IVF (IN VITRO FERTILISATION) AND GIFT (GAMETE INTRA FALLOPIAN TRANSFER)

What is IVF?

In vitro fertilisation (IVF) is a technique in which egg cells are fertilised by sperm outside the woman's womb. IVF is a major treatment in infertility when other methods of achieving conception have failed.

The process involves hormonally controlling the ovulatory process, removing ova (eggs) from the woman's ovaries and letting sperm fertilise them in a fluid medium. The fertilised egg (zygote) is then transferred to the patient's uterus with the intent to establish a successful pregnancy.

What is GIFT?

Gamete intrafallopian transfer (GIFT) is an infertility treatment in which eggs are removed from a woman's ovaries, and placed in one of the fallopian tubes, along with the man's sperm. This allows fertilization to take place inside the woman's body.

It takes, on average, four to six weeks to complete a cycle of GIFT. First, the woman must take a fertility drug to stimulate egg production in the ovaries. The doctor will monitor the growth of the ovarian follicles, and once they are mature, the woman will be injected with Human chorionic gonadotropin (hCG). The eggs will be harvested approximately 36 hours later, mixed with the man's sperm, and placed back into the woman's Fallopian tubes using a laparoscope.

A woman must have at least one normal fallopian tube in order for GIFT to be suitable. It is used in instances where the fertility problem relates to sperm dysfunction, and where the couple has idiopathic (unknown cause) infertility. Some patients may prefer the procedure to IVF for ethical reasons, since the fertilization takes place inside the body.

As with most fertility procedures, success depends on the couple's age and the woman's egg quality. It is estimated that approximately 25-30% of GIFT cycles result in pregnancy, with a third of those being multiple pregnancies.

Many specialists in infertility would look at GIFT as a procedure that is outdated (2004) as pregnancy rates in IVF tend to be equal or better and do not require laparoscopy.

IVF Method

Ovarian stimulation

Treatment cycles are typically started on the third day of menstruation and consist of a regimen of fertility medications to stimulate the development of multiple follicles of the ovaries. In most patients injectable gonadotropins (usually FSH analogues) are used under close monitoring. Such monitoring frequently checks the oestradiol level and, by means of gynaecologic ultrasonography, follicular growth. Typically approximately 10 days of injections will be necessary. Endogenous ovulation is blocked by the use of GnRH agonists or GnRH antagonists.

Oocyte retrieval

When follicular maturation is judged to be adequate, human chorionic gonadotropin (β-hCG) is given. This agent, which acts as an analogue of luteinising hormone, would cause ovulation about 36 hours after injection, but a retrieval procedure takes place just prior to that, in order to recover the egg cells from the ovary. The eggs are retrieved from the patient using a transvaginal technique involving an ultrasound-guided needle piercing the vaginal wall to reach the ovaries. Through this needle follicles can be aspirated, and the follicular fluid is handed to the IVF laboratory to identify ova. The retrieval procedure takes about 20 minutes and is usually done under conscious sedation or general anaesthesia.

IVF laboratory

In the laboratory, the identified eggs are stripped of surrounding cells and prepared for fertilisation. In the meantime, semen is prepared for fertilisation by removing inactive cells and seminal fluid. The sperm and the egg are incubated together (at a ratio of about 75,000:1) in the culture media for about 18 hours. By that time fertilisation should have taken place and the fertilised egg would show two pronuclei. In situations where the sperm count is low a single sperm is injected directly into the egg using intracytoplasmic sperm injection (ICSI). The fertilised egg is passed to a special growth medium and left for about 48 hours until the egg has reached the 6-8 cell stage.

Laboratories have developed grading methods to judge oocyte and embryo quality. Typically, embryos that have reached the 6-8 cell stage are transferred three days after retrieval.

Embryo transfer

Embryos are graded by the embryologist based on the number of cells, evenness of growth and degree of fragmentation. The number to be transferred depends on the number available, the age of the woman and other health and diagnostic factors. In countries such as the UK, Australia and New Zealand, a maximum of two embryos are transferred except in unusual circumstances. This is to limit the number of multiple pregnancies. The embryos judged to be the "best" are transferred to the patient's uterus through a thin, plastic catheter, which goes through her vagina and cervix. Several embryos may be passed into the uterus to improve chances of implantation and pregnancy.

