Dr. Firuza R. Parikh, fertility specialist and Director of Jaslok-FertilTree International Fertility Centre felicitated with Sohrab Pirojsha Godrej Science Technology Award
Thank you very much for this honour. This will have a very special place in a house, in a home, and in my heart. Thank you, Ramesh. You sent me a call, and then Anand followed up and asked me for this. I was delighted, and so was my family. I would like to thank Ms. Bhumgara, Mr. Israni, and all the members of the awards committee. I would like to thank the management of Jaslok Hospital, who have always been very patient and encouraging, and the management of Sir HN Reliance Foundation Hospital. I would like to thank all the members of my team because without them, there would be no award. I would also like to thank my patients for the faith they instilled in us, listened to us, argued with us sometimes, sometimes been happy, sometimes been sad. That’s a part of life, that’s a part of IVF and, of course, without my family, I would be nobody.
Two of my family members are here: Dr. Rajesh Parikh, who is a leading neuropsychiatrist in India, and my son Swapneil, who’s a physician, and he also concentrates on those who are looking for longevity and correcting lifestyle disorders. So, I’m first on your list, Swapneil. If you create something for longevity, then promise your mother you’ll make her live for 100 years.
Now, there’s a beautiful movie called Joy on Netflix, and I would urge you all to see it. It’s the actual story of the evolution of IVF. There were two people and a third one, and the third one, to whom new credit has not been given, as happens sometimes to women. There was Bob Edwards and Patrick Steptoe, a surgeon and a biologist, and there was a nurse called Jean Perdue. They formed a team, and from the 60s, they were looking at how to create life. All their experience came from animal work. Remember, most of the things in IVF or any kind of bioengineering or biology first start with animals, and Jean Perdue gave a lot of inputs and ideas, which led to the birth of Louise Brown, Louise Joy Brown, in 1978.
Unfortunately, Louise was not given credit, even for the Nobel Prize. Her name was not mentioned, and Jean did not get mentioned, and then she passed away through cancer very early in life.
So, just to give you an idea, only look at the ones that are blue in colour. Bob Edwards first ideated about IVF. Before that, of course, Watson and Crick presented the DNA molecule, and it took more than 20 years to have the first IVF baby in 1978. Simultaneously, there were people all over the world, particularly in the UK, where they started looking at embryos, which were aid cells, which were DeFi, and started biopsying them. The first genetic testing of an embryo, which resulted in a baby where there was a genetic defect in the mother that was passed on, was carried out by Handyside. So, the UK was the springboard for IVF and from there, it spread to many places.
Now, by the mid-80s, IVF was picking up all over the world, including in the United States. Then started the era of testing the embryo. OK, we have succeeded now in making babies, but we don’t want to have abnormal babies. Every parent, every couple desires a healthy child.
And that is when pre-implantation genetic testing came in, and there were many, many developments, many, many techniques which started with simple techniques to next-generation sequencing, which today is used for many, many issues. There is some called monogenic disorders and polygenic disorders. Monogenic will only test for a particular gene, like a gene for thalassemia. Now, there is somebody called Nathan Treff, who is in the USA, and he’s trying to do what is called polygenic diseases. It’s not just looking for one gene but looking for diabetes, depending on ethnicity, looking for people who will be more prone to blood pressure, and heart disease. It’s not a very scientific platform now, but he’s getting there. And over the next 10 years, we may have some cures for children, where we may be able to eliminate polygenic diseases before the child is born, or before the child is implanted.
We all know that chromosomes have DNA. DNA will have thousands of genes, and it is when either a small part of the DNA goes amiss, or some genes are either missing or mutated, that we get problems with the baby. This is also responsible for many kinds of cancer. So, abnormalities can occur if there are abnormalities at the sub-microscopic level of the DNA, or even when a chromosome—we are all born with 46 chromosomes. If a chromosome is absent, missing, or partly deleted, then problems can occur.
What can chromosomal abnormalities cause? It can cause miscarriages, infertility in the male and the female, multiple pregnancy losses, ambiguous genitalia (meaning it may be difficult to know whether a baby is born male or female), and many others, like women going into early menopause. Some women never see a period, and that may be because one of the important chromosomes, one of the two X chromosomes, may be missing, and that is called Turner syndrome. Today, we have the technology for fertility preservation, by taking out one ovary of a child who has this, keeping it aside, taking out the eggs, because in Turner syndrome, the eggs vanish very fast. So, today, we have this technology. In fact, the first baby has been born to a girl with Turner syndrome by preserving her ovary and using it when she wanted a baby.
