Preimplantation Genetic Diagnosis (PGD)

Although Rotunda does not presently offer any PGD services, I thought it worthwhile to educate our patients & readers about Preimplantation Genetic Diagnosis. Couples with a family history of a genetic disorder and older mothers are relatively more likely to have a baby with genetic birth defects. Preimplantation genetic testing and diagnosis (PGD) can help these parents dramatically improve their odds of giving birth to a healthy child. Embryos that have certain genetic defects develop improperly. Used with in vitro fertilization (IVF), PGD can help us select the best embryos and avoid specific birth defects.
In PGD, a embryologist removes one or two cells from each embryo created in the IVF cycle(see picture). The cells are tested for abnormal genes. Only the embryos that have normal cells are transferred into the woman. Since PGD is not 100% reliable and only tests for specific defects, parents should presently still use other prenatal genetic tests, such as amniocentesis or chorionic villus sampling. PGD is expensive and still considered an experimental procedure by the majority of IVF laboratories.
Presently, only couples with family history of genetic disease and women over age 35 are advised PGD. PGD can detect genetic disorders when the defect is understood. As we learn more about genes and gene defects, PGD will become useful for more patients. PGD can tell whether an embryo will become a boy or girl, and reveal certain genetic conditions, including Cystic fibrosis, Down Syndrome, Duchenne muscular dystrophy, Hemophilia A, Tay-Sachs disease, and Turner Syndrome.
Prior to PGD, many couples with a family history of severe genetic disorder may have decided against having children. PGD dramatically improves the odds of having a baby without the disorder. In some cases, biologists can see whether the embryo has the defect. Some disorders only affect male offspring, so that female embryos may be selected to avoid the condition even if the exact defect isn't understood.
PGD helps prevent the stress and trauma after an abnormal result from an amniocentesis or chorionic villus sampling. These prenatal genetic tests can only be performed after 10-12 weeks into the pregnancy. Patients who use PGD should follow up with one of these tests, but the odds of an abnormal result will be dramatically reduced.
PGD requires the removal of one or two cells from each embryo. The embryo development is slowed slightly, but is otherwise normal. Most embryos are not adversely affected by the procedure. Some embryos may be damaged during the removal. An embryo that the PGD detects as abnormal may be normal in a small percentage of cases. This embryo would not be transferred, even though it could have become a healthy baby. An embryo that the PGD detects as normal may be abnormal similarly. This embryo would be transferred, and would result in a miscarriage or child with birth defects. Because of this risk, other genetic tests, amniocentesis or chorionic villus sampling, should be performed. To decrease the false positive & false negative results, some IVF teams employ a combination of tests using more than one cell biopsies. Since PGD is performed using embryos from an IVF cycle, the patient should be aware of the risks of IVF. There may be too few or no embryos without the defect. The embryos may not implant and develop even if they do not have the defect. If you decide to pursue PGD, you will prepare for an IVF procedure. The woman will take hormones to stimulate the ovaries to produce many eggs. Just as in a normal IVF procedure, the doctor retrieves the mature eggs from the woman. The eggs are fertilized with sperm. After two days, the embryos grow to four to six cells. The biologist forms a small opening in the outer membrane of the embryo, the zona pellucida. This is a similar process to assisted hatching. The technician gently sucks one or two cells out of the embryo through the hole. These cells are then tested for genetic abnormalities. In most cases, all the cells of an embryo will have the identical genetic makeup. Therefore, the tested cells will show the genetics of the remaining, viable embryo. The remaining cells of the embryo are young enough that they will form a complete, normal fetus. The test itself is a standard genetic test. It takes less than 24 hours to perform, so that the patient follows essentially the same schedule as a standard IVF cycle.
Women over 35 are more likely to have eggs with an extra or missing chromosome (aneuploidy). In these cases, the laboratory will examine the cells to count the chromosomes that usually lead to severe birth defects. Each human chromosome has a number, except the X and Y chromosomes that determine gender. The biologist uses a technique called fluorescence in- situ hybridization (FISH) to attach a particular color to each 13, 16, 18, 21, X, and Y chromosome. The biologist counts the spots of each color for each cell (see picture). Normal cells will have two of each color for the numbered chromosomes, as well as two X chromosomes (female cells) or an X and a Y chromosome (male cells). For a family history of a disorder, the laboratory will test for the specific defect. The laboratory must first test cells from the parent who has the disorder or may be a carrier to determine the exact defect. The embryo cells are then tested in a process that uses FISH to see if they contain that exact defect. The test doesn't reveal other genetic defects. After the tests are completed, the best embryos without the defect are transferred into the woman's uterus as in a standard IVF cycle. Follow the recovery procedures for an IVF cycle. If you become pregnant, be sure to follow up the PGD with another prenatal genetic test.

