My book published in April 2022

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Combined Clomiphene Citrate-Metformin Versus Letrozole-Metformin in Achieving Pregnancy among Women with Polycystic Ovary Syndrome

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Scope of Stem cells in Regenerative medicine

During the journey of conception till birth, the body structure of any species is generated through biological processes.

In Human, development of a mature fetus from a zygote undergoes multiplication of cells and their subsequent controlled and co-ordinated tissue growth, movement, and differentiation. In addition, it also crosses phases of degeneration and regeneration of tissues and organs till a complete Man.

Regeneration continues throughout human life. As a natural process, it is speedy healing of any injury or ill developed body organs by de-differentiation & development of these cells into new similar tissue. Organ such as liver is known to regenerate easily.

But every organ of our body cannot regenerate naturally. Inability to regenerate the responses to injuries or diseases threats our life.

Regenerative Medicine is directed to heal fractured bones, burns, blindness, deafness, damage of muscle, nerve, blood vessel etc. to extend lifespan. Age-related degeneration & damage can also be repaired by such therapy.

The therapy uses patient's own tissue from other part of body to repair the injured site. Similarly, biomaterials, metallic & plastic types are also used to repair tissue damage depending upon the nature of trauma. Often due to bio-incompatibility these materials are rejected by the body & creates great problem in healing the damage.

Body itself has a great role in regenerative process. In case of trauma damaged tissues are replaced naturally by the help of primitive progenitor cells or Stem cells of the body.

Stem cells are broadly categorized in two types: Embryonic stem cells & Adult stem cells.

The embryonic stem cells (ESC) are the inner cell mass of an embryo at blastocyst stage, which has the ability to differentiate & develop into any cell type of our body. These cells have unlimited capacity to self-renewal in culture.

Their abilities were explored only when the cells were available to manipulate in laboratories. The major contributor of these stem cells study is the In Vitro Fertilization (IVF) as an Assisted Reproductive Technology.

IVF generates numerous embryos for the treatment of infertility. Usually 2-3 embryos fertilized in vitro are transferred into uterine cavity per cycle.  If conception takes place, the leftover embryos not necessary for those couples are usually donated for research purposes. Thereby, extensive studies are underway on the use of these embryonic cells in regenerative medicine & cell therapy.

In the mean time, there have been controversies about the use of such embryonic cells for research. Some belief that use of embryonic cells destroys the embryo which could have been born as a Human. Others belief that artificially fertilized embryos unless implanted in the uterus have no legal status & they are not even part of a human being. However, the research is also a means of the welfare of mankind.

The embryonic stem cells are being cultured & engineered into the necessary cell type. For example, development of structurally & functionally similar cells of pancreas which can produce insulin can save life of many suffering from Type1 diabetes (Insulin dependant type). In this condition the cells of pancreas are diseased or damaged, cannot produce insulin to digest the glucose containing meal, hence glucose level rises in blood. Thereby diabetes develops which is controlled only with the help of insulin injections life-long.

Adult Stem cells are localized within wide variety of tissue & organ such as skin, muscle, bone marrow, blood etc. with limited ability to divide, differentiate & self renewal into other cell type. The hematopoietic cells which develop blood cells are also adult stem cells. They have great role in tissue regeneration & repair. In tissue damage, they migrate to the site of injury & differentiate into blood cells, cartilage, bone, fat cells & even outer layer of blood vessels to repair the damage.

Stem cell based therapies currently available adult-derived stem cells are from bone marrow and skin. Little is known about the degree of their plasticity and there are difficulties in purifying and culturing these cells.

Regenerative medicine researches have found similar ability as embryonic stem cells of differentiation & development in Umbilical Cord blood cells. In animal model it has been reported that these cells can be engineered to produce many cell types. In comparison to embryonic stem cell, availability of the cord blood cells is easier. Due to its easy availability, now -a -days, cord blood is used in a variety of conditions as an alternative of bone marrow for transplant, in stroke, in heart diseases etc.

The Human umbilical cord blood stem cells multiply fast & increase their number in laboratory culture. These cells can also change into muscle, liver, bone, nerve, skin cells etc. according to culture conditions. However, culturing these tissues for therapy is not so easy. It utilizes high-tech such as Reverse Transcription–Polymerase Chain Reaction (RT-PCR), Immunostaining and imaging, Flow cytometry analysis techniques etc.

By this method, the cultured specific cells can be isolated, stored & transplanted in need. In case of liver disease, they can be used for replacement of liver cells.

Burns or skin diseases use skin grafts for treatment. These grafts if developed from patients own stem cells there is no danger of tissue rejection.

Researchers have found that bone disease such as osteoporosis can be treated using umbilical cord blood cells. 

In neurological diseases, the damaged nerve can also be repaired by these cells.

These cells also have profound role in Cardiology for repairing heart tissue & blood vessels. Extensively concentrated areas of medical research include Diabetes, Parkinson's disease, Alzheimer's & Cancer.

The disadvantage on the use of cord blood is that it contains not only stem cells but also the non-stem cells with specific immunological properties may sometimes be rejected with severe immunological reaction. More attention is on that line to make these cells easily acceptable to any individual.

