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Friday, December 14, 2012

When does life begin and when does it end?

It always fascinated me from the time, and I was very much concerned about origin of life. I try several times to co-relate things from scrap.
According to Veda and Purana, Bramha, Vishnu and Shiva, also known in the form of OM, were self-born and represent the commencement of the universe. These three are supposed to function as God of creation, God of protection and God of destruction. If something is created, no matter whether it is living or non-living, it has some time, meaning it has life till it is destroyed or dead. Its life depends on the quality of the matter it is made up of.
Veda confirms that Human Body is made up of Panchatatwa, the non-living matters, Water, Air, Heat, Earth and Sky. The modern science and the law of physics also confirm that these are the basis of our life.
Scientific explanation by Aristotle in the 4th century BC formulated that living cells develop from non-living matters. The living cells utilize non-living biomolecules for their developmental stability. It is not yet clear how these simple organic molecules could form a living cell? The Evolution Theory of Panspermia explains that there were seeds of life delivered to earth.
Miller-Urey in 1953 experimented and concluded that simple organic molecules could be building blocks of  life. These biomolecules also control and regulate cellular functions. They also noted that DNA and RNA bases could be formed through simulated chemical reaction.
The unit structure of our body is a Cell. Human body possesses more than 200 different types of cells and there are about 5 trillon cells in our body. These are somatic or body building cells. These cells contain entire human genome to build a human being.
In addition to them, man and woman possess special types of cells, the gamet cells. In Men, it is the sperm cell and in Women, it is an egg cell. In vivo, the life of sperm and egg cell is usually 1-2 days. But in in-vitro conditions, only cryo-preservation in liquid nitrogen can stretch their life to different duration. When these two precious cells are left to unite either in vivo or in vitro conditions, another single celled structure is formed called the zygote. From this zygote cell structure, Man and Woman will be developed and born in this world as individuals with the life expectancy of more than 100 years! Is not it interesting? 
The zygote seems to have some tricks of programming the developmental process and, may be, life expectancy too. How, when and what level does it program life expectancy of an individual cell? The zygotes undergo phases of cell cleavage and continuously divide into different cell types when it becomes an embryo.  During differentiation process, in a fetal life, they form different organs and systems of human body.
I have closely watched these cells during In-Vitro Fertilization treatment process, their cleaving process in cultured environment, the two-celled stage, four-celled stage, till blastocyst stage and pre-embryo. They then start differentiating into several cell types. There are specialized and responsible for the development of special organs, while the unspecialized cells are popular as stem cells now-a-days as they can be used to repair abnormal tissues of the body. These cells are extracted from a pre-embryo, cultured after their nucleus is removed from another cell without removing nucleus and allowed to fuse and grow. Thus, these fused growing cells carry the property of nucleus carrying cell. This is now a cloned cell prepared for particular purpose.

These days, not only cells and tissues, but a whole human can be cloned like an identical twin but clones differ in age. After the advent of cloning, it is clear that genetic material determines traits. Among all other cells, the embryonic tissue seems best for tissue cloning. It is not easy, but possible to clone any type of body cell or tissue. Its role is great in different disease state like Alzheimer's, Genetic disorders, where there is irreversible tissues damage. As such, the damaged tissue and be replaced by cloned tissues, so that the organ can function well. This is therapeutic  cloning. Modification and insertion of new type of genes delays the disease process. In addition, cloned embryos are supposed to produce smarter children. On the other hand, cloning technique has some answers to the origin of life given in Purana. In those era, the devil, Raktabiz was created by a drop of blood, and today fetal cord blood is used as one of the sources of stem cells for cloning, which may further be useful to create the whole human if not the similar Devil.
Overall these techniques have opened a new era in the line of Tissue engineering and Medicine apart from different types of grafts of different origin for replacement therapy. The successful application of implants, organ transplant and separation of conjoint twins assures a lot to develop in area.
On the other hand, there is also a great danger of such knowledge being misused. Unethical insertion of genes apart from the therapeutic purposes may even causes disasters.
There may be cross breeding of Human embryos with animal cells and some day pure human being with 46 chromosomes may be rare to identify . This part of science may develop newer creatures which may neither look like a human nor like an animal. With this technology, it looks possible to have ten headed Ravana, elephant-headed Ganesha and goat-headed Dakchhaprajapati around us in the years to come.
Such knowledge of creation and development has led to much confusion in this era. What is the eventual destiny of all these creatures? How do they vanish? Do they really vanish?
What is death and when does a man die?  Is it supposed to be the end of life?
There is also a great concern about death of an individual which is death of a million celled human. Does a human die when heart stops working, the ECG goes flat and there is no consciousness? It is just the death of these functional units, but all the cells and organs have not died. What about the organs transplantation (like eyes, kidney etc.)
after death? If these organs can be functional in another living individual how can we call it a dead? It is very important to note the death of different organs. Do we really know when all these organs die?
It is well known fact that in human context, a clinical death is declared after failure to regularize the functions of heart and lungs by all resuscitation measures. When there is loss of consciousness with cessation of all activities of the brain, brain death is declared and the individual is biologically dead.
Brain death can be compared to the death of central processing unit (CPU) of computer which loses the command to particular activities of body. This causes loss of command to pump blood by the heart, death of heart leads to loss of ventilation to lungs, death of lungs stops the blood flow into blood vessels and eventually there will be loss of response to all stimuli due to unavailability of nutrition.
Loss of blood circulation decreases the body temperature, gradually down below 37 degree which stops cellular metabolism and production of energy. When the source of free energy production in the body, necessary for the living cell function is stopped, the cells turn harder, change in color from pink to pallor to bluish to black.
If a young man's heart fails, transplantation of heart itself or an artificial circulation system to other organs along with the application of an artificial heart pump in place of  the heart may well revive the individual for quite some time though there may not be total consciousness. We can also switch on a ventilator and check all his survival possibilities. These are all trials to buy the time lag which has something to do with revitalization. In Hindu ritual a dead body should be cremated before it gets damaged. How long does the body take to be damaged? None of the religious books properly define death in relation to individual cell life.
In conclusion,
Ø  Every cell has definite life but who programs its life is yet not clear.
Ø  Human life begins from zygote stage.
Ø  Human cell has definite life but who programs its life is yet not clear.
Ø  All human body cells do not die when man dies.
Ø  There must be proper Scientific and religious outlines to declare when a man really dies. Perhaps there is no Life of human beings, rather, it is the lives of all cells in Toto, yet to be identified.
                                                                                                                       Dr.Uma Shrivastava

Wednesday, October 10, 2012

An old article about Test-tube baby

Nepali ‘test-tube baby’ could become a reality


By Suvecha Pant

KATHMANDU, July 9: 2002 

What can be termed as a breakthrough in science and technology in Nepal, "test-tube" baby production is underway for couples who are without children or who have not had one for a long time.
A treatment centre at Putalisadak, Kathmandu, which for over eight years has been helping treat infertile males and females, from Sunday has begun the initial stages of producing test-tube babies for couples without children. Already two childless women are beginning the initial tests.
"This is good news for the fifteen percent of the population in Nepal who are childless" said Dr. Uma Shrivastava, working at the Infertility Research Centre. She further added that equipment required for the production of test tubes had been brought and the research to produce the first test-tube baby in Nepal was underway.
So, how are test-tube babies produced? "In Vitro Fertilisation (IVF) or test-tube babies are the basic assisted reproduction technique in which fertilisation occurs in vitro (literally in glass)," explained Shrivastav. She further added that the man’s sperm and the woman’s egg are combined in a laboratory dish, and after fertilisation, the resulting embryo is then transferred to the woman’s uterus.
"The five basic steps in an IVF treatment cycle are superovulation (stimulating the development of more than one egg in a cycle), egg retrieval, fertilisation, embryo culture, and embryo transfer," said Shrivastav adding that the stimulation period would begin by August.
"IVF will benefit Nepali couples that are not able to conceive for various reasons and presently have to travel to India spending hundreds of thousands of rupees," said the doctor who is also a masters degree holder from the University of London in Reproductive Endocrinology. "Although some of these couples have given birth to children, there are still many women who have had to return without conceiving."
Therefore, at a cheaper price than India, the centre plans to provide the same services of IVF. However, IVF is not a foolproof solution, warns Shrivastav. "IVF does increase the chances of conceiving as it is assisted reproduction in which the doctor lends a helping hand to the natural process, and the success rate is around 20 per cent."
Inspite of this, for those parents who are without children, even this success rate brings some sense of hope.
Although very common in developed nations, both the lack of highly trained doctors in Nepal and the expense of producing test-tube babies have restricted its use.
Travelling back in history, the first test-tube baby was born in England only 20 years ago. This birth through in vitro fertilisation revolutionised medical treatments for infertility, making it possible for thousands of women to conceive.
On the other hand, the birth of the first test-tube baby caused an international sensation, with some critics denouncing conception outside the body as immoral.