Hydrosalpinx

A leading consequence of infertility in women is fallopian tube blockage. A blockage can be caused by a number of reasons, one of which is fluid retention forming a hydrosalpinx(see picture). A hydrosalpinx is a swollen, sausage-shaped blocked fallopian tube which is often the result of a past tubal infection. When injury causes the end of the fallopian tube to close up, glands within it produce a watery fluid which fills up the tube. Although this watery fluid generally poses no harm to the body, studies conducted on women who had undergone in vitro fertilization have shown that this substance is somewhat toxic to implanted embryos. The women with hydrosalpinges had significantly lower chances for a successful pregnancy as compared with those who had their hydrosalpinges removed prior to implantation.The failure of the in vitro attempts at pregnancy is seen to be rooted on the spillage of the hydrosalpinx fluid into the uterine cavity which houses the implanted embryo. The fluid could dislodge the embryos or kill them thereby resulting in a miscarriage.

In the presence of an infection, the body is often able to naturally fight back and heal itself. However, scar formation may result and cause injured tissues to stick together which is the case in a hydrosalpinx. The injured fimbriae (fingerlike projections at the end of the fallopian tube near the ovary) seal up through adhesions from the scarring brought about by an infection(see picture). Both fallopian tubes are often affected when infection is present. However, a hydrosalpinx is usually seen only in one tube with the other tube left with abnormalities. This is the reason why women with only one hydrosalpinx can also experience infertility.

Hydrosalpinges can be caused by a number of infections and two of the most common are Gonorrhea and Chlamydia both of which are sexually transmitted diseases. Generally speaking, sexually transmitted diseases are the more likely culprits when hydrosalpinges occur. However, they are not the only causes. Any form of injury to the fallopian tube tissues can result to a hydrosalpinx. Some other causes for the formation of a hydrosalpinx are ectopic pregnancies, abortions, miscarriages, abdominal surgeries and endometriosis. These conditions can damage or affect the fallopian tubes and the resulting scar adhesions can likewise seal up the tubes.A hydrosalpinx is often seen to form after pelvic inflammation which can be caused by a number of reasons. Pelvic inflammation, are also often caused by infections and can also result from sexually transmitted diseases. However, other causes exist, including fungal or yeast infections as well as infections from the usage of intrauterine devices. A hydrosalpinx can occur in any woman and the chances of occurrence will increase in the presence of infection-causing microorganisms and/or, injury to the fallopian tubes or to the tissues near them. Unfortunately, it is rarely diagnosed early -if diagnosed at all -because the symptoms are generally mild and some women even experience no symptoms at all. The physical discomforts from the condition are often mistaken to be symptoms of bladder infection or bowel problems.

In mild cases fertility may be restored by opening the tube surgically, otherwise IVF is the treatment of choice. There is some evidence that hydrosalpinx reduces the success rate of IVF and increases the risk of mscarriage. For this reason, some doctors may advise removing, or occluding the hydrosalpinx before the IVF treatment.

Hysterosalpingogram (HSG), Laparoscopy & Laparotomy

Knowing the condition of the fallopian tubes is essential for proper and effective treatment of fallopian tube blockage. This is because, although you may know your tubes are blocked, you won't know which approach to take in unblocking them unless you have an idea of what type of blockage you have. Each treatment procedure addresses a specific problem hence, your doctor or your treatment provider will need at least, a general view of the condition of your tubes and the location of the blockage to be able to prescribe an appropriate action to take to relieve the blockage. There are generally three tests that are employed in determining the condition of the fallopian tubes -Hysterosalpingogram (HSG), Laparotomy and Laparoscopy. We will discuss each test individually in this article.

