FitSugar

Should You Avoid Carrageenan?

FitSugar — Wed, 05 Mar 2008 09:30:00 -0800

If you're a label reader, and let me tell you I sure am, you might have noticed carrageenan listed as one of the ingredients. When I first saw it listed on a Ben and Jerry's pint (yes, ice cream is OK when eaten in moderation), it brought up a couple of questions for me – What exactly is carrageenan and is it something I should avoid?

Carrageenan is actually extracted from red seaweed, and the name comes from a type of seaweed found growing on the coast of Ireland. It's used as a food additive and sometimes is referred to as kelp extract. It helps to stabilize, thicken, or emulsify dairy products, reprocessed meats (like sausages or beef jerky), dog food, toothpaste, pudding, salad dressings, and even shoe polish.

Carrageenan is a safe ingredient and should not be confused with poligeenan. This is a chemically degraded derivative of carrageenan, which is used for industrial (non-food) purposes. It was improperly named "degraded carrageenan" for a while which gave the true carrageenan a bad name. Research indicates that poligeenan creates unfavorable health effects, but food-grade carrageenan has no known toxicity or carcinogenicity, and is recognized as safe by the FDA.

So go ahead and enjoy foods made with carrageenan, especially Ben & Jerry's (in moderation of course).

What in the World is Maltodextrin?

FitSugar — Tue, 05 Jun 2007 12:30:00 -0700

You know I have become obsessed with reading labels, and since I keep coming across maltodextrin I decided to find out what it really is.

Maltodextrin is an easily digestible carbohydrate made from rice, corn or potato starch. It's a white powder used in processed foods as a thickener, or a filler since it's fairly inexpensive. Also used in pharmaceuticals as a binding agent, it is also found in sugar substitutes, like Splenda for example.

Maltodextrin is made by cooking down the starch, and then acid and/or enzymes break the starch down even further, kind of like what the body does to digest carbohydrates. It's usually used in such small amounts, so it doesn't have a significant impact in terms amount of protein, fat, carbohydrate, or fiber. Every gram of maltodextrin has 4 calories, which is not really a significant caloric load.
Although maltodextrin is processed and it's not the best thing to be consuming, at least now we know that it's made from real food - not some nasty chemicals.

Fit's Tip: Celiacs beware! In Europe, maltodextrin can be derived from barley or wheat, but then it should be labeled as "wheat maltodextrin."

Source

Spooky News on Smoke, Booze, Blood, and Bones

FitSugar — Thu, 30 Oct 2008 03:00:00 -0700

You all know that I am a firm believer in moderation, but I do also know that everyone occasionally takes moderation in moderation and has a wild night. Once again, I nominate myself to play the role of party-pooper and tell you social smoking and binge drinking are really bad for you, and not just for your brain cells and lungs. Partying too hard and smoking socially can harm your bones and your blood.

Simply put, binge drinking makes for brittle bones. Alcohol interferes with the body's calcium supply, and in cases of excessive drinking, can create alcohol-induced bone loss. Add to the brittle bones the higher incidence of falling when inebriated and your chances for breaking a bone increase. New research from Loyola's Alcohol Research Program shows the exposure to alcohol disrupts the way genes work to maintain "bone integrity." This happens with prolonged drinking, but also in shorter, three-day bouts of "binge drinking," which was defined as four drinks in two hours for women and five drinks in the same time period for men.

To see what smoking socially does to you, just read more.

Having just one or two cigarettes over the course of a weekend affects your arteries and they begin to function more slowly. A decline in arterial health is an early risk factor for heart disease. The decrease in function lasts for more than just a couple of days and may continue well on for a week. A recent study at the University of Georgia found that two cigarettes can reduce the rate that blood flows through the arteries by 24 percent in healthy, young adults. For me, the take-home message is don't light up at all, even with your friends.

Source

What's With All the Different Kinds of Oats?

FitSugar — Wed, 14 Oct 2009 07:00:31 -0700

Need a little extra fiber and protein? Then reach for some oats. You can make oatmeal, use them to make cookies, add them to smoothies to thicken them up, or grind them to make flour. There are a few different kinds of oats, so how do you know which to choose? Check out the chart below.

	Steel cut oats	Old-fashioned oats	Quick oats
Description	Also called Irish or Scotch oats, these are cut, not rolled. They look like chopped up rice, take the longest to cook, and have a slightly chewy consistency.	Sometimes called rolled oats, these look like flat little ovals. When processing these oats, the kernels are steamed first, and then rolled to flatten them. They take longer to cook than quick oats, but are quicker than steel cut oats.	Also called instant oats, these oats are pre-cooked, dried, and then rolled. They cook in a few minutes when added to hot water, and have a mushy texture.

Want to know how they compare nutritionally? Then keep reading

Scleroderma

FitSugar — Wed, 08 Oct 2008 17:35:17 -0700

In This Report

Highlights
Introduction
Symptoms and Complications...
Causes
Risk Factors
Prognosis
Diagnosis
Treatment
Medications
Other Treatments
Treatment for Raynaud's Phe...
Treatment for Skin Thickeni...
Treatment for Lung Complica...
Treatment for Gastrointesti...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Symptoms

Because significant depression can affect more than 50% of people with scleroderma, researchers say it may be beneficial for scleroderma patients to get routine screening for depression.

Causes

Researchers have discovered a gene called connective-tissue growth factor (CTGF), which they say is more common in people with systemic scleroderma than in those without the disease.

Prognosis

The prognosis for patients with systemic scleroderma has improved since the 1970s. Ten-year survival rates are up, and deaths from kidney crises have dropped. However, deaths from pulmonary fibrosis have increased during this time period.

Treatment

High-dose immunosuppressant therapy with cyclophosphamide significantly improved skin and overall function in patients with scleroderma.
Evidence shows that intravenous iloprost given in progressively increasing doses can reduce the duration and frequency of Raynaud's phenomenon attacks.
A potential new therapy using PVAC, a substance derived from the bacterium, Mycobacterium vaccae, can improve skin symptoms without causing significant side effects.

Introduction

The name scleroderma comes from the Greek words skleros, which means hard, and derma, which means skin. The disease is categorized as a rheumatologic disorder because it affects the connective tissues in the body.

Scleroderma is a rare disease marked by the following:

Damage to the cells lining the walls of small arteries
An abnormal buildup of tough scar-like tissue in the skin

Patients with scleroderma may develop either a localized or a systemic (body-wide) form of the disease.

Localized scleroderma usually affects only the skin on the hands and face. Its course is very slow, and it rarely, if ever, goes throughout the body (becomes systemic) or causes serious complications. There are two main forms of localized scleroderma: morphea and linear scleroderma.

Morphea Scleroderma. In morphea scleroderma, patches of hard skin form and can last for years. Eventually, however, they may improve or even disappear. There is less than a 1% chance that this disorder will progress to systemic scleroderma.

Linear Scleroderma. Linear scleroderma causes bands of hard skin across the face or on a single arm or leg. Linear scleroderma may also involve muscle or bone. Rarely, if this type of scleroderma affects children or young adults, it may interfere with growth and cause severe deformities in the arms and legs.

Systemic scleroderma is also called systemic sclerosis. This form of the disease may affect the organs of the body, large areas of the skin, or both. This form of scleroderma has two main types: limited and diffuse scleroderma. Both forms are progressive, although most often the course of the disease in both types is slow.

Limited Scleroderma (also called CREST Syndrome). Limited scleroderma is a progressive disorder. It is classified as a systemic disease because its effects can be widespread throughout the body. It generally differs from diffuse scleroderma in the following ways:

Most often the internal organs are not affected.
Patients with scleroderma have a less serious course, unless they develop pulmonary hypertension (a particular danger with the CREST syndrome). Pulmonary hypertension is high blood pressure in the lungs (see the Lung Complications section).

Limited scleroderma is commonly referred to by the acronym CREST, whose letters are the first initials of characteristics that are usually found in this syndrome:

Calcinosis. With this condition, mineral crystal deposits form under the skin, usually around the joints. Skin ulcers filled with a thick white substance may form over the deposits.
Raynaud's phenomenon. In this syndrome, the fingers of both hands are very sensitive to cold, and they remain cold and blue-colored after exposure to low temperatures. This occurs in nearly all cases of scleroderma, both limited and diffuse. It is caused by abnormal changes in small blood vessels. These changes cause the vessels to narrow, and blood flow is temporarily interrupted, usually in the fingers.
Esophageal motility dysfunction. The esophagus carries food from the mouth to the stomach. In esophageal motility dysfunction, the muscles in the esophagus become scarred by scleroderma and do not contract normally. This can cause severe heartburn and other symptoms of gastroesophageal reflux disorder (GERD).
Sclerodactylia (also called acrosclerosis). This is the stiffness and tightening of the skin of the fingers, a classic symptom of scleroderma. Bone loss may occur in the fingers and toes.
Telangiectasia. In this situation, widening of small blood vessels causes numerous flat red marks to form on the hands, face, and tongue.

Click the icon to see an image of symptoms that are known as CREST.

In general, people with limited scleroderma develop Raynaud's phenomenon long before they develop any of the other symptoms. One or more of the CREST conditions can also occur in other forms of scleroderma.

Diffuse Scleroderma. Diffuse scleroderma, the other systemic sclerosis, has the following characteristics:

It can affect wide areas of the skin, connective tissue, and other organs.
It can have a very slow course, but it also may start quickly and be accompanied by swelling of the whole hand. If it gets worse quickly early on, the condition can affect internal organs and become very severe -- even life threatening.
Diffuse scleroderma can overlap with other autoimmune diseases, including systemic lupus erythematosus and polymyositis. In such cases, the disorder is referred to as mixed connective disease.

Click the icon to see an image of systemic lupus erythematosus.

Symptoms and Complications

Raynaud's phenomenon is often the first sign of the scleroderma disease process. With this condition, small blood vessels narrow in the fingers, toes, ears, and even the nose.

Attacks of Raynaud's phenomenon can occur several times a day, and are often brought on or worsened by cold. Warmth relieves these attacks. In severe cases, attacks can develop regardless of the temperature. Severe cases may also cause open sores or damage to the skin and bones, if the circulation is cut off for too long. Stress also can trigger the syndrome.

Typically, the fingers go through three color changes:

First, they become very pale.
As the blood flow is cut off, they turn a bluish color, usually in the top two sections of the second and third fingers.
Finally, when blood flow returns, the fingers become red.

Tingling and pain can occur in the affected regions.

Click the icon to see an image of Raynaud's phenomenon.

Raynaud's is very common and occurs in 3 - 5% of the general population. It's important to note that more than 80% of patients with Raynaud's phenomenon do not have scleroderma, lupus, rheumatoid arthritis, or other more serious illnesses. Raynaud's is more likely to be a symptom of scleroderma or some other connective tissue disease if it develops after age 30, if it is severe, and if it is accompanied by other symptoms (such as skin changes and arthritis).

Course of Typical Skin Changes. The primary symptoms of scleroderma occur in the skin. They often take the following course:

Typically, pitted scars appear first on the hands. The skin begins to thicken and harden on the hands, feet, and face. The fingers may swell. This condition is called sclerodactylia or acrosclerosis. Patients with diffuse scleroderma may have swelling of the whole hand before the skin significantly thickens.
Thickened or hardened patches may also develop on other areas of the body. (Their appearance on the trunk and near the elbows or knees tends to be a sign of a more severe condition.)
For the first 2 or 3 years, the skin continues to thicken and feel puffy.
This process then stops, and can even get better. The skin may soften.
As the disease progresses further, however, the skin loses its ability to stretch, and becomes shiny as it tightens across the underlying bone, particularly in the fingers, toes, and around the mouth.
Eventually, in severe cases, the fingers may lose the ability to move, and can be difficult to bend. The hands and feet may curl from the tightness of the skin. It may be difficult to open the mouth widely.

Click the icon to see an image of sclerodactylia.

Other Skin Changes. The following skin symptoms may also occur:

Flat red marks, known as telangiectasis, may appear in various locations, usually the face, palms, lips, or the inside of the mouth.

Click the icon to see an image of telangiectasia.

