STORY OF ROUND WORMS

Nina came to our hospital in June1960; I was a bit more experienced as a doctor. It had been just over a year since I graduated. She complained of a lump on the lower left side of her abdomen, with frequent abdominal pain. She was a young girl of about 20 years of age and not married. She was nonvegetarian. She looked under nourished. She had not had a menstrual period for six months her blood count showed, what we call mild eisinophilia, we did not pay much attention to this , although Ascaris can cause an eisinophilic pneumonitis. This can happen even without Ascaris her ESR was raised. Surprisingly the stool examination did not show any Ascaris ova this means that she had an infection somewhere.  Genital Tuberculosis was fairly common in India in those days. This can cause pelvic mass and absent periods. We had very basic x-ray services and ultrasound was unknown in the sixties. A clinical diagnosis of pelvic tuberculosis was entertained. She was given Anti tubercular treatment for three months but nothing changed. It was decided to do a laparatomy: guess what we found. A lump made of 16 Ascaris worms totally sealed by the peritoneum, arising from the fallopian tubes. There were sixteen worms in all. They were all removed. No holes could be seen in the bowel. The abdominal cavity was cleaned and closed. Nina made an uneventful recovery. She was subsequently given more treatment to clean her bowel of any Ascaris. It was also explained to her about personal hygiene and the meat she consumed. The cause of her not having a period was probably due to her poor nutrition. Her chest x-ray was clear 

Ascaris is one of the most common worm infections in the world. About one billion people suffer from it. It is a big fat round worm,

which can grow up to 35 cmin length. It can go round different parts of the body via the blood stream. Initially it can cause eisinophilia in the blood which we ignored, as there were no Ascaris ova in the stool.  In gynaecological literature many cases of Ascaris in the fallopian tubes have been described, and the first one was in 1926. 

TRIPLET PREGNANCY

It was November 1962; it was the second day of my new job at Benares Hindu University where; the government had just opened a new medical school. I and another doctor, from the same medical school were appointed as lecturers in obstetrics and gynaecology, after getting our masters of surgery qualifications in Obstetrics and gynaecology and under the supervision of a professor of surgery.

It was up to us to establish the department, attend to the paper work, and do whatever else was required. It was my second day in my new job. There was a registrar on duty in the department and she called me at about 5 am to come to the hospital urgently. An ambulance was sent to pick me up, which was the general rule because this way we were assured, that we would arrive very quickly. When I arrived in the labour ward, there was this woman Sitara Devi aged thirty-four in very strong labour, shouting and howling. This was her seventh pregnancy. She had six other children, all girls at home between the ages of twelve and two. She had never had any problems with any of her other pregnancies. They lived in a nearby village, her husband was a rickshaw driver, and they had decided to have a tubal ligation hoping that this baby surely would be a boy. She had never seen a doctor or a doula during this pregnancy. When I saw her she looked weak and emaciated what else could I expect. Her blood pressure was on the low side, she had an enormous belly. There was no time to measure it, we started her on an iv infusion in case she bled. In this hospital there was an x-ray department, but it was so early in the morning and there was no time for all this. I was sure that this was at least a twin Pregnancy with too much fluid; I was hoping that the babies were not abnormal. Within the next five minutes she delivered her first baby. This was a female weighing 4.6lbs. I was starting to wonder if there were three babies. I had never seen a triplet pregnancy the incidence of triplets is quoted as I in 60 000 or 1 in 200 million. They are now commoner with assisted technology. In the next ten minutes she delivered her second baby this was also a girl. I gave her an injection called syntocinon so that she will not bleed even though I was suspecting a third baby. It was very silly of me. This baby was lying with feet first which meant it was going to be a breach birth so I had to do a breech extraction. The baby came out in good condition; it was also a little girl. These babies were identical.  I felt very sad for the couple as they had wanted a boy but now had nine girls. l left the labour ward telling my registrar to deal with them Sitara did very well. She went home after 4 days with 3 new healthy girls. They did not have a tubal ligation hoping for a son in the future. Nearly 55 years down the track I still wonder about these girls. At medical school I had another Asha in my class who had 8 sisters. They came from a good family, they all became doctors. I wonder if any of these sisters made something of their lives. 