Published article on The Kathmandu Post, July 09, 2002

Saturday, October 6, 2012

An interesting case with Genetic disorder



Mrs. N.  Bajiko 30 yrs. married for 5 years came to Infertility centre with secondary infertility in 2009. She complained of three abortions at 7-8 weeks gestation, two of them were curetted & one of which was ruptured ectopic right sided, for which she had undergone laparotomy.
Karyotyping of the abortus tissue showed Trisomy 20 (47 XX) (tested in Delhi).
Her blood PCR for MTB showed negative.
She had undergone treatment of danazol for six months for unknown reason.
Her menstrual history had normal cycle 35-36days with average flow for 3-4 days.  On examination, Wt = 70 kg BP = 120/80mmHg.
Laboratory investigation:
Semen analysis - Sperm count 200 mln/ml with 80% motility & 70% morphology
HSG showed both fallopian tubes patent
Hormone profile (D2) at Infertility centre
FSH = 6.5                  
LH = 2.3           
E2 = 120
PRI = 3.9
TSH = 10.9
Both ova & sperm could have role in recurrent abortion. Therefore, ovulation was induced with clomiphene form D4-D8.  When 2 follicles reached 18-20mm on transvaginal ultrasound, 10,000IU HCG was injected for complete development of follicles & maturation of ova which was followed by Intrauterine insemination(IUI) recovered conception.
Hypothyroidism was treated with 50mg thyroxin even during conception. She was also supplemented with Didrogesterone, Folic acid 10gm, vitamin B-complex till 12 weeks gestation, iron, calcium, prophylactic Anti-TORCH treatment with Rovamycin 3mIU till 20 weeks.
All routine tests at 20 weeks gestation including RBS were within normal limits.
She had severe itching at 28 weeks gestation which was treated with calamine lotion as her liver functions were normal. An early labor sign at 31 weeks were treated with isoxsuprine & salbutamol.
At 38 weeks, when placental maturity was assessed by scanning, an elective Caesarean section was planned & a beautiful baby girl was delivered. As the girl has completed 2 years, she came again for second trial for fertility & has conceived with just progesterone supplement & folic acid. Her pregnancy is at 20 weeks & the scan shows normally growing fetus.

Was this a case of genetic abnormality? If yes what cured her defective gene?

Friday, September 28, 2012

Pregnancy after 35


SHRADHA PAL
KATHMANDU: Get married soon, time is running out, if you marry late (30’s is the dreaded age), you won’t be able to conceive’ — such naggings never stop till the daughter succumbs to parents’ wishes. But is it true? Is it risky to conceive when you are in your 30’s? Society says yes, but the doctor disagrees.

“It is not true. The egg count will lessen as you age, but there is a possibility to become pregnant,” clears Dr Bimala Lakhey, Sr Consultant Obstetrician Gynaecologist.

Despite this information people may still be sceptical as old habits die hard. Therefore, relating to the pressures a woman faces, is it a good idea to become pregnant during mid 30’s? Nepali society is such that many women are financially dependent on their husbands, so if a woman marries late followed by pregnancy, it is a sound decision. “If a woman opts to be pregnant in her 30’s, then she is emotionally ready to handle the responsibility and is financially secure, so I support this decision,” encourages Dr Lakhey.

Some risks

With this you also have to understand that till the age of 35 there won’t be any problems as such, but after that there can be complications, which should be noted.

Some risk or complications are —

• Low birth rate.

• Chances of miscarriage — “If in 20’s chances of miscarriage is 25 per cent, in 40’s it is double due to chromosomal abnormality,” says Dr Lakhey.

• Child can suffer from Down’s syndrome.

• As the egg count is less in this age group, becoming pregnant may take longer.

• Chances of having twins increase. “This is because of egg increasing medicine.”

• Developing high blood pressure, which is an age factor.

“Nonetheless, it is not alarming though comparatively to younger age, the complications can be more,” adds Dr Lakhey. There are treatments and diagnosis that can deal with such issues.

Also good health will help before you conceive, for which you need to eat food with folic acid content “present in green vegetables”, a balanced diet also becomes important, limiting your caffeine consumption, exercising regularly, not drinking alcohol and not smoking.

Talking about pregnancy, the role of the biological father is also important to mention. “If the father is more than 50 years old, then the child born will have chances of being autistic,” says Dr Lakhey.

So what after the pregnancy?

“She has to be alert about the diabetes and has to be under constant medical supervision, also screening test should be conducted to check chromosomes,” answers Dr Lakhey.

Other than that one need not worry.

Boon of medical

science 


When one door closes, the other opens. If it doesn’t work naturally for you, then there is an alternative — In Vitro Fertilisation (IVF).

So who should opt for this process? “There are many indications for IVF,” says Dr Uma Shrivastava, Infertility and IVF Specialist and Director at Infertility Centre, Bijulibazar, New Baneshwor which are —

1. If both the fallopian tubes are blocked.

2. Male infertility

3. Failed IVF

4. Failed conventional treatment

5. Failed ovulation

6. Endometriosis

7. Unexplained infertility

This is definitely a boon of medical science, but Dr Shrivastava asserts that it shouldn’t be fashion, which is the trend these days. This process is a blessing for many, but to understand every aspect is also equally important. There are complications of IVF, “which should be highlighted,” asserts the doctor, such as —

• Multiple pregnancy

• Ovarian Hyperstimulation Syndrome (OHSS) in Polycystic Ovarian Syndrome (PCOS), “which can also lead to death,” warns Dr Shrivastava.

• Other hormonal complications like increasing cyst and failed stimulation, “where after one IVF, the woman can go into early menopause”, which means she can never become pregnant.

The more knowledge you have, the better decisions you can make. Therefore, before opting for IVF, proper hormone test is vital. You have to first visit the hormone specialist known as endocrinologist. After s/he gives the green signal, then it is the gynaecologist’s job and so the process moves forward.

However, not everyone can opt for IVF. If you have inactive ovary, do not think about IVF instead “you should take a donor egg,” suggests Dr Shrivastava. Another case is — if you have tumour in your uterus, an alternative for such women can be “surrogacy”.

Every woman at some point of her life wants to be a mother, when she is ready. Or what is wrong if she doesn’t want to be pregnant? More than science or societal pressure, ultimately the choice should to be hers!


Article Published on The Himalayan Times
2012-09-17

Thursday, September 27, 2012

Protocol for Infertility Treatment in Nepal


HIMALAYAN NEWS SERVICE
KATHMANDU: Health experts today suggested for a practical protocol on infertility to handle legal, ethical and technological issues.

The Ministry of Health and Population is drafting the ‘Protocol for Infertility Management in Nepal’ to determine necessary investigations of underlying cause of infertility and for the management of infertility by conventional methods.

Dr Uma Shrivastava, reproductive endocrinologist at Infertility Centre Nepal, said the protocol is essential for the management of infertility by Artificial Reproductive Technologies and for managing the complication of infertility treatment. In addition, the policy is also essential to follow the common procedure by health personnel to identify and treat the cases of infertility.

After identification of the underlying cause, treatment should be managed according to the available facility in rural or urban areas. For unavailable necessary treatment, cases should be referred to the appropriate centres for proper management, said the endocrinologist.

According to Dr Shrivastava, the infertility is estimated to affect about 10-15 per cent of Nepali population.

About one third of infertility cases are due to male factors, other one third due to female factors and the remaining third due to combination of both male and female factors, she said. The origin of the condition of about 20 per cent cases is unidentified or unexplained.

Infertility is more of a social priority than an individual’s need. In most ethnic communities, it is accepted as a defect in the female partner, even though male partners contribute equally, said Dr Shrivastava.

Due to joint family trend, women are emotionally distressed as a consequence of infertility. Therefore, she said, the treatment should target more on counseling the couple about their personal, social and marital distress before their cure.

Chances of infertility are higher in couples who have gone through abortion. The country has recorded 95,000 abortions in the fiscal year 2010/11.

Dr Babu Ram Marasini, chief of the health sector reform unit at the ministry, said the policy is going to incorporate legal issue of surrogate mother, biological father, test tube baby and other ARTs within it.

ARTs are methods used for fertilisation or making women pregnant by artificial means in case of infertility.

