A Proud Mother

On the way to her clinic, Avantika looked at her appointment list. The first listed patient was some Mrs. Nisha Singh.  There were four other patients in the list who were suddenly pushed down by this last minute entry. The hospital PRO Mr. Vishwajeet had informed her about the special nature of this patient. Mrs. Nisha was the wife of an influential politician. PROs are trained to flag patients based on their status in the society. An elite would automatically get a first seat in the queue and a visibly ill poor farmer will usually be the last.

Avantika worked with patients who look outwardly normal despite being chronically tortured with life. It is not possible to triage them. Not having a child is a hard situation. How can this be less hard for one couple than another? To her each couple was special with their unique problems and solutions. She wondered how presence of one special person makes all others less special. And if everyone is special then why we do we strive to be different. Does this have an evolutionary basis? The survival of the fittest competing for scarce resources! These were not scarce resources but just an appointment list of a little known reproductive clinician in a sleepy town of Kanpur. Our animal instincts sometimes take over our common sense. She would wait to see that sometimes our collective sense could ruthlessly suppress our basic instincts.

Avantika had never interacted with a politician as a patient before. And she thought it would have been better if this bit of information was not shared with her. Firstly like anyone else she was a bit cynical about both the police and politicians. There is a sense of insecurity that one feels in the company of these security establishments. Gory tales of unscrupulous use of power are a common knowledge and common men especially women keep a calculated distance from them.  And secondly she also hoped to finish the clinic in her scheduled time despite this surprise entry. People of importance always demand an extra bit of time than is needed. Avantika hated that.

Mrs. Nisha was an impressively dressed middle-aged woman. She walked inside the clinic extra carefully and sat quietly on the couch. Mr. Singh unlike an average Indian politician was dressed in branded casuals. There are two categories of politicians in India. Kurta clad tobacco-chewing versions who speak local dialects fluently. Two other kurta clad minions, one carrying netaji’s mobile phone and other carrying his Pan-masala, usually accompany them.  This was the popular version depicted by Bollywood movies. The second less common category was of Armani clad English speaking ones who look educated and modern. They are usually the sons or close relatives of the politicians of the first category. They represent a new generation of Indian politicians. Mr. Singh undoubtedly belonged to this category. He sat on the seat with his elbows resting over the table. He had placed a transparent folder containing some pictures of ‘Blastocysts’. Next to the folder he had his latest iPhone 7.

Even before a formal introduction of names, Mr. Singh asked” Doctor what’s an MFM?” 

“It’s a short form for Maternal and Fetal-Medicine. This is a sub-specialty of Obstetrics that deals with high-risk pregnancies. Sometimes such pregnancies require interventions on the baby while it is still inside the mother’s womb. A specialist trained in this field is skilled to do such procedures,” explained Avantika with patience.

“Are you an MFM?” inquired Mr. Singh. Avantika thought this question was both rude and wrong, as this is a subject not a degree.

“What exactly is the problem Mr.?” she waited with a pause to highlight there hasn’t been an introduction. “Mahindra Singh. I’m the MLA from the ruling party. I have direct links with the chief minister doctor.” Avantika thought that the last two lines were unnecessary. She looked towards Mrs. Singh. “She is my wife Nishi”

Mahindra handed over his smart phone to Avantika. There was an email from ‘The fertility institute of Bangkok’, which read through a complicated problem that Nishi was facing.

The ultrasound report confirms a quadruplet pregnancy. There are three intra-uterine gestational sacs.  The first sac contains two live pregnancies of eight weeks gestation each. There is no dividing membrane between them. The other two sacs also contain a live pregnancy of eight weeks gestation each. The diagnosis confirms a high order multiple pregnancy with one set of ‘Monochorionic monoamniotic twins and another set of Diamniotic dichorionic twins. The patient is referred to a MFM specialist for further management and advice.

Nishi was carrying four pregnancies simultaneously in her womb, a quad-ru-plet pregnancy. Two out of these were identical twins that are derived from a single embryo. “Same sac embryos are always identical”, Avantika was analyzing as she was reading. The other two pregnancies occurred in separate sacs.  Avantika reasoned they could rarely still be identical but more likely to be separate embryos.

At this stage the pregnancies were very tiny, less than a centimeter in size. But having four fetuses simultaneously was a very high-risk situation for both Nishi and her babies. As the pregnancy advances, Nishi could develop high blood pressure and diabetes that could cause an extra load on her heart besides the four babies. There is risk of hemorrhage and risk to her life. There is a significant chance of miscarriage of such a pregnancy.

