Modern Wonders of India

India's rise as a 21st century global economic force is mirrored in a new building boom of corporate campuses, shopping malls, movie studios, and skyscrapers, many of which reflect a growing trend of sustainable architecture. Just as the classic Indian wonders of the world—from the elegant Taj Mahal to the spectacular temples at Khajuraho—evoke a characteristically South Asian style, India's newest wonders distinguish themselves from other nations' contemporary building types.
International powerhouse companies headquartered in India, such as Tata Consultancy Services, Wipro, and Infosys, are planning and constructing show-stopping offices that recall and update traditional Indian edifices, rather than mirror the generic glass boxes of Silicon Valley. Here are 10 examples of the new Indian architecture, by a spectrum of designers based around the world and in India. All of these superlative projects share one thing: They bridge India's rich history and bright economic future.
The latest available statistics from the World Bank indicate that India's gross domestic product has seen annual growth of 8.5%—more than doubling the 4% of 2000. Reflecting this growth and the country's increasing presence on the international stage as an IT and economic powerhouse, the nation's leading companies, including Wipro (WIT ), Infosys (INFY ), and Tata Consultancy Services are constructing new corporate campuses. Similar to China's architectural boom , India's forthcoming wave of slick contemporary architecture, even beyond offices, symbolizes the Asian nation's rocketing economy, which first began to open up 15 years ago. Via a series of superlative skyscrapers, shopping centers, and residences that are the tallest, the largest, the "greenest," or the first of their kind, the country is quickly presenting itself as a 21st century global power.
In 2005, for example, Infosys Technologies opened its $65.4 million Global Education Center in Mysore. Located on a 270-acre, $119 million campus, the facility is the largest IT training center in the world, accommodating 4,500 trainees at any given time and hosting up to 15,000 per year. The center is being expanded to handle double the number of employees. While its glassy, futuristic design might evoke corporate buildings in Silicon Valley, the campus also features an Indian touch: a cricket pitch. Software, engineering, and management-consulting giant Wipro commissioned Indian architect Vidur Bhardwaj to design an office in Gurgaon based on the traditional structure, the haveli (a house built around an open-air courtyard). Meanwhile, Tata Consultancy Services, a division of mega-conglomerate Tata Group, will soon see a sprawling, $200 million campus in Chennai designed by noted Uruguayan architect Carlos Ott (a nod to Tata's expansion into Latin America). Buildings will feature a step-like structure recalling those found in centuries-old South Indian temples—only these are rendered in ultra-contemporary glass. It's scheduled to be completed next year and will boast the tallest tower in Southern India.
New York architects Tod Williams and Billie Tsien, have designed a new Bombay campus for Tata Consultancy Services (to be completed by 2010) that incorporates elements such as a jali, a traditional carved screen used for centuries as both sunshade and ventilated wall. Williams and Tsien's jali is more angular and contemporary and less florid than screens of the past. But it serves as a nod to Indian architectural history as well as providing an eco-friendly way to keep offices cool using natural shade and ventilation. Projects such as Williams and Tsien's design for Tata make use of natural light and ventilation, cutting down on energy consumption that contributes to air pollution. Vidur Bhardwaj's haveli design for Wipro is not only an homage to traditional Indian buildings, but also provides cost-effective cooling—via the open-air public courtyard — that's necessary for hot Indian days. Carlos Ott's forthcoming Chennai campus for Tata Consultancy Services uses these ideas and also recycles waste water to conserve resources, following the lead of the 2003 CII—Sohrabji Godrej Green Business Center in Hyderabad. This 20,000-square-foot minimalist office building became the only structure outside of the U.S. to receive the LEED (Leadership in Energy & Environment Design) Platinum ranking when it opened.
Will the new forms of Indian architecture endure as long as the spectacular Elephanta rock-cut temples (built circa 600 A.D.) or the elegant Taj Mahal (a wonder of the world dating back to the 17th-century Mughal era)? Only time will tell.

Tiger Woods in Ireland

On a golf tour in Ireland , Tiger Woods drives his BMW into a petrol station in a remote part of the Irish countryside.

The pump attendant, who knows nothing about golf, greets him in a typical Irish manner completely unaware of who the golfing pro is.

"Top of the morning' to yer sir'", says the attendant.

Tiger nods a quick "Hello" and bends forward to pick up the nozzle.

As he does so, two Tees fall out of his shirt pocket onto the ground.

"What are those ?'" asks the attendant.

"They're called tees," replies Tiger.

"well, what on good God's earth are they for?" inquires the Irishman.

"They're for resting my balls on when I'm driving"' says Tiger.

"Fooking Jaysus," says the Irishman, "BMW thinks of everyting........"