In calcinosis, small white lumps form beneath the skin, sometimes oozing a white substance that looks like toothpaste. Calcinosis can lead to infections.
Small blood vessels at the base of the fingernails may be lost in some places, and may widen in other places. This is an indication that internal organs might be involved.
The entire surface of the skin may get darker over time, and contain patches of abnormally pale skin.
Hair loss may occur.
About 1% of patients have Sjogren syndrome, a group of symptoms that include dry eyes and dry mucus membranes (such as those in the mouth).
Inside the mouth, scleroderma can also cause changes that impair gum healing.

Changes in bones, joints, and muscles can cause the following symptoms:

Mild arthritis. The condition is usually distributed equally on both sides of the body.
Bone loss in the fingers. The destruction is not as severe as it is in rheumatoid arthritis, although the fingers may shorten over time.
Trouble bending the fingers, if the disease has affected the tendons and joints.
Muscle weakness may occur, especially near the shoulder and hip.

Complications in the Upper Digestive Tract.

Esophageal motility disorder develops when scarring in the muscles of the esophagus causes them to lose the ability to contract normally, resulting in trouble swallowing, heartburn, and gastroesophageal reflux (also known as GERD). Some experts believe that patients with severe GERD may breathe in microscopic amounts of stomach acid, which in turn may be a major cause of lung scarring.
About 80% of patients also experience impaired stomach activity. A delay in stomach emptying is very common.
Some patients develop "watermelon stomach" (medically referred to as CAVE syndrome), in which the stomach develops red-streaked areas from widened blood vessels. This causes a slow bleeding that can lead to anemia (low red blood cell counts) over time.
There may be a higher risk for stomach cancer.
Problems with movement of the food through the intestines (motility) also develop. Patients may experience an increase in bacteria and have trouble absorbing nutrients from foods through the intestines.

Complications in the Lower Digestive Tract. Complications in the lower tract are uncommon. If they do occur, they can include the following:

Scarring can cause blockages and constipation. In rare cases, constipation can become so severe that the bowel develops holes or tears, which can be life threatening.
Scarring can also damage the absorption of fats in the intestines. This can lead to an increase in the number of bacteria, which causes watery diarrhea.
Fecal incontinence (the inability to control bowel movements) may be more common than studies indicate, because patients are reluctant to report it.

Many patients, however, have few or even no lower gastrointestinal symptoms.

In severe cases, the lungs may be affected, causing shortness of breath or difficulty in taking deep breaths. Shortness of breath may be a symptom of pulmonary hypertension, an uncommon but life-threatening complication of systemic scleroderma.

Click the icon to see an image of the respiratory system.

Lung problems are usually the most serious complications of systemic scleroderma. They are now the leading cause of death in scleroderma patients. Two major lung conditions associated with scleroderma, pulmonary fibrosis and pulmonary hypertension, can occur either together or independently.

Interstitial Pulmonary Fibrosis. Scleroderma involving the lung causes scarring (pulmonary fibrosis). Pulmonary fibrosis occurs in about 70% of scleroderma patients, although the progression is very slow and patients have a wide range of symptoms:

Some patients may not experience any symptoms.
When pulmonary fibrosis progresses, patients develop a dry cough, shortness of breath, and reduced ability to exercise.
Severe pulmonary fibrosis occurs in about 16% of patients with diffuse scleroderma. About half of these patients experience the most profound changes within the first 3 years. In such cases, lung function worsens rapidly over that period, and then the progression slows down.

This condition also places the patient at higher risk for lung cancer. One study suggested that interstitial lung disease may be due to severe dysfunction in the esophagus, which causes patients to breathe in tiny amounts of stomach acid.

The most important indication of future worsening in the lungs appears to be inflammation in the small airways (alveolitis). Doctors detect alveolitis by using a lung test called bronchoalveolar lavage.

Pulmonary hypertension is the narrowing of the pulmonary arteries in the lung. The narrowing of the arteries creates resistance and increases the workload of the heart. The heart becomes enlarged from pumping blood against the resistance. Some symptoms include chest pain, weakness, shortness of breath, and fatigue. The goal of treatment is to control the symptoms, although the disease usually develops into congestive heart failure.

Pulmonary Hypertension. The primary symptom of pulmonary hypertension is shortness of breath, which becomes severe over time.

Pulmonary hypertension can develop in one of two ways:

As a complication of pulmonary fibrosis
As a direct outcome of the scleroderma process itself. In this case, it is most likely to develop in patients with limited scleroderma after many years.

Click the icon to see an image of cor pulmonale.

Signs of kidney problems, such as increased levels of protein in the urine and mild high blood pressure (hypertension), are common in scleroderma. As with pulmonary hypertension, the degree of severity depends on whether the kidney problems are acute or chronic.

Slow Progression. The typical course of kidney involvement in scleroderma is a slow progression that may produce some damage but does not often lead to kidney failure.

Renal Crisis. The most serious kidney complication in scleroderma is renal crisis. It is a rare event that occurs in a small number of patients with diffuse scleroderma, most often early in the course of the disease. This syndrome includes a life-threatening condition called malignant hypertension, a sudden increase in blood pressure that can cause rapid kidney failure. This condition may be fatal. However, if the condition is successfully treated, it rarely recurs.

Until recently, renal crisis was the most common cause of death in scleroderma. Aggressive treatment with drugs that lower blood pressure, particularly those known as ACE inhibitors, is proving to be successful in reducing this risk.

Many patients with even limited scleroderma have some sort of functional heart problem, although severe complications are uncommon and occur in only about 15% of patients with diffuse scleroderma. As with other serious organ complications, they are more likely to occur within 3 years after the disease begins.

Fibrosis of the Heart. The most direct effect of scleroderma on the heart is fibrosis (scarring). It may be very mild or it can cause pain, low blood pressure, or other complications. By damaging muscle tissue, the scarring increases the risk for heart rhythm problems, problems in electrical conduction, and heart failure. The membrane around the heart can become inflamed, causing a condition called pericarditis.

Click the icon to see an image of pericarditis.

Pulmonary hypertension and hypertension associated with kidney problems in scleroderma can also affect the heart.

Other complications of scleroderma may include the following:

Patients with CREST may be at increased risk for biliary cirrhosis, an inflammatory autoimmune disorder of the liver.
Nerve damage may occur in the extremities (legs and feet, arms and fingers), causing numbness and pain. This damage can progressively worsen and lead to severe open sores (ulcerations), particularly in the hands. The feet are less often affected, but when they are, the disease tends to affect the joints and cause pain.
Bone loss (osteoporosis) can occur because of impaired blood flow.
About half of patients develop underactive thyroid gland (hypothyroidism).

Click the icon to see an image of hypothyroidism.

Impotence, usually due to scarring of the penis, may be one of the first complications of the disease in men.
Some studies using imaging techniques have found changes in brain tissue, but because the brain has little connective tissue, scleroderma appears to have little effect on mental functioning, except possibly in the late stages of severe disease.
Systemic scleroderma does not generally affect fertility in women. Pregnant women with scleroderma, however, have a slightly increased risk of premature birth and low-birth-weight babies. Although they can carry a baby to term, because complications such as kidney crisis can occur with the disease, pregnant women with scleroderma need to be monitored closely in a high-risk obstetric facility.
More than half of scleroderma patients are likely to experience significant depression. Researchers say it may be beneficial for scleroderma patients to be routinely screened for depression.

Causes

Most likely this disease is caused by a number of inherited (genetic) abnormalities, which are triggered by environmental factors.

Researchers have found a gene, called connective-tissue growth factor (CTGF), which they say regulates the production of a protein that may be a key to systemic scleroderma. This gene is more common in scleroderma patients than in people without the condition. However, researchers say the gene is just one factor that affects the development of the disease.

Research published in 2005 also showed that the growth of new blood vessels is abnormal in people with scleroderma, particularly those whose disease affects the blood vessels in the lungs. Researchers now know that cells in the blood vessels and skin of scleroderma patients make too much of certain chemicals, and not enough of others. Studies revealed that the cause is an alteration in the hereditary material, DNA. These changes "turn off" some genes and "turn up" others. It is hoped that certain drugs, some of which are already used in cancer treatments, can some day be used to stop these DNA changes.

The disease process leading to scleroderma appears to occur as an autoimmune response, in which an abnormal immune system attacks the body itself. In scleroderma, this response produces swelling (inflammation) and too much production of collagen. Collagen is the tough protein that helps build connective tissues such as tendons, bones, and ligaments. Collagen also helps scar tissue form. When normal tissue from skin, lungs, the esophagus, blood vessels, and other organs is replaced by this type of abnormal tissue, none of these body parts work as well, and many of the symptoms previously described occur.

Antigens are large molecules (usually proteins) on the surface of many cells -- both human cells, and cells of viruses, fungi, bacteria, and some non-living substances such as toxins, chemicals, drugs, and foreign particles. When the immune system recognizes an antigen as being foreign (not part of the human body), it starts offensive and defensive actions against them by producing antibodies and other chemicals such as cytokines that destroy any cells in the area.

Much of this activity is directed by T cells, which are categorized as killer T cells or helper T cells (TH cells).

The actions of the helper T cells are of special interest in scleroderma. For some unknown reason, the T cells become overactive in scleroderma and mistake the body's own collagen as a foreign antigen. This triggers a series of immune responses to destroy the collagen. When the body creates antibodies against itself in this way, it is called an autoimmune response.

Cytokines and the Inflammatory Response. Helper T cells also release powerful immune factors called cytokines. In small amounts, cytokines are necessary for healing. If overproduced, however, they can cause serious damage, including inflammation and injury.

Neutrophils. Cytokines attract to the scene large numbers of other white blood cells known as neutrophils. Neutrophils help activate chemicals known as leukotrienes. Scleroderma patients have high levels of specific leukotrienes that may contribute specifically to lung disease in scleroderma.

A process called microchimerism has been proposed as a cause of scleroderma. The theory arose from the fact that scleroderma occurs mostly in women, and its symptoms resemble those of graft-versus-host disease (GVHD). GVHD occurs in bone marrow transplant patients who have received cells from another person. It happens when the transplanted donor immune cells launch an attack against the patient's cells.

Chimerism occurs when cells from two different individuals exist in the same body. When there is a low number of cells of one body in another, the condition is referred to as microchimerism.

However, if microchimerism plays a role, it most likely does so only in a subset of patients.

It is still not clear why the immune system responds abnormally in people with scleroderma. Some experts believe that environmental factors, such as a virus or a chemical, may trigger the response in individuals with a genetic vulnerability.

Oxygen-Free Radicals and Abnormal Metal Accumulation. One focus for researchers investigating scleroderma involves an observation that, as blood vessels narrow and become inflamed, destructive particles known as oxygen-free radicals are produced. Oxygen-free radicals are made by natural processes in the body. They cause harm by setting off a chemical chain reaction, which can damage any type of cell in the body. Environmental toxins, infections, and other factors may cause very high amounts of these oxygen-free radicals to build up in the body.

Chemicals. Occupational exposure to certain chemicals can cause blood vessel constriction and attacks of Raynaud's phenomenon. Despite the fact that women are at higher overall risk for scleroderma, among people who are exposed to solvents at work, men face a higher risk for the disease. However, no specific work-related factors have been proven to cause the disorder.

It is nearly impossible to determine whether specific chemicals may actually cause systemic scleroderma, primarily because few people develop the disease, even though many people are exposed to such chemicals. In addition, research has been unable to consistently repeat studies that have reported links with chemicals.

Studies have found, however, that certain industrial toxins are significantly associated with severe lung problems in people with scleroderma. The toxins most likely to be associated with severe disease include epoxy resins, white spirit, solvents, and silica mixed with welding fumes.

Repetitive Stress Injuries. Raynaud's phenomenon and symptoms of scleroderma have been associated with jobs that require intense repetitive hand and arm movements, such as working jackhammers or other vibrating tools. However, many workers are involved in such occupations, yet scleroderma is still very rare, even in this group. If there is a link, the disease would most likely develop in individuals with genetic factors that make them susceptible to the disease in the first place.

Radiation. Radiation therapy has been reported to cause local patches of scleroderma (morphea) or worsen preexisting scleroderma in a few patients. In some cases, scleroderma may occur years after radiation treatments.

Researchers think that infections may play a role in triggering the process leading to some cases of scleroderma. There is no real evidence of any single type of bacteria or other organism that might be responsible, although some are of particular interest.