This method is also used in fertile couples for genetic reasons. Some of the ART methods practiced in Nepal are Artificial Insemination of Husband, Artificial Insemination Donor and In Vitro Fertilisation.

The country does not have any legal backing for surrogate mother, biological father and ARTs which can create a problem regarding property right, citizenship rights and protection rights in near future, said Dr Marasini.

Pregnancy followed by ARTs could bring many ethical and legal challenges in the country. The government should give the mandate to carry out the procedure for Test tube babies or IVF, he added.  
Article Published on The Himalayan times dated 6/7/2012

Monday, June 25, 2012

Friday, June 15, 2012

Polycystic ovary (PCOS) pictures - Infertility Centre
















Sunday, May 27, 2012

Prevalence of Polycystic Ovarian Syndrome in Nepal


                                                                                                           Dr. Uma Shrivastava 
                                                                                          Infertility Centre, Bijulibazar, Kathmandu

Introduction   

Most common cause of female infertility
(Nestler JE Fertil. Steril:77: 209 March 2002)                                                              
Presents with Anovulation & Infertility
Multiple small cortical follicles with typical necklace like appearance in both ovaries
Vague multi-systemic endocrine disorder
High level of hormones LH: FSH ratio, DHEAS, Prolactin, TSH, Insulin etc.
By the age of 40 years up to 40% of women may develop type 2 diabetes or impaired glucose tolerance
Women with PCOS are at the risk of MI & heart disease seven times more than normal women
                     

Prevalence rate 

Among women of reproductive age 28-31%
(Knochenhauer ES. J Clin Endocrinol Metab. 1998 Sep;83(9):3078-82 & 2000 Jul;85(7):2434- 8)
Among obese women 28-30%
Alvarez-Blasco F. Arch Intern Med. 2006 Oct. 23;166(19):2081-6)
Among Hirsute 23%
(J Clin Endocrinol Metab. 2000 Vol. 85, No. 11 4182-4187)
Among Frank diabetics 33%
(Fertil Steril. 2006 Aug;86(2):405-10. Jun8)
Genetic link –affected sisters up to 80%
(Fertil Steril. 2001 Jan;75(1):53-8)
Among ischaemic heart disease 46%
(MJA 1998; 169: 537-540)

Signs & Symptoms 

Anovulation
1. Early Cycle
2. Regular Cycle
3. Late Cycle
Obesity
Hirsutism
Acne
Alopecia
Acanthosis nigricans

 Etiology 

Clearly unknown – an Enigma
Insulin resistance
Hyper-secretion of Lutenizing hormone
Hyperandrogenism
Genetic predisposition  

 Pathogenesis


 I. Insulin Resistance
Normally glucose is passed into the cell through insulin receptors doorway
The average healthy body contains 20,000 insulin receptor sites per cell
The average overweight individual with PCOS can have as few as 5,000 insulin receptor sites
In PCOS few receptor sites will not allow all the glucose into the cell
Glucose remains in the blood stream
Glucose is converted into fat and stored via the blood stream throughout the body
Excess fat lead to weight gain and obesity

II. Increased peripheral Estradiol & estrone levels
Stimulates numerous follicular growth
Some follicles undergo luteinization
Stimulates stroma & theca of ovary, increase surface
Multiple follicles surrounded by hyperplastic theca
Some follicles remain stunted & few undergo atresia
Prevent normal follicular development - Anovulation !
III. Androgen excess
Stimulates stroma & theca of ovary, increase surface
Multiple follicles surrounded by hyperplastic theca
P450 aromatase gene mutation
Production of excess Androgen & testosterone

IV.  Abnormal gonadotropin dynamics
Altered diurnal rhythm of LH secretion
Increased LH pulse frequency
Stimulates numerous follicular growth
Feedback increase in FSH
More new follicles growth
Accelerates LH production & suppress FSH
Elevated LH:FSH ratio

Materials & Methods

Retrospective study conducted at the Infertility & IVF Centre, Kathmandu
A counseling & laboratory based study
Duration (Sept. 2003 - Nov. 2006)
The study population- women willing to conceive & adolescence with irregular menstrual cycle
Total female analyzed = 3740

 PCOS diagnostic criteria

A. Symptomatic (Counseling)
Irregular cycle
Positive family history
Hirsutism
Obesity
B. Laboratory Evaluation
High level of hormones (LH, Insulin, Androgen, Prolactin, Estrogen etc.)
Ultrasonic evaluation – Abdominal & trans-vaginal ultrasonography of the ovaries
•       Black pearl necklace-like appearance of multiple cortical cysts
Ovarian volume of more than 10 cm3
C. Exclusion of secondary causes
       

Management of PCOS

Ovulation induction - Clomiphene citrate , FSH, GnRH etc.
Insulin sensitizing agents – Glucophase, Pioglitazone, D-chiro inositol etc.
Weight reduction - Diet management
OC pills
Ovarian volume reduction-Surgical procedure

Conclusion

Previous studies          

Up to 31% prevalence PCOS
(Asuncion M. J Clin Endocrinol Metab. 2000 Jul;85(7):2434-8)
Higher prevalence in Indian than Chinese ethnic
       (Williamson K. Aust N Z J Obstet Gynaecol.2001 May;41(2):202-6)

Our study (Infertility Centre)

Total female analyzed = 3740
Hormonal & other disorder = 2200 (58.9%)
Structural & functional PCOS = 1500 (40%)
Cut off = 40
About 400 PCOS (40%) in 1000 reproductive disorders
More studies needed in this area
                                                                      (Paper presented at NESOG Conference 2007)

Tuesday, May 1, 2012

Nepali ‘test-tube baby’ could become a reality

By Suvecha Pant
Kathmandu Post
KATHMANDU, July 9 2002.
What can be termed as a breakthrough in science and technology in Nepal, "test-tube" baby production is underway for couples who are without children or who have not had one for a long time.
A treatment centre at Putalisadak, Kathmandu, which for over eight years has been helping treat infertile males and females, from Sunday has begun the initial stages of producing test-tube babies for couples without children. Already two childless women are beginning the initial tests.
"This is good news for the fifteen percent of the population in Nepal who are childless" said Dr. Uma Shrivastava, working at the Infertility Research Centre. She further added that equipment required for the production of test tubes had been brought and the research to produce the first test-tube baby in Nepal was underway.
So, how are test-tube babies produced? "In Vitro Fertilisation (IVF) or test-tube babies are the basic assisted reproduction technique in which fertilisation occurs in vitro (literally in glass)," explained Shrivastav. She further added that the man’s sperm and the woman’s egg are combined in a laboratory dish, and after fertilisation, the resulting embryo is then transferred to the woman’s uterus.
"The five basic steps in an IVF treatment cycle are superovulation (stimulating the development of more than one egg in a cycle), egg retrieval, fertilisation, embryo culture, and embryo transfer," said Shrivastav adding that the stimulation period would begin by August.
"IVF will benefit Nepali couples that are not able to conceive for various reasons and presently have to travel to India spending hundreds of thousands of rupees," said the doctor who is also a masters degree holder from the University of London in Reproductive Endocrinology. "Although some of these couples have given birth to children, there are still many women who have had to return without conceiving."
Therefore, at a cheaper price than India, the centre plans to provide the same services of IVF. However, IVF is not a foolproof solution, warns Shrivastav. "IVF does increase the chances of conceiving as it is assisted reproduction in which the doctor lends a helping hand to the natural process, and the success rate is around 20 per cent."
Inspite of this, for those parents who are without children, even this success rate brings some sense of hope.
Although very common in developed nations, both the lack of highly trained doctors in Nepal and the expense of producing test-tube babies have restricted its use.
Travelling back in history, the first test-tube baby was born in England only 20 years ago. This birth through in vitro fertilisation revolutionised medical treatments for infertility, making it possible for thousands of women to conceive.