Additionally there is a chance of premature birth of these babies much before the nine months are completed. Premature babies have immature underdeveloped organs and many do not survive the ordeal. Care of such babies requires neonatal ICU admission for months. A significant number of those who survive frequently develop permanent disabilities like blindness, deafness and sometimes mental retardation.

This couple was facing a very difficult situation and Avantika didn’t know what could have lead to this.

“How could this have happened? Our doctor in Bangkok told us they are transferring only two embryos.” Nishi asked stammering. This was the first time she had spoken since the meeting began. Her lips were trembling while she spoke. It was obvious that she was scared. She looked at Mr. Singh  “ I told you we didn’t need another baby, boy or girl.” Avantika’s job sometimes puts her into awkward situations like these when the secrets of the couple suddenly tumble out.    

“I need to know the full story before I can explain this” Avantika interrupted.

Mr. Singh handed over the transparent folder to her. The front page had a picture of a ‘Blastocyst’ with a text written underneath “The FIB: Fertility Institute of Bangkok.”

Nishi had undergone an IVF cycle at the FIB in January this year.  She had formed 16 embryos in total. The embryos were cultured for 5 days in the laboratory up till the ‘Blastocyst’ stage.  On the third day of culture each embryo underwent a procedure known as the PGS or Pre-implantation Genetic Screening. This is a highly advanced micromanipulation technique done by only a few centers around the world.  In this procedure, the outer shell of an embryo is drilled by a laser. A cell of the embryo is removed through a rent thus formed. Genetic tests are done on the cell to screen various suspected hereditary diseases.

Why would Nishi need such a technique? Avantika thought she had a clue.

PGS is a boon for families that have a predisposition to a hereditary disorder.  Such disorders run in a family through abnormal genes. Abnormal genes are transferred from the mother, father or both to their babies. Thalassemia, a life threatening hereditary anemia, is one such common disorder. One in 500 Punjabis is a carrier of the β Thalassemia gene. Thalassemia minor is a mild form of the disease that occurs when the individual carries only one abnormal gene. A person with this milder version of the disease has a minimal anemia that many times goes undetected. If two persons with Thalassemia minor mate, they have a 50% chance of a baby with Thalassemia major, as the baby gets two abnormal genes one each from the mother and father. A child suffering with Thalassemia major has severe anemia requiring multiple blood transfusions. Many such children succumb to complications even before reaching teenage years. Avantika had seen couples that had lost babies to this disorder. They are scared to have another child for the trauma both physical and psychological of going through the pain again is unbearable. Such parents can use PGS to select a healthy disease free baby even before the next pregnancy is conceived. Many such diseases can be screened in a similar fashion by the PGS.

“Why did we need a PGS?” inquired Avantika. The couple looked at each other with a strange glance. The answer was on the next page of the patient records.

Nishi’s embryos underwent PGS on the day 3 of culture.  At this stage the embryos are made up of 6-8 cells. Two cells each of the embryos were biopsied to analyze for Karyotyping. Karyotyping is study of the number and type of chromosomes present in the cells.

Every living organism is made up of cells. While a tiny embryo is made up of few cells, as adults we have trillions of them. Cells are the smallest unit of an organism just like a brick is the smallest unit of a house. Cells are very unique and specific to a species, sex and an individual. A human cell is different from a simian cell. Cell of man can be differentiated from that of a woman. And Osama’s cell can be precisely differentiated from that of Obama’s.

Each cell is equipped with a nucleus, which is like a hard drive controlling its functions. This “hard drive” also stores information regarding the details of the individual to which the cell belongs. This information is stored in ‘folders’ made up of the DNA. In a human cell there are 23 pairs of these folders, one each coming from the mother and the father. These folders are called ‘The chromosomes’.

Each chromosome contains a specific file for specific information. These files are called “The genes”. So both pairs of chromosome 16 of Aishwarya Rai contain a file on locus p.21 that makes her eyes look green. There is gene to decide the type of nose, the size of your heart or whether you will have a strong sun-line on your palm or not. This general information is stored in the first 22 pairs of chromosomes called the “somatic chromosomes”. There are groups of files that decide whether the individual will be a man or a woman. These sex-determining files are located on the 23^rd pair of these folders in humans. This pair is therefore is called the “sex chromosomes”. They are the X and Y-chromosomes. A woman has two X chromosomes. An individual with an XY karyotype is a male.