Some studies reported an association between Borrelia burgdorferi, the cause of Lyme disease, and some cases of morphea (localized scleroderma). However, the evidence is weak. If there is a connection, it is possibly limited to a specific type of the bacteria in Europe and Asia. There is no connection between systemic scleroderma and Lyme disease.

Other infections associated with scleroderma include parvovirus and hepatitis C. However, there is no evidence of a cause-and-effect relationship.

Risk Factors

Scleroderma is uncommon. It afflicts about 300,000 Americans, but only about 49,000 have the systemic form of the disease. The cause of scleroderma has not been determined, and there are few specific risk factors. The incidence tends to be higher in certain groups, however.

Age. Systemic scleroderma usually develops between the ages of 35 and 55. Localized scleroderma is more common in children than adults, but is extremely rare even in the young age group. It occurs in between 0.2 and 0.4 per 100,000 people. Systemic scleroderma in children is even more rare.

Gender. The incidence of scleroderma is three to eight times higher in women than in men. This may reflect a different cause of the disease in these two genders. (It should be noted that pregnancy itself is not a risk factor for scleroderma.)

Family History. A family history is the strongest risk factor for scleroderma, but even among family members, the risk is very low (less than 1%).

Genetics. Genetic factors appear to play a role in triggering the disease, but most cases are unlikely to be inherited. Preliminary research suggests that patients with certain gene variations may be more susceptible to scleroderma than those who do not carry these variations.

Ethnicity. Limited data on risk by ethnic group in the United States suggests that the risk from highest to lowest is the following: Choctaw Native Americans (highest), African-Americans, Hispanics, Caucasians, Japanese Americans.

African-Americans have a higher rate of diffuse scleroderma, lung involvement, and a worse prognosis than Caucasians. Other studies also found lower survival rates among Japanese Americans.

Genetic factors affect population groups differently. Studies are finding that ethnic groups differ in the number of specific scleroderma-related antibodies they produce. Caucasians, for instance, have a higher rate of anti-centromere antibodies, which are associated with limited disease, while African-American patients have higher rates of autoantibodies and genetic factors that are associated with a more severe condition.

Geography. There appears to be certain geographic clusters of scleroderma, or specific types of scleroderma related to location. This may suggest an infectious or genetic factor at work, but the reasons are largely unknown. The following are some examples:

Studies reported significantly higher-than-average scleroderma mortality rates in male patients (both African-American and Caucasian) who live in two specific regions of the Southeast: one cluster around Coffee, Tennessee, and two others near Northampton, North Carolina.
A cluster of scleroderma cases has been observed in South Boston, Massachusetts.

Prognosis

At this time there is no cure for scleroderma and no treatment to change its course, but outlook varies widely. Many patients, even those with systemic scleroderma, can expect a normal lifespan.

General Outlook of Localized Scleroderma. Localized scleroderma nearly always carries a good prognosis and a normal life span. Even localized scleroderma, however, can cause some severe effects in children, including impaired growth, limb imbalance, and problems in flexing and bending muscles.

General Outlook of Systemic Scleroderma. The outlook for patients with systemic scleroderma has generally improved over the years. Ten-year survival rates rose from 54% in 1972 to 66% in 2001.

The causes of death related to systemic scleroderma also have changed. The proportion of deaths from kidney crises dropped significantly, from 42% to just 6% in that time period; however, the proportion of deaths from pulmonary fibrosis increased from 6% to 33%. Today, lung complications account for 60% of scleroderma-related deaths.

Limited Scleroderma. Patients with limited CREST scleroderma can usually expect a favorable outlook and normal lifespan if the disease affects only the hands and face. The course of this type of scleroderma still tends to be slowly progressive and, in some cases, may affect internal organs.
Diffuse Scleroderma. The severity of diffuse scleroderma varies widely, and it is very difficult to predict its course. It generally follows one of two paths: If it is acute or rapidly progressing, it may be a life-threatening condition that affects internal organs. The most critical period for rapid progression is usually within the first 2 - 5 years of the start of the disease. In the absence of rapid progression, or if the patient survives the initial acute progression, the disease tends to progress very slowly. The more severe the condition of the skin is at the start of the disease, the poorer the survival rates.

Many patients with systemic scleroderma experience a plateau in which the condition stabilizes. This plateau is followed by a period of improvement and skin softening. No one knows why this occurs, and it can happen regardless of treatment. In one study, patients with systemic scleroderma who experienced such improvements also had better survival rates (80% at 10 years) than those whose skin did not improve (60% 10-year survival rate).

The many complications of scleroderma can have a major impact on a person's sense of well-being. Patients are greatly concerned about changes in their appearance, particularly those changes caused by tightening of the facial skin. A 2002 study on scleroderma patients reported that 63% experienced at least mild pain, and half of them had some degree of depression. Depression had the greatest impact, even more than pain, in reducing patients' ability to function socially.

Diagnosis

There are no specific tests for scleroderma. The doctor may suspect scleroderma after taking a history of the symptoms and performing a physical examination. As part of this examination, the doctor does the following:

Checks the skin for thickened and hardened areas. The major signs of scleroderma are hardening and thickening of the skin in any areas on the fingers and toes.
Presses affected tendons and joints to detect crackling or grating sensations, which can indicate changes related to scleroderma beneath the skin.
Examines the fingernails underneath a microscope. The doctor may find changes in capillaries that are characteristic of scleroderma and mixed connective tissue disease.

Scientists recently found that antibodies that are often found in patients with scleroderma and systemic lupus erythematosus (SLE) bind to different parts of a single protein. Scientists hope this finding will one day lead to a specific diagnostic test for scleroderma.

Tests may be done to detect immune factors called antinuclear antibodies (ANAs). Detecting specific types of ANAs may help diagnose scleroderma. ANA subtypes include the following:

Rheumatoid factor, anti-single-stranded DNA, and antihistone antibodies are autoantibodies associated with scleroderma, but they are also common in other autoimmune disorders, such as rheumatoid arthritis and systemic lupus erythematosus. Some ANAs attack RNA or DNA, the genetic material in cells.
Anti-RNA polymerase III, anti-topoisomerase I (also called anti-DNA topo 1) and anti-centromere antibodies (ACA) are three other autoantibodies. Most patients with systemic scleroderma (but not localized scleroderma) have one or more of these autoantibodies. They do not appear at the same time, and seem to relate to different phases of the disease process. For example, anti-DNA topo 1 often occurs with diffuse skin scleroderma and lung complications. Anti-centromere antibodies usually occur with a less severe form of the disease.
Higher-than-normal levels of autoantibodies to fibrillin 1, a protein found in muscle and other connective tissues, is more common in patients with both systemic and localized scleroderma. This autoantibody in localized scleroderma is more common in some ethnic groups (such as Japanese and Native Americans) than in others (Caucasians). It is not found in other autoimmune diseases.

These antibodies are also found in other rheumatologic disorders, so detecting them does not necessarily prove that a patient has scleroderma. At the same time, studies have found that specific antibodies are associated with specific aspects of the disease. Therefore, identifying their presence could help diagnose, treat, and monitor people with scleroderma. Here are a few examples:

Anti-U1-RNP and anti U3-RNP are associated with muscle inflammation.
ACA is commonly associated with pulmonary hypertension and vascular disease.
TOPO is associated with pulmonary fibrosis.
RNA Polymerase III (Pol 3) is rarely linked to severe interstitial fibrosis, although this autoantibody is strongly present in patients with kidney crisis.
Patients with diffuse scleroderma who have Pol 3 have the best survival rate.

Diagnosing Lung Complications. Changes in the lungs may occur early in scleroderma lung disease, and prompt treatment is very important to prevent complications. For this reason, once a diagnosis is made, the doctor will check for lung changes in the following ways:

Listen to the lungs through a stethoscope. Rales, a crackling sound at the base of the lungs as the patient breathes in, is a sign of pulmonary fibrosis, even if breath function is normal.
Perform respiratory function tests to determine lung capacity.
Take a chest x-ray (however, x-rays do not always find lung disease, especially in children).
Have patients inhale nitric oxide to test the ability of blood vessels to open.
Perform more extensive tests, such as high-resolution computed tomography (CT) scans and bronchoalveolar lavage, if the doctor suspects severe lung scarring.

Newer tests showing promise in diagnosing lung complications include:

The induced sputum test, which looks at cells taken from coughed-up phlegm
Another test that uses the inhaled chemical, technetium-labeled diethylenetriamine pentaacetate (99mTC-DTPA), to detect lung damage

Diagnosing Heart Complications. Patients with suspected heart complications should have the following tests:

Electrocardiography (ECG): A test of the heart's electrical activity
Echocardiography: A look at the beating heart through the use of sound waves
Radionucleotide ventriculography: An evaluation of the working heart using a radioactive dye

Advanced imaging techniques, which provide a more detailed picture of the heart, may also be useful to determine the extent of heart complications in scleroderma patients.

Diagnosing Pulmonary Hypertension. Echocardiography is a noninvasive imaging technique for detecting pulmonary hypertension, a common and life-threatening complication of scleroderma. (Neither materials nor equipment are put into the body.) To confirm the diagnosis, doctors sometimes use an invasive procedure called right-heart catheterization. Right-heart catheterization involves the passage of a catheter (a thin flexible tube) into the right side of the heart to get diagnostic information about the heart.

Diagnosing Gastrointestinal (Digestive) Complications. Endoscopy may detect gastrointestinal problems. Endoscopy is an invasive procedure in which a tube is inserted down the esophagus. The tube contains a small camera and other instruments. Another diagnostic test is manometry, which measures the pressure that the muscles in the esophagus apply.

Electrogastrography (EGG) measures the electrical activity in muscles in the stomach, and may be an effective method for detecting stomach problems.

Diagnosing problems in growth of blood vessels. Capillaroscopy is the microscopic examination of blood vessels under the skin. It is now considered a useful tool for identifying problems with the growth of blood vessels, because more than 95% of patients will have some capillary abnormalities. Such problems can show the severity and progression of scleroderma. In a technique called nailfold capillaroscopy, the doctor places a drop of oil on the nailfolds (the skin at the base of the fingernails), and then looks at the nailfold under a microscope for signs of changes in the capillaries that may indicate a connective tissue disease such as scleroderma.

Click the icon to see an image about endoscopy.

Other Autoimmune and Connective Tissue Disorders. Several other autoimmune conditions that affect connective tissue can strongly resemble, or occur together with, scleroderma. They include the following:

Rheumatoid arthritis
Systemic lupus erythematosus
Polymyositis

Symptoms of such diseases may also include fever, arthritis, muscle aches, rash, and lung and heart problems.

Eosinophilic Fasciitis. Eosinophilic fasciitis is a muscle disorder that is known to occur after intense hard work. It can cause symptoms similar to scleroderma, including pain, swelling, and tenderness in the hands and feet, as well as skin thickening. The disorder can be ruled out with blood tests.

Although Raynaud's phenomenon occurs in most scleroderma patients, over 80% of the cases of Raynaud's phenomenon are harmless. In one study, only 12% of Raynaud's cases were associated with some other condition, and few of those were scleroderma. The following are other problems that might accompany or cause Raynaud's phenomenon:

Other autoimmune connective tissue diseases
Diabetes (patients with diabetes may develop Raynaud's phenomenon and other scleroderma-like symptoms)
Certain drugs, including bleomycin, ergot derivatives (used for migraines), and methysergide
Hereditary hemorrhagic telangiectasia (a very rare condition that is very similar to CREST syndrome)

Click the icon to see an image of a keloid.

Repetitive stress injuries (particularly from vibrating tools)
Hypothyroidism

Treatment

Scleroderma treatments vary depending on these variables:

Is it local or systemic, and if systemic, is it limited or diffuse?
If the disease is systemic, what organs, if any, are involved?

Although there is still no treatment for the underlying process of scleroderma, specific drugs and treatments help combat the various mechanisms and consequences of the disease.

Some medications keep blood vessels open (prostacylins, endothelin receptor antagonists, ACE inhibitors, phosphodiesterase 5 inhibitors, and others) and are used to treat Raynaud's phenomenon, heart and kidney problems, and pulmonary hypertension.
Other drugs reduce inflammation and block damaging immune factors. These treatments, which include cyclophosphamide, penicillamine, bone marrow transplantation, and others may be helpful for improving skin thickness and reducing scarring, even in the lungs.
Doctors use other treatments for specific complications, such as proton pump inhibitors and pro-kinetic agents for gastrointestinal problems, or light treatments for skin thickening.
Various investigative approaches exist, including stem-cell transplants.