PCOS - A Brand New Approach To Treating This Metabolic Disorder

Women with polycystic ovary syndrome who are hoping to conceive have reasons for both hope as well as concern. I hope this article will introduce you with newer treatment options and educate you to choose well prior to entering into any infertility treatments. When I order the anovulation Profile (a series of blood tests), I simply want to determine if responsibility for your ovulatory disturbance lies with another condition such as thyroid disorders, diabetes, age related ovarian failure, stress infection, ovarian cysts, or pituitary or ovarian tumors. Once these conditions have been ruled out and a normal semen analysis and tubal patency has been confirmed, a treatment plan can be considered.
Traditionally, the first step has been clomiphene therapy regardless of whether or not PCOS was diagnosed. Studies report ovulation rates of up to 80% and pregnancy rates in approximately half those who ovulate have demonstrated in the literature using this method. However, in women with PCOS, miscarriage rates once conception occurs have been higher than normal, running as high as 60% loss in those women with a history of a prior loss. Multiple birth rates may be higher and ovarian hyperstimulation more frequent when using clomiphene therapy.
However, it appears that ovulation therapy in Hyperinsulinemic PCOS patients with metformin when combined with a low glycemic diet and a moderate exercise program may provide much better results and provide significant health benefits. Ovulation rates by three months of metformin therapy appear similar to clomiphene, yet the rates of multiple births, miscarriage and gestational diabetes may all be reduced. Added health benefits may include normalization of elevated blood pressure, weight loss, normalization of blood lipids, and better sugar control in diabetics.
First do no harm. That means , before starting the Metformin therapy, please confirm if your PCOS patient has Insulin Resistance. I ask for a 12 hour fasting Serum Insulin Test. If this value is more than 10, I consider the patient Hyperinsulinemic. My approach to metformin therapy is to start the medication gradually. During the first week a single tablet of the Metformin 850 mg is taken with a full glass of water toward the end of a meal. After a fortnight an additional tablet is added with another meal. This gradual introduction of the 1700mg full dose adds to patient compliance with minimal upset stomach or diarrhea, the usual transient side effects when starting this medication.
But, what happens if this approach does not restore fertility? At that point I will consider use of ovulation induction with or without intrauterine insemination. Clomiphene or the oral anti-estrogen medicine letrozole which is administered in a fashion similar to clomiphene are the first medications considered. Despite the failure to respond in prior attempts at clomiphene therapy when combined with metformin, the effectiveness of these oral medications is greatly enhanced. I must stress the importance of ultrasound monitoring at the start of each cycle to avoid significant ovarian hyperstimulation (OHSS). Many doctors don't realize that OHSS can occur even on clomiphene and don't bother to check the ovaries at the start of each treatment cycle. These women have a progressive increase in pain with each month of therapy and show up at the clinic with grapefruit-sized ovaries which require months off therapy to allow them to return to normal size before considering additional treatment. One last caveat is that if you have not conceived after three months of a particular therapy, it is time to meet with your physician to review your case and determine whether other therapies may be more appropriate.
One alternative that appears effective is laparoscopic ovarian drilling. For women who have a specific indication for diagnostic laparoscopy, this procedure should be considered. We prefer to use a monopolar needle placed into each ovary six to eight times. An electrical current is placed through the needle and ultimately destroys some of the male hormone (androgen) producing tissue in the central portion of the ovary. It is thought that excess androgen production interferes with normal follicle development. Those who demonstrate a normalization of male hormone levels after this procedure have the greatest benefit, while the procedure appears less effective in those who smoke. Despite successfully restoring ovulation in up to 80% of women, the expense and surgical risks make injectable therapy and IVF appropriate considerations.
In order to understand present day management with injectable medications, you must first understand a bit of the history surrounding these drugs. The first group of medications in this class were urinary derived hMG (Menogon, GMH), a mixture of two hormones, FSH and LH. FSH stimulates development of the follicle cells and the conversion of male hormones to estrogen. LH stimulates the production of male hormones and assists in the maturation of the egg. As the number of women in treatment increased, the demand for these drugs increased so drug companies were forced to consider alternative means to generate a sufficient supply of drug to meet the demand. This required large investments to produce pure recombinant (genetically engineered) forms of FSH (Gonal-F). Studies revealed that most women responded well to treatment protocols that included only FSH. They found that the body produced, on its own, sufficient LH to generate healthy eggs. It was surmised that since women with PCOS had high LH levels, they would do best using an FSH only product and avoiding LH entirely. We now know that may not be the case.We now do most of the treatment cycles using Menogon or GMH.
Let's look at this a bit closer. But first, a bit more basic review of the ovulatory process. Hormones work by attaching to the receptor on the outside of the cell and triggering some action inside the cell. In the early follicle phase (prior to ovulation), small follicles only have FSH receptors and therefore respond to FSH only. There are no follicular cell receptors for LH at this early stage. As the follicles grow FSH levels decrease and the follicles develop receptors for LH (approximately 12-14mm in size) and thus are able to respond to either FSH or LH by increasing the cellular levels of the chemical cyclic AMP. Smaller follicles lack LH receptors and as FSH levels drop, these smaller follicles die off. This fact has lead to a novel approach to ovulation induction that appears promising.
Initial work by Italian physician, Dr. Marco Filicori, has revealed that adequate continued growth and maturation of larger follicles can occur in the absence of FSH. He has shown that a switch to low dose hCG (equivalent to LH) promotes satisfactory follicular growth while smaller follicles die off. Well- designed studies will confirm whether this approach reduces the risk of ovarian hyperstimulation and multiple births. Additional studies will be required to determine whether this approach is appropriate for IVF patients where in many cases we find that "more is better" when it comes to the number of follicles that develop to maturity. We have found this result promising in a few patients whose prior cycles generated hyperstimulatory responses. I will consider this protocol in any patient who, during the course of stimulation, appears to develop an excessive number of follicles of varying sizes. We give micro-doses of hCG ranging from 50 IU to 200 IU. In addition to low dose hCG during the late follicular phase, follicular reduction (removal of eggs) or conversion to IVF with GnRH antagonist administration are alternatives to consider if excessive follicular development is noted.
These new therapeutic options offer exciting alternatives. Hopefully, well- designed studies will allow prediction of the best approach for each patient. Until that data is available, it is important that you consult your fertility physician to understand all possible alternatives and options prior to making treatment decisions.

