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Thursday, February 2, 2012

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.

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: 

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.