Patients should receive treatments for specific complications as early as possible in the course of the disease, to reduce progression before irreversible hardening of tissues occurs.

There is no cure for scleroderma. Many drugs that are useful for other autoimmune inflammatory disorders have not proven to be very effective for scleroderma. Experimental work is ongoing to develop procedures or to find drugs that can treat the underlying processes that cause damage. Developing effective treatments for scleroderma is very problematic, however, for the following reasons:

The course of scleroderma is hard to predict, making it one of the most difficult rheumatic diseases to treat. It also makes drug development complicated.
The disease, when advanced, affects many organs. Designing treatment strategies that will improve symptoms in some organs without affecting other organs is very difficult.
The disease is so uncommon that there are few patients available for clinical trials. Studies, then, are very small, sometimes having only four or five patients. It is very difficult to design studies of this size that can provide strong evidence on treatment effects. Drugs that seem promising on small groups of patients often fail to show effectiveness on larger groups.

The disease can evolve slowly over time with few symptoms, or progress rapidly and become very severe. The patient, then, must live with considerable uncertainty and emotional stress. Support associations, non-medical aids to help relieve symptoms, and other lifestyle measures can be extremely important and helpful.

Medications

Calcium-channel blockers are the standard drugs to open the blood vessels, and may be used for pulmonary artery hypertension and Raynaud's phenomenon. Short- or sustained-release nifedipine (Adalat, Procardia) is the gold standard. Other drugs used include diltiazem (Cardizem, Dilacor), and the newer dihydropyridines (felodipine, amlodipine, and isradipine). Side effects vary among different medications, and may include fluid buildup in the feet, constipation, fatigue, gingivitis, impotence, flushing, and allergic symptoms. Calcium channel blockers should not be taken with grapefruit juice, as it appears to boost the effects of these drugs. [The medications listed below are also discussed under many of the sections covering treatment complications.]

Nitrates

Nitrates relax smooth muscles and open arteries, and are therefore sometimes used for the short-term management of Raynaud's phenomenon. They are available in topical and oral (by mouth) forms. Side effects of nitrates include headaches, dizziness, nausea, blurred vision, fast heartbeat, and sweating. Lying down with the legs elevated can relieve low blood pressure and dizziness. Alcohol, beta blockers, calcium-channel blockers, and certain antidepressants can significantly worsen these side effects. Withdrawal from nitrates should be gradual. Some severe reactions have occurred when people have stopped taking these drugs too quickly.

Prostacyclins (also called Prostaglandins)

Prostacyclins open blood vessels and also have anti-blood-clotting properties. One or all of these drugs is used to treat pulmonary artery hypertension and Raynaud's phenomenon. Several prostacyclins are being used for scleroderma, although none have been approved specifically for the condition. Promising prostacyclins or similar drugs include iloprost (Ventavis), alprostadil (prostaglandin E1), epoprostenol (Flolan), and treprostinil (Remodulin).

Endothelin Receptor Antagonists

Bosentan (Tracleer) is a drug taken by mouth. It is called an endothelin receptor antagonist. It controls endothelin, a powerful molecule that causes blood vessels to narrow. It improves blood flow and is becoming important for treating patients with scleroderma, especially for preventing finger ulcers and improving hand function. This drug is also a treatment option for pulmonary hypertension.

The most effective approach at this time for preventing kidney (renal) crises is to start aggressive blood pressure-lowering treatment before blood tests show kidney damage has occurred.

Angiotensin Converting Enzyme (ACE) Inhibitors. Many medications are available for controlling blood pressure, but ACE inhibitors appear to be the most effective for scleroderma patients, because of their protective actions in the kidney. These drugs are also used to treat patients with evidence of kidney damage, whether or not they have high blood pressure. ACE inhibitors include captopril (Capoten), enalapril (Vasotec), quinapril (Accupril), benazepril, and lisinopril (Prinivil, Zestril). Side effects are uncommon, but may include an irritating cough, large drops in blood pressure, and allergic reactions. The drug picotamide can help reduce the frequency of coughs.

Angiotensin II Receptor Antagonists. Angiotensin II receptor antagonists (losartan, candesartan cilexetil, and valsartan) have benefits similar to ACE inhibitors and may have fewer or less severe side effects, including coughing. They may also have positive effects on blood vessels. Small studies showing improvement in Raynaud's phenomenon warrant further research.

One major approach to scleroderma is to use treatments that suppress the immune system, and therefore reduce the activity of the harmful processes that lead to scleroderma. Such treatments are used effectively in other autoimmune diseases. Their use in scleroderma varies, depending on the location and severity of the disease process.

Cyclophosphamide (Cytoxan). Cyclophosphamide is the most important immunosuppressant currently used for scleroderma. This drug can be taken through a vein (intravenous) or by mouth. It blocks some of the destructive actions of scleroderma in the lungs. Intravenous cyclophosphamide can be life-saving for patients with pneumonia caused by interstitial lung disease. Side effects of this drug include hair loss, infection, and bleeding into the urinary tract. To date, no other immunosuppressive drugs have shown any significant benefits for scleroderma.

Other drugs used to suppress the immune system may be useful in specific cases. They include D-penicillamine (which may be useful for skin symptoms), methotrexate (Rheumatrex), corticosteroids, cyclosporine (Sandimmune, Neoral), and chlorambucil (Leukeran). All of these drugs have potentially severe side effects.

Other Treatments

Tumor-Necrosis Factor Modifiers. Tumor-necrosis factor (TNF) modifiers are major breakthroughs in the treatment of rheumatoid arthritis. They interfere with specific parts of TNF, a powerful immune factor. Researchers believe they should be tested in other inflammatory conditions, including scleroderma. The current agents include infliximab (Remicade), etanercept (Enbrel), alefacept (Amevive), and adalimumab (Humira).

Blood Exchange (Plasmapheresis or photopheresis). Plasmapheresis is a process in which the liquid part of the blood, called plasma, is separated from blood cells. The procedure involves first withdrawing blood from the patient. The plasma, which contains the active immune factors, is discarded and replaced with other fluids. The blood is then returned to the patient.

Autologous Stem-Cell Transplantation. Researchers are investigating a possible benefit of transplanting the patient's own stem cells (an autologous transplant). (Patients with autoimmune diseases cannot be given cells from donors.) The transplant procedures introduce normal white blood cells that replace the abnormal autoimmune cells. The procedure has improved or stabilized systemic scleroderma in some patients, with remissions lasting up to 5 years or more, and improvements in skin and overall function. Initial results of ASTIS, a major study evaluating stem-cell transplants and high-dose immunosuppressive therapy in severe scleroderma, indicate that this combination has led to sustained remission in more than one-third of patients. Randomized controlled trials comparing stem cell transplants to monthly cyclophosphamide therapy are underway in Europe and the U.S.

Although the risk of death from having a transplant is now less than 10%, the procedure has serious side effects. Experts suggest that the best candidates are those at high risk for complications from scleroderma. In general, such patients would have diffuse scleroderma, experienced their first symptoms within the previous three years, and have evidence of at least mild abnormalities in the heart, lungs, or kidney. In general, patients with advanced scleroderma would not be the best candidates, because the risks of the procedure would outweigh the risks from the disease.

Extracorporeal Photopheresis: Another phototherapy treatment under investigation, extracorporeal photopheresis, involves withdrawing the patient's blood and treating it with ultraviolet light. Little data exists on its effectiveness. One study found that the therapy improved skin and joint symptoms, but the authors say it's possible that a placebo effect was at least partly responsible for the results. Experts do not recommend photopheresis at this time, but some feel that it does hold promise and warrants more research.

Intravenous immunoglobulin (IVIg). Animal studies have found that administration of IVIg, an agent that modifies the immune system, may reduce the severity of scleroderma and other autoimmune diseases. So far, only extremely small studies including fewer than 10 patients have been conducted, but the treatment is showing promise for relieving joint pain and tenderness and improving function. The exact role of this therapy in scleroderma treatment, if any, has yet to be determined.

Because of the difficulty in treating scleroderma, many patients are tempted to try high-dose supplements or other alternative treatments. Some natural treatments have been evaluated for the treatment of scleroderma, including para-aminobenzoic acid, vitamin E, evening primrose oil, and an avocado/soybean extract. However, these treatments have not been proven effective, and using alternative remedies can be dangerous.

There is almost no published research on the use of herbal remedies for patients with scleroderma. Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been numerous reported cases of serious and even deadly side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Treatment for Raynaud's Phenomenon

The following are some lifestyle tips for managing Raynaud's phenomenon:

Keeping warm is the primary goal for preventing the onset of Raynaud's phenomenon. Air-conditioning and exposure to refrigeration can trigger this syndrome. If patients go out in cold weather, they should dress warmly with many layers. Wearing a hat is essential.
Living in a warm climate may help relieve symptoms, although a recent study found that weather changes themselves had little effect on the disorder.
Exercise is helpful for maintaining a sense of well-being, keeping warm, and sustaining skin flexibility. Patients with Raynaud's phenomenon may want to avoid exercising outdoors in cold weather, however.
Quitting smoking is, of course, essential for anyone, but it is critical for people with scleroderma.
Learning relaxation and anti-stress techniques might help reduce some triggers of Raynaud's phenomenon.
Using moisturizers and antibiotic ointments may be helpful for keeping skin flexible and preventing infections in the fingers.
Avoiding medications such as nonselective beta blockers (such as propranolol), certain common cold preparations, and narcotics, can help avoid aggravating Raynaud's phenomenon.

Vasodilators. Vasodilators open blood vessels and so are important for Raynaud's phenomenon.

Calcium-channel blockers, including diltiazem (Cardizem, Dilacor) and nifedipine (Adalat, Procardia) are the standard vasodilating drugs used for Raynaud's phenomenon. Nifedipine is the best studied of these drugs, but there are also newer dihydropyridines, including felodipine, amlodipine, and isradipine.

Nitrates, available in topical or oral forms, are vasodilators that are also used for Raynaud's phenomenon, and for short-term relief.

Prostacylins. Iloprost and other prostacylins are proving to be effective agents for Raynaud's phenomenon. Small but well done studies seem to show these drugs to be helpful for this condition, and possibly as effective as calcium channel blocker drugs such as nifedipine. Evidence shows that intravenous iloprost given at progressively increasing doses over 3-month cycles can reduce the duration and frequency of attacks. In general, these drugs are used when a patient's symptoms are severe, particularly when the doctor is considering amputating a finger.

Endothelin receptor agonists have also been shown to help with Raynaud's phenomenon.

Anti-Platelet Drugs. Aspirin, dipyridamole, and other drugs that prevent blood clotting and keep blood flowing freely are sometimes recommended to patients with Raynaud's phenomenon. However, these drugs haven't shown much benefit in studies.

Estrogen Therapy in Women. Short-term treatment with estrogen may benefit older women with Raynaud's phenomenon and scleroderma. It is important to note, however, that hormone replacement therapy for more than 5 years can increase a woman's risk for breast cancer, heart attacks, strokes, and blood clots.

PDE5 Inhibitors. Studies have suggested that a class of drugs called PDE5 inhibitors, which includes sildenafil, helps improve symptoms and blood flow, and speeds ulcer healing in patients with Raynaud's phenomenon. This treatment is still experimental.

Sympathectomy and Hand Surgeries. Sympathectomy uses procedures that block or remove the nerve responsible for narrowing blood vessels in the hand. The result is increased blood flow in the hand.

The local anesthetics lidocaine or bupivacaine may be very effective in temporarily restoring blood flow and reducing pain.

For finger ulcers that won't heal and are resistant to standard treatments, sympathectomy surgery may be done.

Treatment for Skin Thickening

Nitroglycerin is a quick acting nitrate and is used as an ointment (Nitro-Bid, Nitrol, Nitrong, Nitrostat) to treat hardened skin. Before applying it, remove any ointment that remains from the previous application.