Hysterosalpingogram(HSG)
A hysterosalpingogram is also known as a hysterogram or an HSG and is a form of x-ray which provides a visual of the inner part of the uterus(see picture). A special liquid (dye) is injected into the cavity of the uterus which is then observed (through an x-ray of the abdominal area) as it travels into the fallopian tubes. The liquid should be seen to spill out of the ends of the fallopian tubes near the ovaries to conclude the absence of any significant blockage. However, if only some of the liquid drips out of the tube or if not a single drop falls out, a blockage automatically becomes a possibility. However, additional tests would be likely recommended as spasms from the procedure can produce a similar restriction or stoppage in the flow of the liquid from the ends of the tubes. In addition, this type of test is not advisable for pregnant women or for those with infection in the pelvic area (procedure can spread infection through the liquid contrast dye used).

Laparotomy
Laparotomy is also known as coeliotomy and is a procedure used either for diagnostic or therapeutic purposes(see picture). This procedure involves surgery, with incision made through the abdominal wall thereby providing access to the abdominal cavity which houses the organ to be checked or treated. This is an ancient procedure & is not recommended for diagnostic purposes in present-times. Diagnostic laparotomy was generally used to find out what may be wrong with a certain structure in the abdominal cavity (e.g. fallopian tubes). This was a significantly invasive form of diagnostic tool and hence women tend to choose the similar yet less invasive procedure, laparoscopy.

Laparoscopy
Laparoscopy is similar to laparotomy in that, it also involves an incision through the abdomen. However, the incision need only be large enough to accommodate a laparoscope, which is a thin telescope-like instrument (laparoscope) to be used in inspecting the organ with the problem. A visual image of the abdominal cavity and the structures in it is projected in a monitor connected to the laparoscope(see picture). The fallopian tube along with any blockages within it can be seen hence the extent, location and general characteristics of the blockage can be determined. This diagnostic tool provides approximately the same quality of diagnosis as laparotomy and is also used in treatment procedures.

Advantages and Disadvantages
All three diagnostic procedures have their benefits as well as disadvantages. A hysterosalpingogram provides minimal information about the condition of the tube and the risks associated with it makes it unavailable to pregnant women and those with pelvic infections. However, it is non-invasive and cheaper as against the two other procedures.

A laparotomy on the other hand provides the clearest access to checking the condition of the tubes but is largely invasive & is not recommended. Laparoscopy is a less invasive procedure and provides the best quality of diagnosis with a magnified image which helps in both diagnosis as well as therapeutics.

Blocked Fallopian Tubes- Treatment Options

Tubal factors are said to account for about 20 to 30 percent of all infertility cases around the world. The main contributing factor: blocked fallopian tubes. A blocked fallopian tube, although not necessarily life threatening, can be a very serious cause for concern because although conventional surgery may provide relief from the condition, damage to the tubes are generally considered irreversible and hence, subsequent pregnancy may prove almost impossible -but not quite. The fallopian tubes play a major role in conception. It is within a fallopian tube that fertilization normally occurs and the tubes serve as the pathways for the egg to travel from the ovaries towards the uterus for implantation. When the tubes are substantially blocked, the meeting of the sperm and egg may be prevented and hence, natural fertilization might be impossible. During the times when fertilization does happen, the zygote may still be unable to reach the uterus and ectopic pregnancy, a life threatening condition, could occur.

Pregnancy in the presence of blocked tubes is often difficult but not impossible. Assisted Reproductive Technology (ART) techniques provide artificial conception or a meeting of the egg and sperm outside the woman's body. The resulting mix or the zygote is then delivered into the uterus or the unaffected fallopian tube and pregnancy can result. These techniques however, are not always successful. ART practitioners try to increase the chances of impregnation by delivering more than 1 zygote or egg-sperm mix hence, this procedure can often lead to multiple births.