Researches are underway around the world to make proper use of the cord blood cells. Large scale expansions of these stem cells into numerous cell types are produced by culture. They are packed & stored at an appropriate temperature before use. These cells have a very good International market & are promoting medical industries. There is a great need of such activities in this country as well. At least cord blood storage & transfusion would have saved a lot of life.

Moreover, the technique would be of a great interest to all the Medics. In India, there are many such institutions where regenerative medicine has been well advanced. The potential of such activities centre could be the Biomedical engineering institutions where tissue engineering can be expanded with foreign collaborations if our hospitals demand.

In the last decade all the miracles of stem cells were highlighted. This decade some utilization of stem cells is underway. In coming decade we may be using stem cells in every disease conditions as tablets, ointments, injections etc. & reduce the use of chemicals.

The ability of stem cells seems much more than what we know till date. We can assume that stem cell therapy & gene therapy may even extend Human life expectancy.

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A guide to those seeking treatment of infertility at Infertility Centre, Bijulibazar, Kathmandu, Nepal

 A guide to those seeking treatment of infertility at Infertility Centre, Bijulibazar, Kathmandu, Nepal

Investigations of your infertility for proper diagnosis

1.      Both the couple needs to see a Consultant Reproductive Endocrinologist (RE) at the Infertility Centre in addition to other doctors for counseling infertility. You need to bring reports of any treatment you had before. You can come any day of your menstrual cycle. The Centre is open 24 hrs. 7 days a week but you can see doctors strictly with appointments.  Appointments are made at 10am-7pm except Saturdays. The clinic is open on Govt. Holidays

2.      Counseling is a longer session when you will be told about the whole process & treatment pattern you may need.

3.      On D2/D3 of your menstrual cycle you need to test your hormone levels.  

4.      Husband's semen will be tested after 3 days of abstinence within 1/2 hr. of ejaculation.  Sperm Count >50million with >50% motility is accepted as normal test.

5.      Hormones will be assayed if the sperm count is abnormal.

6.      USG of pelvis is done on D2/D5 of period by trans-vaginal route to see any cyst or tumors around your uterus & ovaries. There may be multiple small cysts as black pearl necklace which is a case of Polycystic Ovarian syndrome. 

7.      A  Radiological or Sonographic Hysterosalpingography (HSG) is done after the bleeding stops on D6/9 of your period to assess the patency of your fallopian tubes.  Normally both are patent.

8.      Those couples who had recurrent abortions are tested for TORCH test, Blood glucose & genetic testing.

Treatment of the problem you may be having

1.      Fertility is possible only when all the above tests result are normal.

2.      Treatment may take several months till fertility recovery.

3.      In case of abnormal hormone profile RE will adjust hormone levels. RE will take care of this condition & also regularize your period if they are irregular.  This may take several months.

RE will also guide you about your weight if you are overweight or underweight.  If your ovaries are inactive RE will provide some ovarian stimulants to induce proper egg development in the ovaries.  This will be followed -up by USG usually after a week of stimulation & hormone therapy may continue for sometimes till recovery.

4.      Poor sperm count will be taken care by hormone therapy, sperm tonics as well as Intrauterine Insemination (IUI) of husband' sperm.

5.      In case of nil sperm in semen analysis, IUI of donor's sperm is done with a written consent of the couple.

6.      Recurrent abortions are treated according to their test results.

7.      Blocked fallopian tubes are offered a very effective non-invasive technique of Clear Passage Therapy using pelvic maneuver followed by hydrotubation. This is non-surgical treatment, may take 1-3 cycles for recovery.

8.      Unsuccessful treatment cases whom tubes could not be open, if they can afford, In Vitro Fertilization (IVF-test-tube treatment) is the treatment of choice for these couples.

9.      Couples who cannot afford IVF are advised for adoption.

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Improvement of pain in endometriosis

Endometriosis is identified as 3D disease. There is Dysmenorrhoea- painful menses, Dyspareunia- painful sex, & Dyschezia- painful defecation. The patients do not suffer from the size of the cysts they develop, but they severely suffer from the formation adhesions & inflammations.

After a small study on 50 patients, the Infertility centre has been successful in treating the 3Ds of endometriosis. A complex therapy of vitamins & calcium have been very effective in reliving all three types of pain.

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Nepalese believe

In Nepal infertility is bio-psychosocial problem therefore counseling is the most important part of infertility assessment before any medical intervention.

In western part of Nepal some men prefer remarriage easier & cost-effective than going through the diagnostic & therapeutic line in female infertility.

Similarly, in male infertility, some men prefer to remain infertile than getting donor inseminated children. 

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.”

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Blasctocyst transfer baby

Blastocyst transferred Baby was born at 33 wks. gestation with 1.3 kilogram body weight four months ago. The baby survived with difficulty & has gained weight of 5 kilogram.

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Asherman Syndrome

A successful full term Baby girl delivered one month ago in a case of Asherman Syndrome. 

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Outcome of First ICSI -FET (frozen embryo transfer)

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Good News

The Infertility Centre team feels blessed to have 23 -25 pregnancies per month for last 4 months. In addition, there are some days even 5 pregnancy tests show positive results.
This is due to all hard work & dedication of the team members which includes the patient attandants, nurses & the doctors.

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