INJURY TO THE VAGINAL VAULT AFTER DELIVERY (CHILD BIRTH)

Pyarai aged 22 was discharged home on the third day after a normal child birth. This was her third child. She was sent home with her mother. She was explained about contraception. According to the latest Indian rules we were happy to do a tubal ligation as this was her third child. Her age did not matter. She did not want this, we advised her to return in 6 weeks so that we could fit an intra uterine loop, that is what we used in those days, it was 1959. However to my disgust she was brought over by her alcoholic husband to the hospital at about 2.00 AM, with a loop of bowel hanging between her legs. I was horrified; I did not know what to say or do. Obviously he came home dead drunk and forcibly raped her, the soft vaginal wall tore and a loop of bowel came down, for a change this was an easy case. I first started an intravenous drip, put her head down, and examined the bowel made sure it was not damaged. I replaced it very gently, gave her antibiotics and repaired the torn vagina. We kept her in hospital for 5 days, seeing her husband’s behavior; my boss put an intrauterine device in for her before she went home. This was not   a routine, but we had to do it for her. These days we keep talking about cruelty at home, I have been seeing this as an obstetrician, particularly in countries like India for last 60 years. Nothing has changed, cruelty towards women continues. I so much wish that organizations, like The Melinda and Bills Gates charities, governments, Millennium Development program's, prevention of domestic violence can help these women with education equality and empowerment. Happy families make happy societies’, happy nations and in the end a happy world.

MOLAR PREGNANCY (HYDATIFORM MOLE)

It was still the month, of August 1959; I am still the junior most resident posted in the septic labour ward (labour ward for neglected women who were very ill). Najma a 37 year old woman from a nearby village came in, apparently in labour, with some bleeding, This was her fourth pregnancy; she did not know how pregnant she was. She conceived while she was breast feeding the last baby who was born two years ago. She never had any problems with her previous pregnancies. She had not seen a doula or a village doctor. She was on the obese side; we could not get her weight as she was not so well. I started to examine her; she had a fast pulse and a somewhat low blood pressure. On abdominal examination I was unable to feel any baby parts, there was no foetal heart. The abdominal girth was forty two centimetres. I tested her blood on my small pocket Haemoglobinometer (HB) which we carried in our pockets for emergency. The Haemoglobin was 2.  The average HB in Indian women is often between 8 -12.  In those days we had no Ultrasound (never even heard of it). The x-ray department was about half a kilometer away. The patient could not be moved in any case. It was five AM. I was not sure what was going on. Was it a twin pregnancy with massive fluid or was it a pregnancy with massive bleeding? I sent for my registrar who was a very capable doctor. We decided to put up an IV and emergency blood, which we used to keep O, Rh-negatives. It was only two units. In emergency we had to cross match blood for our need and bleed the donor. The pathology department was also far away in the main hospital. However one of my senior colleagues went to do this cross matching and took the relatives with her .My registrar came over and very gently tried to examine her, by now she was bleeding profusely and passing out tissue which looked like bunch of grapes. Both of us immediately got the diagnosis. It was what we call a molar pregnancy. We had exhausted our emergency blood, the cross matching blood was not yet ready as it takes nearly two hours, and the same doctor had to bleed the donors. The woman was bleeding like a tap, the whole big labour ward full of blood and within two hours of admission, she passed away, as if she had come to the hospital for dying. Her relatives were very angry. They wanted to kill me, as I was their first contact my registrar advised me to hide myself in the duty doctor’s room, in the bathroom, which I did. They hung around the hospital to find me and kill me, I was so frightened. However it all settled in the end. Our professor explained to all of them, that they have to take greater care of their mothers to be. From then on we had a regular flow of pregnant women from that village.

Molar pregnancy and many other complications of placental diseases, are together addressed as gestational (pregnancy) trophoblastic (arising from the placenta) diseases. Molar pregnancy is when; an abnormal fertilized egg plants itself inside the uterus and fails to grow like a normal baby. It is a disease of the placental tissue; it grows like massive tissues which look like grapes. The word mole simple denotes a mass of tissue .It is a noncancerous placental tumour, which can turn cancerous, it is then called Choriocarncinoma. Choriocarcinoma can also rarely arise after a normal miscarriage or a normal birth. There are two types of molar pregnancies, a complete mole or a partial mole; it is called a complete mole when an egg is fertilized by one sperm, all the female chromosomes die. The father’s chromosomes duplicate and make 23 pairs which is the normal chromosome number. No embryo, foetus or a normal placental tissue is formed. A partial mole is when the egg is fertilized by two sperm or one sperm duplicates, mother’s chromosomes remain, hence the embryo has 69 chromosomes. This happens if the egg has no nucleus or an inactive nucleus. Molar pregnancies are common among the Asian population say 1 in 100 as compared to western population where it happens 1 in 1000. The risk factors are, if you are of Asian descent, you are older than 40 (5times) or younger than 20 (1.5 times) you have had a previous mole (30times) and a previous miscarriage (twice as often). I have often seen molar pregnancies in young girls at the time of a miscarriage. It is a part of the same process of pregnancy failure. When a woman has a molar pregnancy she often suffers severe vomiting as compared to a normal pregnancy, intermittent vaginal bleeding and pelvic pressure pain. They can even pass grape like tissue pieces with their bleeding; they often get early rise of blood pressure or even like toxaemia of pregnancy which is a disease of late pregnancy. I have seen excessive vomiting causing liver failure in very malnourished young girls. Najma also had excessive vomiting; her blood pressure was never checked. On admission she had  low blood pressure as she had been bleeding, when a person bleeds the blood pressure goes down. A very small number of women may also develop symptoms of overactive thyroid that is they feel agitated, shaky, anxious, and cannot sleep. This happens because the very high levels chorionic gonadotrophins ( the pregnancy hormone in molar pregnancy )upset the control of thyroid  production. About one third of women with molar pregnancy also develop ovarian cysts on one or both sides because of high levels of pregnancy hormones. They almost always resolve, when the mole is gone. They are not cancerous.