UVA-1 Phototherapy. Phototherapy (light therapy) is now considered by some experts to be the treatment of choice for local scleroderma. Specifically, doctors favor an approach called ultraviolet A-1 (UVA-1) radiation. This treatment produces long UVA wave lengths that do not cause sunburn and may actually repair DNA in damaged skin cells. Research suggests that UVA-1 therapy blocks inflammatory immune factors and the process leading to over-production of collagen, addressing the underlying mechanisms of scleroderma. The procedure is effective for all stages of morphea. It increases skin elasticity and in some cases, completely clears up symptoms. In one small study, patients with localized scleroderma received 30 phototherapy treatments over a period of 12 weeks. In the majority of patients, 80% of the skin patches disappeared or significantly improved. There were no side effects.

UVA-1 phototherapy is quite expensive and requires a special light source not available everywhere. In addition, studies are reporting an increased risk with UVA radiation. Whether this applies to UVA-1 phototherapy is not yet clear. Nonetheless, phototherapy is still an effective and important treatment of scleroderma. It may prove to be even more beneficial when combined with certain medications, such as calcipotriene (Dovonex), a form of vitamin D3.

PUVA. An alternative phototherapy regimen called PUVA uses drugs called psoralens taken by mouth before UVA treatment. PUVA has been used for other skin diseases, including psoriasis. It may prove useful for patients with early-onset diffuse scleroderma. In one study, most patients treated with PUVA 2 days a month for up to 8 years experienced improvement or stabilization in nearly all scleroderma symptoms. Tests for kidney function remained normal. This treatment is known to increase the risk for skin cancer.

Phototherapy with Psoralen Water Bath. Yet another procedure uses UVA light therapy after patients take a bath containing a solution of psoralen 8-methoxypsoralen (8-MOP). This treatment is safe and well tolerated, although benefits appear to be minor and occur only in a small subset of patients.

A form of vitamin D3, calcipotriene (Dovonex), appears to help block skin cell production. This vitamin is called calcipotriol in Europe. It also has anti-inflammatory properties, and is being investigated as a rub-on treatment and oral treatment for local scleroderma. It may prove beneficial when combined with low-dose ultraviolet A1 phototherapy.

D-penicillamine is proving to be an effective agent for softening skin and reducing thickness. (Improvements in thickness with this drug have also been associated with improved survival.)

Methotrexate (Rheumatrex) is another commonly used drug, and may be even more effective than penicillamine.

Corticosteroids taken by mouth, such as prednisolone and prednisone, are also often used.

Pilocarpine (Salagen) has been approved for treating dry mouth in people with scleroderma and Sjögren syndrome. In one study, patients with Sjögren syndrome experienced increased salivation after the first dose. Patients reported improvement in speaking, sleeping, and swallowing food without drinking. Side effects of this drug include sweating, increased need to urinate, chills, and flushing.

Other Surgeries. Disabling deformity of the hand is a common feature of scleroderma. Various surgical procedures can relieve pain, prevent tissue loss, protect hand function, and improve the appearance of the hands.

Treatment for Lung Complications

Cyclophosphamide. Cyclophosphamide (Cytoxan), an immunosuppressive drug, may be effective for preventing lung deterioration and is the important medication for treating pulmonary fibrosis, particularly when given early in the course of the disease.

Use of this drug may improve survival in patients who show early signs of lung deterioration, notably inflammation in the small lung airways (alveolitis). The drug is not recommended for patents with existing stable pulmonary fibrosis and no signs of inflammation. In one study, patients with early signs of lung inflammation were given a course of intravenous pulses of the corticosteroid methylprednisolone (MP) and cyclophosphamide. Nearly all patients experienced improvement or stabilization during the first year, although the disease had progressed in two-thirds of them after 2 years.

Other Treatments. Lung transplantation may offer hope for people with advanced pulmonary hypertension or interstitial fibrosis that does not respond to conservative treatments.

Several types of drugs are used to treat pulmonary hypertension. Anticoagulants taken by mouth, such as warfarin (Coumadin), are a standard treatment used to prevent blood clots from forming. Diuretic treatment and supplemental oxygen are recommended for patients with fluid retention and low blood oxygen, respectively.

Vasodilators help open blood vessels and relieve pressure in arteries of the lungs. Vasodilators used to treat pulmonary hypertension fall into several different drug classes:

Calcium Channel Blockers (CCBs). Some patients with pulmonary hypertension benefit from these drugs. They help relax blood vessels in the heart and lungs, and increase the supply of oxygen. However, calcium channel blockers are only appropriate for patients who meet certain diagnostic criteria, including those who don't have right-sided heart failure. Long-acting nifedipine or diltiazem, or amlodipine, are the preferred calcium channel blockers.

Prostacyclins (Prostaglandins). Prostacyclins, which open blood vessels, are now the primary agents for treating pulmonary hypertension.

Iloprost (Ventavis) is available in inhaled and intravenous forms. Studies suggest that the inhaled form improves exercise capacity and survival in some patients with pulmonary hypertension. In addition, infusions of iloprost remain effective over long periods (up to 3 years) of use.
Treprostinil (Remodulin) is similar to epoprostenol but is more stable. It can also be administered using a portable pump that delivers the drug under the skin. This is less expensive, cumbersome, and invasive than the delivery methods for epoprostenol.
Epoprostenol (Flolan), which is administered intravenously, has improved exercise capacity and symptoms in both the short and long term in a number of patients. In some patients, survival is increased significantly. However, not all patients respond to this drug. The implanted catheter needed to deliver the drug can also cause serious complications.

Endothelin Receptor Antagonists. Bosentan (Tracleer) was the first drug taken by mouth that was approved for pulmonary hypertension. Bosentan controls endothelin, a powerful substance that causes blood vessels to narrow. Studies have reported improved exercise capacity in patients with pulmonary hypertension. Sitaxsentan and ambrisentan (Letairis) are two new drugs being studied.

PDE5 Inhibitors. Sildenafil (Revatio) was approved in 2005 as the first pill for patients with early-stage pulmonary hypertension. Sildenafil is the same medication contained in the erectile dysfunction drug Viagra. However, Revatio is prescribed at a lower dosage than Viagra, and is a different color and shape than Viagra pills.

Other Treatments. Lung transplantation may offer hope for people with advanced pulmonary hypertension that does not respond to conservative measures.

Treatment for Gastrointestinal Problems

Treatments for abnormalities in the esophagus and stomach are generally the same as those for gastroesophageal reflux (GERD) or heartburn. Many non-prescription agents are available for the relief of heartburn.

Proton-pump or acid-pump inhibitors are probably the best drug treatments for reflux symptoms related to scleroderma. They work by inhibiting the so-called gastric acid pump that is required for the cells of the stomach to release acid. The standard drug has been omeprazole (Prilosec). Newer drugs -- including lansoprazole (Prevacid), pantoprazole (Protonix), esomeprazole (Nexium), and rabeprazole (Aciphex) -- are more potent, but few comparison studies have been done on them.

Side Effects. Side effects are uncommon, but can include allergic reaction, headache, stomach pain, diarrhea, and flatulence. Of some concern was a report of a very severe and widespread skin rash caused by omeprazole in a woman with scleroderma. It should be noted that this is only one incident, but patients should be cautious about any skin change when taking this medication.

Metoclopramide. Metoclopramide (Reglan) is sometimes used for patients who have delayed stomach emptying.

Octreotide. Octreotide (Sandostatin) is related to a natural hormone that suppresses growth hormone, and may prove to be very helpful for scleroderma patients. Small studies have reported that this drug improved weight and nutrition. It may even help other symptoms of scleroderma.

Prokinetics. Prokinetics improve the muscle action of the esophagus and enhance stomach emptying. Prucalopride is an investigative pro-kinetic agent that significantly improved symptoms and relieved constipation. Similar medications, such as cisapride (Propulsid), are showing promise; however these types of drugs can have serious side effects.

Antibiotics may be effective for the malabsorption syndrome associated with an increase in bacteria. Octeotride may also be used for this problem.

Strictures (abnormally narrowed regions in the esophagus) may need to be opened with surgery.

Resources

www.scleroderma.org -- Scleroderma Foundation
www.srfcure.org -- Scleroderma Research Foundation
www.arthritis.org -- The Arthritis Foundation
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.rheumatology.org -- American College of Rheumatology
www.sclero.org -- International Scleroderma Network
www.sctc-online.org -- Scleroderma Clinical Trials Consortium
www.phassociation.org -- Pulmonary Hypertension Association
www.thoracic.org -- American Thoracic Society

References

Badesch DB, Abman SH, Simonneau G, Rubin LJ, McLaughlin VV. Medical therapy for pulmonary arterial hypertension: updated ACCP evidence-based clinical practice guidelines. Chest. 2007;131:1917-1928.

Feldman M, Friedman LS, Brandt LJ. Sleisenger and Fordtran's Gastrointestinal and Liver Disease. 8th ed. Philadelphia, Pa: Saunders; 2006.

Goldman L, Ausiello D. Goldman: Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders, 2007.

Grader-Beck T, Wigley FM. Raynaud's phenomenon in mixed connective tissue disease. Rheum Dis Clin North Am. 2005;31:465-481.

Henness S, Wigley FM. Current drug therapy for scleroderma and secondary Raynaud's phenomenon: evidence-based review. Curr Opin Rheumatol. 2007;19:611-618.

Knobler RM, French LE, Kim Y, Bisaccia E, Graninger W, Nahavandi H, et al. A randomized, double-blind, placebo-controlled trial of photopheresis in systemic sclerosis. J Am Acad Dermatol. 2006;54:793-799.

Kreuter A, Hyun J, Stücker M, Sommer A, Altmeyer P, Gambichler T. A randomized controlled study of low-dose UVA1, medium-dose UVA1, and narrowband UVB phototherapy in the treatment of localized scleroderma. J Am Acad Dermatol. 2006;54:440-447.

Mason RJ, Murray JF, Broaddus VC, Nadel JA. Mason: Murray & Nadel's Textbook of Respiratory Medicine. 4th ed. Philadelphia, Pa: Saunders; 2005.

Nash RA, McSweeney PA, Crofford LJ, Abidi M, Chen CS, Godwin JD, et al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study. Blood. 2007;110:1388-1396.

Ostojic P, Cerinic MM, Silver R, Highland K, Damjanov N. Interstitial lung disease in systemic sclerosis. Lung. 2007;185:211-220.

Pfizenmaier DH 2nd, Kavros SJ, Liedl DA, Cooper LT. Use of intermittent pneumatic compression for treatment of upper extremity vascular ulcers. Angiology. 2005 Jul-Aug;56(4):417-22.

Schachna L, Medsger TA Jr., Dauber JH, Wigley FM, Braunstein NA, White B, et al. Lung transplantation in scleroderma compared with idiopathic pulmonary fibrosis and idiopathic pulmonary arterial hypertension. Arthritis Rheum. 2006;54:3954-3961.

Shoenfeld Y, Katz U. IVIg therapy in autoimmunity and related disorders: our experience with a large cohort of patients. Autoimmunity. 2005 Mar;38(2):123-37.

Steen VD. Pregnancy in scleroderma. Rheum Dis Clin North Am. 2007;33:345-358.

Tashkin DP, Elashoff R, Clements PJ, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006; 354(25):2655-66.

Thombs BD, Taillefer SS, Hudson M, Baron M. Depression in patients with systemic sclerosis: a systematic review of the evidence. Arthritis Rheum. 2007;57:1089-1097.

Tyndall A, Furst DE. Adult stem cell treatment of scleroderma. Curr Opin Rheumatol. 2007;19:604-610.

van Laar JM. High-dose immunosuppressive therapy and autologous progenitor cell transplantation for systemic sclerosis. Best Pract Res Clin Haematol. 2004; 17(2): 233-45.

Review Date:
1/15/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

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adam.com

What's the Difference Between Regularity Remedies?

FitSugar — Fri, 01 May 2009 03:00:00 -0700

Nobody's likes being irregular. Even if you get your daily quota of 25 to 30 grams of fiber, stress, traveling, and lack of exercise can cause constipation.

If you have issues with regularity, there are many over-the-counter products that can help, but it's tough to know which one will work, which ones are safe to take regularly, and which ones won't cause annoying side effects. If you're curious about the differences between these remedies, then read more.