Quiz Case
Infertility Centre

A 32 yrs. old healthy looking, actively working for women development lady visits Infertility Centre with complaints of missed period for about three months. She also complained of no issue with eight years of married life. She does not have any significant medical history. In the menstrual history, she got her menses at the age of sixteen. Since then, the cycle is irregular which comes at the interval of 40 days to 10 months period. During menses she has very scanty flow for about four days. She often has abdominal discomfort during flow period. She has two sisters who were not married. She does not smoke nor drinks.
Her husband 33 yrs old, physically active & has one elder brother who has two children. He drinks alcohol only during weekend but does not smoke.
 Physical examination of the lady: General look fair; weight = 48kg; height = 5'2''; B.P. 110/70mmHg. She had normal female type hair growth, normal breasts & female type voice. Pelvic examination showed normal vulva & vagina. Per speculum examination showed the cervix was normal size but little pale. On per manual examination, uterus  anteverted, normal sized, adnexae free. Thus she was found to be a physically a normal lady.
Hemogram: HB = 10.8; TC = 7000; N = 68 ; L = 20; E = 7 ; M = 5 ; ESR = 16 mm/hr
Urinanalysis: Nothing significant
Hormone profile on D2: FSH = 43.1mIU/ml; LH = 6.4 mIU/ml; Prolactin = 112.9; Estradiol = 16.6 pg/ml; TSH = 2.0 mIU/ml
Her HSG showed patent both fallopian tubes.
Basal ultrasound with transvaginal probe showed both ovaries with immature follicles. The uterus was slightly small in size with midline endometrium.
This lady was treated only for two cycles for conception. She has a healthy baby boy & is living very happy life. 
Can anyone outline the treatment for her conception?

Saturday, April 7, 2012

Adenomyosis

Adenomyosis is uterine thickening that occurs when endometrial tissue, which normally lines the uterus, moves into the outer muscular walls of the uterus. 

Symptoms of Adenomyosis:

  •     Heavy or prolonged menstrual bleeding
  •     In some women, adenomyosis is "silent" — causing no signs or symptoms — or only mildly  uncomfortable. But other women with adenomyosis may experience
  •     Severe cramping or sharp, knife-like pelvic pain during menstruation (dysmenorrhea)
  •     Menstrual cramps that last throughout your period and worsen as you get older
  •     Dyspareunia
  •     Bleeding between periods -intermenstrual bleeding
  •     Passing blood clots during your period
  •     Uterus may increase to double or triple its normal size, lower abdomen seems bigger or feels tender.


Causes of Adenomyosis


The cause of adenomyosis isn't known. Expert theories about a possible cause include:

    Invasive tissue growth. Some experts believe that adenomyosis results from the direct invasion of endometrial cells from the surface of the uterus into the muscle that forms the uterine walls. Uterine incisions made during an operation such as a cesarean section (C-section) promotes the direct invasion of the endometrial cells into the walls of the uterus.
    Developmental origins. Other experts speculate that adenomyosis originates within the uterine muscle from endometrial tissue deposited there when the uterus was first forming in the female fetus.
    Uterine inflammation related to childbirth. Still another theory suggests a link between adenomyosis and childbirth. An inflammation of the uterine lining during the postpartum period might cause a break in the normal boundary of the cells that line the uterus.

Regardless of how adenomyosis develops, its growth depends on the circulating estrogen in a woman's body. When estrogen production decreases at menopause, adenomyosis goes away.

Thursday, April 5, 2012

Luteinized Unruptured Follicle(LUF)

-Dr. Uma Shrivastava


Luteinized Unruptured Follicle(LUF) is the condition when there is normal ovum development within the follicle which turns into the corpus luteum without its release from the follicle due to inability of follicle rupture.
The possible cause of LUF is absence of LH surge at the time of ovulation. LH indirectly lutenizes the follicle by inducing progesterone production in the follicle. Formation of corpus luteum continues & production of both estrogen & progesterone hormones also continues as in normal folliculogenesis.

Wednesday, March 28, 2012

Recurrent abortions

Dr. Uma Shrivastava, Infertility centre

Most of the recurrent abortions at early weeks are due to TORCH infections, high prolactin hormone levels, folate & other vitamin deficiencies.
Therefore correction of prolactin level before conception & supplement of Vitamin B6 during conception period will help normal fetal development at early weeks & further.
TORCH infection can be tested before conception by IgM & IgG.
In case of IgG positive cases also it is worthwhile using Spiromycin 3mIU for 3 weeks before conception, which will prevent very early attack from the virus in next conception. When conception occurs, supplementation of Spiromycin 3mIU till 20 weeks will prevent effect of the virus.
In both the above conditions supplement of Vitamin B complex & folate 1gm should be continued for at least 25 weeks of gestation. In addition, Iron & calcium supplements should be continued till term.
The above conditions should be well supported by progesterone till 12 weeks of gestation. It is always good not to let patient move around on her own. Rest can be allowed for 12 weeks till complete placentation.
The patient must be in well contact to the doctor for any emergency which can be managed in time.



Wednesday, March 14, 2012

Surrogacy issue has a legal hole

Article published on Kathmandu Post, April 30 by: DEV KUMAR SUNUWAR
Lack of legislation to recognise surrogacy has led to disputes, complications and insecurity for couples opting for it, say experts.
The Kathmandu District Court settled the first surrogacy related lawsuit last month but left a legal vacuum. In the lawsuit involving Shambhavi Shah and her husband Ujjwal Shumsher Rana, the court issued a verdict stating that a surrogate child is equally entitled to inheriting parental property. 
The verdict, however, does not resolve the problem. Surrogacy is common in infertile Nepali couples, at hospitals inside or outside the country. Since surrogacy is legal in India many couples and surrogate mothers flock to Indian hospitals. 
“Since the country lacks legal provisions on surrogacy, I had to take several references from other countries while issuing a verdict on this particular case,” said Judge Tek Narayan Kunwar. The judge said that though the case was not one of surrogacy as there seemed no consensus between husband and wife, lack of laws to govern such problems could give rise to disputes.
Surrogacy, as practiced in India, requires a couple’s agreement and the egg of the biological mother is fertilised with sperm of the father in a test tube and the embryo then transferred into the uterus of the surrogate mother. 

“Childless couples prefer surrogacy to adopting a child, because the baby is genetically theirs,” says Dr Uma Shrivastava, an Infertility and In Vitro Fertilisation (IVF) specialist. “I do not see any problem giving legal recognition to surrogacy.” 
According to doctors, mostly women who undergo several IVF cycles, multiple miscarriages, or have had their uterus removed fail to conceive. An estimate has it that around 15 percent of Nepali married couples are infertile.  
“The agony of infertile couples is more severe than that of those with HIV/AIDS, cancer or uterine prolapse,” said Dr Bhola Rijal, a senior gynaecologist and obstetrician. 
Since July 2004, Dr Rijal and his team have offered IVF services for over 350 test tube babies and treated over 1300 infertile couples at the IVF centre in the Chabahil-based Om Hospital and Research Centre.
“Many countries including India and Malaysia have given recognition to surrogacy. This has long been in practice in Nepal and many Nepali women go to India to act as surrogate mothers. Therefore, it is better to give legal recognition to surrogacy here,” added Dr Rijal. 
 Sapana Pradhan Malla, a Constituent Assembly member and women’s rights activist, says that surrogacy could be a boon for needy couples but she argued that when it comes to legal recognition, much has to be discussed. “Surrogacy should not be promoted haphazardly. If it is to be legalised, there should be a provision whereby needy couples could do it only after medical recommendation.”

Monday, March 12, 2012

Be conscious!


If you are having irregular menstrual cycle, you may have fertility problem but if you have a regular cycle even then you may have fertility problem. Therefore get your reproductive hormones profile done on D2/D3 of the cycle, you will know whether you have any problem or not.

Sunday, March 4, 2012

Sonosalpingography vs. Hysterosalpingography

Objectives:
This study was conducted to bring into focus the value of pelvic sonograms in assessing tubal patency in order to overcome the radiation hazard associated with hysterosalpingogram (HSG), reduce the cost of examination and encourage it as first – line office based procedure for the diagnosis of female infertility. Hence the present study was undertaken to evaluate uterine outline and tubal patency in infertile patients by transvaginal sonosalpingography (SSG) and to compare it with HSG.
50 infertile patients undergoing routine infertility investigations were selected randomly who agreed to participate in the study.  Within three – four months before or after hysterosalpingography, sonosalpingography was performed. The uterus and tubes were identified using a 6.5 MHz vaginal ultrasound probe and around 10 – 20 ml of normal saline was injected into the uterine cavity through an endocervical catheter. In addition, the procedure was performed with prophylactic antibiotics
Main outcome measures:
The shape of the uterus and its cavity, the flow of saline through the tubes, the presence of hydrosalpinges before or after the injection of saline and the presence of free fluid in the pouch of Douglas.
Results:
Most of the cases studied were between the age group of 25-30yrs (51 percent), and the mean duration of infertility was around 6-10 yrs (39 percent).  Sonosalpingography revealed bilateral patent tubes in 60 percent cases, and the remaining 40 percent cases showed either bilateral or unilateral block of the tubes. The sonographic and hysterosalpingographic findings were similar in 94% of the women with respect to uterine assessment and in 81% with respect of tubal findings. The sensitivity of sonosalpingography in diagnosing tubal patency was 85% and the specificity 84%. Adverse events of sonosalpingography included mild to moderate pelvic pain was noted in 6 patients. Infectitious complications was not revealed.
Conclusion:
The results confirm that sonosalpingography utilizing saline as a contrast medium is a reliable, inexpensive, simple and well-tolerated method to assess tubal patency in an outpatient setting.
Sonographic hysterosalpingography is a simple office procedure which should be used in the preliminary assessment of the uterine cavity and the fallopian tubes. Its use will reduce the need for hysterosalpingography. 
However, in case where surgical interventions had taken place HSG may still prove useful.
 