Post-transfer

The patient has to wait two weeks before she returns to the clinic for the pregnancy test. During this time she may receive progesterone—a hormone that keeps the uterus lining thickened and suitable for implantation. Many IVF programmes provide additional medications as part of their protocol.

Success rates

Chance of a successful pregnancy is approximately 15% for each IVF cycle, although selected clinics are now able to claim rates up to 50% per cycle. There are many factors that determine success rates including the age of the patient, the quality of the eggs and sperm, the duration of the infertility, the health of the uterus, and the medical expertise. It is a common practice for IVF programmes to boost the pregnancy rate by placing multiple embryos during embryo transfer. A flip side of this practice is a higher risk of multiple pregnancy, itself associated with obstetric complications.

IVF programmes generally publish their pregnancy rates. However, comparisons between clinics are difficult as many variables determine outcome. Furthermore, these statistics depend strongly on the type of patients selected.

There are many reasons why pregnancy may not occur following IVF and embryo transfer, including

• The timing of ovulation may be misjudged, or ovulation may not be able to be predicted or may not occur
• Attempts to obtain eggs that develop during the monitored cycle may be unsuccessful
• The eggs obtained may be abnormal or may have been damaged during the retrieval process
• A semen specimen may not be able to be provided
• Fertilization of eggs to form embryos may not occur
• Cleavage or cell division of the fertilised eggs may not take place
• The embryo may not develop normally
• Implantation may not occur
• Equipment failure, infection and/or human error or other unforeseen and uncontrollable factors, which may result in the loss of or damage to the eggs, the semen sample and/or the embryos.

Potential Complications

The major complication of IVF is the risk of multiple births. This is directly related to the practice of transferring multiple embryos at embryo transfer. Multiple births are related to increased risk of pregnancy loss, obstetrical complications, prematurity, and neonatal morbidity with the potential for long term damage. Strict limits on the number of embryos that may be transferred have been enacted in some countries (e.g., England) to reduce the risk of high-order multiples (triplets or more), but are not universally followed or accepted. Spontaneous splitting of embryos in the womb after transfer does occur, but is rare (<1%)>

Another risk of ovarian stimulation is the development of ovarian hyperstimulation syndrome.

INFERTILITY What is infertility?

Most experts define infertility as not being able to get pregnant after at least one year of trying. Women who are able to get pregnant but then have repeat miscarriages are also said to be infertile.

Pregnancy is the result of a complex chain of events. In order to get pregnant:

• A woman must release an egg from one of her ovaries (ovulation).
• The egg must go through a fallopian tube toward the uterus (womb).
• A man's sperm must join with (fertilize) the egg along the way.
• The fertilized egg must attach to the inside of the uterus (implantation).

Infertility can result from problems that interfere with any of these steps.

Is infertility a common problem?

About 1 in 10 women have difficulty getting pregnant or carrying a baby to term.

Is infertility just a woman's problem?

No, infertility is not always a woman's problem. In only about one-third of cases is infertility due to the woman (female factors). In another one third of cases, infertility is due to the man (male factors). The remaining cases are caused by a mixture of male and female factors or by unknown factors.

What causes infertility in men?

Infertility in men is most often caused by:

• problems making sperm -- producing too few sperm or none at all
• problems with the sperm's ability to reach the egg and fertilize it -- abnormal sperm shape or structure prevent it from moving correctly

Sometimes a man is born with the problems that affect his sperm. Other times problems start later in life due to illness or injury. For example, cystic fibrosis often causes infertility in men.

What increases a man's risk of infertility?

The number and quality of a man's sperm can be affected by his overall health and lifestyle. Some things that may reduce sperm number and/or quality include:

• alcohol
• drugs
• environmental toxins, including pesticides and lead
• smoking cigarettes
• health problems
• medicines
• radiation treatment and chemotherapy for cancer
• age

What causes infertility in women?

Problems with ovulation account for most cases of infertility in women. Without ovulation, there are no eggs to be fertilized. Some signs that a woman is not ovulating normally include irregular or absent menstrual periods.

Less common causes of fertility problems in women include:

• blocked fallopian tubes due to pelvic inflammatory disease, endometriosis, or surgery for an ectopic pregnancy
• physical problems with the uterus
• uterine fibroids

What things increase a woman's risk of infertility?