Product	Price	Dosage	Main Ingredient	Negative Side Effects	Benefits
Metamucil Coarse Milled Texture Drink Mix	44.2 oz. for $15.99	1 rounded tbsp, 3 times daily	Psyllium husk (has a gritty texture)	Can cause bloating and gas	Helps lower cholesterol, provides good source of fiber.
Metamucil Strong Bones Capsules	120 for $12.99	5 capsules, up to 4 times daily	Psyllium husk	Can cause bloating and gas	Each serving contains 300 mg of calcium.
Citrucel Powder	32 oz. for $27.49	1 rounded tbsp, 3 times daily	Methylcellulose (no gritty texture)	None	Each dose contains 105 mg of potassium.
Citrucel Caplets	180 for $27.99	2 caplets, up to 6 times daily	Methylcellulose	None	Each caplet contains 10 mg of calcium.
Fibercon Caplets	140 for $18.29	2 caplets, up to 4 times daily	Calcium Polycarbophil	None	Each caplet contains 140 mg calcium and 10 mg magnesium.
Benefiber Powder	16.7 oz. for $18.99	2 tsp, 3 times daily	Wheat Dextrin	Can cause bloating and gas	Dissolves completely in beverages, is non-thickening, can cook with it, sugar free, gluten free.
Benefiber Chewables plus Calcium	90 for $12.29	3 tablets, up to 3 times daily	Wheat Dextrin	Can cause bloating and gas	Gluten free, and each dose provides as much calcium as 8 oz. of milk, and you don't need to take them with water.

Infertility in women

FitSugar — Wed, 08 Oct 2008 17:35:02 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New At-Home Fertility Test for Couples

Fertell is a new at-home fertility test kit for couples. It screens for sperm motility concentrations and follicle-stimulating hormone (FSH) levels. Fertell may be helpful as an initial test for infertility, but for a definitive diagnosis it is important to consult a doctor. Infertility can be due to many different factors.

Intracytoplasmic Sperm Injection Overused for Female Infertility

The assisted reproductive technology intracytoplasmic sperm injection (ICSI) is being increasingly used in combination with in vitro fertilization (IVF), even for couples who do not have problems with male infertility, suggests a 2007 study in the New England Journal of Medicine. Researchers found that use of ICSI has increased 5-fold in the past decade. Some doctors are now recommending ICSI for women who have failed prior IVF cycles or who have few or poor-quality eggs. Doctors caution that ICSI should be used only to improve pregnancy chances for couples with male-factor infertility.

Clomiphene Best for PCOS-Associated Infertility

The infertility drug clomiphene (Clomid) works better than the diabetes drug metformin (Glucophage) for treating infertility resulting from polycystic ovarian syndrome (PCOS), indicates a 2007 study in the New England Journal of Medicine.

Fertility Drugs and Breast Cancer

Fertility drugs such as clomiphene and gonadotropins do not increase the risk for breast cancer, indicate several studies. In fact, according to a 2006 study in the Archives of Internal Medicine, clomiphene may decrease breast cancer risk.

Iron Deficiency and Female Infertility

Iron deficiency may increase the risk for ovulatory infertility, suggests a 2006 study in Obstetrics and Gynecology. Researchers found that women who took daily iron supplements were 40% less likely to be infertile than women who did not take supplements. Some experts recommend screening for iron deficiency as part of the clinical evaluation for infertility.

Introduction

Infertility is the failure of a couple to become pregnant after one year of regular, unprotected intercourse. In both men and women the fertility process is complex.

About 10% of couples who wish to have a baby are still unable to after a year of unprotected sex. About half of these couples can achieve pregnancy within 2 years after appropriate treatment of the woman, the man, or both. Even under ideal circumstances, the probability that a woman will get pregnant during a single menstrual cycle is only about 30%. And, when conception does occur, only 50 - 60% of pregnancies advance beyond the 20th week. (The inability of a woman to produce a live birth because of abnormalities that cause miscarriages is called infecundity and is not discussed in detail in this report.)

Males and females each account for 40% of infertility. In the remaining 20%, either both partners are responsible or the cause is unclear. Although this report specifically addresses infertility in women, it is equally important for the male partner to be tested at the same time. [See In-Depth Report #67: Infertility in men.]

The Reproductive System

The Primary Organs and Structures in the Reproductive System. The primary structures in the reproductive system are:

The uterus is a pear-shaped organ located between the bladder and lower intestine. It consists of two parts, the body and the cervix.
When a woman is not pregnant the body of the uterus is about the size of a fist, with its walls collapsed and flattened against each other. During pregnancy the walls of the uterus are pushed apart as the fetus grows.
The cervix is the lower portion of the uterus. It has a canal opening into the vagina with an opening called the os, which allows menstrual blood to flow out of the uterus into the vagina.
Leading off each side of the body of the uterus are two tubes known as the fallopian tubes. Near the end of each tube is an ovary.
Ovaries are egg-producing organs that hold 200,000 - 400,000 follicles (from folliculus, meaning "sack" in Latin). These cellular sacks contain the materials needed to produce ripened eggs, or ova.
The inner lining of the uterus is called the endometrium. During pregnancy, it thickens and becomes enriched with blood vessels to house and support the growing fetus. If pregnancy does not occur, the endometrium is shed as part of the menstrual flow. Menstrual flow also consists of blood and mucus from the cervix and vagina.

The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

Reproductive Hormones. The hypothalamus (an area in the brain) and the pituitary gland regulate the reproductive hormones.

Click the icon to see an image of the hypothalamus and pituitary gland.

The pituitary gland is often referred to as the master gland because of its important role in many vital functions, many of which require hormones. In women, six key hormones serve as chemical messengers that regulate the reproductive system:

The hypothalamus first releases the gonadotropin-releasing hormone (GnRH).
This chemical, in turn, stimulates the pituitary gland to produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

Click the icon to see an image of the pituitary gland.

Estrogen, progesterone, and the male hormone testosterone are secreted by the ovaries at the command of FSH and LH and complete the hormonal group necessary for reproductive health.

Ovulation. The process leading to fertility is very intricate. It depends on the healthy interaction of two sets of organs and hormone systems in both the male and female. In addition, reproduction is limited by the phases of female fertility. Nevertheless, this astonishing process results in conception within a year for about 80% of couples. Only 15% conceive within a month of their first attempts, however, and about 60% succeed after 6 months.

A woman's ability to produce children occurs after she enters puberty and begins to menstruate. The process of conception is complex:

With the start of each menstrual cycle, follicle-stimulating hormone (FSH) stimulates several follicles to mature over a 2-week period until their eggs nearly triple in size. Only one follicle becomes dominant, however, during a cycle.
FSH signals this dominant follicle to produce estrogen, which enters the bloodstream and reaches the uterus. There, estrogen stimulates the cells in the uterine lining to reproduce, therefore thickening the walls.
Estrogen levels reach their peak around the 14th day of the cycle (counting days beginning with the first day of a period). At that time, they trigger a surge of luteinizing hormone (LH).

LH serves two important roles:

First, the LH surge around the 14th cycle day stimulates ovulation. It does this by causing the dominant follicle to burst and release its egg into one of the two fallopian tubes. Once in the fallopian tube, the egg is in place for fertilization.
Next, LH causes the ruptured follicle to develop into the corpus luteum. The corpus luteum provides a source of estrogen and progesterone during pregnancy.

Click the icon to see an image of the corpus luteum.

Fertilization. The so-called "fertile window" is 6 days long and starts 5 days before ovulation and ends the day of ovulation. Fertilization occurs as follows:

The sperm can survive for up to 3 days once it enters the fallopian tube. The egg survives 12 - 24 hours unless it is fertilized by a sperm.
If the egg is fertilized, about 2 - 4 days later it moves from the fallopian tube into the uterus where it is implanted in the uterine lining and begins its 9-month incubation.
The placenta forms at the site of the implantation. The placenta is a thick blanket of blood vessels that nourishes the fertilized egg as it develops.

Click the icon to see an image of the placenta.

The corpus luteum (the yellow tissue formed from the ruptured follicle) continues to produce estrogen and progesterone during pregnancy.

If the egg is not fertilized, the corpus luteum degenerates into a form called the corpus albicans, and estrogen and progesterone levels drop. Finally, the endometrial lining sloughs off and is shed during menstruation.


Menstrual Phases	Typical No. of Days	Hormonal Actions
Follicular (Proliferative) Phase	Cycle Days 1 - 6: Beginning of menstruation to end of blood flow.	Estrogen and progesterone start out at their lowest levels. FSH levels rise to stimulate maturity of follicles. Ovaries start producing estrogen and levels rise, while progesterone remains low.
	Cycle Days 7 - 13: The endometrium (the inner lining of the uterus) thickens to prepare for the egg implantation.
Ovulation	Cycle Day 14:	Surge in LH. Largest follicle bursts and releases egg into fallopian tube.
Luteal (Secretory) Phase, also known as the Premenstrual Phase	Cycle Days 15 - 28:	Ruptured follicle develops into corpus luteum, which produces progesterone. Progesterone and estrogen stimulate blanket of blood vessels to prepare for egg implantation.
	If fertilization occurs:	Fertilized egg attaches to blanket of blood vessels that supplies nutrients for the developing placenta. Corpus luteum continues to produce estrogen and progesterone.
	If fertilization does not occur:	Corpus luteum deteriorates. Estrogen and progesterone levels drop. The blood vessel lining sloughs off and menstruation begins.

Onset of Menstruation (Menarche). Previous evidence had set the onset of menstruation, called the menarche, at an average age of 12 or 13. Recent studies, however, set the time of onset earlier by about 1 year in Caucasian girls and 2 years in African-American girls. Currently, the youngest possible age for normal puberty is 7 years old for Caucasians and 6 years old for African-Americans, down from a previous low of 8 years for both.

Evidence is pointing to the increasing incidence of childhood obesity as a major cause of the trend in earlier menarche onset. (Obesity is also highly associated with hormonal disorders in girls entering puberty at young ages.) Environmental estrogens found in chemicals and pesticides are also suspects.

Length of Monthly Cycle. The menstrual cycle can be very irregular for the first 1 - 2 years, usually being longer than the average of 28 days. The length then generally stabilizes to an average of 28 days, although the cycle length may range from 20 - 45 days and still be considered normal. A variation of 10 days or more -- either more or fewer days -- may have an impact on fertility, however. When a woman reaches her 40s the cycle lengthens, reaching an average of 31 days by age 49. Several factors can affect cycle length at any age.


Risk Factors for Shorter Cycles	Risk Factors for Longer Cycles
Regular alcohol use	Being under 21 and over 44
Stressful jobs	Being very thin (also at risk for short bleeding periods)
	Competitive athletics (also at risk for short bleeding periods)

Length of Periods. Periods average 6.6 days in young girls. By the age of 21, menstrual bleeding averages 6 days until women approach menopause. However, about 5% of healthy women menstruate less than 4 days, and 5% menstruate more than 8 days.

Normal Absence of Menstruation. Normal absence of periods can occur in any woman under the following circumstances:

Menstruation stops during the duration of pregnancy. Some women continue to have irregular bleeding during the first trimester. This bleeding may indicate a threatened miscarriage and requires immediate attention by the doctor.
When women breastfeed they are unlikely to ovulate. After that time, menstruation usually resumes, and they are fertile again.
Perimenopause starts when the intervals between periods begin to lengthen, and it ends with menopause itself (the complete cessation of menstruation). Menopause usually occurs at about age 51, although smokers often go through menopause earlier.

Risk Factors

In the U.S., an estimated 10.2% of women ages 15 - 44, or about 6.1 million women, have impaired fertility, and the incidence is increasing. About 25% of women experience some period of infertility during their reproductive years.

As a woman ages, her chances for fertility decline. Infertility in older women appears to be mostly due to a higher risk for chromosomal abnormalities that occur in her eggs as they age. Older women are also more likely to have health problems that may interfere with fertility. If fertilization occurs, older, healthy women can usually successfully bear a fetus to term, although they have a higher risk for miscarriage. Using population studies, experts have come up with estimated odds for pregnancy at different ages, given no fertility intervention. One analysis of pregnancy rates based on conception on the day of ovulation suggested that women ages 19 - 26 have twice the pregnancy rates as those ages 35 - 39.


Age	Fertility %
Up until age 34	90%
By age 40	Declining to 67%
By age 45	Declining to 15%

Although most of a woman's estrogen is manufactured in her ovaries, 30% is produced in fat cells by a process that transforms circulating adrenal male hormones into estrogen. Because a normal hormonal balance is essential for the process of conception, it is not surprising that extreme weight levels, either high or low, can contribute to infertility.