 
Following, is an article regarding the first test tube (IVF) baby of India, extracted from the website of Deccan Herald:



Saturday, October 04, 2003




I feel like Edison’s bulb, says India’s first ‘test tube baby’
 D H News Service BANGALORE, Oct 3
She sat in the corner of the auditorium quietly listening to the presentations. Suddenly her name was announced and all eyes turned to her. The audience applauded and the lensmen clicked on Kanupriya, India’s first and world’s second test tube baby, now a 25-year-old marketing executive in Delhi.

“I often feel like Edison’s bulb. Everybody talks about the bulb, very few know about the man who founded it. I wish this applause could go to Dr Subhash Mukherjee, the architect of In-Vitro Fertilisation (IVF) in India. Unfortunately he is now no more,” said Durga alias Kanupriya while addressing a gathering of doctors and specialists at the 25th anniversary celebration of IVF in the world, here today. It was organised by Indian Council of Medical Research (ICMR), Hope Infertility Clinic and Inter Academy Biomedical Science Forum, Bangalore.

“I feel no different from others, thanks to my parents, especially my father, who kept me away from media glare. I was told in phases about my birth but I understood more as I grew up. My first question to my parents was regarding Dr Subhash because his name was often mentioned. They told me he was the man who helped in my birth. Unfortunately I could not spend much time with the doctor as he died when I was very young,” said Kanupriya.

Her father P K Agarwal, a businessman from Kolkata came all the way to celebrate his daughter’s birthday in Bangalore, which was commemorated as IVF’s 25th anniversary. He said he was averse to media because, “Media was skeptical about the technology employed by Dr Subhash. The irony is that it was the time when the rest of the world was celebrating the birth of Mary Louise Brown, who preceded my daughter by 67 days and became the world’s first test tube baby,” said Mr Agarwal. India’s first recorded test tube birth was in 1984 in Mumbai.

He narrated his first visit to Dr Subhash who was a noted endrocronologist, physiologist and gynecologist at Nilratan Sarkar Medical College, Kolkata. “I told him we were a childless couple and my wife’s fallopian tubes were blocked.

He said he could help but he warned that the child could be deformed or disabled. He explained to me the IVF procedure. I agreed ,” said Mr Agarwal. Born on October 3, 1978, Kanupriya’s birth remained unrecognised in the medical history because Dr Mukherjee could neither document his research in IVF nor make it public because of the controversy it would have raised. 

Monday, February 20, 2012

An Infertility Case Study

Mrs. K. P. aged 46 visited Infertility Centre with the complaints no living issue for 21 yrs. married life. They were referred to infertility centre by a Senior Gynaecologist for their complicated infertility problem.
They had two abortions at three to four months gestation. The last abortion took place six years ago. Since then she could not conceive but the details of the previous treatment was kept confidential within the doctor & the husband. Their past treatment record showed that she had artificial insemination of donor sperm because the husband had no sperm in his semen. She did not know that she got pregnant by donor insemination. During our counselling, the lady did not show any interest in treatment for herself because her menstrual cycle was already getting late & she lost hope of getting pregnant.
On examination, her physical built was good with her body weight of 65 Kg. Her cycle interval was 23-43 days with flow of 1-2 days scanty flow.
On the second visit however she was ready only for Hysterosalpingography (HSG) which revealed normal looking uterus with patent both fallopian tubes.
On third visit she brought her sister & wanted us to examine her whom the lady forced to marry with her husband for the sake of a child in their family.
 The second wife Mrs. S. Paudel 31 yrs. married five years ago & she also could not conceive. She was thin built with short height but her general physical condition looked quite fair with body weight of 39 Kg. Her menstrual cycle was 28-30 days with 5-9 days of flow. On pelvic examination the use of speculum could not clearly distinguish the cervix from vagina. In addition, the vaginal cavity was also narrow. The outline of cervix looked rather rudimentary. Careful surgical excision was done to separate the vaginal flaps which covered the cervix. She was then asked not to try conception for at least three months.
After surgical correction she was properly investigated for conception.
Her D2 hormone profile: FSH=7.4mIU/ml; LH=1.1mIU/ml; Estradiol=40.5pg/ml; Prolactin=30.8ng/ml; TSH=3.3mIU/ml.
Hyperprolactinemia was corrected with bromocriptin therapy.                                                                                           
This time, it was easy to access the cervix to perform HSG. Her HSG showed normal uterine cavity with patency of both tubes.
Semen was analysed which had no sperm. Thus, the conception was only possible with donor insemination. With written consent of the couple, Intra Uterine Insemination (IUI) of donor sperm was planned. Ovulation was stimulated for recruitment of more follicles with cyclic clomiphen citrate 50-150 mg. Development of follicles was serially monitored by transvaginal ultrasound. When at least one follicle reached 18mm, Human Chorionic Gonadotropin was injected & IUI was done within 30-48 hrs. Since they lived far away, their treatment was not regular. However, she finally conceived after total six months of IUI treatment.  She was followed up by us till 30 wks of gestational period & referred back to the same doctor for the delivery. She delivered a healthy baby boy. 

Thursday, February 2, 2012

Scope of stem cells in regenerative medicine


Article Published On Kathmandu Post, February 12



    FEB 12 - 

    From conception till birth, the body structure of any species is generated through biological processes. In humans, the development of a mature foetus from a zygote involves multiplication of cells and their controlled and co-ordinated tissue growth, movement, and differentiation. And following further phases of degeneration and regeneration of tissues and organs, man comes to full form.

    Regeneration continues throughout human life. It is what is responsible for speedy healing of any injury or ill-developed organs. Some organs, such as the liver, are known to regenerate easily. But this isn’t the case with all organs and the inability to regenerate in response to injuries or diseases can sometimes be fatal.

    Regenerative medicine is thus directed towards healing fractured bones, burns, blindness, deafness, damage of muscle, nerve, blood vessel, etc. Age-related degeneration and damage can also be repaired by such therapy. The therapy uses the patient’s own tissue from other body parts to heal the injured site. Metallic and plastic materials are often used to repair tissue damage, but the chances of the body rejecting these materials and creating hurdles in healing are high owing to their bio-incompatibility.

    Damaged tissues are generally replaced naturally with the help of primitive progenitor cells or ‘stem cells’ within the body itself. Stem cells can places into two categories, embryonic stem cells, and adult stem cells. The embryonic stem cells (ESC) have an unlimited capacity for self-renewal. Their abilities were explored only when the cells were first available to manipulate in laboratories. The major contributor to the study of these stem cells was the rise of In Vitro Fertilization (IVF) as an Assisted Reproductive Technology.

    IVF generates numerous embryos for the treatment of infertility. Two to three embryos fertilised in vitro are transferred into the uterine cavity per cycle. If conception takes place, the leftover embryos are usually donated for research purposes.

    Controversies have been aplenty over the use of such embryonic cells for study and experimentation, but their significance in expanding our understanding of the human body cannot be argued—neither can their benefits, considering how they can be cultured and engineered into necessary cell types. For example, the development of insulin producing cells of the pancreas could save the lives of many sufferers of Type 1 diabetes.

    Adult stem cells, on the other hand, are localised within a variety of tissues and organs but possess limited ability to divide, differentiate, and renew. Little is known about the degree of their plasticity and there are difficulties in purifying and culturing these cells. These still play a great role, however, in tissue regeneration and repair; they migrate to the site of injury and differentiate into blood cells, cartilage, bone, fat cells and even outer layer of blood vessels to help in healing.

    Interestingly, research has found similar properties of differentiation and development in umbilical cord blood cells as those seen in ESCs, except that cord blood cells are much more readily available. These also multiply fast and can be channelled into many areas according to culture conditions—useful in replacing liver cells, producing skin grafts for skin diseases, in helping deal with osteoporosis, neurological conditions, and in repairing heart tissue and blood vessels. So far, extensively concentrated areas of medical research include diabetes, Parkinson’s disease, Alzheimer’s and cancer.