Many things can affect a woman's ability to have a baby. These include:

• age
• stress
• poor diet
• athletic training
• being overweight or underweight
• tobacco smoking
• alcohol
• sexually transmitted diseases (STDs)
• health problems that cause hormonal changes

How does age affect a woman's ability to have children?

More and more women are waiting until their 30s and 40s to have children. Actually, about 20 percent of women in the United States now have their first child after age 35. So age is an increasingly common cause of fertility problems. About one third of couples in which the woman is over 35 have fertility problems.

Aging decreases a woman's chances of having a baby in the following ways:

• The ability of a woman's ovaries to release eggs ready for fertilization declines with age.
• The health of a woman's eggs declines with age.
• As a woman ages she is more likely to have health problems that can interfere with fertility.
• As a women ages, her risk of having a miscarriage increases.

How long should women try to get pregnant before calling their doctors?

Most healthy women under the age of 30 shouldn't worry about infertility unless they've been trying to get pregnant for at least a year. At this point, women should talk to their doctors about a fertility evaluation. Men should also talk to their doctors if this much time has passed.

In some cases, women should talk to their doctors sooner. Women in their 30s who've been trying to get pregnant for six months should speak to their doctors as soon as possible. A woman's chances of having a baby decrease rapidly every year after the age of 30. So getting a complete and timely fertility evaluation is especially important.

Some health issues also increase the risk of fertility problems. So women with the following issues should speak to their doctors as soon as possible:

• irregular periods or no menstrual periods
• very painful periods
• endometriosis
• pelvic inflammatory disease
• more than one miscarriage

No matter how old you are, it's always a good idea to talk to a doctor before you start trying to get pregnant. Doctors can help you prepare your body for a healthy baby. They can also answer questions on fertility and give tips on conceiving.

How will doctors find out if a woman and her partner have fertility problems?

Sometimes doctors can find the cause of a couple's infertility by doing a complete fertility evaluation. This process usually begins with physical exams and health and sexual histories. If there are no obvious problems, like poorly timed intercourse or absence of ovulation, tests will be needed.

Finding the cause of infertility is often a long, complex and emotional process. It can take months for you and your doctor to complete all the needed exams and tests. So don't be alarmed if the problem is not found right away.

For a man, doctors usually begin by testing his semen. They look at the number, shape, and movement of the sperm. Sometimes doctors also suggest testing the level of a man's hormones.

For a woman, the first step in testing is to find out if she is ovulating each month. There are several ways to do this. A woman can track her ovulation at home by:

• recording changes in her morning body temperature (basal body temperature) for several months
• recording the texture of her cervical mucus for several months
• using a home ovulation test kit (available at drug or grocery stores)

Doctors can also check if a woman is ovulating by doing blood tests and an ultrasound of the ovaries. If the woman is ovulating normally, more tests are needed.

Some common tests of fertility in women include:

• Hysterosalpingography: In this test, doctors use x-rays to check for physical problems of the uterus and fallopian tubes. They start by injecting a special dye through the vagina into the uterus. This dye shows up on the x-ray. This allows the doctor to see if the dye moves normally through the uterus into the fallopian tubes. With these x-rays doctors can find blockages that may be causing infertility. Blockages can prevent the egg from moving from the fallopian tube to the uterus. Blockages can also keep the sperm from reaching the egg.
• Laparoscopy: During this surgery doctors use a tool called a laparoscope to see inside the abdomen. The doctor makes a small cut in the lower abdomen and inserts the laparoscope. Using the laparoscope, doctors check the ovaries, fallopian tubes, and uterus for disease and physical problems. Doctors can usually find scarring and endometriosis by laparoscopy.

How do doctors treat infertility?

Infertility can be treated with medicine, surgery, artificial insemination or assisted reproductive technology. Many times these treatments are combined. About two-thirds of couples who are treated for infertility are able to have a baby. In most cases infertility is treated with drugs or surgery.

Doctors recommend specific treatments for infertility based on:

• test results
• how long the couple has been trying to get pregnant
• the age of both the man and woman
• the overall health of the partners
• preference of the partners

Doctors often treat infertility in men in the following ways:

• Sexual problems: If the man is impotent or has problems with premature ejaculation, doctors can help him address these issues. Behavioral therapy and/or medicines can be used in these cases.
• Too few sperm: If the man produces too few sperm, sometimes surgery can correct this problem. In other cases, doctors can surgically remove sperm from the male reproductive tract. Antibiotics can also be used to clear up infections affecting sperm count.

