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Mr and Mrs Swamy have lived for most of the 12 years of their blissfully wedded life. Not so blissful it turns out to be, for each time Mrs Swamy’s pregnancy wouldn’t last more than six-seven weeks. The Swamys tried for a baby seven times using a process called Intrauterine Insemination (IUI), which entails placing a sperm inside the uterus to facilitate fertilisation. They also tried in-vitro fertilisation (IVF) in the UK and India; another process in which the egg is combined with sperm outside the body. Mrs Swamy failed to get pregnant. The Swamys, now based in Australia, then flew to hometown Chennai to meet Dr Geetha Haripriya at Prashanth Fertility Research Centre. She started a fresh round of investigations that revealed aneuploidies (presence of an abnormal number of chromosomes in the foetus) in Mrs Swamy’s case. She had no family history of chromosomal abnormalities and the doctor attributed her age as a contributing factor to her condition. Dr Haripriya recommended intracytoplasmic sperm injection (ICSI) to enable fertilisation and subsequently preimplantation genetic screening (PGS) for the embryos. In the next IVF cycle, 11 embryos were screened using PGS at MedGenome Labs in Bengaluru. The report recommended the best embryos for transfer to Mrs Swamy’s womb with happy results and the stork visited them in May.
Forty years ago to this week, the first IVF baby was born in India. On October 3, 1978, Dr Subhash Mukhopadhyay and his team in Calcutta had delivered happiness to the lives of a childless couple in the adorable form of Durga, brought into the world using the revolutionary method. Dr Mukhopadhyay, a pioneer in the world of fertility research, had created history because Durga is only the second IVF baby in the world.Infertility is spreading at an alarming pace in India, especially in metros. It is estimated that of the 60-80 million infertile couples that are yearly recorded across the globe, between 15-20 million are in India. Doctors say the stigma of barrenness is curable and infertility is like any other medical condition. Dr Keshav Malhotra of Rainbow IVF, Agra, cites the case of a patient with a history of recurrent IVF failure. He used two of the latest technologies—embryoscope and PGS—to generate a pregnancy. Embryoscope provides digital images of the embryos every 20 minutes through unprecedented details of early embryonic development that help select the best ones for transfer.
IVF is a process of pain and gain with a hefty price tag. It involves the use of advanced medical techniques and procedures on women with abnormalities of reproductive organs or genetic complications. But it is easier said than done. “For any IVF specialist, success is about bringing a baby home. It is done first by increasing the pregnancy rate and secondly by reducing the miscarriage rate. I start with a thorough initial consultation to understand the couple’s journey. Only then can I provide personalised care and choose the perfect treatment,” says Dr Narmada Katakam, Medical Director, Genesis Fertility & Laparoscopy Centre, Hyderabad.
The myths around infertility treatments are legion. Some of them are outright ignorance: infertility is a female problem; women of all ages can become pregnant through IVF; IVF results in multiple babies and herbal supplement is enough to give a woman kids, are just some of them. Breaking the popular misconception that IVF has a low success rate, Dr Aniruddha Malpani of Malpani Infertility Clinic in Mumbai, says, “It’s an effective option if done properly, and millions of babies have been born the world over with IVF. And they are healthy and normal.”
A latest Ernst & Young (E&Y) report records high prevalence of infertility affecting nearly 10-15 percent of married couples in India, of which women account for 40-50 percent. Infertility attributable to male factors is on the rise and constitutes 30-40 percent of the segment. “Factors such as poly-cystic ovarian syndrome, blocked or damaged fallopian tubes, the ovarian tissue disorder (endometriosis), low sperm quality and quantity, lifestyle changes, stress and marrying late contribute to infertility. In the past two decades, there has been considerable progress. However, IVF does not have a 100 percent success rate,” says Dr Haripriya.
Only 1 percent of infertile couples in India seek treatment, says the E&Y report. It highlights the rise in the population of women in reproductive age (20-44). This proportion could go up by 14 percent between 2010 and 2020. The climb is skewed towards women aged between 30 and 44 (20 percent increase estimated between 2010 and 2020), who typically display lower fertility rates. This shifting demographic trend coupled with rising contraceptive use is likely to scale up infertility rates in India.
Age has an important part to play in conception. “The child bearing capacity of a woman begins to diminish significantly at 32. Once she reaches 35, the decline accelerates, and by 45, her fertility quotient has fallen by half. The female body is more vulnerable to pregnancy risks and birth complications at a later age. The sperm quality of men begins to decrease after 40. Even sperm mobility, a sperm’s ability to reach an egg and fertilise, diminishes. Hence, the number of IVF trials involving men over 40 is higher,” explains Dr Archana Dhawan Bajaj, who runs Nurture IVF Clinic in Delhi.