    As promising as stem cell research might be, the actual process of culturing these tissues for therapy—and isolating, storing and transplanting them—is not easy. It is a high-tech procedure that employs Reverse Transcription—Polymerase Chain Reaction, immunostaining and imaging, and flow cytometry analysis techniques among others.  Numerous researches are underway around the world, of course, and large scale expansions of these cord blood cells into numerous cell types are already being produced. These cells have a very good international market, but Nepal has yet to jump on the bandwagon. India, for instance, boasts many institutions where regenerative medicine has been well advanced. It is therefore important that we too establish biomedical engineering institutions where tissue engineering can be expanded with foreign collaboration.

    It was only in the last decade that the miracles of stem cells became known to man. Already many countries are making use of the newfound knowledge. If all goes well, we might be using stem cells to counter all

    diseases in the form of easy-to-access tablets, ointments, or injections in the near future, hopefully reducing the use of chemicals. There is much to learn in this still largely unexplored, fascinating field of study and the time to do it is now.
    Dr. Uma Shrivastava
    Article Published On Kathmandu Post, February 12




    Our experience of infertility problem & treatment in Nepal

    Infertility has been identified as a problem to a couple since the history of mankind. In recent world, about 10-15% married couples are childless. In Nepal, infertility rate is about 13 -15%. It is experienced that about 40% of these couples have male factor infertility, 40% female factor & remaining 10% are those in whom no diagnosis can be made even after complete investigation.
    In this part of the world, due to joint family trend, infertility is not only a problem of the couple but it is a problem of the whole family & also society. During counseling, the ladies patients express their tearfulness, depression, shame, isolation, guilt, anger & suicidal feelings. Due to lack of education, it is generally accepted that men are usually fertile & female have to be treated or the man must be allowed second marriage. Polygamy is still a very popular method of infertility treatment even in male factor infertility due to male dominating behavioural aspects which ends up in no result.  Interference by family members, not allowing the treatment but rather convincing for second marriage often complicates the counseling process. Therefore the doctor is forced to remove the family members during the counseling session. 
    The treatment seeking behavior of patients differs from villages to cities. The villagers still believe in the witch doctors or alternative medicine etc. Unfortunately, some ladies have been victim of rape during the course of such infertility treatment. We heard two suicides news among the treatment seeker during our 18 years of tenure.
    The villager's belief is so strong that someone treated with positive result by some doctor will be known to all villagers and they will inform the whole community of infertile couples about the type of treatment that is necessary and try to send them for the same. Their friends come to the doctor with full preparation & they believe that the doctor has divine power. It is very easy to convince least educated couples about their treatment. They take the medicine exactly how the doctor prescribes. The fertility recovery is better in these groups than the city dwellers. In the city however, the health facilities are better but patients do not have patience. Thus they keep changing doctor without understanding the exact test & treatment provided to them. Some patients are treated for years without success yet these patients do not know what caused their infertility.
     Investigations have identified that in females, the problem of ovulation failure (anovulation) is critical in this country. Obesity, stress, anemia, irregular cycle with primary or secondary amenorrhoea, weight loss & excessive hair growth & skin patches are major complaints of these patients. On thorough examination, majority of them have polycystic ovarian syndrome (PCOS). If these conditions are not treated in time they may even turn into irreversible conditions with damage of normal hormone producing cells of the ovaries. Quite often we have found that these cases are investigated properly & the hormone test even ultrasound results show clear diagnosis, yet proper treatment are not prescribed. Trial hormone treatment can not cure these conditions, it rather complicated them.
    Developmental anomalies of uterus, fallopian tubes & ovaries, hormone secreting  tumors, ovarian cysts & dysfunctional uterine bleeding may also result anovulation. Rare anovulatory conditions include premature ovarian failure which may be due to primarily failure of hypothalamus or pituitary.
    Higher levels of prolactin & abnormal thyroid hormone levels often cause irregular cycles, primary infertility, secondary infertility & miscarriage with anembryonic sac. These cases are easily identified by imaging & prolactin assay.
    Reproductive hormones assay has proved to be crucial in diagnosing anovulatory conditions but test result interpretation is poor due to lack of Endocrinologists. The test is expensive & not all hormone tests are available in reliable laboratories. Patients with amenorrhoea bring normal hormone reports. In addition, patients with frank galactorrhoea show normal prolactin levels. The related technicians or doctors should be aware of the conditions why the patient is being investigated. At least the symptoms of the patient should be correlated with the test reports. It becomes awkward to the doctor to ask the patient to redo the test which becomes a financial burden to the patient. On the other hand the doctor has to find out the abnormal level of hormone which has to be corrected to regularize their irregular cycle. It is specially noted down for the attention of responsible authorities.
     Transvaginal Ultrasonography is also a useful test measure to differentiate normal pelvic organs from pathological ones. It provides a reference of pelvic organs before the treatment cycle. PCOS is easily diagnosed by this technique. It is very easy to assess the ovaries & follicles specially to retrieve the oocytes for In Vitro Fertilization (IVF) treatment method.  Presence of any cyst or endometriosis can be eliminated & simple ovarian cystic contents can be easily aspirated under its guidance as a minor operative measure.
    There was a general trend few years ago that most of the infertile ladies underwent D&C as an indirect ovulation test or even a treatment measure.  It has been found that majority of these women undergo D&C during post menstrual period which is not a test of ovulation. To test ovulation the curettage must be obtained during premenstrual period when the endometrium is expected to be at the secretory phase. Anovulatory conditions due to Primary or Premature ovarian failure do not have properly developed endometrium. Such cases show scanty endometrium in their curettage. Overzealous curettage in these cases may even cause trauma of the basal layer of endometrium leaving adhesions. Such endometrium is irresponsive to estrogenic action, hence does not proliferate. On the other hand, implantation of functional layer of endometrial tissue into the myometrium may facilitate development of adenomyosis.
    Often it has been found those who who have undergone several D&C procedures lose their endometrium & cannot proliferate even with Hypothalamic & pituitary hormonal stimulants.
    Postmenstrual D&C remains only a treatment procedure in conditions where cervical obstruction & due to polyposis or developmental anomaly.
    Before the use of clomiphene citrate as ovulation inducer, reproductive hormones profile must be done. Its use may prove harmful in low estrogenic conditions. Clomiphene citrate possesses some anti-estrogenic effect which may prevent recruitment of good quality follicles & it may also thicken the cervical mucus which prevents the access of sperm to ovaries via cervical & uterine cavities. 
    As proper investigations for fertility are not available everywhere & patients have been undergoing same investigations by different techniques. For example, the patency of the fallopian tubes can be tested by the most economic, lesser invasive & simple radiological method of Hysterosalpingography (HSG).
    Hysterosalpingography as a simple radiological test method is useful to detect Tubo-uterine factors including patent or blocked tubes, intrauterine cavity fibroids, polyps, adhesions, developmental anomalies like septa within the uterus, bi-cornuate uterus, double uterus.
    Similar non-radiological HSG, by using sonography is used for the same purpose & has been introduced at the infertility centre from 2002 onwards as Sonosalpingography (SSG), and has been proved to be easy & better test method.
     During counseling, couple's past treatment records are analyzed. Some patients undergo even laparotomy for tubal surgery without any obvious reason. Often tubal surgery held for patients with normal hysterosalpingography. This is because of lacking guidelines to proper evidence based treatment in this area. The Ministry of Health has to provide guidelines in this regard & must outline the condition for referral to centre of super-specialization.  The RCOG, 1998 recommends that infertile patients should be seen in a dedicated specialized secondary care infertility clinic by an appropriately trained team with facilities for investigating and managing problems in both partners. Moreover, any ART procedure including IUI or IVF requires laboratory based training with specialist knowledge & multidisciplinary skills.
    In Nepal, endoscopic surgery is not advanced therefore least successful. This technique has been proved better than laparotomy in tubal reversal. However, conception after tubal surgery has higher possibility of ectopic.
    Presence of free fluid in the peritoneal cavity on ultrasound scan is suspected of peritoneal tuberculosis. Such cases must get Mantoux test done & in case of positive test results they must undergo anti-tubercular therapy. We have detected several cases of tubercular infertility with free ascitic fluid in the peritoneum in female.
    Endometriosis in the form of severe dysmenorrhoea with para-uterine or ovarian chocolate cystic structures & adhesions is regarded as serious infertility conditions. It has been experienced that even after removal of such cysts, fertility does not easily recover. Recent trend is to use Gonadotropin agonist depot to stop further progress of the disease. These patients may conceive by careful retrieval of oocytes & fertilization in vitro with the transfer of the embryo into the uterus using Assisted Reproductive Technology.
    Uterine tumours developed in the form of sub-serous are less harmful than intramural & sub-mucus ones. In addition, adenomyosis as extension of endometrium in the form of tumour is another difficult condition of infertility. As yet, major surgical removal is only choice of treatment in these conditions Laparoscopic method of removal of these tumours has very useful role but this skill has yet to develop in this country. Although this has not been very useful in infertility practice as a treatment procedure, however it is very much popular as a diagnostic method of tubal patency test.
    The role of cervical factor is crucial in the fertility process. Presence of cervical polyp obstructs the passage of sperm leading to infertility. Inadequate quality & quantity of cervical mucus also hampers sperm passage to the uterine cavity & towards ovaries. Presence of sperm antibodies in the cervical mucus may kill the sperm as soon as they are deposited in the vagina. This is tested by using Post-coital test (PCT). If all the sperms are found dead after few minutes of intercourse there is no chance of fertility. We experienced only about 5-7% of female infertility is due to cervical factor.
    As mentioned above, almost 40% of infertility in this country is found to be due to male factor. Majority of these men are professionals, working as policemen, military men, accountants, drivers, engineers, doctors etc. Careful evaluation of these men is necessary to relate the present condition with the history of male organ development, history of surgery, childhood mumps & tuberculosis. In addition, any narcotics used in the past, eating habits, alcohol & tobacco consumption must also be enquired about during counselling. In our early infertility practice there were only few couples attending counselling sessions. Usually the female partners are brought by their relatives for counselling. In contrast, in recent years men having done the semen analysis find out their defects & they come alone with the report for counselling. Occasionally, they counsel for themselves & get their test done before the wife is disclosed about their infertility factor. We experienced two suicide cases news due to polygamy in male factor infertility during our 12 years tenure.
    A standard fertility centre with andrology lab can provide the facility to test sperms within normal parameter, which makes diagnosis of male factor infertility easier.
    In our experience, majority of male factors presented with normal physical activities even when they had no sperms in their semen. On the other hand some fertile men with children in the past had no sperms at all in three episodes of semen analysis. The major problems observed were low sperm count & motility rather than poor sperm morphology.
    Anti-sperm factors may be present in the male themselves which form anti-sperm antibodies after intercourse in the cervical mucus thus creating difficulty for conception. In such cases, conception may be possible only either with specially processed husband's or donor's sperms carefully deposited into the uterine cavity with the help of a special intrauterine catheter, the process commonly known as intrauterine insemination (IUI)  Before insemination, each specimen is evaluated and washed in preparation for intrauterine insemination (IUI) into the female. The sperm washing process removes impurities from the semen improving motility of sperms thus increasing pregnancy rates. Insemination of unwashed sperms can cause serious adverse reactions. This is one of the popular treatments for male factor infertility. For this process, ovulation has been optimized in the female and her fallopian tubes are known to be open. Ultrasound is used to time the IUI procedure.  Poor quality semen, the husband's or the donor's, are processed in the same way. All the sperms used for donor insemination must be stored frozen in liquid nitrogen jars. It is not wise to use the semen from known donors because of the psychological and social problems. In our centre donors must undergo a rigorous screening including HIV, HBsAg, and VDRL testing as well as documentation of medical, family, and genetic history. The donors also sign consent about keeping the matter confidential to all except his wife. The semen is frozen and quarantined for use for six months.
    We strictly take consent from the couple undergoing donor insemination, ovum donation & IVF. In this society, it is quite usual that male factor is regarded as an ordinary defect. If the wife is normal the husband & the family members instantly decide for donor insemination to the wife. Often the male partners try to convince us to keep such treatment information from the female about the need of donor insemination for their fertility.The situation is not the same if the wife is not able to conceive due to blocked tubes or irreversible anovulation. At this point the husband & his family start arrangement for his second marriage. In such situations the doctor has a great role to convince the family about availability & possibility of conception with Assisted Reproduction with ovum donation & IVF at home or abroad.
    On the other hand, few azoospermic cases were due to blocked vas. Some cases of blocked vas were opened and the couple conceived. Rarely but few cases come with the request of reversal of vasectomy either due to loss of children or due to polygamy or after divorce.
    All the couples are tested for STD, HIV, HBsAg, men during semen analysis. We identified only three cases of HIV positive infertile cases till date but many were treated for STD and few for HBsAg were asymptomatic. These cases were especially cared during ante-natal period followed by careful deliveries of these babies. They were followed-up till all the tests were negative.
    After having ten years of practice of only Infertility treatment, we experienced that the internationally available treatment for infertility must be made available to those Nepalese who cannot afford treatment abroad. These are couples with blocked fallopian tubes, severe male factor, Endometriosis, failed IUI & idiopathic or unexplained infertility. Except these conditions, any couple who cannot conceive should not accept IVF. In this program stimulation of ovulation is done by injecting excessive doses of hypothalamic, pituitary, ovarian hormone analogues. There are usually three stimulation protocols laid out for this purpose. However we have found the long protocol very useful for IVF treatment. If conception does not take place, such higher doses of stimulants may prove harmful for normally functioning ovaries. There may be cystic growth in these ovaries. Due to their hazardous effect, IVF should not be recommended to those who really do not need it. 
    Monitoring growth of the follicles is done by using serial scanning of the ovaries with transvaginal ultrasonography & hormone assay. When at least two follicles reach 18mm ovulation is triggered & within 34 hrs. follicles are aspirated to collect the eggs. They are cultured with the sperm for fertilization & growth of embryos. When the embryos reach four-cell stage of development, maximum two embryos are transferred carefully into the uterine cavity for implantation & development of foetus. The extra embryos are frozen in liquid nitrogen jars for transfer in subsequent cycles. We check for conception after two weeks of transfer. The successful ones will be switched into the antenatal group. The failed IVF couples will have disastrous feeling, feeling of loss of money & loss of only chance of pregnancy. They will be counseled again for further attempt. The probability of success depends on many factors including age of the patient, cause of infertility, and the talent and experience of the IVF team.
     However, proper investigation will help problem identification as to whether it is a case of anovulation or mechanical blockage of the tubes or a case of male factor. The cost is another factor which may not be within the reach of all till conception takes place in both conventional infertility treatment & Assisted Reproductive Technology. It seems necessary to balance between cost & effectiveness of the treatment.
    However, the pain of treatment becomes negligible in them as soon as their fertility returns.