Various fertility medicines are often used to treat women with ovulation problems. It is important to talk with your doctor about the pros and cons of these medicines. You should understand the risks, benefits, and side effects.

Doctors also use surgery to treat some causes of infertility. Problems with a woman's ovaries, fallopian tubes, or uterus can sometimes be corrected with surgery.

Intrauterine insemination (IUI) is another type of treatment for infertility.IUI is known by most people as artificial insemination. In this procedure, the woman is injected with specially prepared sperm. Sometimes the woman is also treated with medicines that stimulate ovulation before IUI.

IUI is often used to treat:

• mild male factor infertility
• women who have problems with their cervical mucus
• couples with unexplained infertility

What medicines are used to treat infertility in women?

Some common medicines used to treat infertility in women include:

• Clomiphene citrate (Clomid): This medicine causes ovulation by acting on the pituitary gland. It is often used in women who have Polycystic Ovarian Syndrome (PCOS) or other problems with ovulation. This medicine is taken by mouth.
• Human menopausal gonadotropin or hMG (Repronex, Pergonal): This medicine is often used for women who don't ovulate due to problems with their pituitary gland. hMG acts directly on the ovaries to stimulate ovulation. It is an injected medicine.
• Follicle-stimulating hormone or FSH (Gonal-F, Follistim): FSH works much like hMG. It causes the ovaries to begin the process of ovulation. These medicines are usually injected.
• Gonadotropin-releasing hormone (Gn-RH) analog: These medicines are often used for women who don't ovulate regularly each month. Women who ovulate before the egg is ready can also use these medicines. Gn-RH analogs act on the pituitary gland to change when the body ovulates. These medicines are usually injected or given with a nasal spray.
• Metformin (Glucophage): Doctors use this medicine for women who have insulin resistance and/or Polycystic Ovarian Syndrome (PCOS). This drug helps lower the high levels of male hormones in women with these conditions. This helps the body to ovulate. Sometimes clomiphene citrate or FSH is combined with metformin. This medicine is usually taken by mouth.
• Bromocriptine (Parlodel): This medicine is used for women with ovulation problems due to high levels of prolactin. Prolactin is a hormone that causes milk production.

Many fertility drugs increase a woman's chance of having twins, triplets or other multiples. Women who are pregnant with multiple foetuses have more problems during pregnancy. Multiple foetuses have a high risk of being born too early (prematurely). Premature babies are at a higher risk of health and developmental problems.

What is assisted reproductive technology (ART)?

Assisted reproductive technology (ART) is a term that describes several different methods used to help infertile couples. ART involves removing eggs from a woman's body, mixing them with sperm in the laboratory and putting the embryos back into a woman's body.

How often is assisted reproductive technology (ART) successful?

Success rates vary and depend on many factors. Some things that affect the success rate of ART include:

• age of the partners
• reason for infertility
• clinic
• type of ART
• if the egg is fresh or frozen
• if the embryo is fresh or frozen

The US Centers for Disease Prevention (CDC) collects success rates on ART for some fertility clinics. According to the 2003 CDC report on ART, the average percentage of ART cycles that led to a healthy baby were as follows:

• 37.3% in women under the age of 35
• 30.2% in women aged 35-37
• 20.2% in women aged 37-40
• 11.0% in women aged 41-42

ART can be expensive and time-consuming. But it has allowed many couples to have children that otherwise would not have been conceived. The most common complication of ART is multiple foetuses. But this is a problem that can be prevented or minimized in several different ways.

What are the different types of assisted reproductive technology (ART)?

Common methods of ART include:

• In vitro fertilization (IVF) means fertilization outside of the body. IVF is the most effective ART. It is often used when a woman's fallopian tubes are blocked or when a man produces too few sperm. Doctors treat the woman with a drug that causes the ovaries to produce multiple eggs. Once mature, the eggs are removed from the woman. They are put in a dish in the lab along with the man's sperm for fertilization. After 3 to 5 days, healthy embryos are implanted in the woman's uterus.
• Zygote intrafallopian transfer (ZIFT) or Tubal Embryo Transfer is similar to IVF. Fertilization occurs in the laboratory. Then the very young embryo is transferred to the fallopian tube instead of the uterus.
• Gamete intrafallopian transfer (GIFT) involves transferring eggs and sperm into the woman's fallopian tube. So fertilization occurs in the woman's body. Few practices offer GIFT as an option.
• Intracytoplasmic sperm injection (ICSI) is often used for couples in which there are serious problems with the sperm. Sometimes it is also used for older couples or for those with failed IVF attempts. In ICSI, a single sperm is injected into a mature egg. Then the embryo is transferred to the uterus or fallopian tube.