Management of Male Infertility

Treatments for male infertility range from surgical intervention or intrauterine insemination (IUI) to in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Depending on the source of the problem, sperm can be taken from the man's ejaculate for use in assisted fertilization procedures. One treatment option for men who do have sperm in the ejaculate is intrauterine insemination (IUI). Intrauterine insemination is an infertility treatment in which sperm are placed directly into the upper uterine cavity near the time she ovulates. IUIs are commonly performed when there is a low sperm count or low motility. The sperm that will be injected during the procedure are prepared using a process called sperm washing. The sperm are "washed" to remove any extra cells and debris in an effort to obtain the greatest concentration of the highly motile sperm that will be used for the insemination. One of the most common problems affecting male sperm levels is a varicocele, a tangle of swollen veins surrounding the testicle. Surgical correction of large varicoceles may improve sperm DNA quality and semen analysis results, as well as restore fertility in about two-thirds of cases.
In some cases there is no sperm in the ejaculate so surgical options for sperm retrieval are explored. Advanced sperm retrieval techniques, including TESA, PESA testicular microdissection and testicular biopsy, combined with IVF and ICSI, now allow men with either a low sperm count or no sperm in their ejaculate the chance to produce a child. For some couples, the use of donor sperm remains the best option for building a family. Obviously, donor sperm is the only option for men whose testicular biopsy reveals complete azoospermia - no trace of sperm in the testicular tissue. The use of donor sperm may also be considered when genetic screening indicates a possibility of passing on hereditary conditions such as cystic fibrosis to male offspring.
An increased understanding of male factor infertility and the recent advances made in assisted sperm retrieval techniques are now giving men who never thought they could have biological offspring the chance to father a child. Successful fertility outcomes at Rotunda-The Center For Human Reproduction result from a combination of technological advances, scientific expertise and consistent andrology laboratory standards.

Varicocele - Modern Management

Varicocele is a dilation (enlargement) of the internal spermatic veins that drain the testicle (picture on left). It is a very common condition present in 15% of the general male population and 40% of men evaluated for infertility. A varicocele develops because of defective valves that normally allow for blood to flow away from the testicle toward the abdomen. Testicular injury occurs due to abnormal back flow of blood from the abdomen into the scrotum and this creates a hostile environment for sperm development. The significance of this condition has been known for a thousand years. The first century Greek physician Celsius originally described the varicocele: "The veins are swollen and twisted over the testicle, which becomes smaller than its fellow in as much as its nutrition has become defective".
Numerous theories postulate how a varicocele can affect fertility:
1. Testicular temperature increases due to abnormal blood flow in the veins draining the testicle and in the artery entering the scrotum. Prolonged elevated testicular temperature has detrimental effects on sperm production.
2. Abnormal concentrations of adrenal and renal substances may impede development of normal sperm.
3. Abnormal venous blood flow from the scrotum increases metabolic waste products and decreases the availability of oxygen and nutrients required for sperm development.
4. Abnormal blood flow can also interfere with testosterone concentration, which in turn can interfere with sperm production. The long-term effects of compromised circulation may interfere with normal male androgen production.

Left-sided varicoceles are found in 85% of men with this problem and a right-sided varicocele is seen in 15%. The problem involves both sides in 20% of men. A unilateral varicocele may affect both testicles. The most probable explanation for the more frequent development of a varicocele on the left side alone is because the left spermatic vein is longer than the right. The left vein enters the left renal vein at a right angle near a site of compression by the mesenteric artery while the right spermatic vein drains at a softer angle into the vena cava. These anatomical factors (and the aid of gravity) promote backflow of blood in the left spermatic vein, resulting in pooling of blood and increased temperature and congestion in the testicle.

