fond of prescribing treatments, and a lot of these are empirical - based on their personal clinical experience. This is especially true in IVF , because there's so much we don't understand about reproductive medicine. Thus, when we say someone has failed an IVF cycle because of " failed implantation" , this is just a label to disguise our ignorance , because we cannot study embryo implantation in utero.

The truth is that we have no idea why the embryo failed to implant, but patients don't want to hear the truth. This is why doctors don't want to admit that we are clueless ! The patient is very anxious, and if you acknowledge you are not sure , the patient will go hunting for a second opinion, because they want a doctor who can inspire confidence !

This is why empirical therapy has become so prevalent.  Empirical therapy simply means therapy based on experience. Its efficacy hasn't been verified by controlled clinical trials , because these are quite expensive .
Empirical therapy is of two type - good and bad.  Good empirical therapies are usually cheap, inexpensive, short-term and have no side effects. Thus, prescribing a 15-day course of antibiotics for a patient whom you suspect has endometritis is unlikely to do much harm.  Yes, it may not help, and that's something the patient needs to be aware of.

The big problem is that there a lot of very expensive empirical therapy as well, some of which can be harmful. Thus, many IVF specialists put all their patients on 9 months of anti-TB treatment based on unreliable TB PCR tests . Patients are subjected to expensive, time consuming treatment which can have a lot of toxicity - and this also harms the community by causing the spread of drug-resistant TB. You can read more about this at http://blog.drmalpani.com/2015/03/laboratory-tb-versus-genital-tb.html

Lots of other "treatments" are very expensive , and have many side effects . These include stuff like intravenous immunoglobulins ( IVIg); paternal lymphocyte immune therapy for treating " high levels of NK cells" ; intralipid infusions; and  PGS. It's a long list and that's why it's very important to explain to patients before starting  that this is therapy which has not been proven. The doctor needs to be honest and say, given the fact that we have limited options, we'd like to try this on you . However, we need to get informed consent from patients that this is treatment which has not been established as being scientifically sound because we don't have enough data, but if you want to try it, we're happy to go ahead and do this for you.

Sadly, most doctors don't do this, which is why IVF patients end up wasting so much money on wasteful and useless tests and treatments.

Need help in getting pregnant ? Please send me your medical details by filling in the form at www.drmalpani.com/free-second-opinion so that I can guide you !

TB PCR testing is a waste of time and money, and causes harm

A patient just sent me this email

Sir I have 5 year baby girl...I have started treatment for conceive second baby before 4 year. ...but unfortunately I m not getting result... doctor give mi advice for doing laparoscopy because of both tubes are blocked.i have done laproscopy in april. after laproscopy I have try natural conceive for but result was not getting gud....I forgot to take report of tbpcr ...I was called the report in august.and unfortunately my tbpcr is come positive.and I was take AKT4 near about 15 days.but this medicine not suit to me.i stop medicine...and same month I conceive baby....I confused .....what I can do...baby pregnancy continue or abort.plz  give mi advice.thanku 

This poor patient never had genital TB, and was mis-diagnosed as having TB because of the TB PCR test result, which is extremely unreliable, because it is riddled with false positives .
Read more about this at http://blog.drmalpani.com/2015/03/laboratory-tb-versus-genital-tb.html

She fortunately decided to stop the medicines on her own, and then promptly got pregnant - without any medical "help".

However, she is now worried that her "TB" will harm the baby, and is thinking about terminating a completely healthy pregnancy.

Gynecologists should be ashamed of the harm they are causing to their patients by this kind of irrational prescribing !

The futile quest for certainty in IVF treatment.

Every couple who does IVF wants to get pregnant in the first cycle, and of course, every IVF doctor wants their patients to get pregnant in the first cycle as well ! It's very fulfilling to be able to add so much happiness to your patients' life by giving them a deeply loved baby, and if we had a 100% success rate, our life would be much easier !

Unfortunately, our IVF technology still has a long way to go .While we're good at doing certain things, there are lots of gaps in our knowledge . This is especially true after we've transferred an embryo back into the uterus. This is literally a black box , and we have no idea what's going to happen to the embryo in utero.