ART procedures sometimes involve the use of donor eggs (eggs from another woman), donor sperm, or previously frozen embryos. Donor eggs are sometimes used for women who can not produce eggs. Also, donor eggs or donor sperm is sometimes used when the woman or man has a genetic disease that can be passed on to the baby.

FOLIC ACID is Pregnancy

What is folic acid?

Folic acid is a B vitamin. Folic acid helps the body make healthy new cells.

Why should women take folic acid?

All women need folic acid. When a woman has enough folic acid before and during pregnancy, it can help prevent major birth defects of her baby's brain or spine.

Be sure to get enough folic acid every day. Start before you are pregnant. Folic acid is needed during the first few weeks, often before a woman knows she is pregnant. And half of all pregnancies in the U.S. are not planned. That is why it's so important to start taking folic acid each day, even when you are not planning to get pregnant.

Folic acid might also have other benefits for men and women of any age. Some studies show that folic acid might help prevent heart disease, stroke, some cancers, and possibly Alzheimer's disease.

How can women get folic acid?

All women should aim to get at least 400 micrograms (400 mcg) of folic acid each day. There are a few easy ways she can do this.

• Take a daily vitamin that has folic acid in it. Most multivitamins sold in the U.S. have enough. Check the label on the vitamin to be sure. It should say �400 mcg� or �100%� next to folic acid. Some labels might use the word �folate� for folic acid. Or you can take a vitamin pill that only has folic acid in it. You can find both of these types at your local grocery, drug store, or discount store.

• Another way to get enough folic acid is to eat a serving of breakfast cereal that contains 100% of the daily value (DV) for folic acid each day. Check the label on the box to be sure it has enough.

• Eat a healthy diet that contains lots of fruits and vegetables and other foods that have folic acid (or folate) in them or added to them. Foods that contain folic acid (or folate) include broccoli, asparagus, bananas, oranges, peas, nuts, bread, cereal, and flour.

How much folic acid should you take?

Read the descriptions below to see how much folic acid you should take. Check off the one that applies to you.

	You are able to get pregnant. Take 400 mcg of folic acid every day.
	You are pregnant. Take 600mcg of folic acid every day.
	You are breastfeeding. Take 500mcg of folic acid every day.
	You had a baby with spina bifida or anencephaly and want to get pregnant again. Talk with your doctor, and ask for a prescription for a higher dose of folic acid. You should take 4,000 micrograms (4,000 mcg) starting at least one to three months before getting pregnant and during the first 3 months of pregnancy. That's 10 times the normal amount! But don't try to get the larger amount by taking more than one multivitamin or prenatal vitamin a day. You could get too much of another vitamin that could harm you or your baby.
	You had a baby with spina bifida or anencephaly. You are not planning to have another baby. Take 400 mcg of folic acid every day.

What is Ectopic Pregnancy

An ectopic pregnancy is one in which the fertilized ovum is implanted in any tissue other than the uterine wall. Most ectopic pregnancies occur in the Fallopian tube (so-called tubal pregnancies), but implantation can also occur in the cervix, ovaries, and abdomen.

An Overview of ectopic pregnancy

In a normal pregnancy, the fertilized egg enters the uterus and settles into the uterine lining where it has plenty of room to divide and grow. About 1% of pregnancies are in an ectopic location with implantation not occurring inside of the womb, and of these 98% occur in the Fallopian tubes.

In a typical ectopic pregnancy, the embryo does not reach the uterus, but instead adheres to the lining of the Fallopian tube. The implanted embryo burrows actively into the tubal lining. Most commonly this invades vessels and will cause bleeding. This bleeding expels the implantation out of the tubal end as a tubal abortion. Some women thinking they are having a miscarriage are actually having a tubal abortion. There is no inflammation of the tube in ectopic pregnancy. The pain is caused by prostaglandins released at the implantation site, and by free blood in the peritoneal cavity, which is locally irritant. Sometimes the bleeding might be heavy enough to threaten the health or life of the woman. Usually this degree of bleeding is due to delay in diagnosis, but sometimes, especially if the implantation is in the proximal tube (just before it enters the uterus), it may invade into Sampson's artery, causing heavy bleeding earlier than usual.