In this day and age the diagnosis of molar pregnancy is easily made by ultrasound as early as eight weeks. Sometimes a vaginal ultrasound is required. The others tests that are done are to measure the blood levels of pregnancy hormones; a Thyroid function test, blood for haemoglobin and blood count, general liver and kidney function tests.

The treatment is simple under general anaesthesia in a hospital the molar pregnancy is removed by vacuum aspiration .Your clinician will explain all the details. All the tissue is sent to pathology. You will be able to go home in 4 hours. Rarely if the molar pregnancy is extensive or it is invading the uterus and you do not want any future pregnancies the uterus is removed.

After this initial treatment you require follow up regular pregnancy hormone tests and ultrasound to make sure there is no molar tissues in your body and your ovarian cysts have also resolved. Thyroid function tests and blood tests are also done to make sure that you are fully recovered. You are advised not to get pregnant for one year while the molar pregnancy is fully resolved.

In about 20 to 30 percent of Molar Pregnancies and rarely after a normal pregnancy and miscarriage a Choriocarcinoma (Cancer of the placental tissues) develops and it requires special investigation, treatment and follow up which we are not discussing in the post.

SURGICAL METHODS OF CONTRACEPTION

SURGICAL METHODS OF CONTRACEPTION

Sterilization for women and men 

What we need to understand

Sterilization with reference to family planning means permanent prevention from getting pregnant. For this to happen; the individual needs an operation. For women it is called tubal ligation or occlusion, for men it is called vasectomy. The partners need to consider it very carefully because it is permanent. Sometimes a single woman feels she never wants to have a baby and has a sterilization fairly young. I feel they need to think about it seriously. It can be reversed, however the success rate cannot be predicted. It also depends on the method of tubal ligation and what method was originally used.  If they were burned or totally removed it cannot be reversed.

pictures

Before the advent of so many methods of contraception, sterilization was very common. In countries like India, when India was trying to control its population the public was encouraged to use sterilization or vasectomy; if they did so they were given a transistor radio as a gift. It was unfortunate that many young men had a vasectomy in the greed of a transistor radio without understanding its serious consequences. Now since we have long term reversible contraceptives such as, intrauterine devices or hormone implants, the frequency of operative contraception has gone down.

VASECTOMY

It is an operative method of contraception for men. The tube called vasdeferens carrying the sperm from the testicles to the penis is cut and tied so that when ejaculation occurs, there are no sperm and the partner cannot get pregnant. This takes few months as the residual sperm will still be there. They are stored in the Epididymis as shown in the diagram below. A test is performed on your ejaculate before you are cleared for sexual relations and that there is no sperm. The sperm in your body is naturally absorbed, and there is no build up.  There may be infection or bleeding as a result of the operation but it is rare. Before you decide to have this operation performed, a man needs to think very carefully about the fact that he will no longer be able to produce any offspring however we now have the medical technology to freeze sperm should a child be desired. A vasectomy can be reversed however the results are uncertain. A vasectomy is simple and has less extra complications; it can be done under local anaesthesia.

TUBAL OCCLUSION

If you decide to have a tubal ligation, you and your partner should discuss that this is what you want. You may also discuss the alternatives with your doctor, maybe one of these appeals to you. Make sure you never want a baby or another baby. It is better if you are, older than thirty years of age. Research has shown that women often regret if they had a tubal ligation very young. The frequency of divorce also complicates matters further. In modern times the tubal occlusion is almost always performed by keyhole surgery called, laparoscopy. In developing countries where there are no surgeons who can do it or there is no equipment, as this is expensive, it is done by open surgery. Give yourself time to think about it. Keep up with your regular contraception until the very last day or to the last tablet.