Some men with major varicoceles may show no evidence of testicular injury, while others with small or "subclinical" (detected only by radiological tests) varicocele may be infertile. The effects of a varicocele on sperm quality and quantity are thus difficult to define and predict. The so-called "stress pattern" frequently found in men with a varicocele consists of an increase in tapered abnormal sperm forms and decreased motility. The diagnosis of a varicocele can usually be made on physical examination of the scrotum while the patient is standing. The varicocele feels like a "bag of worms" and disappears or becomes significantly reduced when the patient lies down. The patient is asked to bear down and frequently the backflow of blood can be felt in these veins. Occasionally a varicocele may be so prominent that it can be seen through the skin. Often the testicle on the side of the varicocele is smaller than the other side. Ancillary tests such as the Doppler stethoscope and technetium isotope study may id in the diagnosis. Recently the scrotal ultrasound has been found to be an accurate way of confirming the presence of a varicocele. The size of the veins and abnormal blood flow can be seen and measured using the ultrasound.
Repair of the varicocele is indicated when the couple has documented infertility with normal or potentially normal female partner but a male with one or more abnormal semen parameters and the presence of a varicocele on physical exam. Repair should be done when a varicocele causes testicular pain or discomfort or there is a significant discrepancy between the size of the two testicles. Treatment options to aid with fertility include surgical varicocele repair, angiographic embolization, intrauterine insemination, in-vitro fertilization and medical therapy with clomiphene citrate. Surgical repair offers the best results. Semen improvement is expected in up to 70% of men and pregnancy in up to 60% of couples within the first two years after successful repair. Even in men with worst case scenarios who were not candidates for In Vitro Fertilization because they had no sperm in the ejaculate or no moving sperm, varicocele repair restored sperm or motility in 55-69% of patients. Twenty percent of these men were able to father children after varicocele repair without any other assistance.
Surgery is performed through a one and one half inch incision made below the belt line with a technique called microsurgical inguinal varicocele repair. The abnormal veins are identified using an operating microscope and are interrupted so blood can no longer pool around the testicle. The testicular artery and small lymphatic channels are identified using the microscope and are preserved. This limits potential complications. Surgery is performed on an outpatient basis and generally takes 30-45 minutes to complete. Using this approach the success rates for varicocele repair are close to 95% and the complication rate is about 1%.
Depending on the individual circumstances and the severity of the sperm abnormalities, multiple approaches to this problem can be taken. Surgical correction, intrauterine insemination and clomiphene citrate therapy can be used simultaneously to achieve a pregnancy. A recent study published in the Journal of Urology in May 2001 showed that varicocele repair improves intrauterine insemination success rates by almost double in men who have varicoceles. The most severe cases of male infertility may require in-vitro fertilization. The varicocele remains the most treatable cause of poor semen parameters and male infertility.

Acupuncture Shoots Up IVF Success Rates

Women undergoing fertility treatment could have their chances of success shooting up with acupuncture. German researchers said they have increased success rates by almost 50% in women having in vitro fertilization (IVF). The theory is that acupuncture can affect the autonomic nervous system, which is involved in the control of muscles and glands, and could therefore make the lining of the uterus more receptive to receiving an embryo. But the scientists admit they do not know for certain why the complementary therapy helped, and plan to carry out more studies in a bid to find out. Fertility techniques are used to help couples who cannot conceive naturally.
The theory of acupuncture is based on pathways called meridians. Research has shown it can help relieve nausea caused by anaesthetics during surgery or chemotherapy and to relieve dental pain. It may also help relieve other conditions including headaches and menstrual cramps. A report published in the journal Fertility and Sterility found the pregnancy rate in the group receiving acupuncture group was 42.5%, compared to the group which did not receive the therapy, where the rate was 26.3%. The German researchers worked with doctors at the Department of Traditional Chinese Medicine at Tongji Hospital in Wuhan, China. Of 160 women undergoing IVF, half received standard in vitro fertilization, while half were given acupuncture treatments before and after. The researchers chose acupuncture points which traditional Chinese medicine says relax the uterus. They also used needles to stimulate meridians involving the spleen, stomach and colon, to improve blood flow and create "more energy in the uterus." Key relaxation points were also stimulated. The research team, led by Dr. Wolfgang Paulus and colleagues at the Christian-Lauritzen-Institut in Ulm, Germany, wrote in the journal: "Acupuncture seems to be a useful tool for improving pregnancy rate after assisted reproductive techniques. They add: "To rule out the possibility that acupuncture produces only psychological or psychosomatic effects, we plan to use a placebo needle set as a control in a future study."
Such a study would involve people having needles inserted in the same way as in acupuncture, but not at the acupuncture points. Dr. Sandra Carson, president-elect of the American Society of Reproductive Medicine, which publishes the journal, said: "If these findings are confirmed, they may help us improve the odds for our (in vitro fertilization) patients' achieving pregnancy." We had a doctor couple from the US with multiple previous failed IVF cycles who came in for Surrogacy. The husband used to stick in the acupuncture needles into the spouse’s body couple of hours before the oocyte retrieval. They are proud parents of a bonny baby boy now. The gestational surrogate conceived on the second attempt early this year.