If left untreated, about half of ectopic pregnancies will resolve without treatment. These are the tubal abortions. The advent of methotrexate treatment for ectopic pregnancy has reduced the need for surgery; however, surgical intervention is still required in cases where the Fallopian tube has ruptured or is in danger of doing so. This intervention may be laparoscopic or through a larger incision, known as a laparotomy.

What causes an ectopic pregnancy

The cause of ectopic pregnancy is unknown. After fertilization of the oocyte in the peritoneal cavity, the egg takes about nine days to migrate down the tube to the uterine cavity at which time it implants. Wherever the embryo finds itself at that time, it will begin to implant.

There are some speculative specific causes or associations. Smoking, advanced maternal age and prior tubal damage of any origin are well shown risk factors for ectopic pregnancy.

Cilial damage and tube occlusion

Hair-like cilia located on the internal surface of the Fallopian tubes carry the fertilized egg to the uterus. Damage to the cilia or blockage of the Fallopian tubes is likely to lead to an ectopic pregnancy. Women with pelvic inflammatory disease (PID) have a high occurrence of ectopic pregnancy. This results from the build-up of scar tissue in the Fallopian tubes, causing damage to cilia. If however both tubes were occluded by PID, pregnancy would not occur and this would be protective against ectopic pregnancy. Tubal surgery for damaged tubes might remove this protection and increase the risk of ectopic pregnancy. Tubal ligation can predispose to ectopic pregnancy. Seventy percent of pregnancies after tubal cautery are ectopic, while 70% of pregnancies after tubal clips are intrauterine. Reversal of tubal sterilization carries a risk for ectopic pregnancy. This is higher if more destructive methods of tubal ligation (tubal cautery, partial removal of the tubes) have been used than less destructive methods (tubal clipping). A history of ectopic pregnancy increases the risk of future occurrences to about 10%. This risk is not reduced by removing the affected tube, even if the other tube appears normal.

Excessive oestrogen and progesterone

There has been speculation about the role of hormones in the genesis of ectopic pregnancy. No proven association has been established. High levels of oestrogen and progesterone are thought possibly to increase the risk of ectopic pregnancy because these hormones slow the movement of the fertilized egg through the Fallopian tube. However, advancing age is a risk factor for ectopic pregnancy, although this is a period of declining hormone levels.

Role of intrauterine devices (IUD)

The use of intrauterine devices (IUDs) was thought at one time to increase the risk of ectopic pregnancy. However the older model copper based IUDs were only effective in preventing intrauterine pregnancies, not tubal pregnancies. As the IUD is effective in reducing pregnacy overall, the relative risk only of ectopic is increased. The old copper-based IUDs reduced the overall pregnancy rate so effectively that even the gross ectopic rates were reduced. Nonetheless any pregnancy conceived with an IUD in situ must be investigated to exclude possible ectopic pregnancy.

The newer hormone-based (levonorgestrel) IUS creates such a profound suppression of the endometrium that overall pregnancy rate is lower even than that of male or female sterilization. There are some data available for ectopic pregnancy with the IUS, but the relative risk is extremely low, around 0.01%.

Association with infertility

Infertility treatments are highly variable and specific to individual patients. IVF is used for patients with damaged tubes which are an inherent risk factor for ectopic. Ectopic pregnancies have been seen with In Vitro Fertilization, but is uncommon and quickly diagnosed by the early ultrasounds that these intensively surveyed patients undergo.

Other

Patients are at higher risk for ectopic pregnancy with advancing age. Also, it has been noted that smoking is associated with ectopic risk. Vaginal douching is thought by some to increase ectopic pregnancies. Women exposed to diethylstilbestrol (DES) in utero (aka "DES Daughters") also have an elevated risk of ectopic pregnancy, up to 3 times the risk of unexposed women.

What are the symptoms of an ectopic pregnancy

Early symptoms are either absent or subtle. Clinical presentation of ectopic pregnancy occurs at a mean of 7.2 weeks after the last normal menstrual period, with a range of 5 to 8 weeks. Later presentations are more common in communities deprived of modern diagnostic ability.