I’m going to concentrate on two things right now. One is the genetic testing of embryos, and the other is fertility preservation because both of these are of great value to infertile couples. Here, you see on the right, a fully formed embryo, and on the right side, you see a pipette. Now, this pipette is thinner than human hair—much thinner, 30 times thinner than human hair—and what it will do is it will take out a few cells from the placental side of the embryo. These then can be subjected to testing and can tell the doctor whether this embryo is safe for implanting back, whether it is abnormal or normal. The faster you put a normal embryo back, the better the chances of conception.
Now, these are beautiful embryos, but sometimes a beautiful embryo may be genetically abnormal, and you may say, “Oh, I want to transfer the one in the lower row, the second one, because that looks very nice,” but it could turn out to be abnormal. So, what genetic testing will do is enable us to put in what looks like a good embryo as well as a genetically normal embryo. So, that is Dr. Prochi Mandal, my colleague. She’s a superb geneticist of great standing. We started PGT, preimplantation genetic testing, at Jaslok Hospital way back in 2000. This is our entire team. Some people are missing, but we have a team of about 50-plus people at Jaslok and another 10 at HN Reliance, and each one is a specialist in what they do. Whether it be the nurse, the social worker, the psychologist, the psychiatrist, or the embryologist, they are all world-class, and they are completely dedicated to the treatment and completely compassionate in helping couples to have healthy children.
So, what is important in IVF is to have a team. You have to have compassion, you have to be vulnerable when you listen to patients, and you have to be dedicated. In our team, we have no Sundays, no holidays. We work all days of the week. Of course, we do it in turn so everybody gets a break and rest from work. So, we started in 1999-2000, and then we quickly had a lot of firsts in India with looking at chromosomal abnormalities in children.
Let’s briefly touch upon some haematological disorders. The two I want to talk about are thalassemia, which can be very devastating for the family, and sickle cell disease. Now, sickle cell disease you’ll see in central India, Madhya Pradesh, and Nagpur—those are the regions where sickle cell disease is very common. Sometimes we have a young couple, I’ll just give you an example. Someone was 28-29, got married, obviously didn’t test because it was an arranged marriage, and they got married very quickly. They conceived fast, and the child had thalassemia major.
Now, thalassemia major is like… I won’t say it’s a death warrant, but it has a lot of obstacles. One child with thalassemia major, through the entire lifespan—which may be short—the cost of giving blood transfusions, hospital admissions, and chelations comes to about 90 lakhs. And, of course, the Thalassemia Society of India looks after some of them, but these children need blood transfusions every two weeks, once a month. So, it is very devastating for the family. So, what we did is we started screening the patients, and those who were carriers for thalassemia, we have ways by genetic testing to make sure that the embryo which we are going to put in is not a child who will carry thalassemia major.
So, this is something which is not just infertility, not just helping someone with infertility. These are fertile couples, but they are faced with such problems. In India, 10,000 children are born every year with thalassemia major. So, imagine the burden of disease on them.
This is a very sweet couple. What happened is their first child had thalassemia major. Now, they were very well-read, they had researched how to save this child and have another baby. So, they came to us, and there is something called looking for an embryo which is free from the thalassemia gene and is matched in certain genes, which are called the HLL genes, with the baby with thalassemia major. So, we did multiple cycles, and imagine we just got one embryo out of so many embryos that we created, which was free of thalassemia plus matched the older sibling. And it was quite an effort. It took us almost 8 to 9 months to get that one embryo, which was free of disease. When the younger child grew up, he donated his stem cells to his sister. He is called a “saviour sibling,” and the sister now is completely cured. She dances, she sings, she plays with other children—no more blood.
So, of course, many will say there are certain moral issues—you’re using somebody else to help another. I personally feel that these are certain issues that we have to overcome because, after all, we are helping another human being, and this is called a “saviour sibling.” The sibling saves the life of the older sibling. There are women who carry the BRCA1 and BRCA2 genes, and we know that they are responsible for breast cancer, ovarian cancer. If the man carries it, he can be afflicted with prostate cancer and breast cancer.
So, we had a couple, again a young couple, who knew that the wife had BRCA1 and BRCA2 mutations, and her family had a whole history of breast cancer and prostate cancer. One of the uncles also had breast cancer. So, we did the PGT, we did IVF, we did the PGT, and we managed to get embryos that were free of the BRCA1 gene. She insisted on putting in two embryos free, and luckily, she got twins. Now, this was in 2018; now this is very common. This is what we do day in and day out. So, there are many malignancies, there are many diseases that we can take care of.