There are two ways, how tubal ligation is performed.

 OPEN METHOD

This means that you belly is cut open. This is like any other surgical operation. The operation is explained to you and your partner. You have to be very sure that you want this done. In some countries they coerce to have this done by giving you money or electronic, goods. In my view it is safe if you have a good marriage, you have three children and you are above thirty years of age. After the basic things are decided, you go to the operating theatre after having given the, consent. The operation is generally done under general aesthesia by an anaesthetist. The surgeon then makes a cut near the bikini line, which is about 3-4 cms long. He then identifies the tubes and blocks them.  Different methods are used by different surgeons to block them. The urinary bladder which lies in this area is always emptied, to prevent it from being injured. The belly is then closed by sutures that do not need to be removed. Generally you can go home the same day or the next day. This operation is called mini laparatomy. It is done when you are not pregnant and using a proper contraceptive. I had an incidence when a woman who had sex the night before her operation was due, thinking this cannot do any harm, She did not turn up for her six weeks visit in spite of my requests finally when she arrived, she was twenty weeks pregnant. It was worked out that she became pregnant the night before, as she did not use the condom that night which was her normal usual contraceptive. It is best to do tubal ligation soon after a period (Proliferative phase of menstrual cycle) when the woman is not likely to get pregnant .Tubal ligation can be done at the time of caesarean section, however the failure rate of these tubal ligations are slightly higher than the ones done when you are not pregnant. Also the other problem can often be that if the baby is found to have a serious medical condition and he can die, than it can be a disaster. I am not very keen on doing tubal ligation during the time of a caesarean section or at the time of an abortion, as at that time one may not be emotionally ready.

There are several methods of Tubal ligation usually named after the Surgeon who described them. There are different parts of the tube shown in the picture below.

It is best to lift up the tube in a tissue forceps, make sure this is the part of the tube where the blood supply is least. This protects the ovaries from their blood supply being compromised. The tube is then compressed, tied and cut. About one cm loop of the tube is cut and sent to pathology. This confirms that the tube was cut. It is also very useful in any medico legal situations if they arise in case the tubal ligation fails and the cut end of the tubes are diathermied to prevent recanalisation. We make sure there is no bleeding. This is done on both sides. The tubes are put back in the abdominal cavity. When the suture material is absorbed, the cut ends of the tube separate.

This method of tubal ligation is called Pomeroy’s method. It is very simple and can be taught easily. The failure rate is 1 per 1000 at the end of one year, 7.5 per 1000 at the end of10 years. There can be deaths due to bleeding or infection although it is rare. I have seen one death after a postpartum tubal ligation probably due to deep venous thrombosis.

The Aldrige method is more temporary, where the  Fimbrial  end of the tube is tucked in . It is good for a successful reversal.

A number of surgeons remove the whole tube. This can interfere with ovarian blood supply however the recent research has shown it to be protective against ovarian cancer.

 In another method called the Madleners methods, the tube are crushed at two points and tied. No tube is removed. I have seen two cases of hydrosalpinex (swollen tubes full of fluid) following Madleners tubal ligation.

Tubal ligation can also be performed via the vagina. The vaginal tubal ligation is hardly used anywhere in the world. It also has a high risk of infection. The tubal ligation even by laparatomy can sometimes be difficult if, a woman had many pelvic surgeries or infections, as this can make difficult to identify and lift up the tubes. If following a tubal ligation, you feel you may be pregnant see your doctor urgently. If it is an early pregnancy it can be aborted if you so desire otherwise   doctors can look after your pregnancy.  Tubal ligation as such does not do any harm to your pregnancy.  Always call your doctor if you have unusual pain, fever, abnormal bleeding, pain in the calf and any other problem that is worrying you. Complications of tubal ligation are generally minor and easily managed; your surgeon always discusses these with you.

KEYHOLE SURGERY OR LAPARASCOPY

Keyhole surgery is the method used in most countries. It is often not used if the woman is obese, or is likely to have pelvic problems which can make the identification and picking up of the tubes difficult. It is usually done under a general anaesthesia in a well equipped hospital by a properly trained surgeon. The surgeon explains the procedure to you. The complications, failure rate and reversibility is also explained to you depending upon the method he uses. After general anaesthesia, he then makes two cuts one near the belly button and other at the bikini line in the middle or to one side. The belly is filled with gas, he identifies the pelvic organs, once the surgeon has access to fallopian tubes, and he usually seals them off by using, Filshie clips or rings. Sometimes they burn them and then may or may not cut them. It is harder to reverse the tube once they have been burnt.  Filshie clips are expensive and require an extra gadget, so it is not often used.