Implantation is a biological process which we cannot study in vivo . Since you're putting a live embryo back into the body , we have no non-invasive way of being able to monitor its progress or track its fate .

We need to be mature and accept the fact that our technology has limitations. We don't have answers for all our questions, , and we need to learn to live with this uncertainty .

However,  this is something which patients are unhappy about. They desperately want answers, and they will often ambush doctors into providing these answers. They will often unknowingly push their doctors into ordering lots of completely pointless and unnecessary tests. Doctors then add insult to injury, by offering " treatments " based on these " abnormal" test results.

It's easy to justify these tests saying, " These tests will give us more information," but the bitter reality is they don't provide any useful clinical information at all , whether it's PGS ( preimplantation genetic screening)  or ERA ( endometrial receptivity assays) .  While these maybe useful research tools, they  should be used only during clinical trials, and patients should not have to pay for the privilege of serving as guinea pigs !  Some Indian doctors are so creative that they offer tests which are available only in India ( such as PAMP testing) because these have never been validated anywhere else in the world !

While these tests may seem to make  a lot of scientific sense, sadly many of the equally logical treatments  touted widely in the past have failed to live up to their original hype - and this includes treatments such as paternal lymphocyte immune therapy;  or intravenous immunoglobulins ( IVIg);  or NK cell testing  -  it's a long list of useless tests and wasteful treatments.

This is why patients should be extremely careful before accepting the justifications which doctors trot out for justifying the use of these tests. The standard reply is - In my experience, it's helped other patients, so let's try it for you ! Any treatment can be justified by calling it empirical treatment - treatment based on experience, but not on evidence.

Fads and fashions come and go in medicine, and they change every few years, but the reality is that none of these treatments have been proven to be of any value at all. I think it's unfair that doctors use their patients as guinea pigs and try out  all these expensive and unproven experiments on them. Even worse, they charge their patients an arm and a leg for carrying out treatments which have not been  proven to be effective.

Yes, doctors would also love to attain certainty, and this is great if you're a researcher in a laboratory where you want to explore reproduction and embryo implantation in a mouse model - after all, that's the job of a researcher. We need to advance our understanding in the laboratory so we can apply this in the clinical setting.

However, clinicians should not be doing this kind of research outside of clinical trial, and it's completely unfair to patients who are being used as subjects of clinical trials.

Doctors add insult to injury by charging them for interventions which have not been proven to be effective in clinical practice, Not only do doctors need to shape up and improve by being more open and transparent with their patients, patients also need to start pushing back when doctors suggests these tests and treatments ! Please ask for medical journal articles from reputed medical journals, which prove that the .treatment being offered has been proven to work in a controlled clinical trial !

Want to make certain your doctor is giving you good advice ? Please send me your medical details by filling in the form at www.drmalpani.com/free-second-opinion so that I can guide you !

The ovarian rejuvenation scam using PRP

I had this email conversation with a patient recently

Greetings. Writing to you from Mumbai. I am 40 years old with an extremely low AMH  and regular periods. Wanted to find out if you are doing ovarian rejuvenation using PRP ( platelet rich plasma) ? If yes, how do I go about getting in touch with your team ? I know doctors are doing it in Gujarat, Hyderabad and Chennai but not sure if anyone is doing this in Mumbai. Kindly revert at the earliest. 

I wrote back to her :

This is now the latest scam in IVF and reproductive medicine. Doctors offer to inject autologous "stem cells"  ( derived from the patient's own blood) into the ovary, with the promise that this will "rejuvenate" old ovaries and get them to start producing young eggs again.

Doctors are promising older women that they have now found the "elixir of life", and will be able to help them to have a baby, even though their ovaries are no longer producing any eggs.
The truth is that this just does not work, and these unscrupulous and unethical doctors are taking their patients for ride. They are using them as guinea pigs - and even worse, charging them for the privilege of serving as experimental subjects !