Tech to Rescue
The fertility treatment landscape has drastically improved over the years. The services at a fertility centre range from the simplest that involves IUI to the most advanced ones such as IVF,
IMSI (intracytoplasmic morphologically selected sperm injection), ICSI (intra-cytoplasmic sperm injection) and PICSI (a new method of sperm selection for ICSI).Today any IVF specialist is lucky to possess the latest techniques to combat the disadvantage of advanced maternal age, prevent unnecessary transfer of embryos, prevent and reduce implantation failure and give quick results. Dr Jayesh Amin, Director, Wings Hospital, Ahmedabad, who has been on the fertility treatment scene for over a decade and a half, says, “It is the age of personalised embryo transfer using pre-implantation genetic tests (PGT) that include screening/diagnosis (PGS/PGD) and endometrial receptivity array (ERA). This coupled with Day 5 embryo transfer has upped the success rate.”
Explaining the finer details of the two techniques, he says in the PGT method, a few cells from the embryo are analysed to determine the chromosomal number for mutations. The result allows the clinician to selectively transfer embryos which have a normal chromosome number and are free from disease-causing mutations.
PGT is the best cutting-edge mechanism available today to gauge the defect in the genetic material of an embryo. Of 100 women who fail to conceive through IVF, 75 percent have defects in the genetic material of their embryos. However, 25 percent cases are implantation-related, Dr Amin claims. He has a two-point advisory:It is necessary to discover any defects in uterine lining, or endometrial receptivity. Personalised timing of implantation called the window of implantation (WOI) should be carefully calibrated since it could differ from person to person.“We conducted the biopsy of the uterine lining of a patient to figure out her personalised timing of implantation, which turned out to be 87+3 hours.Surprisingly for all previous transfers at other centres, it was 124+3 hours, though all the embryos were healthy. We transferred morphologically and genetically healthy embryos during the personalised WOI, and she conceived,” adds Dr Amin.
The right embryo plays a crucial role in IVF where an estimated 60 percent of pregnancy losses are associated with chromosomal abnormalities in embryos. Performing genetic diagnosis prior to embryo implantation could prevent abnormal pregnancies. Various categories of hopeful mothers are advised this screening method. They are:
1. Women who suffered repeated implantation failure or recurrent pregnancy loss while undergoing IVF
2. Patients aged 35 years
3. Women with recurrent miscarriages after IVF
4. Women with a positive history of chromosomal aneuploidies in the family or are diagnosed carriers of chromosomal abnormalities
5. Or have a combination of some of the above factors
Explains Dr Malhotra, “IVF centres do not have all the necessary facilities to conduct the special tests and depend on labs like MedGenome. It is a genomics-driven research and diagnostics company that offers over 400 genetic tests across key diseases at its CAP-certified lab in Bengaluru. It also has the highest success rate throughout NGS labs in Southeast Asia,”
The miracle of motherhood, thanks to IVF, has touched the lives of women with biological disadvantages. Dr Kokila Sreenivas, Director, Sukrutha IVF and Hospital, Tumkur, recounts helping a 36-year-old woman who was born without an uterus but had ovaries become a mother using a surrogate. “The cysts in her ovaries were inhibiting the number of eggs being produced. Her ovaries were stimulated to grow follicles and using ultrasound guidance, her eggs were collected into which technicians injected her husband’s sperm. Then these embryos were cultured inside an incubator. Subsequently two of them were transferred into the uterus of a surrogate mother who delivered twins,” Dr Sreenivas chuckles.
IVF also works wonders for women with Turners Syndrome. Dr Katakam says, “The mucous membrane lining of the uterus of one of my patients was stimulated using hormones.” The membrane gets ready during the menstrual cycle in preparation for a possible implantation. Once it was thick enough, Dr Katakam’s team put her on IVF treatment and the woman became pregnant. She’s into her second trimester. Dr Katakam says pregnancy is not a problem in such cases, but the heart has to be carefully monitored using MRIs to check for signs of ‘dissection of the aorta’.
Freezing eggs is another infertility treatment option. The patient’s reproductive potential is maintained by extracting her eggs, which are then frozen and stored as a proactive way. Once she decides to be a mother, the eggs can be defreezed. Doctors believe egg-freezing works best for women diagnosed with cancer but have not yet started on chemotherapy or radiotherapy. It also works for women using assisted reproductive technologies and do not wish to freeze their embryos. Then there are those who are prevented from becoming mothers due to personal or medical reasons but would like to preserve their ability to bear children in the future. The egg-freeze procedure is gaining popularity among women in the late 20s or early 30s who are either not married or do not want a child at present. They live in Tier 1 and Tier 2 cities and are childless out of choice than default. Dr Katakam cites the case of a 19-year-old girl who was diagnosed with ovarian cancer and had one of the ovaries removed. “She chose to freeze her eggs at my centre well in advance. This will help her conceive when she is ready.” The doctor uses both embryo glue and laser hatching for the procedure. Both treatments are included in the package for every IVF cycle so that the patient isn’t burdened with high costs.