Some surgeons often prefer either to do the removal of either the tubes, or do a removal of Fimbrial ends of the tubes only. Recent research has shown that it is protective against ovarian cancer, as most of the ovarian cancers seem to arise from the Fimbrial end of the tube. One ovarian cancer is prevented after 100 such operations have been performed.

A new surgical method of achieving tubal occlusion has been added to help women. This is called hysteroscopic sterilization.It is only available in limited countries. It can be done under light sedation even in the surgeon’s office.

The surgeon inserts a small titanium coil, going through the vagina into the uterine cavity and than going through the tubal opening deposits the coil in the tube this coil is called ESSURE. At present this is the only hysteroscopic method available. After this operation you have to wait three months so that your body has created scar tissue around it totally blocking your tubes. At the end of three months a special test is performed to make sure that in fact your tubes are blocked. During this time you have to continue using your normal contraception before they confirmed that they are blocked. This was considered to be a negative factor regarding Essure. The failure rate is higher than laparoscopic sterilization. Reversibility has been tried with some success.
In recent times there has been some controversy about Essure because many women have required repeat operations. Some of these women who had this done in many situations were already compromised because of obesity, previous surgery, and co-morbidities. The repeat procedure had to be performed under a general anesthetic, which was not completely satisfactory. In view of these recent objections, please be sure that you are happy to have this procedure performed upon yourself.

HYDROCEPHALUS

STORY ABOUT HYDROCEPHALUS

This is also my story from August 1959, I was still posted in the septic labour ward, and the ward was where the women who were neglected in labour outside the hospital came in for further care and management.  Sarla a beautiful 19 year old was one such woman. She never had any care for her pregnancy. She had been in labour for two days; her waters had also broken two days ago. The baby was not coming, her Doula looking after her asked her to go to the big hospital as she was unable to do anything for her. It was early morning when she arrived, I was on duty, when I saw her, she appeared to be a fit young woman. I was unable to hear the foetal heart sounds therefore I assumed that the baby was gone. At that time we had no sonic aids, CTG, machines or any x-ray facilities.

On abdominal examination it felt like a big head when I did a pelvic examination, I felt a tense bag of fluid. I was not sure if this could be a hydrocephalic head or a bag of membranes, which may not have ruptured. (Please do not forget that I had graduated only few days ago)

I requested the nurse, for A lumber puncture needle (a long fine needle used to do a spinal puncture). With this needle I punctured the tense bag of fluid. With a great rush, lots of fluid and a baby came out hitting me on my chest. Obviously it was a hydrocephalic head.

In the human brain there are spaces which are fluid filled called the Ventricles. The spaces in the Heart are also called the ventricles.

There is a set of four ventricles in the brain, they are all connected with each other and a central canal of the spinal cord. The fluid that flows thorough these canals is called cerebrospinal fluid (for short CSF). Of these, there are two lateral ventricle right and left on each side of the front part of the brain, there is a third ventricle in the middle part of the brain which is connected to the lateral ventricles by a small opening called ,Foramen  of  Monro . The fourth ventricle lies in the posterior part of the brain. It is connected to the third ventricle by a very narrow channel called aqueduct of sylvius.

Besides these, there are other spaces called cisterns and foramens. All these together allow the free flow of CSF.

In each ventricle there is a network of specialised blood vessels with special cells called ependymal cells. It is the choroid plexus which produce two thirds of CSF the rest is produced by the lining of the ventricles and a special space around the brain called subarachnoid space.

CSF contains the same amount of sodium like blood . It has much less protein. Its osmolarity is the same as the blood. 500 ml of CSF is produced each day. It constantly moves all the time, 3.7 times each day, the resultant fluid present at any one time is 100 to 160 mls

CSF serves very important functions for the brain. It keeps the buoyancy of the brain, weight of the brain is 1400 gms, however when it floats in the CSF it records only 25 gms. It protects the brain from injury during sport and accidents. It also maintains the chemical stability of the brain and protects it from infections.