“Karyotyping” is like arranging all the 23 pairs of folders on the desktop and taking a picture. Abnormalities of number and type of chromosomes can be easily detected by this pictorial exercise. Down’s syndrome is one such   chromosomal abnormality.  Individual with downs syndrome have three copies o chromosome 21 instead of two. Mum or Dad gives an extra copy of this chromosome besides the usual two, resulting in an unbalanced Karyotype. This excessive information leads to clutter and the individual has multiple abnormalities from birth ranging from subnormal intelligence to congenital heart disease. There are many such chromosomal disorders that can be detected through Karyotyping.

Nishi’s embryos underwent Karyotyping not to detect any abnormality but to differentiate a male embryo from a female one. On day5 of culture the Blastocysts that were female were “discarded” and the males were selected for transfer into Nishi’s womb. This is called “Pre-conception Sex selection”. In simple words it is manipulating science to shop for a male baby.

Avantika had suspected this right from the beginning of her meeting with the couple. The FIB had become very famous as a sex-selection haven for well to do couples in India. The law in India bans sex selection. Couples find their way to Bangkok to work around the law to fulfill their desire of having a male child. Sex of an un-born child can be easily known by an ultrasound scan. Illegal scans are available even in villages for this. These ultrasound units are attached to so-called maternity homes where a pregnancy termination is offered in case the fetus is a girl. This illegal sex-selection is an industry in India, worth of millions of rupees. The law of the land is trying to catch this mafia but proving to be tooth less in breaking the supply and demand chain.  Avantika needed to know why Nishi took the PGS for this, when ultrasounds were ubiquitous.

“You see she only conceives female babies. That’s her problem. And that’s why we had to take so much pain to go all the way to Thailand and get this procedure done” explained Mr. Mahindra Singh.

Nishi and Mahindra had been married for 12 years. Together they had two girls, Nivedita and Neha.  Nivedita was 10 years and Neha was 8 years old. Both were bright kids attending one of the posh schools of Kanpur. They tried to have a third baby and Nishi conceived three more times. Each time an ultrasound revealed a female fetus and the pregnancy was terminated.

“My doctors told me that I couldn’t afford any more pregnancy terminations. We read about this technique over the Internet and thought to try it.”  Nishi went on “Why did God make me like this? Why can’t I give birth to a baby boy like normal women?  Sonia my sister in law has two boys. Revathi my friend had a baby boy. She underwent only one termination before that. I had three. There are pressures from the family. Mahindra is the only son. You don’t know doctor how much pain I’ve undergone for this pregnancy”.  Avantika knew her pain but Nishi knew nothing of reproduction.

Whether an embryo will be a male or a female is determined by the genetic information it contains. This information stacked in the chromosomes, comes from mom and dad. There are two copies of each chromosome. One copy comes from Dad and the other copy from mum. A 46XX embryo is a female embryo. It has 22 pairs of somatic chromosomes and 1 pair of sex chromosome, the X and X. A 46XY male embryo has X and Y as the sex chromosomes. Mum forms an egg that has half the genetic information, 22 somatic folders and one X folder.  A sperm from Dad has the other half of information. The other 22 somatic folders of the pair and a sex chromosome, either X or a Y.

While mum forms only one type of egg which always has an X chromosome, Dad forms two types of sperms which either has a Y or an X chromosome. When an egg fuses with an X sperm, an XX or female embryo is formed and when it fuses with a Y sperm an XY male embryo results. So it’s Dad who decides whether the embryo and finally the baby will be a boy or girl and not the mother.

Why did God make Nishi like this? Avantika thought that God was probably not replying Nishi’s direct question because the question itself was wrong.

But why do some men tend to have more girls than boys as their babies, is a research question. While it may be different for individual families, overall populations produce equal number of male and female progeny. It’s an Evolutionary stable strategy to have an equal number of boys and girls at birth for a population. The sex ratio at birth approximates to 1:1 for most populations around the world with a slight bias towards boys. It’s a ratio of 105 as its called. This means there are 105 baby boys for 100 baby girls at birth. But as the age advances the sex ratio starts favoring the female gender. At 15 years the ratio is equal and after the age of 65 there are only 72 males for every 100 females. Contrary to popular belief, a female gender is stronger and sturdier than the male gender. They outlive their male counterparts by on an average 10 years. Therefore nature provides for more males at birth so that there is an equal number of both genders during the reproductive age groups with equal mating opportunities.

Nishi didn’t care for evolutionary stable strategy. Her problem was, Sonia and Revathi, who already had boys. And she had none. Strangely she blamed herself for this and not Mahindra.