There are infertile men, too. A recent report established that nearly 50 percent of infertility issues in India are male-related. Some patients man up to admit it and take the treatment, but others have inhibitions.Smoking, alcohol, stress, working in high temperature regions, deficiency of minerals, micro nutrients and vitamins contribute to male infertility. Another cause is the presence of a varicocele—a venal enlargement in the loose bag of skin that contains the scrotum which commonly leads to low sperm production and quality. Remarkable advances in infertility treatments have happened in the past decade, which range from medication to new microsurgery techniques and advanced assisted reproductive technologies. Like women’s eggs, men can save their sperm for future use. “If a man wants to delay fatherhood, preserving fertility by freezing sperm is a relatively inexpensive way. An older man looking to conceive will find a semen analysis of shape and mortality can provide valuable intel into the possibility,” advises Dr Monica Sachdeva, Medical Director and Senior IVF Consultant, who runs Pravi IVF & Fertility Centre, a first of its kind in Kanpur.
The initial fertility evaluation for men is non-invasive and comprises a physical exam, semen analysis and blood work. A low sperm count can raise flags: it could mean potentially life-threatening diseases such as testicular cancer that are reversible provided they are diagnosed and treated on time.
On the other hand, azoospermia, or the complete absence of sperm, ails about 1 percent of all men and approximately 15 percent of infertile men. “Azoospermia can be divided into two broad groups: obstruction problem or blockage,” explains Dr Malhotra.
Until the mid-1990s, using donor sperm was the only treatment for azoospermia. A minor outpatient procedure called TESA (testicular sperm aspiration) may be offered to obtain sperm directly from the testes. If successful, the sperm can then be used with IVF/ICSI. “In some cases, a small incision is made in the testes and observations are conducted under a high power, operating microscope for swollen seminiferous tubules that contain sperm. The procedure is known as TESE (testicular sperm extraction) or micro-TESE and is considered the gold standard to increase the chance of retrieving sperms,” explains Dr Haripriya.
Prashanth Fertility Research Centre has introduced a breakthrough technology for super microsurgery under which seminiferous tubules are examined and identified as these have a much higher chance of containing sperms. Seminiferous tubules are where sperm cells germinate, mature and are transported within the testes. “The results are sent to the embryology lab for evaluation. If the tubules are found to contain sperm, they are preserved through freezing. The stored sperm can be later used for IVF procedures. This has proved to be a boon for men,” she says.
Folic acid, which is always advised for women as a preventive to certain birth defects, is now an important supplement in male fertility. “Researchers at the University of California have found men had a higher rate of chromosomal abnormalities in their sperm when their diet was low in folic acid. Coenzyme Q10 has also been found to increase sperm count and sperm mobility while Vitamin E improves low sperm count,” says Dr Rit Shukla, Scientific Director, Pravi IVF & Fertility Centre, Kanpur.
The E&Y report attributes low rates of infertility treatment in India to its high cost; each IVF cycle costs Rs 1.5-2 lakh, which often has to be repeated multiple times. Only 20 percent of desperate couples in India can afford them. There is a huge lack of skilled IVF specialists and embryologists in India. Only about 3-4 percent (700-1,000) of the pool of gynaecologists perform IVF procedures. The skewed geographical distribution of infertility centres further adds to the challenge. The study notes that 55 percent of all IVF cases in India are performed in the top eight metro cities.
The absence of a regulatory framework for quality management of ART centres and patient-safety has led to mushrooming of many substandard IVF clinics. Result is low success rate, coupled with a lot of pressure—emotional, physical, and even financial. As Delhi-based Supriya Sen recounts how she has been undergoing IVF treatment for four years, and in vain. “Every failed cycle breaks my heart. The process drains me physically and emotionally, and leaves me poorer by a few lakhs. I am still hopeful that one day the baby will make up for all that is lost. That reward is what makes me go through the pain of it every time I think of giving up.”
But the report has concluded that the IVF treatment market has the potential to grow by 20 percent as barriers to treatment are progressively addressed. “The IVF cycles are estimated to increase from an estimated 1,00,000 cycles currently to 2,60,000 cycles by 2020, driven by an increase in the number of infertile couples seeking treatment,” it says.
IVF treatment is expensive, and the patients need to doctor-shop, to find the clinic which offers the most cost-effective option. “Commercial IVF clinics often advertise their packages at the minimum costs and use this trick as a bait to lure patients. After signing up for IVF treatment, the patient realises that the costs of tests, scan, medications, medical procedures for IVF are hidden and not included in the basic package. When the cycle fails, the resentment is understandable. So the best deal is to ask for an up-front, all-inclusive package cost,” warns Dr Malpani.