The early signs are:

• Pain and discomfort, usually mild. A corpus luteum on the ovary in a normal pregnancy may give very similar symptoms.

• Vaginal bleeding, usually mild. An ectopic pregnancy is usually a failing pregnancy and falling levels of progesterone from the corpus luteum on the ovary cause withdrawal bleeding. This can be indistinguishable from an early miscarraige or the 'implantation bleed' of a normal early pregnancy.

Patients with a late ectopic pregnancy typically have pain and bleeding. This bleeding will be both vaginal and internal and has two discrete pathophysiologic mechanisms.

• External bleeding is due to the falling progesterone levels.

• Internal bleeding is due to hemorrhage from the affected tube.

The differential diagnosis at this point is between miscarriage, ectopic pregnancy, and early normal pregnancy. The presence of a positive pregnancy test virtually rules out pelvic infection as it is rare indeed to find pregnancy with an active Pelvic Inflammatory Disease (PID). The most common misdiagnosis assigned to early ectopic pregnancy is PID.

More severe internal bleeding may cause:

• Lower back, abdominal, or pelvic pain.
  
• Shoulder pain. This is caused by free blood tracking up the abdominal cavity, and is an ominous sign.
  
• There may be cramping or even tenderness on one side of the pelvis.
  
• The pain is of recent onset, meaning it must be differentiated from cyclical pelvic pain, and is often getting worse.

• Ectopic pregnancy is noted that it can mimic symptoms of other diseases such as appendicitis, other gastrointestinal disorder, problems of the urinary system, as well as pelvic inflammatory disease and other gynaecologic problems.

How is an ectopic pregnancy diagnosed ?

An ectopic pregnancy has to be suspected in any woman with lower abdominal pain and/or unusual bleeding who is or might be sexually active and whose pregnancy test is positive. And abnormal rise in blood hCG levels may also indicate an ectopic pregnancy. The threshold of discrimination of intrauterine pregnancy today is around 3000 IU/ml of Human Chorionic Gonadotropin (HCG). A high resolution, vaginal ultrasound scan showing no intrauterine pregnancy is presumptive evidence that an ectopic pregnancy is present if the threshold of discrimination for HCG has been reached. An empty uterus with levels lower than 3000IU/ml may be evidence of an ectopic pregnancy, but may also be consistent with an intrauterine pregnancy which is simply too small to be seen on ultrasound. If there is uncertainty it might be necessary to wait a few days and repeat the bloodwork and ultrasound.

An ultrasound showing a gestational sac with foetal heart is clear evidence of ectopic pregnancy.

Free fluid which is non echogenic is a normal finding in the late menstrual cycle and early normal pregnacy. This is a transudate and is not presumptive evidence of bleeding. Echogenic free fluid suggests the presence of blood clot and is suggestive of free blood in the peritoneum.

A laparoscopy or laparotomy can also be performed to visually confirm an ectopic pregnancy. Often if a tubal abortion has occurred, or a tubal rupture has occurred, it is hard actually to find the pregnancy tissue. Laparoscopy in very early ectopic pregnancy may rarely show a normal looking Fallopian tube.

Nontubal ectopic pregnancy

2% of ectopic pregnancies occur in the ovary, cervix, or are intraabdominal. Transvaginal ultrasound examination is usually able to detect a cervical pregnancy. An ovarian pregnancy is differentiated from a tubal pregnancy by the Spiegelberg criteria.

While a foetus of ectopic pregnancy is typically not viable, very rarely, an abdominal pregnancy has been salvaged. In such a situation the placenta sits on the intraabdominal organs or the peritoneum and has found sufficient blood supply. In this author's experience this is invariably bowel or mesentery, but other sites, such as the renal (kidney), liver or hepatic (liver) artery or even aorta have been described. Support to near viability has occasionally been described, but even in third world countries, the diagnosis is most commonly made at 16 to 20 weeks gestation. Such a foetus would have to be delivered by laparotomy. Maternal morbidity and mortality from extrauterine pregnancy is high as attempts to remove the placenta from the organs to which it is attached usually lead to uncontrollable bleeding from the attachment site. If the organ to which the placenta is attached is removable, such as a section of bowel, then the placenta should be removed together with that organ. This is such a rare occurrence that true data are unavailable and reliance must be made on anecdotal reports. However, the vast majority of abdominal pregnancies require intervention well before fetal viability because the risk of hemorrhage.