“There must be some problem with Nishi’s uterus itself. It doesn’t take up male babies. That’s why our first IVF cycle failed in January” predictably Mahindra also blamed her.

“I don’t think it’s abnormal to conceive baby girls in every pregnancy. It’s definitely not a part of any disease process. Some men do tend to have more girls than boys as their babies. You can say it’s a tendency at best.” Avantika wanted to highlight the role of Dad in this whole situation without reducing it to a blame game.

“That Nishi’s uterus cannot take up male babies is wrong. She is carrying four of them now and that’s a big problem.” Avantika started reading the records again.

On sex typing of each of the16 embryos it was found that 10 of them were male. Six of the male embryos were abnormal and not transferable, as they would lead to babies with diseases. Thus 12 embryos including the female and abnormal embryos were discarded. In January only a single embryo was transferred into Nishi‘s womb and the other three embryos were frozen. Nishi did not get pregnant in that cycle. That is an acceptable result as the implantation rate of embryos is around 25 to 40 percent.  It’s the same for Sonia Revathi or Nishi. Mahindra was wrong in finding faults with Nishi.

“Having four boys is not a problem for me. I can afford it. Although it will not look good for a young politician to have six kids” Mahindra said proudly. Obviously he neglected the risks of multiple pregnancies as highlighted by Avantika before. Or he didn’t care.

“You say it’s a big problem. Even doctors in Bangkok said something about high order pregnancies. What is it all about doctor?” He started analyzing.

“Human uterus is not designed to carry multiple babies simultaneously. It is risky for both. Its dangerous for Nishi and you could loose all the four pregnancies.” Avantika tried to put the horrid situation in the mildest possible words again.

“Doctors in Bangkok insisted on a single embryo transfer in July too. I couldn’t afford to go there again and again. I told them I’m a busy man. I don’t have time. Do whatever, but I want results this time. They said they couldn’t transfer more than two by law. Twins is not a problem is it? Even Prakash my cousin has had twins. I thought lets take a chance. But how come we have four on transferring two?  I cant understand this” Mahindra looked confused and scared. How quickly a man can be reduced from the most powerful and affording to a vulnerable and weak being is both a sad and amazing sight?  

“There are two parts to this. First we need to understand why this happened and then we need to deal with it to avoid complications. Every problem has its solutions.” Avantika explained in a reassuring tone. Although she was also thinking of something that might shock the couple even more.

In July Nishi underwent a Natural Thaw cycle. In this procedure Nishi was allowed to ovulate naturally. Once the ovulation was confirmed she was planned for an Embryo transfer. This is to mimic a uterine environment conducive for a pregnancy. Two out of her three frozen embryos were “thawed” on the fifth post-ovulatory day and transferred into the womb. Two weeks after the embryo transfer a blood test confirmed a successful pregnancy. An ultrasound scheduled a month after this confirmed a quadruplet pregnancy.

Embryos that have undergone a micromanipulation procedure like embryo biopsy as in Nishi’s case have a tendency to split into two or three. The “splitting” of embryos rarely occurs in nature too but is commonly seen after PGS. On splitting embryos form “identical” twins or triplets. These are the kind of twins that have exactly the same genetic material and are look alikes. The “Ram and Shyam” and the ”Sita and Gita” of Bollywood are actually identical twins formed from the splitting of the same embryos.  

Two of the Nishi’s four pregnancies were definitely identical twins as they were present in the same sac. The twins present in the same water bag are always identical. They are formed when the splitting of embryo occurs after the bag is formed. The other two of Nishi’s pregnancies were present in two separate sacs. They can still be identical twins if the splitting of embryo occurs early enough before the bags are formed. But they can also be another type of twins known as the “non-identical” or the “sibling twins”. Such twins are formed of two separate embryos that have implanted in the womb simultaneously. They are as similar to each other as siblings, just like a brother and brother or a brother and sister twins. Such twins are more common types of twins in nature but never make it big in Bollywood movies, as they are not look alikes.

“So you mean both of our transferred embryos split into two to give us four pregnancies.” Nishi inquired.

“That is the most likely possibility. But it could also be that one embryo split into three and the other didn’t split at all. Clinically it doesn’t make any difference.” Avantika stopped here. That was all she wanted the couple to know. But there was one more possibility which could have shocked the couple had she elaborated it a bit more.