Recurrent Miscarriage - The Immunologic Causes

Immunologic causes of recurrent pregnancy loss are poorly understood. The theories proposed by authorities in this field appear to be constantly evolving and most of the theories that have been proposed to date have been proven to be either incorrect or largely incomplete. Two major categories of immunologic causes of recurrent pregnancy loss are Autoimmune, in which the woman's immune system attacks her own organs and tissues. 
Alloimmune, in which the immune system attacks tissues considered foreign. The immune system is designed to protect oneself against infectious organisms and their toxins. The system identifies, immobilizes and eliminates invaders. The two major mechanisms of surveillance are Nonadaptive immunity, in which cells respond nonspecifically to foreign molecules or material via either phagocytosis and lysis (by macrophages), lysozyme secretion (by lachrymal cells) or cell lysis (by natural killer cells). This type of response does not adapt and so its efficiency is not improved with further exposure . Adaptive immunity, in which action against specific foreign molecules (antigens) is enhanced by re-exposure. This is mediated by lymphocytes which produce highly specific antibodies that bind to the foreign molecules to further elicit (amplify) an immune response. The immune system is constantly operational (turned on) since it must synthesize an enormous catalog of different antibodies and cell surface receptors to deal with the wealth of foreign material that it is presented with.
An important feature of the immune system is its ability to distinguish foreign (unwanted) material from its own (desired) self. If this ability to distinguish non-self from self fails, then the system produces an immune response against itself (or its own tissues). This is called autoimmune disease.
Autoimmune disease or dysfunction may play a role in up to 20% of recurrent pregnancy loss. Phospholipids are molecular building blocks that help to make up a large portion of the walls around the cells of the body, including placental cells. Anti-phospholipid syndrome (APS) is the autoimmune dysfunction that is classically associated with recurrent pregnancy loss.
APS is associated with pregnancy loss in any trimester, placental thrombosis (blood clots), and small placentae. The interruption of the circulation to the fetus via these blood clots is a possible reason for the fetal losses. Identifying the mechanism behind the fetal losses would allow specific treatment to be developed. Clotting mechanisms are difficult to understand without a background in this area. Thrombosis may be caused by a relative deficiency in prostacyclin production within the cells that line the blood vessels (endothelial cells) since prostacyclin is a potent vasodilator and inhibitor of platelet aggregation. Thrombosis may also be caused by a relative insufficiency of the active form of the endogenous anticoagulant protein C, which normally degrades certain clotting factors to limit thrombosis, since phospholipids are required to activate protein C. At this time, the mechanism of thrombosis and fetal loss with APS is largely unknown.
Establishing the diagnosis of APS is important since most of the treatment options involve considerable expense and some added risk. Antiphospholipid antibodies are a large varied group of immunoglobulins directed against several different negatively charged cell surface phospholipids. Many of these phospholipids have been identified, with the best known being cardiolipin. Tests for APS can be divided into coagulation based tests and tests that detect the presence of the antibodies directly.
A group of phospholipid dependent coagulation tests are available (such as the kaolin clotting time, the plasma clotting time, dilute Russell viper venom time, and activated partial thromboplastin time) and serve as popular screening tests for antiphospholipid antibodies. Each of these coagulation tests relies on the activation of a prothrombin activator complex to allow for clot formation. Antiphospholipid antibodies block this activation to delay clot formation, such that in the presence of these antibodies there will be a prolongation of the time required for clotting and an abnormal result for these coagulation tests.
There are several available sensitive and specific assays for anti-cardiolipin antibodies, one of which should be obtained when there is a history of recurrent pregnancy loss. The classic assay for anti-cardiolipin antibodies is the Loizou ELISA, which has been modified over the years. Results that are negative or low positive are generally considered clinically irrelevant and do not require treatment. There are commercial assays for some of the other phospholipids such as phosphatidyl-serine, phosphatidyl-inositol, phosphatidyl-ethanolamine, phosphatidly-choline and phosphatidyl-glycerol. Rather than testing for each phospholipid individually, the more cost efficient test is one that detects a panel (usually all) of these phospholipids (such as an antiphospholipid antibody package). If the panel is positive then more specific detection of specific phospholipids can be considered. Clinically, it is not necessary to test for each of these specific antibodies since the treatment is the same for any of them. Specific testing is most appropriate in a research setting.
To summarize, all couples with recurrent pregnancy loss should be screened for APS. The tests that we routinely order include one of the coagulation tests (aPTT) that relies on the activation of the prothrombin activator complex and which will be appropriately diluted with normal plasma when abnormal,the anti-cardiolipin antibody test (positive in 2-3% of the general population, 7-45% of women with recurrent pregnancy loss- depending on what level is considered abnormal) 
& the lupus anticoagulant test (positive in 1-2% of the general population, 10% of women with recurrent pregnancy loss) We do not routinely order specific anti-phospholipid antibody tests since ourmy management is not altered by the results. Some research centers may order these tests to determine experimental treatment protocols.
APS is classically defined as a triad of recurrent pregnancy loss, thrombosis and autoimmune thrombocytopenia (decreased platelet concentration). For those couples with recurrent pregnancy loss, the positive finding (on 2 separate occasions) of either an appropriately performed coagulation based test or a direct antibody test is generally all that is required to propose treatment. Without treatment, couples with APS have a poor chance of carrying a fetus to term. The worst prognosis appears to occur when there is a prior fetal loss and high anti-cardiolipin antibodies. Treatment options for APS include 1)Low dose aspirin (75-81 mg per day) starting prior to pregnancy. Rationale for this treatment is based on the theory that a relative decrease in prostacyclin is the cause for thrombosis. Aspirin at these low doses has the effect of increasing the prostacyclin to thromboxane (its natural competitor) ratio to enhance the effect of prostacyclin. 
2)Prednisone (30-60 mg per day) to suppress the immune system. This corticosteroid can have several potentially serious complications. When given during pregnancy for this indication, prednisone has been associated with preterm premature rupture of the fetal membranes, preterm delivery and pregnancy-induced hypertension. This medication should only be given by physicians experienced in its use for this indication and typically in a research setting. 
We avoid this approach completely.3)Low molecular weight Heparin (2750 IU s/c per day in the first trimester after fetal viability is seen on ultrasound, continued through to the second trimester). Typically the aPTT test is used to monitor LMW heparin dosing but these test results are abnormal in APS so cannot be used. We generally go by the platelet count (If less than 100,000, we give LMWH on every second or third day). Use of LMW heparin is based on the theory that decreased levels of activated protein C may be responsible for the thrombosis seen, and acts as an anti-coagulant. We have treated over 300 patients using this approach over the last 10 years. 4)Immunoglobulin (Ig) therapy, with intravenous injections of Igs, has been used for several decades in the treatment of immunodeficiency conditions and more recently in the treatment of autoimmune disorders. The mechanism of action is not known, the dosing is not standardized for recurrent pregnancy loss, and this treatment is very expensive. I believe that it is important for this treatment to be administered in a research facility until it is better understood.
Alloimmune dysfunction resulting in recurrent pregnancy loss has also been proposed. Allogeneic antigens are molecular structures that occur in different members of the same species and have the ability to elicit an immune response. Normally, a person will reject dissimilar (non-self) tissues or structures from the body using the immune system. In pregnancy, the placenta and growing embryo are not entirely self but rather are a result of both the maternal and paternal genetic heritages (referred to as a semi-allograft). The placenta (and pregnancy) has a privileged relationship with the pregnant woman that allows it to escape rejection. The mechanism for this privilege is not known.There have been several interesting and complex theories attempting to describe how the normal pregnancy achieves its privileged status in the maternal uterus. Thus far, none of these theories has been generally accepted and proven. Some of the theories are based on
Increased sharing of HLA types (genes encoding antigens that distinguish and mark tissue as self) within the maternal and paternal chromosomes. With increased sharing the placenta may not trigger the production of special blocking antibodies which confer privilege . Decreased numbers of blocking factors that normally allow the placenta to be retained as a privileged site, either due to increased HLA sharing or other factors such as decreased numbers of natural suppresser cells in the uterus, which may control the activity of the natural killer cells and allow for placental survival within the uterus. The diagnosis of alloimmune recurrent pregnancy loss is one of exclusion. That is, when all other tests have been performed and the findings have come back normal then some of those with unexplained losses are thought to fall into this category. Several physicians refuse to treat alloimmune recurrent pregnancy loss since there are no direct diagnostic tests, treatment options are expensive and their benefits are largely unproven, and treatment options potentially involve risk. I think that it is prudent to limit treatment to a research facility with expertise in these therapies. Also, you must consider that there is reportedly up to a 60-70% chance of carrying a pregnancy to term even after 3 spontaneous abortions without treatment. The two main treatment options include 1)Unified leukocyte (white blood cell, WBC) immunization with paternal or donor blood cells, using 200-300 million mononuclear cells from the isolated buffy coat of blood, once the woman is pregnant and prior to 6 weeks gestation on one occasion only . 2)Immunoglobulin (Ig) therapy, with intravenous injections of Igs. The mechanism of action is not known, the dosing is not standardized for recurrent pregnancy loss, and this treatment is very expensive. With treatment, viable pregnancy rates of 70-80% have been reported in uncontrolled studies. In my experience, better candidates for this treatment are couples who have no other treatment options available and are willing to commit themselves to the time, energy (especially emotional) and money required to pursue experimental techniques.