    SOCIAL ASPECTS OF INFERTILITY
    Women comprise more than half of Nepal’s 23 million people as given by CBS (Central Bureau of Statistics, 2002). They are less educated and work longer hours than men. In a society where social security does not exist and property is passed on to male descendants, sons are looked upon as old age insurance. It is also widely believed that sons “open the gates of heaven” by carrying out the last rites of parents. Daughters are “given away” in marriage. These explain, to an extent, the prevalence of sayings like “let it be later but let it be a son.” The resultant discriminations in upbringing of girls perhaps explain why Nepal is one of the few countries in the world where men live longer than women. Thus, if a couple fails to conceive the baby after one year of the continue sexual relationship, therefore the women is discriminated and seen in a sinful way and as a result the husband get married to the other woman in order to conceive a baby.  The recent survey of infertility in the country has raised the questions about the biological disability with social stigma that is mostly prevalent in the women.
    Infertility alters an individual’s perception of his/her self, of his/her concept of identity. As a result of the strong link between femininity and motherhood, women may experience an identity crisis as there is a conflict between their ideal sense of self as a woman who can become a mother and their real self as being infertile. The experience of infertility requires both men and women to adapt and to integrate infertility into their sense of self.
    Many Nepalese girls get married soon after the puberty. Nearly, 40 percent of currently married women are married before the legal age of 18 (UNICEF 2002).  Soon after marriage a women is expected to have children. In Nepalese society child bearing is the central in defining the women’s identity, affirming her worth and establishing her position in the household and husband’s Kin group.
    Traditionally our society favors high fertility. Children are a symbol of well being both socially and economically. This is evident from the popular saying which goes "may your progeny fill the hills and mountains". High fertility is desired because by producing children, preferably sons, a woman raises her status in the family. She avoids the chance of having a co-wife, makes herself socially eligible to inherit some property from the family, and above all, wins the support and affection from her husband and the other members of the family, particularly the ever-dominating mother-in-law.
    Marriage is considered the most important event in a Hindu women’s life and girls grow up with a notion of temporary membership in her parent’s home. In the process of her socialization there is a considerable emphasis on submissiveness, obedience and as feminine ideals. She learns to accept that preference is always shown to male children and learns to accept her brothers are privileged family members.
    Women are materially connected to food, water and energy, biologically connected to reproduction, and socially connected to family and community in ways that men are not (Jiggins, 1994). Although women's infertility is of greater research consideration, health care attention and social blame, male conditions cause or contribute to around half of all cases of infertility.
     According to Manusmriti, where it refers to the most important and earliest metrical work of the (Dharmasastra) textual tradition of Hinduism, woman and servant are of same value in the Nepalese patriarchal society. Before marriage a father has the responsibility to take care after his daughter and find a husband for her and after marriage it is husband's duty to protect her and with the passage of time when she gets old the son takes care after her. Son is felt essential in Nepalese society. And a woman is often made guilty for not bearing a son. Thus, a woman does not have any right to make any decision regarding herself or her family. In other words, women do not have their independent personality.  Whatever the male member does that should always be acceptable to female. Thus, in the socialization process while women are taught to be non aggressive, submissive, soft spoken and shy. Men on the other hand are taught aggression, violence and boldness.
    Majority of women in Nepal are engaged in household works. Their expenses depend on their husband’s income and will. There is high level of domestic violence, mental torture and trend of polygamy. The domestic violence stems from the assumption that once a man marriage a women he has absolute control over her. It is usually due to the right to domination of females. This principally owes to the influence of the tradition idea of men “Men are senior to women". It has severe effect on human rights and dignity of women. It is the result of unequal power relation between women & men.
    In our society sons are desired more because they represent insurance for old age and patrilineal inheritance ensures that property is passed on through the male line. The necessity for a son is to carry out the death rites for parents. Therefore, there is rejoicing in the birth of a son and unhappiness at the arrival of daughter. To be born a daughter is a misfortune “let it be late, but let it be a son”. Special attention has been given to male baby from early child hood and sons have a special priority over issues such as education and (boarding school for male baby and government school for female baby) nutrition (sons always have a priority to have special and tasty food and daughter have to eat only after him). Similarly, sons can have choice over clothing but daughter is compelled to wear whatever the parents provided to her. There was a common understanding that rituals surroundings, the birth, naming and introduction of supplementary foods for male babies are more colorful and extravagant occasions than in the case of girls.
    In such a son preferred society like Nepalese society, infertility can become a huge problem for a happily married couple for not being able to conceive the baby resulting to various social and psychological problems on women such as polygamy, domestic violence etc. In a society where social security does not exist and property is passed on to male descendants, sons are looked upon as old age insurance. It is also widely believed that sons “open the gates of heaven” by carrying out the last rites of parents. Daughters are “given away” in marriage. These explain, to an extent, the prevalence of sayings like “let it be later but let it be a son.” The resultant discriminations in upbringing of girls perhaps explain why Nepal is one of the few countries in the world where men live longer than women.
    Currently many stigmas and myths about infertility exist. Although there is much more scientific information about the biological or medical aspects of infertility, understanding the psychological and social implications of infertility have lagged behind. One of the most prevalent myths about infertility is that since women ultimately conceive and become pregnant, infertility or the inability to conceive and become pregnant is perceived almost exclusively as a “woman’s” problem.
    The infertile women are socially stigmatized and have to bear the impact of being infertile, irrespective of who is responsible for infertility. The infertility has negatively affected the marital relationship and subjected the women to hatred and exploitation. These women, who could not reproduce at all, faced poor outcomes of pregnancy or were unable to give birth to sons, were being laughed at or ridiculed.  These women not only faced the threats of divorce, husband’s remarrying or sending back to parents’ home but experienced these consequences too.  Moreover, due to the problem of infertility, the women become the victims of verbal and physical abuse both by the husbands and in laws. The resulting trauma could be immense.  
    Being a female they have to suffer a lot. Women are known as the image of patience, they can bear everything their husbands do even if that does not respect her. But it is said that a woman cannot bear if her husband marriages another wife if she is unable to conceive a child. Nepalese women have incomplete access to resources, due to the existing social structure, strong patriarchal norms and practices, few opportunities and mobility constraints due to which they cannot take necessary decisions regarding the infertility treatment. Finally this leads to psychological impact leading to isolation from the family. To be infertile, is not only because of the women, there is equal chances of weakness from the part of husband. Due to ignorance of this fact, women were blamed for infertility.
     Family should be the safest place for women in time of trouble. It is an institution where one should get emotional support, comfort, care, food and shelter. Yet this institution can be the unsafe place for women. In Nepalese society, women are known as the image of patience, they can bear everything their husbands do even if that does not respect her. But it is said that a woman cannot bear if her husband marriages another wife if she is unable to conceive a child. Nepalese women have limited access to resources, due to the existing social structure, strong patriarchal norms and practices, few opportunities and mobility constraints due to which they cannot take necessary decisions regarding the infertility treatment. Eventually this leads to psychological impact leading to isolation from the family.
    Similarly, the infertile women are also affected and bounded by the strong traditional norms of the society where she cannot express herself without frustrations. As our society is a patriarchal or male dominating society, male is recognized as the bread winner and female is recognized as the homemaker where she has to play the role of various characters as such the mother, sister, wife etc. In our society, women are categorized as the child bearing machine where if she is unable to give birth to the child then she is termed as the failure being a female and her husband and their family would give various kinds of tortures and tries to verbally abuse them.
    Being physically unable to conceive a baby thus becomes the greatest sin that a woman commits in her life.  It can be concluded that the literacy, occupation, age at marriage, income status knowledge and accessibility are the major variables which are playing vital and determinant role for determining the social status of a female in the society. Hence, due to illiteracy, patriarchy, traditional social norms and backwardness among the females has leaded them to suffer, take stresses and depressed in society