Treatment of ectopic pregnancy

Nonsurgical treatment

Early treatment of an ectopic pregnancy with the drug methotrexate has proven to be a viable alternative to surgical treatment since 1993. If administered early in the pregnancy, methotrexate can disrupt the growth of the developing embryo causing the cessation of pregnancy.

Surgical treatment

If haemorrhaging has already occurred, surgical intervention may be necessary if there is evidence of ongoing blood loss. However, as already stated, about half of ectopics result in tubal abortion and are self limiting. The option to go to surgery is thus often a difficult decision to make in an obviously stable patient with minimal evidence of blood clot on ultrasound.

Surgeons use laparoscopy or laparotomy to gain access to the pelvis and can either incise the affected Fallopian and remove only the pregnancy (salpingostomy) or remove the affected tube with the pregnancy (salpingectomy).

Chances of future pregnancy after an ectopic pregnancy

The chance of future pregnancy depends on the status of the tube(s) that are left behind, but is decreased. The chance of recurrent ectopic pregnancy is about 10% and is independent of whether the affected tube was repaired (salpingostomy) or removed (salpingectomy). Successful pregnancy rates vary widely between different centres, and appear to be operator dependent. Pregnancy rates with successful methotrexate treatment compare favourably with the highest reported pregnancy rates. Often, patients may have to resort to IVF to achieve a successful pregnancy. The use of IVF does not preclude further ectopic pregnancies, but the likelihood is reduced.

Complications with ectopic pregnancy

The most common complication is rupture with internal bleeding that leads to shock. Death from rupture is rare. Infertility occurs in 10 - 15% of women who have had an ectopic pregnancy.

Down's Syndrome Explained

What is Down's Syndrome?

Down's syndrome is set of mental and physical symptoms that result from having an extra copy of Chromosome 21.

Normally, a fertilized egg has 23 pairs of chromosomes. In most people with Down syndrome, there is an extra copy of Chromosome 21 (also called trisomy 21 because there are three copies of this chromosome instead of two), which changes the body's and brain's normal development.

What are the signs and symptoms of Down syndrome?

Even though people with Down syndrome may have some physical and mental features in common, symptoms of Down syndrome can range from mild to severe. Usually, mental development and physical development are slower in people with Down syndrome than in those without the condition.

Mental retardation is a disability that causes limits on intellectual abilities and adaptive behaviors (conceptual, social, and practical skills people use to function in everyday lives). Most people with Down syndrome have IQs that fall in the mild to moderate range of mental retardation. They may have delayed language development and slow motor development.

Some common physical signs of Down syndrome include:

• Flat face with an upward slant to the eye, short neck, and abnormally shaped ears
• Deep crease in the palm of the hand
• White spots on the iris of the eye
• Poor muscle tone, loose ligaments
• Small hands and feet

There are a variety of other health conditions that are often seen in people who have Down syndrome, including:

• Congenital heart disease
• Hearing problems
• Intestinal problems, such as blocked small bowel or oesophagus
• Celiac disease
• Eye problems, such as cataracts
• Thyroid dysfunctions
• Skeletal problems
• Dementia�similar to Alzheimer's

What is the treatment for Down syndrome?

Down syndrome is not a condition that can be cured. However, early intervention can help many people with Down syndrome live productive lives well into adulthood.

Children with Down syndrome can often benefit from speech therapy, occupational therapy, and exercises for gross and fine motor skills. They might also be helped by special education and attention at school. Many children can integrate well into regular classes at school.

Who is at risk for Down syndrome?

The chance of having a baby with Down syndrome increases as a woman gets older�from about 1 in 1,250 for a woman who gets pregnant at age 25, to about 1 in 100 for a woman who gets pregnant at age 40. But, most babies with Down syndrome are born to women under age 35 because more younger women have babies.

Because the chances of having a baby with Down syndrome increase with the age of the mother, many health care providers recommend that women over age 35 have prenatal testing for the condition. Testing the baby before it is born to see if he or she is likely to have Down syndrome allows parents and families to prepare for the baby's special needs.

Parents who have already have a baby with Down syndrome or who have abnormalities in their own chromosome 21 are also at higher risk for having a baby with Down Syndrome.

Once the baby is born, a blood test can confirm whether the baby has Down syndrome.