My Daily Routine

Twin Trouble

Do We Really Need To Use Immunosuppressant Therapy For Antiovarian Antibodies?

Over three decades ago researchers observed a high rate of premature ovarian failure associated with poly-endocrine autoimmune disease and suggested that there might be an autoimmune disease of the ovary. At about the same time IVF workers observed auto-antibodies to eggs in the ovary in women with infertility and also suggested there might be an autoimmune disease of the ovary. Since that time, the concept of ovarian autoimmune disease has become more widely recognized but significant advances in our understanding are only just beginning to occur.
Such antibodies would bind to important functional sites in the ovary and granulosa cells and impair the normal response. The anti-ovarian antibodies were found fairly recently, and their complete function is not well known yet. It is believed that these antibodies cause disturbances that are a cause of ovarian failure/non-ovulation or poor ovulation. They are believed also to be a cause of less-than-expected response to various medications to stimulate proper ovarian function, and possibly even formation of less-than-excellent and normal eggs. The treatment of this condition is more or less experimental. Very infrequently, this condition can be helped through in vitro fertilization and if everything else fails an egg donation from a fertile donor is the evidence based-medicine’s answer to this disorder. When such a pregnancy is properly supported by administration of exogenous hormones – progesterone and sometimes even estrogen – it has an excellent chance to lead to normal delivery.
Ovarian autoimmune disease is principally associated with Premature Ovarian Failure (POF) and with unexplained infertility. It is possible that autoimmune unexplained infertility is an early stage of autoimmune POF but this remains to be demonstrated conclusively. POF is the onset of menopause before age 40 and occurs in one to two percent, or about one to two million women. Like natural menopause around age 50, premature menopause is identified by cessation of menstrual cycles for one year, accompanied by elevated follicle stimulating hormone (FSH) and reduced estradiol levels in blood . While some cases of POF have a genetic cause (such as Turner syndrome), or are due to chemotherapy, recent studies suggest that about half the cases of premature menopause are due to an autoimmune attack on ovarian follicles and the eggs (oocytes).
There is still a lack of information on the specific features of autoimmune POF. Some women with POF may have a family history of POF but most do not. However, women with POF have a higher risk for other autoimmune endocrine diseases, such as thyroid disease, Addison disease, type 1 diabetes, and autoimmune poly-glandular syndromes.
Women with infertility and ovarian auto-antibodies tend to have lower than expected estradiol responses to gonadotropin hormone stimulation (i.e. poor responders) and lower pregnancy rates following infertility treatment. Poor responders with ovarian antibodies were younger than poor responders without ovarian antibodies. This suggests that although some poor responses are associated with early stages of the menopause progression and reduced number of functional follicles, others are associated with an autoimmune process.
Ovarian autoimmunity is identified by the presence of anti-ovarian antibodies. There are several different types of tests and consequently different names for these antibodies. Antibodies specifically to eggs and to the zona pellucida (an area surrounding the eggs), or to ovarian cells have been described (9). Some women have antibodies to both ovarian cells and to eggs and others have only one of these antibodies. Ovarian autoimmunity is not identified by traditional tests for ovarian function, such as elevated pituitary follicle stimulating hormone in POF. Although the cause may differ, the symptoms of autoimmune and non-autoimmune POF are the same as in a normal menopause, including hot flashes, dry vaginal tissues, painful sex, infertility, bone loss, and an increased risk of cardiovascular disease. Likewise, autoimmune infertility can only be distinguished from non-autoimmune infertility by specific antibody tests.
As with other endocrine disorders, POF is treated by replacing the lost hormone, in this case hormone replacement therapy (HRT) with estrogen and progesterone to protect the heart, bones, genital and urinary tract tissues, and the nervous system. However, if a woman with infertility or POF wants to become pregnant, treatment with hormones that stimulate ovarian follicles to grow and produce eggs can be tried. If hormone stimulation alone does not result in a pregnancy, women may be treated by more aggressive methods such as in vitro fertilization (IVF). There have been reports of success in combination with low dose immunosuppression. However, success rates are relatively low and there are concerns about the side effects of immunosuppressant therapy. We, at Rotunda do not believe in Immunosuppression with steroids. This sort of approach has not been helpful or useful for any patients in our experience. In some rare cases of POF, follicular function may spontaneously resume, and a pregnancy can occur.
The next significant advance in characterizing ovarian autoimmune disease will be identification of the specific ovarian proteins recognized by the auto antibodies. Once we have tests that detect specific auto-antigens, we will be moving closer to some evidence-based medicine answers. This will permit development of tests based on use of specific antigens, which will improve clinical diagnosis. An understanding of how these proteins become targets of an autoimmune attack would be a significant step toward designing therapies for reversing the effects of this disorder.
As of now, the only known treatment which gives results for this disorder is Donor Egg IVF.