Being Overweight. Being overweight or obese (fat levels that are 10 - 15% above normal) can contribute to infertility in various ways. Obesity is highly associated with polycystic ovarian syndrome (PCOS), which is the cause of infertility in some cases. In one study, overweight women without PCOS were classified in one of five grades, depending on the severity of the obesity. The risk for irregular or absent periods increased two-fold by each increase in grade. In this group, amenorrhea (absent periods) was also highly associated with type 2 diabetes and blood sugar abnormalities.

Being Underweight. Body fat levels 10 - 15% below normal can completely shut down the reproductive process. Women at risk include:

Women with eating disorders, such as anorexia or bulimia.
Women on very low-calorie or restrictive diets are at risk, especially if their periods are irregular.
Strict vegetarians might have difficulties if they lack important nutrients, such as vitamin B12, zinc, iron, and folic acid.
Marathon runners, dancers, and others who exercise very intensely. (Lower body fat contributes to menstrual irregularities in competitive athletes, but other mechanisms are also involved.)

Exposure to environmental hazards (herbicides, pesticides, industrial solvents) may affect fertility. Estrogen-like hormone-disrupting chemicals are of particular concern for infertility in men and for effects on offspring of women.

Phthalates, chemicals used to soften plastics, are under particular scrutiny for their ability to disrupt hormones. Specific phthalates of special concern include dibutyl phthalate (DBP) and others found in many products, including cosmetics and clay products sold to children (Fimo, Sculpey). Animals exposed to phthalates have significantly impaired sperm count and abnormalities in reproductive structures, such as the testes. In addition, there is some concern that exposure in pregnant women may affect the offspring.

Neurotransmitters (chemical messengers) act in the hypothalamus gland, which controls both reproductive and stress hormones. Severely elevated levels of stress hormone can, in fact, shut down menstruation. Whether stress has any significant effect on fertility or fertility treatments is unclear. One 2005 study found that psychological stress does not affect the success or failure of in vitro fertilization.

Click the icon to see an image of the hypothalamus.

Causes

Causes of infertility can be found in about 90% of infertility cases but, despite extensive tests, about 10% of couples will never know why they cannot conceive. Between 10 - 30% of cases of infertility have more than one cause. Male or female infertility each account for about 30 - 40% of cases. In men, sperm defects (their quality and quantity) are usually responsible. Female infertility is more complex.

Pelvic inflammatory disease (PID) is the major cause of female infertility worldwide. PID comprises a variety of infections caused by different bacteria that affect the reproductive organs, appendix, and parts of the intestine that lie in the pelvic area. The sites of infection most often implicated in infertility are in the fallopian tubes, a specific condition referred to as salpingitis.

Causes of PID. PID may result from many different conditions that cause infections. Among them are:

Sexually transmitted diseases (cause of most PIDs). Chlamydia trachomatis is an infectious organism that causes 75% of infertility in the fallopian tubes. Gonorrhea is responsible for most of the remaining cases.
Pelvic tuberculosis (a growing global problem as tuberculosis cases increase)
Nonsterile abortions
Ruptured appendix
Herpes virus (suggested for some cases, but not confirmed as a cause).

Symptoms of PID. The infection may be subclinical (occurring without any symptoms), or there may be fever, chills, or pelvic pain indicating inflammation of the entire pelvic area.

Effects of PID. Severe or frequent attacks of PID can eventually cause scarring, abscess formation, and tubal damage that result in infertility. About 20% of women who develop symptomatic PID become infertile. PID also significantly increases the risk of ectopic pregnancy (fertilization in the fallopian tubes). The severity of the infection, not the number of the infections, appears to pose the greater risk for infertility.

Endometriosis may account for as many as 30% of infertility cases. Some evidence suggests that between 30 - 50% of women with endometriosis are infertile. Often, however, it is difficult to determine if endometriosis is the primary cause of infertility, particularly in women who have mild endometriosis. Endometriosis rarely causes an absolute inability to conceive, but, nevertheless, it can contribute to it both directly and indirectly.

Endometriosis is the condition in which the tissue that normally lines the uterus (endometrium) grows on other areas of the body causing pain and irregular bleeding.

Direct Effect of Endometrial Cysts. Endometrial cysts may directly cause infertility in several ways:

If implants occur in the fallopian tubes, they may block the egg's passage.
Implants that occur in the ovaries prevent the release of the egg.
Severe endometriosis can eventually form rigid webs of scar tissue (adhesions) between the uterus, ovaries, and fallopian tubes, thereby preventing the transfer of the egg to the tube.

Immune Factors and the Inflammatory Response. Researchers are focusing on defects in the immune system that not only may be responsible for endometriosis in the first place but may also cause the infertility associated with endometriosis. Even in early stage endometriosis, investigators have observed increased immune system activity.

Other Conditions Linking Endometriosis and Infertility. Researchers have sometimes noted unusually low levels of specific substances that enable a fertilized egg to adhere to the uterine lining. (Such abnormalities are more often a factor in infertility in women with mild-to-moderate endometriosis than in those with severe cases.)

One study found that the eggs in women with endometriosis appeared to have more genetic abnormalities than those in women without the disorder.

Polycystic ovarian syndrome (PCOS) is a condition in which the ovaries produce high amounts of androgens (male hormones), particularly testosterone. PCOS occurs in about 6% of women, and amenorrhea or oligomenorrhea (infrequent menses) is quite common. According to one study, nearly 30% of obese women with PCOS had amenorrhea. (The rate was lower -- 4.7% -- in women with normal weight.)

Click the icon to see an image of polycystic ovarian syndrome.

In PCOS, increased androgen production produces high luteinizing hormone (LH) levels and low follicle-stimulating hormone (FSH) levels, so that follicles are prevented from producing a mature egg. Without egg production, the follicles swell with fluid and form into cysts. Every time an egg is trapped within the follicle, another cyst forms, so the ovary swells, sometimes reaching the size of a grapefruit. Without ovulation, progesterone is no longer produced, whereas estrogen levels remain normal.

The elevated levels of androgens (hyperandrogenism) can cause obesity, facial hair, and acne, although not all women with PCOS have such symptoms. Other male characteristics, such as deepening voice and clitoral enlargement, are rare.

PCOS also poses a high risk for insulin resistance, particularly in women who are also obese. Insulin resistance is associated with diabetes type 2, in which insulin levels are normal or high but the body cannot use this hormone efficiently. About half of PCOS patients, in fact, also have diabetes.

Premature ovarian failure is the early depletion of follicles before age 40, which, in most cases, leads to premature menopause. It affects about 1% of women and is typically preceded by irregular periods, which might continue for years. In this condition, follicle-stimulating hormone (FSH) levels are elevated, as they are during perimenopause. Premature ovarian failure is a significant cause of infertility, and women who have this condition have only a 5 - 10% chance to conceive without fertility treatments.

Causes of Premature Ovarian Failure. There are numerous causes of premature ovarian failure. Often the cause of this disorder or other causes of premature ovarian failure is unknown. In some cases, premature ovarian failure may represent an acceleration of the aging process.

The following conditions may produce premature ovarian failure:

Adrenal, pituitary, or thyroid gland deficiencies.
Genetic factors related to the X chromosome. A woman needs two functioning X chromosomes for normal reproduction. When one is abnormal, ovarian function fails. The most severe example is Turner syndrome, a genetic condition, in which one of the two X-chromosomes is missing or malfunctioning. Milder cases of ovarian failure can occur in fragile X syndrome and other rare inherited conditions that cause partial X-chromosome abnormalities.
Cancer treatments (radiation, chemotherapy, or both). Women who are undergoing cancer treatments and who want to become pregnant should see a reproductive specialist to discuss their options. According to the American Society of Clinical Oncology's 2006 guidelines, the fertility preservation method with the best chance of success is embryo cryopreservation. This procedure involves harvesting a woman's eggs (oocytes), followed by in vitro fertilization and freezing of embryos for later use. Other treatments under investigation include egg preservation, collecting and freezing unfertilized eggs, removing and freezing a part of the ovary for later reimplantation, and using hormone therapy to protect the ovaries during chemotherapy. Women may be able to access these investigational approaches through enrolling in clinical trials.
Autoimmunity. Autoimmune diseases -- including type 1 diabetes, systemic lupus erythematosus, autoimmune hypothyroidism, and autoimmune Addison's disease -- are associated with a higher risk for early menopause. Autoimmunity, however, may also play a role in some cases of premature ovarian failure without the presence of specific autoimmune diseases. In such cases, antibodies specifically attack the cells that secrete reproductive hormones thus causing ovarian failure.
Other causes of premature ovarian failure include sarcoidosis, mumps, some sexually transmitted diseases, and tuberculosis. Women with epilepsy are at higher risk for premature ovarian failure.

Idiopathic hypogonadotropic hypogonadism is a rare condition in which follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are underproduced, preventing the development of functional ovaries. There are no other abnormalities in the hypothalamus-pituitary axis (such as tumors or abnormal stress hormones or prolactin). In most cases, the causes of hypergonadotropic hypogonadism are unknown. Genetic factors, including Kallman syndrome, have been identified in about 20% of these cases.

Functional hypothalamic amenorrhea (FHA) is the absence of menstruation due to disturbances in the thyroid gland and hypothalamus-pituitary-adrenal (HPA) system, which regulates reproduction and other important functions. The eating disorders anorexia and bulimia are most often associated with FHA. FHA may be due to other different factors, most unknown.

Luteal phase defect is a general term referring to problems in the corpus luteum that result in inadequate production of progesterone. Because progesterone is necessary for thickening and preparing the uterine lining, the ovum fails to successfully implant in the endometrium. Between 25 - 60% of women who have recurrent miscarriages may have a luteal phase defect. A luteal phase defect, however, can also occur in fertile women, so other factors may be responsible for implantation failure.

Benign fibroid tumors in the uterus are extremely common in women in their 30s. The effect of fibroids on fertility is controversial. One analysis suggested that they may account for infertility in only 1 - 2.4% of women who are having trouble conceiving.

Large fibroids may cause infertility impairing the uterine lining, by blocking the fallopian tube, or by distorting the shape of the uterine cavity or altering the position of the cervix.

Some evidence suggests that even small fibroids may reduce the chances of pregnancy in women who are undergoing assisted reproductive techniques. Treatments to reduce fibroids may be helpful in such women, although there has been little research on this subject.

Click the icon to see an image of uterine fibroids.

Prolactin is a hormone produced in the pituitary gland that stimulates breast development and milk production in association with pregnancy. High levels of prolactin (hyperprolactinemia) reduce gonadotropin hormones and inhibit ovulation. Hyperprolactinemia in women who are not pregnant or nursing can be caused by hypothyroidism or pituitary adenomas. (These are benign tumors that secrete prolactin. They can cause headache and visual problems as well as breast secretions.) Some drugs, including oral contraceptives and some antipsychotic drugs, can also elevate levels of prolactin.

Secretions from the breast not related to pregnancy or nursing (called galactorrhea) are a telltale symptom of high prolactin levels and should be investigated.

Inborn Abnormalities. Inborn genital tract abnormalities may cause infertility. Mullerian agenesis is a specific malformation in which no vagina or uterus develops. Even in these cases, some women can become mothers by undergoing in vitro fertilization and having the fertilized egg implanted in another woman who is willing and able to carry the pregnancy (a surrogate mother).

Uterine or Abdominal Scarring. Bands of scar tissue that bind together after abdominal or pelvic surgery or infection (called adhesions) can restrict the movement of ovaries and fallopian tubes and may cause infertility. Asherman syndrome, for example, is scarring in the uterus that can cause obstructions and secondary amenorrhea. It may be caused by surgery, repeated injury, or unknown factors. Laparoscopic surgery is less likely to cause adhesions than standard open surgery.

In some of these cases, surgery may be helpful. One technique, called pressure lavage under ultrasound guidance (PLUG), may prove to be useful for treating some cases of mild scarring in the uterus (intrauterine adhesions). This technique is based on transvaginal sonohysterography, which uses ultrasound along with saline infused into the uterus to enhance visualization. Continuous accumulation of saline in the procedure is used to break up the scars.