Another option for pregnancy-hopeful women with blocked tubes is to resort to Endoscopic Fallopian Tube Recanalisation; which works best with proximal tubal occlusion & a method of Tactile Cannulation using Laparoscopic guidance has been pioneered by us and published in peer-reviewed journals (see pictures) . Alternative remedies have proven quite effective in helping women get pregnant. The generally accepted method of unblocking fallopian tubes was through tubal surgery which can be done through microsurgical techniques either during open abdominal surgery (laparotomy) or using laparoscopy through a small incision in the abdomen. The latter procedure however must be conducted by a surgeon trained in the field of microsurgery and has hands-on knowledge of laparoscopy. There are many different surgery techniques for unblocking fallopian tubes and the differences generally involve the length of the incision, the area affected, the type of blockage present, and the method of unblocking applied (e.g. complete removal or creation of another opening). Tubal reanastomosis involves the complete removal of the blocked portion of the tube and a subsequent joining of the healthy ends. This procedure is usually done with laparotomy or abdominal incision.

Salpingectomy involves the surgical removal of the infected or blocked fallopian tube. It is usually done on patients who have a hydrosalpinx and want to improve their chances at pregnancy through in vitro fertilization (IVF). This procedure is preferred over salpingostomy which is another surgical procedure available for dealing with hydrosalpinges (fluid-filled blocked fallopian tubes).

Salpingostomy is a procedure that requires an incision through the affected fallopian tube. In neosalpingostomy, the idea is to create a new opening in the part of the tube closest to the ovary while in linear salpingostomy the incision serves as the pathway to release the blockage. Neosalpingostomy is generally used in dealing with hydrosalpinges. This technique however more often than not merely provides temporary unblocking as it is a common occurrence for scar tissue growth to reseal the new opening created by neosalpingostomy thereby effectively blocking of the tube once more.

When the problem is a partial blockage or a scarring in the fimbriae (fingerlike projections at the end of the fallopian tube near the ovary), Fimbrioplasty is an option where the blockage or the scar adhesions are removed and the fringed ends are rebuilt such that wafting motion of the fimbriae are restored. The fimbriae move in sweeping motions such that the egg released by the ovary will be caught then guided towards the uterus.

The relative success of the surgery will depend on the health and condition of the patient and the location of the blockage. It is shown that clearing blockages near the uterus are more likely to be successful. Furthermore, the amount of tube that remains after the surgery will determine the ability of the tube to regain its normal function and hence, the subsequent ability of the woman to get pregnant.

Surgery is generally an invasive form of treatment but recent technologies already provide for less invasive procedures as against the traditional open abdominal option such as Laparoscopy. It involves the use of a laparoscope (camera or ultrasound) which is inserted into a small incision through the abdominal wall. The body part requiring surgical treatment will be seen through a monitor which, is connected to the laparoscope.

Surgery procedures also involve risks some of which are spread of pelvic infection, the formation of scar adhesions among the reproductive organs or with the abdominal cavity, and the increase in the possibility of tubal ectopic pregnancy.

Dyspareunia or Painful Intercourse

Intercourse pain can be totally debilitating. Complaints range from pain at initial penetration, to pain at deep penetration, to a combination of the two. While physicians can give varying primary or accompanying diagnoses, there is little doubt that the pain is of "mechanical" cause. In fact, the pain generally comes from adhesions or scar tissue left by a prior surgery, inflammation or trauma. In some cases, this is accompanied by an anteverted (forward tilting) tailbone.

During the course of life, the female reproductive tract may be subjected to numerous traumas, infections, inflammations, and surgeries, which can lead to adhesions and scar tissue. Some women absorb these repetitive traumas and stresses to the pelvis without experiencing symptoms or negative side effects. However, some women experience significant, long lasting symptoms including anorgasmia (the inability to have an orgasm or reach a full orgasm), decreased desire (libido) and dyspareunia (intercourse pain).