Is Co-culture The Magic Recipe For Improving IVF Implantation Rates?

Although I am writing about co-culture in IVF, we are not currently doing any co-culture. With recent improvements in IVF culture media and techniques, our IVF pregnancy rates (without co-culture) have improved dramatically. Therefore, we no longer see a need for co-culture. In vitro fertilization with co-culture has been utilized in animal in vitro embryo culture systems for over 30 years and more recently in some clinical human in vitro fertilization laboratories as well. The basic concept involves growing embryos in a culture medium on top of a proliferating monolayer of cells such as fallopian tube cells or cells from the lining of the uterus called endometrial cells. The idea is that these cells, which are sometimes referred to as "feeder" cells or "helper" cells, will stimulate development of the embryos by removing toxins from the medium, adding growth factors, or some other beneficial effect. Some studies have demonstrated improved pregnancy rates and delivery rates with utilization of co-culture for human in vitro fertilization.
Why don't all IVF centers use co-culture? There are several reasons that co-culture is not currently more widely used for human IVF:
1. Co-culture involves a lot of tedious work in the laboratory which leads to additional expense.
2. Most IVF labs are not experienced with culture of cells other than eggs, sperm, and embryos. Although culturing cells from the endometrium or fallopian tube is not extremely difficult, it does involve learning some new techniques.
3. There is no universal agreement that co-culture is necessary to provide optimal pregnancy rates from human in vitro fertilization.
4. Another issue is that depending on the source of cells used for the co-culture there may be concerns about transmission of infectious diseases such as viruses from the cell line to the developing embryos. To date there have been no reported cases of viral transmission to a human fetus. Non-autologous cell lines should be screened for infectious diseases prior to use in human embryo coculture.
Coculture is usually not applied universally to all cases in an IVF program. It is usually reserved for use in the "poor prognosis" patients. Studies have suggested that these patients can benefit the most from IVF with co-culture. Examples of poor prognosis patients include women over 40, women with previous IVF failures, women with elevated FSH (follicle stimulating hormone) levels, and women who respond poorly to ovarian stimulation with gonadotropins.
In general there are two schools of thought in this area. One school says that co-culture can be of a benefit for some patients undergoing in vitro fertilization. The philosophy here is that we do not need to know the exact mechanism of the benefit of co-culture, or exactly how standard in vitro culture systems are deficient - what we want is to help the couple get their baby. More like experienced hunches & claims rather than solid evidence based medicine. The other school says co-culture is a crutch that masks the real problem which is sub-optimal in vitro embryo culture systems. These people would prefer to use very pure and carefully defined media in order to maximize the culture environment. They believe that this can yield an equally high pregnancy rate without the use of co-culture. This is what we strongly believe in. I believe that the heart of an IVF clinic are good solid culture systems.
Clinical in vitro fertilization programs that are utilizing co-culture for their human IVF generally use one of three cell types. However, there are numerous other cell lines that have been successfully utilized as well. The cell lines most often used are fallopian tube cells which can be from either human or animal origin, endometrial cells from the lining of the uterus, or Vero cells which are from an immortalized cell line derived from African Green Monkey kidney cells. Cumulus cells from around the egg with or without granulosa cells from the walls of the ovarian follicles where the eggs develop can also be used for co-culture.
Most commonly the eggs and sperm are mixed together on the day of egg retrieval without the co-culture cells. The next morning, after identification of the fertilized eggs (called zygotes), these embryos are then transferred on to the co-culture cells which have been prepared several days in advance. The embryos are then cultured with the helper cells until the time of embryo transfer. This is usually two more days of culture.
Another potential application of co-culture for human in vitro fertilization programs is that of culturing embryos to the blastocyst stage and then performing blastocyst transfer. This allows selection of embryos that have been able to survive through the early cleavage stages of the first five days after fertilization. It is generally very difficult to get good numbers of high quality blastocysts when culturing in defined medium (no co-culture). This technique can allow transfer of fewer embryos while still maintaining an excellent pregnancy rate. For example, some programs have cultured embryos to blastocyst stage and had very good pregnancy rates resulting from transfer of only two blastocysts. This would greatly reduce the risk of high order multiple pregnancy that is seen in some programs transferring higher numbers of embryos.
Further research is needed in order to define exactly which patients would be benefited by co-culture. Also, the co-culture technique itself may be able to be further modified such that in vitro embryonic development is even better than what can be achieved with current technology. For example, many aspects of the co-culture technique could be altered, such as using a different cell line, a different medium, smaller droplets for culture, changing the medium more frequently, or other changes. By varying the usual co-culture techniques, we might obtain a further improvement in embryonic development over what is currently possible.
A practical problem with research in this area is that studies using variations on standard techniques are relatively easy to perform using animal embryos, but studies using human embryos are problematic to set up and implement. Results from co-culture studies done with animal embryos will not necessarily be applicable to IVF with human embryos.
Much has been learned about co-culture both for animal in vitro embryo culture and for in vitro culture in the human as well. Studies continue to attempt to discover exactly how co-culture improves embryonic development. If the cells make certain products that stimulate development of healthier embryos, these products might be able to be produced commercially and added to conventional culture media.
It is possible that pure and exactly defined chemical media might someday be so improved as compared to what is now in use that co-culture would not offer any increase in pregnancy rates, even for poor prognosis patients. However, we do not appear to be at that point today. Further co-culture research is needed before we make tall claims about this being a panacea & a potential Nobel prize winner.