It protects the brain from ischemia, if by chance the CSF volume  drops CNS pressure drops, it then sets up a blood flow. Besides all this CSF supplies the nutrition to the brain and removes waste products and toxins. It also acts as basic immunological protector

It seems that normal head and CSF is very important for the normal human life and function. After all the brain is the band master of the body orchestra. So why we get hydrocephalus? And how do we deal with it. Again this means too much water(hydro)around the head(cephalus)

Congenital hydrocephalus means hydrocephalus present at birth. It is not an inherited disorder; it only means it is present at birth. It usually happens if the CSF cannot move normally and one of the passages is blocked. This often happens if the baby is born with other brain abnormalities. These together are called neural tube defects. One of the commonest one is spinabifida others are less common such as hydrancephaly .

This can happen if the

1) Foetus has a haemorrhage

2) Aqueductal stenosis

3) Blocking of the cisterns or foramina

4) Neural tube defects encephaocoele

5) Infections in the mother, Toxoplasmosis or syphilis

6) Tumours in the foetus or baby

7) Genetic abnormalities

So obviously the flow of the CSF is obstructed or even too much is being produced. At the time when I had a demised hydrocephalic foetus we had no tests not even a post-mortem to see if any abnormalities where present.

Now of course you can suspect a hydrocephalic head very early in pregnancy, and also look for any other abnormalities.

Now we do a chromosome analysis. These are found in 20% of cases of hydrocephalus. Further assessment can be done by MRI. If the problem is complicated a termination of pregnancy is offered. If it is isolated hydrocephalus, progress of ventricles is monitored. Delivery is done at a place where there are facilities for neonatal intensive care. Surgical drainage is generally done for the blocked ventricles. Foetal shunting has been attempted, but needs further  improvement . Mothers Needs to be advised to take 400 micrograms of folic acid when they want to get pregnant again.

The above photo is by ultrasound. It is floating choroid plexus and dilated ventricles.