And this is just to enlist some of the monogenic disorders where we have helped patients: haemophilia, G6PD, TASAC syndrome, retinoblastoma, and many others.
Okay, now let’s come to fertility preservation. Why is fertility preservation important? It can be done in men and in women. In men, we can freeze the sperm, we can freeze testicular tissue. In women, we can freeze eggs, the embryos, the oocytes, and now also at the Reliance Foundation Hospital, we can freeze ovarian tissue. This is a new technique that we have introduced for the first time in India, and it has benefited a lot of women.
So, there is a biological clock, tick-tock, tick-tock, and women start hearing it by the age of 36 or 37. So, that is why we say that you should respect your biological clock and please have your first baby by the age of 32 or 33. Even if a woman cannot have a baby by 32 or 33, please freeze your eggs or please freeze your embryos. Women say, “No, we are too busy with our work, and I’m rising on the career path, and I’ve not found a man of my dreams.” I’ve met many men during the day, but I’ve not met a man of my dreams, so I cannot get married right now. So, this is the tick-tock, tick-tock that goes on.
So, can we hold the biological clock? Yes, a 30-year-old woman can gift herself, at the age of 40, her 30-year-old eggs, if she does the freezing of the eggs or embryos at an early stage. So, we can freeze eggs, we can freeze embryos. There are different techniques: there’s something called slow freezing, there’s something called vitrification, and the results of thawing the eggs and embryos are excellent. Almost, there is a 95 to 97% fertilisation rate and recovery rate and very good pregnancy rates. Practically every day of the week, we get at least one girl in her early 30s, mid-30s, or even late 30s come to us for egg freezing or embryo freezing. There are married couples who say, “We don’t want a baby now, but as biological insurance, we want to freeze the eggs or embryos so that we will be safe later on.”
And this is what we do in terms of freezing the entire ovary. For women who are afflicted with cancer and who have to start chemotherapy very soon, we don’t have that luxury of time to freeze our eggs because freezing eggs requires hormonal treatment. So, what we can do, before the chemotherapy starts, is remove one ovary, slice it into tiny pieces by a special technique, and freeze it. When the woman goes into remission, this is just a cartoon which shows that the ovary is removed by laparoscopy and then it is frozen.
When the woman is cured and the oncologist declares that now you are safe to have a baby, this can be put back by laparoscopy into her body.
Now, fertility preservation in males. I must share with you that there are so many men affected and boys affected with cancer, particularly testicular cancer. And somehow, oncologists and urologists don’t seem to be sending them as much as they should.
Also, the return rate for someone who freezes his sperm, the return rate to come back to use it is very low. I have failed to understand because sperm freezing is such a simple concept. So, I always urge doctors that if you have a patient who is a young boy, please send him for sperm freezing. It is not expensive. It hardly costs 7,000 rupees to freeze the sperm. Then, that becomes the biological insurance. For very young boys who are still not having mature sperm, one can even freeze testicular tissue.
So, this is particularly for cancer. In boys who are young, we can even take a piece of the testes and freeze it so that we can derive the stem cells later on and use them. So, this is a picture of the egg and the sperm. They are floating around freely, but our dream is to make sure they get together and produce a healthy baby.
Thank you very much for your patience.
ROTARIANS ASK
You mentioned longevity. A friend told me that amniotic fluid is the best condition for longevity too, if you can recreate it later. But my question is, has the government abolished this surrogacy? Why is that? If I am a woman and I am earning money, and now someone directs me, I mean, I don’t think it’s fair. And why is there the proclivity to have twins when you do IVF?
So, we’ll address your second question first. If you put in two embryos, then the chances of getting twins are higher. Very rarely, an embryo will split in the uterus and give what is called monozygotic twins, so that answers your second question. The first question is surrogacy. Now, I don’t have an answer to your question because surrogacy today is the need of the hour for women who don’t have a uterus, who have immunological conditions, who are diabetic, who are hypertensive, who have abnormalities like fibroids—so many conditions where the woman just cannot carry the child. Now, the government has put in some regulations which are not bad, but what happened is there were some clinics in India which were not doing things the right way. So, because of a handful of clinics that were exploiting the surrogates, the whole programme got closed, and it affected not so much us. I have a patient right now who doesn’t have a uterus, and she’s producing eggs. So, how is she going to have a baby? She had her one child with us via surrogacy. Now, she still has embryos and she’s desirous of a second child, but the Indian law does not permit her to have another child. So now, she’s taking the embryos from our clinic and moving them to, I think, Tanzania or someplace like that, Georgia or Tanzania. So, these are certain things that, unless there’s a drastic change, unless patients are going to, you know, put their foot down and represent themselves, I don’t think it is really—I have a feeling surrogacy is going to see a slow death in our country.