She replied :

Dear Dr Aniruddha,

Thank you so much for replying. My husband is also not a fan of this experimental treatment primarily happening in Greece, California, New York and a few places here and there. He doesn't believe in it. But Dr I am a part of a patient community and online forum, and lots of ladies who have  done PRP claim that their hormones have balanced out , and their AMH has also increased. Maybe it's a temporary increase , but I am really tempted to try it. I have even heard about PRP done in the endometrium, which helps strengthen the lining. My husband feels that this is just a fad and I should not go for it and stick to tried and tested fertility treatments but I am still confused with all this information coming by way. 

This was my reply :

Don't trust everything you read on online bulletin boards ! Many of these so-called patients are actually agents of the IVF clinic , who are paid to post positive reviews for them. The reviews are false and designed to deliberately mislead.
Please use your common sense ! If this really worked, then wouldn't all IVF clinics offer the treatment to their patients ?

The problem is that it's easy to take emotionally vulnerable , desperate patients for a ride - after all, hope lives eternal in the human breast !

Patients will continue getting cheated by crooked doctors out to make a quick buck at their expense, because good doctors don't speak up against these unethical and unproven practices ,and allow their patients to be duped !

Why are we seeing an epidemic of new IVF clinics in India?

There seems to be a new IVF clinic starting in practically every nook and corner in every town in India. Why this sudden spurt of IVF clinics coming up all over the place? Is it that the number of infertile couples has increased so dramatically that the requirement for IVF has gone up so sharply?

The reason is actually far more crass and commercial. Senior obstetricians and gynecologists who are tired of delivering babies and hysterectomies want to do something new and different and cutting-edge. Many think IVF is a very lucrative field, and rather than referring their patients to an IVF specialist and  losing all that potential income, they feel, "Why don't I just start an IVF clinic myself? After all, how difficult could it be? I've been a gynecologist for so many years, and with my expertise and experience, I am sure I could IVF equally well ! "

Because so many gynecologists want to get on the IVF band wagon, lots of companies have sprung up which are happy to help gynecologists to set up their own IVF clinics. They do this on a turn-key basis, and their charges vary from Rs 10 lakhs to Rs 1 crores, depending on the pay capacity of the gynecologist. This means that you make your payment, and you have an IVF  laboratory set-up for you in a few weeks !  You then just have to attend a workshop, or two, get trained in doing IVF in a few days, and you can call yourself a gynecologist and IVF specialist ! No one can stop you from doing this in this great country of ours, because no one really checks to see whether you have the adequate training ; skills ; experience ; expertise; manpower; or equipment to actually do the IVF for your patients. Once you are ready to go, since you are a practising gynecologist, you already have a captive patient population, and can start doing IVF on them .  In India, it's perfectly acceptable to use your patients as guinea pigs - they are trusting and naive, and don't know any better. And if you want, you can always hire a traveling embryologist and a visiting IVF specialist to come and do the IVF procedures for you, if you don't want to do them yourself !

As long as you're making money, everything's hunky dory , because no one really cares about your success rates - and no one is going to check them ! The tragedy is that this has been going on now for many years now, and the pace has been accelerating over the last four or five years. Sadly, medical colleges don't provide IVF treatment to their patients, which means most MD gynecologists don't have any practical exposure to doing IVF, or even seeing IVF patients.

Finally, it's the poor patients who end up being been taken for a ride . They don't understand any better, and they assume that any doctor who calls himself an IVF specialist must be a good doctor, especially when they're so senior and have been practising a gynecologists for so many years. Sadly, the government of India has turned a blind eye to this exploitation of infertile couples, so that even though the Indian Council of Medical Research is supposed to regulate IVF clinics and make sure that they have the equipment and expertise which is required, they do this purely on paper only.

Most IVF clinics in India do not have the infrastructure or manpower needed to do IVF, and the majority have not even bothered to register with the ICMR, and yet they continue functioning merrily. The Law which was supposed to regulate IVF in this country in order to protect infertile patients is still on the back-burner, and no one knows when it's ever going to be passed. As a result of this, infertile patients continue being taken for a ride, and this is tragic , because doctors who should be speaking up are all keeping quiet, because we don't want to speak any ill of our colleagues.

Indian patients cannot rely on either the government  to protect them; or on doctors to regulate themselves. They need to learn to ask their doctors pointed questions about the IVF treatment they offer , otherwise they will continue being exploited.