PREGNANCY TEST PAST AND PRESENT

It was the first of August 1959 I had just qualified as a doctor. My life’s ambition was achieved, not only have I become a doctor, that I stood first in a class of hundred and fifty men and women. I was on cloud nine. My first day at work, as a Dr started at 7 AM, Dr E called me into her office and asked me to go to the pathology for a pregnancy test. The pregnancy test was to be done for the princess of one of the independent states. There were some states still scattered throughout India after independence. This princess had never had a baby, as it was known that the prince was azospermic.  Maybe the princess had an indiscretion, on this occasion my boss had to know what was going on.  It was a hot day, and it was raining as well, she asked me to take her car which was outside with a chauffeur. For the pregnancy test we had to go to the pathology, it was about one kilometre. The car was a green Chevrolet. I was so delighted with this permission. I forgot all about the test and became very excited about the thought of sitting in this beautiful American car.  I had never sat in a car before. My dad was a lecturer at a prestigious university and we all lived on the university campus.  There was a school for the university staff children.  We never required a car. Sitting in the car, I was not thinking about the pregnancy test which I was thinking of earlier, but now I was thinking when I will be able to have a car. After I finished my training in obstetrics and gynaecology I got married. We went to the UK. My husband was already working there. The very first day we were standing on a bus stop, my husband noticed that I was shivering , he said to me he is coming in few minutes, when he returned, he was in a beautiful  blue  Beatle(VW)  Car . He said to me “let us go”. You cannot imagine my joy.  In my excitement of the car let me not forget the pregnancy test.  My very important job on day one, as a doctor was to get this pregnancy test done. I did not even know at this stage that these tests could be done at our college.  My bosses said go and do an (A Z) test.  She called it  Aschiem-Zondek .This is described further down in the text. There was a similar test, called the toad test which was introduced by, Lancelot Hogban looking for the pregnancy hormone called human chorionic gonadotrophin (hCG ). This was discovered in 1930.  It is produced by the trophoblastic (very young placental cells) cells of the fertilized egg. The hormone is excreted in the urine of the pregnant mothers. The urine from a pregnant woman was important; some ancient Egyptians used to do a very different pregnancy test with the urine. This was in 1350.BC. A woman who was supposed to be pregnant was made to pass urine on wheat and barley seeds over several days. If the seeds grew the woman was supposed to be pregnant. Not only that they declared the sex of the baby as well., however this was disputed, if the barley grew the baby was supposed to be male, if the wheat grew the baby was thought to be female and vice versa. The urine of men, and non pregnant women did not germinate the seeds.  It was speculated that the increased levels of oestrogens in the pregnant woman’s urine may be the cause of this success. The human chorionic  gonadotrophin,  the  pregnancy  hormone  was not discovered as yet. There were many weird tests for diagnosis of pregnancy using urine.  There was the Ribbon test, the ribbon was to be dipped in the urine, if the woman gagged or vomited smelling this ribbon she was considered to be pregnant. Then in 1500AD there was an eye test described by a Dr Jacques Gulliemeau  in which a pregnant woman’s eyes get deeply set with small pupils, drooping eyelids, swollen little veins at the corner of the eyes.By 1900 the piss became an important commodity. At this time the pregnancy hormone chorionic gonadotropin(hCG) was being discovered in the blood and the urine of the mother to be. Two scientists, Selmar Aschheim and  Bernhardt Zondek  invented a test in which the urine of the woman to be tested was injected in an immature rabbit, rat ,or mouse, several doses over many days , after many days the rodent was killed to see if it had ovulated , or ovaries have grown the corpus luteum  has developed , i.e. it is gone on heat  in spite  of the rodent being immature. If this happened the woman was supposed to be pregnant; it became a cliché to say that the rabbit died, which meant that the woman was pregnant. This test was good but expensive and the animal had to be killed. A -Z test did not last for long .By 1930 hCG was studied in detail, it was certain that this hormone is produced by the placenta and can be detected after the implantation of the pregnancy.  The Americans consider the pregnancy to start with implantation.  The toad test was being performed with a vengeance, both on male toads (bufo and female frog (south African clawed toads – xenopus). The male toad laid Sunitpermatzoa and the female toads laid ova. When my boss sent for this pregnancy test it was meant to be the toad test. When I arrived at the lab there was a technician with a few toads in a tank of water, the technician injected one of female frog with some urine, just under the skin. He asked me to come the following day. When I arrived nearly 24 hours later the tanks had a lot of frog’s eggs floating in the tank. This confirmed that the woman was indeed pregnant. She had a hysterectomy performed in the name of fibroid uterus. She indeed had fibroids as well which were causing her trouble. This saved the day for everybody concerned, particularly the princess.These tests for diagnosis of pregnancy were called bioassays the immunoassay tests started instead of bioassay test. Bioassay tests were cumbersome, expensive and required special space, staff and laboratory animals. It was often a false positive because of another hormone, Luteinising hormone ,produced from the pituitary which is produced in the normal menstrual cycle. By now many Hormones were identified, it was also discovered that hCG has a beta subunit fraction which is specific to pregnancy. Special monoclonal anti bodies(proteins specific to particular proteins) were also  discovered for the  beta subunit fraction of  hCG  . Judith Vaitukailis devised the first home based pregnancy test at the national institute of health in 1970 however; she missed out on its patent. These tests are based on antigen (a protein) and antibody reaction. An identifying medium is also added. Initially it was a radioimmunoassay, then they did it with blood, called  haemagglution inhibition test and then later it was a called a latex agglutination inhibition test. A dye was also added for identification. By  1978 all these tests became commercial with an annual sale of 20 million US dollars. In 1968 Margaret Crane got the US patent for 3 million US dollars.

Between the years of 1960 and 1980 ,Further improvement in Immunological techniques and our knowledge on  hormones  increased the bioassay done for pregnancy tests, were totally replaced by immunoassays  for pregnancy testing. Ultrasound also started  playing its role from 1960 onwards. Immunological tests are more sensitive and easier to do. These are a type of tests that measures a protein molecule with another substance for which we are looking for.This is a part of immunology it is called antigen antibody reaction. Proteins called Monoclonal antibodies specific for a particular protein (antigen) were also identified and manufactured.   There   are several thousand types of monoclonal antibodies which react with the special antigens you want them to react with .They are used in thousands of clinical situations in medicine. In pregnancy we want them to pick up  hCG.  Initially researchers identified it as a pregnancy hormone. However they kept getting false positive results. This was due to the presence of another hormone called luteinising hormone which is produced from the Pituitary during each menstrual cycle.  By 1972 it was identified that hCG has 2 fractions alfa and beta subunits. It is the beta sub-unit where the biological and immunological specificity resides as regards pregnancy tests. After all this, different types of pregnancy tests where manufactured, by 1978 the market was full of these tests when we look for the beta sub-unit of hCG the pregnancy tests are 99% accurate. After sexual intercourse the sperm can live in the fallopian tube up to 5 days waiting for the ovulation to occur when the egg   arrives is fertilized and it takes another 10 to12 days for implantation to take place. So the best time to test for pregnancy is about 17 days after sex. These pregnancy tests looking for beta subunit of chorionic gonadotropin, either in blood or urine are highly sensitive. They can be both qualitative  or quantitative. Quantitative  tests in blood can detect beta  hCG  as low as 1mIU/mL while urine test strips can  detect as low as 10mIU/mL  to 100mIU/mL ,depending on the brand of the strip .Most pregnancy  test have a threshold of 25 mIU/ mL  These pregnancy can be false positive. This is generally due to the drugs producing hCG, in accurate testing, some common medications EG; chlorpromazine, phenothiazine and methadone give false positive results Some cancers producing beta hCG, such as liver cancer, germ cell tumours of the ovary, trobhoblastic cancers( these are cancers from the placenta) again give false positive results Treatment of infertility when hCG injection is used for treatment also can give a false positive results . This can often be distressing, you are trying for a pregnancy and you get a false positive result.