Endometriosis and adhesions are major causes of painful intercourse. Painful sexual intercourse is a condition that plagues millions of women worldwide. For some, the pain may occur at first penetration. This is often a very sharp and specific pain in one location, often at or near the opening of the vagina. For others, the pain is experienced at deep penetration. This is often described as a broader, deeper pain, and has been described as if “it feels like my partner is hitting something” and in many cases, he is (see picture). Some women may even experience a combination of the two.

Surgery or a fall can pull your tailbone forward, creating a physical block in your body. This can cause chronic constipation,
or pain during intercourse. In cases of pain or tightness at the opening, we find that adhesions, tiny or large, have formed at some time in the past. As the body heals from infection, inflammation, surgery or trauma, it develops tiny adhesions, which are often invisible to the naked eye. These adhesions can form on the surface of the labia, at the vaginal opening or within its delicate inner tissues. These adhered tissues are stretched at the commencement of intercourse, creating a pull on nerves and other sensitive structures. This pull causes pain at just the time when you should be experiencing great pleasure. The irritation can cause pelvic spasms, which in turn causes more pain and dysfunction, perpetuating the process.

Pain at deeper penetration is often associated with a trauma or repetitive stress to the tailbone (coccyx), generally caused by a fall on the hip, back, or tailbone. Other causes may include pelvic surgery (such as an appendectomy or D&C), inflammation (such as endometriosis), or infection (bladder, yeast, etc.). Abuse and repetitive stresses (such as sitting for long periods of time) are other common causes of this pain. When any of these occur, internal tissues may shorten, pulling the tailbone out of its normal position. The tailbone then acts as a physical block to your partner during intercourse, causing you to experience a deep pain during or after sex. Similar conditions can occur at the cervix, or other vaginal tissues.

Intercourse should be a time of great pleasure. Because the female reproductive organs are susceptible to adhesions and tailbone trauma over time, intercourse can become a time of pain and embarrassment. Our endoscopic surgeons at the Aesculap Academy, Mumbai (www.testtubebabyclinic.com) have with pelvic adhesiolysis & peri-rectal dissection of endometriotic implants, decreased pain, increased sexual function, and restored the pleasures of intimacy and intercourse for most of the women we treat with intercourse pain. In doing so, we enrich their lives and those of their partners.

Intrauterine Insemination is the First Line Treatment For Infertility

Intrauterine insemination (IUI) is a procedure in which sperm are placed directly into the uterine cavity through a catheter near the time of ovulation. This procedure is most commonly performed when there are problems with the sperm, such as low count or low motility, or an incompatibility between the sperm and the cervical mucus. It can also be performed to overcome problems associated with a man's inability to ejaculate inside the woman's vagina due to impotence, premature ejaculation or other medical conditions.It is the most common procedure-in fact, the first line therapy for unexplained infertility. IUI increases the chances of pregnancy because the sperm are placed directly in the uterus, bypassing the cervix and improving the delivery of the sperm to the egg.
IUIs can be performed either with the partner's sperm or with donor sperm. It is recommended that the patient abstain from sexual intercourse for two to three days before the procedure. In some cases, it may be necessary for the female to take medication to induce ovulation if her cycles are not regular. The male will provide a semen sample one to two hours before the procedure is to be performed. The semen will be washed, a procedure in which the sperm is separated from the seminal fluid and the quality of the sperm is analyzed. Following the wash, it is time for the insemination procedure, which only takes a few minutes and does not cause much, if any, discomfort for the female. The doctor will insert a small catheter into the uterine cavity through the cervix and inject sperm directly into the uterus. The patient is able to resume normal activity immediately following the IUI procedure. If pregnancy does not result from the initial IUI, the procedure may be repeated during the following cycles.
We expect a 15% chance of success with IUI cycles combined with clomiphene citrate or letrozole. The success rates go up by nearly 10% with use of gonadotrophins (Fertility Injections). At Rotunda, from 1992, we must have performed over 5000 IUI cycles for in-house patients & over 12,000 IUI cycles for referred cases, who are monitored by their respective gynecologist & walk in only for the IUIs.

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.