The hordes of patients who throng IVF centres at metros come from Tier 1 and Tier 2 cities, but the mushrooming of IVF centres at such places has come as a blessing. The centres keep the affordability factor in mind. Dr Malhotra’s centre in Agra holds a free consultation camp for all female patients on the 9th of every month to support poor patients, and offers low-cost packages for IVF starting from Rs 75,000. It also does one free IVF cycle for such patients every month. On the other hand, Dr Sachdeva doesn’t insist patients undergo pregnancy check-ups at her centre. “We recommend nearby/native gynaecologists after three months of conception. However, our team keeps a complete check on patients personally,” she adds. Likewise, Dr Sreenivas harps on how her hospital in Tumkur is striving to provide advanced and good quality infertility services at an affordable price to rural populace. “Ours is a corporate hospital with rural pricing. Our pharmacy dispenses commonly used medicines at a discounted price. We routinely reimburse a part of the outpatient charges if the couple does not take the treatment in that particular cycle. If an IVF cycle fails, the patient can continue the subsequent cycles at a much lower cost. The registered pregnant women will get a discount on the delivery charges. Those with high-risk pregnancy who need prolonged hospitalisation will be given an option of hospital stay at nominal charges,” she claims.
The cost-effective IVF treatment makes India a sought-after destination for medical tourists from across the world. Dr Malpani’s clinic in Mumbai is thronged by patients from all over the world. “While those from neighbouring countries come here because Indian healthcare facilities are much more advanced, those from the Middle East and Africa say it is for sophisticated treatment options unavailable in their country. Medical tourists from the US come because treatments and procedures are far more affordable here while those from the UK find no waiting period a big reason for choosing India,” he says.
Lack of Regulations
Most centres still follow a secretive route with little transparency and complex detailing that collectively shakes the patient’s trust and confidence. The IVF scenario in India is astonishingly different from that in the UK as Dr Katakam believes after having been trained and worked there for 13 years. She started her IVF centre in India a year ago, but follows the rules that are in place there in the UK by HFEA (Human Fertilisation and Embryology Authority). On the main differences in practice, she says, “Most women are deficient in vitamins and iron, and sometimes simply improving their nutritional status helps them get pregnant. The ageing of the ovaries is another difference between women here and in the UK. Ovarian reserves are at least three years lesser for the age here.” But the starkest difference, she says, is how there are no regulations or restrictions on transfer of more than two embryos. “In the UK, the norm is to transfer only one, and two is an exception, and three is completely unheard of. There was a gory case that was presented at the European Society of Gynaecological Endoscopy Conference from India where a woman with IVF had one pregnancy in each tube (ectopic pregnancy), and triplets in the uterus. In the UK, for transferring two embryos, there has to be a justification, which include age above 40, previous three failed IVF cycles or miscarriages or no high-quality embryos in the cycle. And if the twin rate exceeds more than 10 percent, the licence is at stake. HFEA regulates fertility clinics in the UK, including licensing, inspections and setting standards to ensure high-quality care. In India, there are no such regulations, monitoring or any governing system, and that’s unfortunate,” she complains.
Going through the rigmarole of IVF cycle is a taxing exercise for a patient, and both the doctor and patient bear the pain of disappointment or share the joy if the dream comes true. Dr Archana Agarwal, Medical Director, Mannat Fertility, Bengaluru, uses the power of the mind to inculcate positive thoughts in a patient so that the patient can happily endure both pain and joy, and also find out the cause of infertility that is deep-rooted in the mind. If Dr Agarwal can’t do it herself, she sends her patients to a healer to ascertain the psychological cause behind infertility. “A lot depends on one’s thought process, and chance only favours a prepared mind. If one’s mind is open, and programmed to fill with positive thoughts to visualise success, there’s no way that IVF cycle will not succeed. It does.”
So, realising the dream of parenthood is just an IVF away.
The Genesis in India
On October 3, 1978, due to the pioneering effort of Dr Subhash Mukhopadhyay and his team in Calcutta, a girl—Durga—was born through IVF. It was the second such attempt in the world, a repeat of what his English counterparts Robert G Edwards and Patrick Steptoe had achieved barely days ago, on July 25. The news boded well for thousands of infertile couples, but there was no noise around the achievement. Perhaps because the couple chose to keep mum and didn’t want themselves or the child’s image to be shaped by the manner of conception. Battling ignominy and failure to be recognised for his monumental work led him to take his life on June 19, 1981. But recognition did come his way, posthumously, and 25 years after the birth of Durga, the physician was “officially” regarded as the first doctor to perform IVF in India. Later on August 6, 1986, Dr Indira Hinduja and Dr Kusum Zaveri helped deliver—Harsha—India’s first test tube baby.