The good news is that you need to ask only one question to find out if your IVF doctor is any good. The simple question you need to ask is - Do you give photos of embryos before transferring them ? If the doctor says no, this is a red flag , and means this particular laboratory is not well equipped. If you don't want to get cheated, you need to find someone else !

Need help in getting pregnant ? Please send me your medical details by filling in the form at www.drmalpani.com/free-second-opinion so that I can guide you !

Patient reviews about Malpani Infertility Clinic

We are thrilled when our patients have nice things to say about us !

https://www.tellofy.com/brand/mumbai/malpani-infertility-clinic-shahid-bhagat-singh-road-colaba

Is it worth transferring poor quality Day 3 embryos into the uterus?

Some patients will end up with all their embryos being of poor quality on Day 3, and then they're not certain what to do. Traditionally , most doctors will want to put all of their embryos back into the uterus as quickly as possible , no matter what their quality.

After all, once they've done an embryo transfer, they can tell the patient, "Look , I completed your IVF treatment, and have done everything humanly possible " , so the patient is happy that the doctor did a good job. Of course, it's highly likely that the cycle will fail, but then they can say - Yes, your embryo didn't implant, but that's your bad luck/ kismet/ karma. We now need to study the reason for the failed implantation, so we will run additional tests, so we can improve the chances of embryo implantation for the next cycle."

Unfortunately, this just creates false hope for the patient , and causes a lot of harm.  After all, we know that the chances of poor quality embryos implanting are very poor, and that the reason for the failure was the poor quality of the embryos. However, after the failure, they convince the patient to go through a battery of very expensive, exotic tests , to check her uterus and her immune system, to make sure that her body is not "rejecting" her embryos. These don't provide any useful information at all, but it's not hard to take IVF patients for a ride, because they are so emotionally vulnerable .

So why do doctors do this ? This is because they're not confident about the skills of their own IVF laboratory. However, it's easy to justify transferring on Day 3 ( and even Day 2) by telling the patient - Rather than throw the embryo away, isn't it better to at least put it back inside your uterus ? This way you have a chance, even if it's low?

Ideally, these embryos should be grown to day five blastocysts, and if they arrest in the laboratory before this point, then there is really no point in doing an embryo transfer at all. After all, once the transfer has been done, we create false hope  in the patient, because she's optimistic that she may get lucky and the cycle may work for her. When it doesn't , she is heartbroken , and her willingness to start another cycle drops dramatically , because she has lost confidence , either in the doctor and in her own body.

Much more importantly, the ability to learn from the IVF cycle has been wasted. After all, once you put an embryo back in the uterus , you have no idea what's going to happen to it. On the other hand, if it's in the incubator,  we can monitor it. If it arrests, we can at least tell the patient, "Look , this is the reason why you are not getting pregnant". We can analyse this intelligently, so we can focus on what's important , which is usually the quality of the egg , rather than worry about uterine receptivity.  The truth is that the uterus is usually a passive recipient, and it's very rare that the uterus is the reason for failed implantation, especially when poor quality embryos have been transferred.

So why send patient on a wild goose chase? Why not be upfront and honest with her? This is because most gynecologists don't understand much about embryology , and they don't have full time qualified embryologists who are able to grow embryos to day 5 routinely in the lab. This is because many of them depend on traveling embryologists, who don't have the time or energy to culture embryos all the way to day five. Taking all these shortcuts ends up harming the patient.  Yes, of course patients do get pregnant after Day 3 transfers, but these are good prognosis patients, and it's not right to confuse the two.

Yes, if the embryo arrests in the lab , this does cause a lot of short term heartache, but it gives us valuable information , so we can make changes and maximize the chance of achieving a pregnancy in the next cycle. Patients may have to suffer some short term pain to achieve long term gains.

Need help in getting pregnant ? Please send me your medical details by filling in the form at www.drmalpani.com/free-second-opinion so that I can guide you !

The stem cell therapy racket in India

The stem cell therapy racket in India from Dr Aniruddha Malpani

This is the presentation I gave at the Academy of Clinical Embryologists of India Conference held recently in Hyderabad, India