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The First Steps of an In-captivity born pre-term Panda

When the ancestors of human beings had only just learnt how to walk upright, the footprints of the Giant Panda were already all over East and South East Asia. But the peak population of the family of giant pandas has diminished greatly since then. Today, the total population of Pandas wavers at around one thousand, including some 100 animals in captivity. More seriously, in captivity few seem to have the natural desire to mate.
This year, a record number of 16 pandas have been born in captivity, according to China's Panda Breeding Programme. Because pandas in the wild number less than 1000, these sixteen babies are a significant addition to this endangered species population.This year the Wolong Chinese Giant Panda Protection Center has been successful in breeding two infants in total. It may seem like a small number, but around the world only 50 pandas are born every year and out of this number only 20 have a chance to grow up. Scientists are now investigating ways to get pandas bred in captivity back to where they belong - the wild. It is this that will complete the work of the researchers at the Wolong Chinese Panda Protection Center. Work which is ensuring the survival of the giant panda.
I recently came across these series of pictures of a pre-term Panda baby which would have made a baby-album proud! Pictures speak louder than a 1000 words & I will let you enjoy these from the pre-term delivery to 120 days of life...

Origins of Sex

A study cataloguing the different types of protein found in sperm for the first time could help to unveil some of the questions surrounding infertility and the origin of sex, scientists claim. Researchers from the University of Bath identified 381 proteins present in sperm of the fruit fly, Drosophila melanogaster. This finding is a 50-fold increase in the proteins previously identified.

Writing in the journal Nature Genetics, the researchers claim that their study is the first to characterise the whole-cell protein components of a higher eukaryotic cell (a cell in which all the genetic components are contained within a nucleus). These components (known as the proteome) contain everything the sperm needs to survive and function properly and provide the basis for studies investigating why some sperm are more successful than others. The findings could be significant for researching infertility in men as around half of the genes of the fruit fly sperm proteome have comparable versions in humans and mice. Proteins carry out an immense range of functions, from forming structural materials to catalysing chemical reactions, so knowing exactly what proteins are in sperm is a great step forward in understanding.

"This study offers a tantalising glimpse into how we might begin to answer some of biology's most fundamental questions," said Dr Tim Karr from the University of Bath, who led the study. "Amazingly we know very little about what is in a sperm, which probably explains why we don't really understand sex, let alone how it evolved." He added: "Before we catalogued the sperm proteome, we only knew a few specific proteins in the Drosophila sperm. Being able to compare the structure and content of the proteomes of sperm from different species should help us understand the evolution and origin of sperm."
Research published in Nature Genetics today describes 381 proteins present in sperm of the fruit fly, Drosophila melanogaster. Whilst more proteins may be identified as research progresses, this study marks the first substantial ’whole-cell’ characterisation of the protein components of a higher eukaryotic cell (a cell in which all the genetic components are contained within a nucleus).

By comparing the sperm proteome of the fruit fly with other species, scientists will also be able to rewind evolution and work out the core sperm proteome – the most basic constituents a sperm needs for sexual reproduction. This will shed light on how sex itself evolved.

Angle Matters

Hi Friends,
Here are some super shots taken by amateur photographers.Hope to get some additions on the Blog!
Cheers & Have a Lazy Sunday!
Gautam