    An Infertility Case Study

    Mrs. K. Paudel, aged 46, wife of a prestigious fellow Mr. B. Paudel, aged 46 had visited Infertility Centre in March 1999 with the complaints no living issue for 21 yrs. married life. They lived in Pokhara & were referred to us by a Senior Gynaecologist for their complicated infertility problem.
    They had two abortions at three to four months gestation. The last abortion took place after treatment only with six yrs. ago. Since then she could not conceive but the details of the previous treatment was kept confidential within the doctor & the husband. Their past treatment record showed that she had artificial insemination of donor sperm because the husband had no sperm in his semen. She did not know that she got pregnant by donor insemination. During our counselling, the lady did not show any interest in treatment for herself because her menstrual cycle was already getting late & she lost hope of getting pregnant. Her physical built was good with her body weight of 65 Kg. Her cycle interval was 23-43 days with flow of 1-2 days scanty flow. On the second visit however she was ready only for Hysterosalpingography (HSG) which revealed normal looking uterus with patent both fallopian tubes.
    On third visit she brought her sister & wanted us to examine her whom the lady forced to marry with her husband for the sake of a child in their family.
    Hence, it was clear that the second wife Mrs. S. Paudel was married five years ago & she also could not conceive. The younger sister was 31 years when she came for treatment. She was thin built with short height but her general physical condition looked quite fair. Her body weight was only 39 Kg. Her menstrual cycle was 28-30 days with 5-9 days of flow. On pelvic examination the use of speculum could not clearly distinguish the cervix from vagina. In addition, the vaginal cavity was also narrow. The outline of cervix looked rather rudimentary. Careful surgical excision was done to separate the vaginal flaps which covered the cervix. She was then asked not to try conception for at least three months.
    After surgical correction she was properly investigated for conception.

    Her D2 hormone profile: 
    FSH=7.4mIU/ml; 
    LH=1.1mIU/ml;
     Estradiol=40.5pg/ml;
     Prolactin=30.8ng/ml; 
    TSH=3.3mIU/ml.

    Hyperprolactinemia was corrected with bromocriptin therapy.                                                                                           
    This time, it was easy to access the cervix to perform HSG. Her HSG showed normal uterine cavity with patency of both tubes. Semen was analysed again had no sperm. Thus, the conception was only possible with donor insemination. With written consent of the couple, Intra Uterine Insemination (IUI) of donor sperm was planned. Ovulation was stimulated for the recruitment of more follicles with cyclic clomiphen citrate 50-150 mg. Development of follicles was serially monitored by transvaginal ultrasound. When at least one follocle reached 18mm, Human Chorionic Gonadotropin was injected & IUI was done within 30-48 hrs. Since they lived far away, their treatment was not regular. However, she finally conceived after total three months of IUI treatment.  She was followed up by us till 30 wks & referred back to the same doctor for the delivery. She delivered a healthy baby boy in October 2001. 

    Dr. Uma Shrivastava
    Founder, Director
    Infertility Centre.