Modern pregnancy test  are all immunoassay tests.  A scientist observed that people taking insulin for Diabetes developed antibodies. With this in mind ,researcher started to develop antibodies in animal models. After this immunology progressed; exponentially.  By 1972 the problem of luteinizing hormone was also sorted out as an alpha subfraction of hCG.  Improved prenatal care and legalization of abortion both made it urgent to make diagnosis of pregnancy as early as possible. Initially the immunoassay pregnancy tests were cumbersome needed, test tubes, chemical reagents, filters and so on. But as time moved on they became very simple.

By 1978 FDA approved these tests. Initially they required the help of a doctor or a lab but later 1979 home pregnancy tests were on the market. This gave woman a new opportunity to look after their health and keep the secrecy of their life style to themselves. By now the importance of folic acid in early pregnancy was also known. Further improvement in test techniques made the home pregnancy test very simple and fool proof.  As already mentioned earlier there accuracy was 99%.  They used special monoclonal antibody which reacted with any beat subfraction hCG present in the urine. This also had an agent to cause colour change if the level of hCG  was consistent with pregnancy levels . They are best done two weeks after the missed period. However the newer tests can give a positive reading even before you have missed a period. If you are fairly certain that you may be pregnant, and the test comes negative, you can repeat in few days. These tests come on a latex-coated test strip. This has been treated with different antibodies. The antibodies are placed in three distinct zones.  The first zone contains anti-a hCG which combines with any hCG in the urine and the other is immunoglobulin G (IgG). This a control to see that the test strip is working properly. Before the the urine flows to the second zone two things have happened 1) hCG in the urine had combined with anti-ahCG antibody forms a  complex  and 2)urine suspends the IgG. The urine then flows to the second zone carrying with it the IgG and the anti-a antibody complex. This second zone is the test zone contains anti-b hCG and a dye substrate, which reacts further to create a sandwich which turns bright blue in colour. This technique is referred as Elisa sandwich technique. The IgG from the first antibody zone goes into the third zone. This zone contains another antibody which reacts with IgG and forms another coloured line. This indicates that the test was properly done. The blue line in the test zone and another fainter line in the control zone indicate that the pregnancy test is positive, and the test was properly done. There are many different types of pregnancy tests with different designs and details. These tests have been passed by FDA. These tests have now become digital. On the test kits, it reads pregnant or not pregnant. It also indicates how many days of pregnancy. It is estimated that the home pregnancy market is over 200 million in sales per year. Why do we do these pregnancy tests?  These tests can be qualitative and quantitative. Quantitative test are always on the blood in complex situations of diagnosis and progress of malignant diseases. The urine pregnancy tests are done by almost everyone, women, students, teenagers, nurses and clinicians. These tests are very useful to assess the progress of pregnancy, is it alive and well ?failure of hCG levels to rise indicates that all is not well with the pregnancy. hCG levels double in 48 hours if pregnancy is progressing well . Quantitative measurements if small may indicate an ectopic pregnancy (pregnancy outside the uterus often in the Fallopian tubes). This diagnosis is often confirmed with the help of trans-vaginal  ultrasound. Ectopic pregnancy is a life threatening  condition .This requires urgent treatment The pregnancy test is often required after medical abortion to make sure that the abortion was complete especially if the woman continues to bleed or after removal of molar pregnancy (abnormal products of pregnancy these can sometimes turn into cancer.)Ultrasound also helps .Women with a positive pregnancy test, may also need medical check up in many areas, nutrition, sexually transmitted infections, antenatal care,  termination of pregnancy, contraception and psychosocial support.

It has been 56 years since; I first did the toad test for diagnosis of pregnancy. Today a wide range of tests are available for pregnancy and infertility, with the sale of these products exceeding 200 million American dollars. We have come a long way in 35 years or should I considerate 55years saving the martyrdom to poor rabbits.