Nishi and Mahindra was a fertile couple. They had no problem in conceiving babies naturally. They chose IVF for sex selection. Whenever IVF is done in a fertile population there is a chance they can conceive naturally also. Natural conception would bypass a selection procedure. Whenever PGS is done for selecting healthy babies or sex specific babies the families are advised to follow strict abstinence from sex during the IVF cycle.  In Nishi’s case if she conceives naturally also there is a chance that fourth of her pregnancy is a female. It didn’t make any difference to Avantika, as medically this was not a problem. That’s why she chose to skip this information from the couple.

“I’m sure you would have followed strict abstinence from sex during your IVF cycle in July, as advised by your doctors.” Avantika asked bluntly.

“Of course doctor. We are not college students are we?” Mahindra’s face turned red on answering a deeply personal question. He wanted to ask the relevance of this question but he didn’t to avoid an embarrassing situation.

“As I said earlier having four pregnancies simultaneously is a very risky. Besides risks to Nishi there is a significant chance of premature births. Premature babies have very high chance of mortality and severe permanent disabilities. We should reduce the number of pregnancies to avoid complications. We can do this by an ultrasound-guided procedure. Its called ‘Multi-Fetal-Pregnancy-Reduction’ or MFPR in short. A highly sophisticated technique will be employed to reduce the number of pregnancies from four to two.” Avantika explained the solution of their problem in simple words.

“Why don’t we then reduce them to one? We already have two kids. One more I think would be enough for us.” Inquired Mahindra.

Avantika always avoided these “God-like” discussions with the patients. We don’t have a boy and we want one. We utilize the best available scientific advances of humanity to get one. As a side effect we get four rather than one. We employ another set of scientific advances to fine tune our desire. Are we gods on earth?

She wanted to reduce the pregnancy number to avoid complications that Nishi could face. This in no way justifies their action in first place. Her step was like employing a “Ganga action plan” after the untreated sewage was dumped into it. Her goal was to avoid downstream complications. That doesn’t justify untreated sewage being dumped in Ganga in any case. 

Working with embryos for the last ten years Avantika was deeply fascinated with them. To her each embryo that has implanted was a very special embryo. It represented the spirit of life in its purest forms. To grow develop dream and prosper when provided with the love and nurture of the mother’s womb. Reducing them was a destruction of sorts and unjust for the one reduced. It’s a very difficult decision which one to keep and which to reduce. To reduce three because an all-affording Dad has suddenly decided one is enough for him was obnoxious.

“No we should not do that.” Avantika stated in a no-nonsense style. “ MPFR is not a completely safe procedure. Surgical procedures on the babies while they are still inside the mother’s womb are risky. With MPFR there is always a chance of loosing an extra pregnancy.  We never reduce to one because then there is a significant possibility of loosing all.”

“Do whatever doctor but I want results.” It was probably Mahindra’s political habit of flip-flopping.  And he does that after positioning himself in a way that it appears as if he is in command. Avantika ignored his last sentence.

“We will do this procedure after two weeks from now when the pregnancy is around 10 weeks. Till then Nishi needs to continue the following medicines. An ultrasound scan will be needed before the MPFR. I’m sure Mr. Vishwajeet will organize everything for you.” Avantika handed over the clinic sheet and the FIB folder to Nishi.

Mahindra went outside the clinic without a greeting. His gesture was symbolic of his highness’s graceful departure. Nishi in contrast stood up and shook hands with Avantika.

She glanced her clinic sheet and said,“ My name is usually mis-spelt whenever I visit doctors. Even in Bangkok my name was wrongly written as Mrs. Nisha rather than Nishi. Nisha of course is the more common version of my name. I’ve noticed whenever I’m addressed as Nisha I land up into complications. Thanks a lot doctor for writing my correct name. I think I’m at the right place.” Nishi tried to find hope in some Ekta Singh style Namology. Avantika was happy after building the right rapport with her patient.

As she was going out of the consulting room, Nishi turned back and disclosed “We did have sex twice during our IVF cycle in July. What Mahindra told you earlier was wrong. I hope this would not cause any major problems.”

“This should not cause any problem.” Avantika gave her the right answer. Although this meant that there is a chance that Nishi could have had a natural pregnancy in addition to the IVF one. There was a risk of bypassing the sex selection. But for a mother giving birth to a baby girl should never be a problem.

Avantika gave consultations to four more patients that day. Each of these four couples has had many childless years. Sometimes she thought that they were lucky, as they now knew the precious nature of this gift. To most of them it doesn’t matter if the baby is a boy or a girl. They feel deeply deprived of the love the baby brings along while most of us take the gift of childbirth for granted.

To be continued....