So, I have friends in the US who are both from Bombay, and they are both darker-skinned to wheat-skinned people. They had a surrogate baby using a white American mother. And the child is extremely fair, almost looks like a white person. And so, I was wondering whether the actual mother’s genetic composition affects the embryo, or is it just totally of the original parents?
So, what happens is traditional surrogacy does not allow the use of the eggs of the surrogate. It can either be the biological mother’s or it can be a donor egg, which has been fertilised with the father’s sperm. Nothing of the surrogate, not even her blood, will go into the baby because the placenta forms a partition which will only allow the oxygen and the nutrients to go to the baby, not even the blood.
But you know, Doc, just taking off from his point, I read somewhere that it is possible to have Instagram babies. You can modify the genetics to get a particular jawline, get a particular texture, complexion and things like that.
So, it can be done, it should not be done. There is a whole area of polygenics coming up where one can eliminate diabetes and heart disease, but it is still a dream. It has not reached the point where, say, if there is a monogenic disease, you can cure that single gene disorder.
As a disclosure, I have a granddaughter who was IVF, and the product is fascinating. But the whole process of having a baby cost us half a million dollars. All this costs money. So, would you please?
Very good question. Let me tell you that if they had come to India and done the IVF with us, it would have cost them Rs 2 lakhs.
Such interesting bits of information regarding fertility and surrogacy today. I feel very strongly about this subject. It’s very personal to me. I wanted to know—you touched upon stem cells. And whenever I tried to get information on stem cells, it’s usually shut down by a lot of medical professionals. And I wanted to know what your opinion is on the success of stem cells in relation to cerebral palsy in particular? And also, who would be the appropriate authority to go to, to get more information on the same?
So, good question, and I know how involved you are with this, Ami. Stem cells gave a lot of hope in the early 2000s. In fact, we had one of the early embryonic stem cell lines, which were recognised by NIH at Reliance Life Sciences. But they did not hold that promise. Today also, there is, of course, a lot of work going on. There is work with insulin-like stem cells, which produce insulin. There is work with cardiomyocytes. But this is very slow. So, you really have to be very careful whom you go to for help and understanding because there will be many people—not to say that there aren’t very good stem cell experts—who can exploit innocent patients. So, you have to, now, there are data banks where you can get in touch with a particular disorder. And this is what you should be looking at: good sites, which are, say, vetted by NIH, vetted by certain people who are very strong in stem cells. See, stem cells will do something good. But as of now, there is not much in terms of cures. But it is moving along very slowly.
And do you think that it’s worth it to have the stem cells stored? Because, in the future, there is a possibility of huge success.
So, it depends on what is stored. Whether they are umbilical cord stem cells or mesenchymal stem cells from the umbilical cord, the jelly—what is the source?
Teeth, because there’s a lot of advertising on dental stem cells.
Not that for sure. No, I had a patient many years ago who had lost her son in a car accident, about an 18-19 year-old son, and she came to me with one tooth, saying, “Now take this and make my baby.” So, there are very high expectations of false expectations. We have to step very cautiously in some of these areas.
There is the saving of an umbilical cord at the time of birth—that itself is debatable. Some doctors say, “Don’t go for it,” and some people have been keeping them, freezing them. If you can throw some light?
When my patients ask me, I say, “Look, we don’t know the utility today, but it may have some utility after 30 years, so there is nothing wrong. It’s a tissue which is available to you, please save it.” As of now, all the stem cell banks are just storing; they are not really doing anything in terms of turning these umbilical cord stem cells into a product, although there is a very big repository and a very big data bank with most of these stem cell banks. If a couple comes to me and says, “I am spending 80,000 rupees on these cord stem cells, should I do it or not?” I will say, “Do it. We don’t know its value today, but it may be very valuable, I will say, 30 years from now.” There is no immediate utility. Like I talked to you about the ovarian tissue freezing. It does not have immediate utility. It’s only when the woman will be cured of her cancer, the oncologist will say that now you are fine, will the thing be put back. But that may be how many years from now?
Would you say it’s wise for newlyweds to come and get this genetic testing done and see if there are any abnormalities, and then you would take only those embryos which are good or safe? Do you think it’s wise for most people to do that?
So, most people now are doing prenups, but I will not advise them to do the full genetic screening. Of course, if they are from areas where thalassaemia is very common, it’s not a bad idea to do the thalassaemia screening. It’s a simple blood test.
But what about cancer?
No, so ma’am, I would not ask anyone to screen for cancer because there are so many multifactorial things. Somebody may have a gene, but it’s not necessary that this gene will be expressed. There are so many things leading to cancer. So, somebody who is getting married, of course, if there’s a very strong family history, then it may be worthwhile for that individual to be protected. Like, if somebody has a history of colon cancer, then their children can do the colonoscopy, can do some screening by the age of 40. Because if the cancer has shown itself at the age of 50, then the children’s progeny should do testing 10 years earlier.
I’m talking about their children—whether they should do embryos, so that, you know, their children don’t get cancer.
Yeah, so if somebody has done a profile or has the history—not everybody—but suppose there’s a very strong family history. Like I showed you, the woman who had BRCA1 had four family members, two with breast cancer, a male with prostate cancer, and one male with breast cancer. Yes, so she did the right thing. She did her profile, and when she had the BRCA1 present, she opted to select embryos that were free of the BRCA1 mutation.
So, what I sense is that in 10 years’ time, maybe less, genetic screening, looking at the clinical exome, all that is going to be very common. We will not raise eyebrows if somebody wants to do the genetic profile.
My question was on thalassemia. You said 10,000 cases come up every year, and this is something that can be controlled because I’ve dealt with kids at Wadia Hospital who have thalassemia. Why is the government, through their programmes, not building more awareness in colleges and amongst the youth that they have to, before they get married, be tested in each way? Why would we reach this? It’s controllable. The main thing is it’s controllable. So why is this not happening as a medical community or as the government participates in this?
The way to catch children or couples is in schools and colleges. Like if there is a programme for checking children’s haemoglobin to see if they’re deficient in iron. This is a very good idea. There should be societies. There should be organisations, NGOs who can test. Because of the burden of somebody having thalassemia major. And it is heartbreaking. When these couples come with the child, it is heartbreaking to see the child. Every two weeks they are taking the blood transfusion.
CIPLA is the only one supporting the whole thalassemia…
Yes, like for HIV they have cut down the cost of medication.
Maybe Rotary can help take up a small project on this, you know schools, municipal schools and you can tie up with a lab which can give us a lot of concessions to do this testing. It’s a very simple test. First of all, if somebody is thalassemic, just doing the haemoglobin is carrying the thalassemia gene, not fully thalassemic, haemoglobin will also show. Also, haemoglobin testing is very cheap, Rs 50. So it’s something that can be considered. I hope from this talk, if even this comes out, it will be a great boon to society.
President Satyan Israni – I think we will give it a serious thought, we will come and ideate with you and plan something out definitely.
I have a relative who is getting married to a boy with high diabetes, he takes insulin every day. Can there be some tests to prevent children getting diabetes?
Swapneil, why don’t you take this question?
Swapneil: So when we talk about diabetes, there are different forms of diabetes. Broadly, we can categorise them into four. So the first being one which is insulin-dependent. And this is an autoimmune condition where the body’s immune system attacks certain cells in the pancreas that help the body produce insulin. The second is where there’s a relative deficiency of insulin because the body has become resistant to insulin. This generally, in the earlier stages, does not require insulin and can be fixed with lifestyle, dietary measures, and occasionally medications, but can progress to requiring insulin. The third is a type which is just inherited from the family. There are many different subtypes in this. And the fourth is finally diabetes that occurs in pregnant women of different aetiologies. So we have to contextualise which one we are talking about.
For the first one, actually, there is a lot happening to kind of prevent that autoimmune destruction of the islets. And even in people who’ve already had it, re-implanting islets that can kind of make them live a normal life. In terms of the second, there is already work happening. I think Dr. Firuza Parikh talked about this a little, where it’s possible with genetic screening in the future. The more common types may be able to be avoided. For the third, again, there is a possibility that with genetic screening, this can occur in the future. And in the fourth, we’re very far away from that right now. So yes, possible, but with the very, very early stages of clinical research on this, it is going to be some time before this can actually go into clinical practice.
The thing that’s closest to long-term progress is not actually preventing it, but curing diabetes. So there’s someone, we met one of my mum’s colleagues, and what they have devised is a very interesting membrane that allows pancreatic tissue to be placed inside it. And then that membrane can be implanted into the body. And it allows insulin and glucagon and other important hormones related to diabetes to pass through. It allows oxygen to pass through and nutrition, but it does not allow the body to mount an immune attack on those cells. So you don’t need to immunocompromise the person. You don’t need to give them drugs so that they can tolerate it. And that is possibly the closest we are, for a cure for diabetes. The other cure has existed for a long time, which is weight loss and eating right.