Ectopic Pregnancies. Ectopic pregnancies increase the risk for infertility, although subsequent pregnancy rates are quite variable. Ectopic pregnancies that terminate without treatment appear to pose a lower risk for future infertility. Even a ruptured tube does not appear to reduce the chance for a future pregnancy in most women. Such an event however can be dangerous and even life threatening for the woman. Laparoscopic surgery to remove a fallopian tube affected by an ectopic pregnancy may preserve fertility better than traditional abdominal surgery.

Click the icon to see an image of an ectopic pregnancy.

Medications. Among the medications that can cause temporary infertility are those used to treat chronic disorders, as well as antidepressants, hormones, painkillers, and antipsychotic drugs.

Inflammatory Bowel Disease. Inflammatory bowel disease (particularly Crohn's disease or surgery for ulcerative colitis) can affect fertility.

Click the icon to see an image of Crohn's disease.

Celiac Sprue. Celiac sprue is a disease in which the patient cannot tolerate gluten, a common food chemical. The disorder is also highly associated with infertility in men and women, possibly through multiple effects on nutrition, immune factors, and hormones. The mechanisms are not altogether clear, but infertility is usually reversible with strict dietary control.

Click the icon to see an image of celiac sprue.

Iron Intake. Nutritional iron deficiency may contribute to female infertility. According to a 2006 study, women who take iron supplements are 40% less likely to experience ovulatory infertility than women who do not take iron supplements. Some researchers suggest that screening for iron deficiency should be part of the standard work-up of infertility tests.

Epilepsy. In one study of women with epilepsy, fertility rates were 33% lower than among women in the general population, perhaps due to certain antiepileptic drugs that increase the risk for birth defects. The social effects of epilepsy may also lead to marriage at an older age, which can be associated with delayed attempts to get pregnant and thereby affect fertility.

Thyroid Problems. Thyroid problems, either too much thyroid hormone (hyperthyroidism) or too little (hypothyroidism), can interrupt cycles.

Click the icon to see an image of hyperthyroidism.

Click the icon to see an image of hypothyroidism.

Metabolic Syndrome (also Called Syndrome X). Doctors diagnose this condition when at least three of the following abnormalities are present:

Abdominal obesity
Low HDL (good) cholesterol levels
High triglyceride levels
High blood pressure
Insulin resistance

Metabolic syndrome is a pre-diabetic condition that is significantly associated with heart disease. One study reported that, as with polycystic ovarian syndrome, women with metabolic syndrome have higher levels of male hormones and are therefore at risk for infertility. Another study estimated that 24% of the population now has this condition.

Other Medical Conditions. Medical conditions associated with delayed puberty and amenorrhea (absence of periods) include Cushing's disease, sickle cell disease, HIV, kidney disease, and diabetes. Genetic mutations that affect luteinizing hormone may also be responsible for some cases of light or absent menstruation. Other rare genetic disorders, such as Kallman syndrome, cause abnormalities in the hypothalamus of the brain.

Diagnosis

In any fertility work-up, both male and female partners are tested if pregnancy fails to occur after a year of regular unprotected sexual intercourse. Fertility testing should be done earlier if a woman is over 35 years old or if either partner has known risk factors for infertility. An analysis of the man's semen should be performed before the female partner undergoes any invasive testing.

The first step in any infertility work up is a complete medical history and physical examination. Sexual technique and timing, menstrual history, lifestyle issues (such as smoking and drug, alcohol, and caffeine consumption), any medications being taken, and a profile of the patient's general medical and emotional health can help the doctor decide on appropriate tests.

Before embarking on an expensive fertility work-up, the following steps are free or low-cost and can be helpful:

Monitor basal body temperature. This is accurate in determining if ovulation is actually taking place.
Test the consistency of your cervical mucus. Collect some mucus between your two fingers and stretch it apart. If you are near the time of ovulation, the mucus will stretch more than 1 inch before it breaks. As an alternative, at-home kits can test saliva as substitute for checking cervical mucus.
Take an over-the-counter urine test for detecting luteinizing hormone (LH) surges. This helps determine the day of ovulation.
Fertell is the first at-home test kit for couples that is approved by the Food and Drug Administration. Women can test their urine for levels of follicle-stimulating hormone (FSH), while men can test their semen for sperm motility (ability of sperm to move). Fertell became available online and in some pharmacies in June 2007.

Several laboratory tests may be used to detect the cause of infertility and monitor treatments:

Hormonal Levels. Blood and urine tests are taken to evaluate hormone levels. Hormonal tests for ovarian reserve (the number of follicles and quality of the eggs) are especially important for older women.

Examples of possible results include:

High follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and low estrogen levels suggest premature ovarian failure or hypogonadotropic hypogonadism.
High LH and low FSH may suggest polycystic ovary syndrome or luteal phase defect.
High FSH and high estrogen levels on the third day of the cycle predicts poor success rates in older women trying fertility treatments.
LH surges indicate ovulation.
Blood tests for prolactin levels and thyroid function are also measured. These are hormones that may indirectly affect fertility.

Clomiphene Challenge Test. Clomiphene citrate (Clomid, Serophene), a standard fertility drug, may be used to test for ovarian reserve. With this test, the doctor measures FSH on day 3 of the cycle. The woman takes clomiphene orally on days 5 and 9 of the cycle. The doctor measures FSH on the tenth day. High levels of FSH either on day 3 or day 10 indicate a poor chance for a successful outcome.

Tissue Samples. To rule out luteal phase defect, premature ovarian failure, and absence of ovulation, the doctor may take tissue samples of the uterus 1 - 2 days before a period to determine if the corpus luteum is adequately producing progesterone. Tissue samples taken from the cervix may be cultured to rule out infection.

Tests for Autoimmune Disease. Tests for autoimmune disease, such as hypothyroidism and diabetes, should be considered in women with recent ovarian failure that is not caused by genetic abnormalities.

If an initial fertility work-up does not reveal abnormalities, as happens in about 40% of cases, more extensive tests will reveal abnormal tubal or uterine findings. The three major approaches for examining the uterus are ultrasound (particularly a variation called saline-infusion sonohysterography), hysterosalpingography, and hysteroscopy. Although combinations of these diagnostic approaches are often used to confirm diagnoses, one study indicated that with the introduction of saline-infusion sonohysterography, all are equally accurate and combinations do not increase accuracy. Furthermore, the ultrasound procedure is significantly less painful than the other two, suggesting that this should be the procedure of choice, if available.

Ultrasound and Sonohysterography. Ultrasound is the standard imaging technique for evaluating the uterus and ovaries, detecting fibroids, ovarian cysts and tumors, and also obstructions in the urinary tract. It uses sound waves to produce an image of the organs and entails no risk and very little discomfort.

Transvaginal sonohysterography uses ultrasound along with saline infused into the uterus, which enhances the visualization of the uterus. This technique is proving to be more accurate than standard ultrasound in identifying potential problems. It is currently the gold standard for diagnosing polycystic ovaries.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) gives a better image of any fibroids that might be causing bleeding, but it is expensive and not usually necessary.

Hysteroscopy. Hysteroscopy is a procedure that may be used to detect the presence of endometriosis, fibroids, polyps, pelvic scar tissue, and blockage at the ends of the fallopian tubes. Some of these conditions can be corrected during the procedure by cutting away any scar tissue that may be binding organs together or by destroying endometrial implants. (It may miss cases of uterine cancer, however, and is not a substitute for more invasive procedures, such as dilation and curettage ( D&C) or endometrial biopsy, if cancer is suspected.)

It is done in the office setting and requires no incisions. The procedure uses a long flexible or rigid tube called a hysteroscope, which is inserted into the vagina and through the cervix to reach the uterus. A fiber optic light source and a tiny camera in the tube allow the doctor to view the cavity. The uterus is filled with saline or carbon dioxide to inflate the cavity and provide better viewing. This frequently causes cramping.

There are small risks of bleeding, infection, and reactions to anesthesia. Many patients experience temporary discomfort in the shoulders after the operation due to residual carbon dioxide that puts pressure on the diaphragm. The wound itself is minimally painful.

Hysterosalpingography. Hysterosalpingography is performed to discover possible blockage in the fallopian tubes and abnormalities in the uterus:

The doctor inserts a tube into the cervix through which a special dye is injected. (The patient may experience some cramping and discomfort.)
The dye passes into the uterus and up through the fallopian tubes.
An x-ray is taken of the dye-filled uterus and tubes.
If the dye is seen emerging from the end of the tube, no blockage is present. (In some cases, hysterosalpingography may even restore fertility by clearing away tiny tubal blockages.)
If results show blockage or abnormalities, the test may need to be repeated. In case of blockage, hysterosalpingography may reveal a number of conditions, including endometrial polyps, fibroid tumors, or structural abnormalities of the uterus and tubes.

The test has significant rates of false diagnoses, both positive and negative. There is a small risk of pelvic infection, and antibiotics may be prescribed prior to the procedure. One study suggested that flushing the tubes with an oil-based fluid (lipiodol) during this procedure may improve fertility rates in women with infertility of unknown causes.

As women age, the number of follicles (and therefore their egg supply) declines. Researchers are developing tests that may help determine how many are left. Such tests include the following:

Calculating the volume of the ovaries. In general, the smaller the ovaries, the fewer the remaining eggs.
Counting antral follicles. Antral follicles are those that develop but do not become dominant follicles. Instead, they form a fluid-filled space called an antrum. Women who have fewer than three to five antral follicles appear to have a poor chance of fertility.
Measuring inhibin B. Inhibin B is a growth factor produced in the ovaries. Low levels suggest fewer eggs.

Eventually these markers may be useful for determining which women need more aggressive treatments.

Genetic testing may be warranted in cases of male infertility or when genetic factors may be causing pregnancy failure in the woman. If genetic abnormalities are suspected in either partner, counseling is recommended.

A technique called preimplantation genetic diagnosis (PGD) is now available in some centers that can examine all the chromosomes in a human embryo. It helps identify abnormalities that increase the risk for infertility, treatment failures, or genetic defects in the offspring.

Treatment

Some doctors recommend that if a couple fails to conceive after 1 - 2 years of frequent unprotected sex, they should consult a fertility expert. Women who are 35 or older, however, may want to begin exploring their options if they do not become pregnant within 6 months to a year.

Several approaches can treat infertility, depending on the cause:

Lifestyle measures (healthy lifestyle, planning sexual activity with ovulation cycle, managing stress and emotions)
Treatments for endometriosis, fibroids, or menstrual disorders
Use of anti-estrogen drugs, such as clomiphene, to induce ovulation in women with ovarian dysfunction
Surgery (standard or laparoscopic) to unblock fallopian tubes
Use of hormone treatments (clomiphene or progestins) for luteal phase defect
Assisted reproductive technologies (ART) such as in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)

Choosing a good fertility clinic is important. Those offering assisted reproductive techniques are not always regulated by the government, and abuses have been reported, including lack of informed consent, unauthorized use of embryos, and failure to routinely screen donors for disease.

The clinic should always provide the following information:

The live-birth rate (not just pregnancy success rate) for other couples with similar infertility problems. (Multiple births, such as twins or triplets, are counted as one live birth.)
Such statistics should include high-risk women, such as those who are older or fail to produce eggs. (Some disreputable clinics give success percentages that exclude high-risk women from their total, thereby making the percentage of success much higher.)

Advanced fertility procedures and medications are extremely expensive and often not covered by insurance. Couples should be cautious about offers of rebates in the event of failure; the clinics offering them are often significantly more expensive than those that don't offer such gimmicks.


Causes of Infertility	Treatments
Endometriosis	Conservative surgery (typically laparoscopy) is the appropriate approach for restoring fertility. GnRH agonists or progestins, used to treat endometriosis itself, have no effect on fertility. Possible exceptions are GnRH agonists used after surgery. In one study, this treatment helped improve conception rates in women who subsequently underwent assisted reproductive techniques. Assisted reproductive technologies (ART). (Fertility drugs alone have no effect.) It is not clear, in any case, whether either laparoscopy for removing endometrial implants or ART has additional advantages in many of these women compared to simply trying to become pregnant through non-aggressive means.
Hyperprolactinemia	Dopamine agonists, including bromocriptine (Parlodel) or cabergoline (Dostinex). Surgery in some cases.
Luteal phase defect	Clomiphene or superovulation drugs (FSH drugs or hMG).
Hyperprolactinemia (elevated prolactin)	Bromocriptine, cabergoline to shrink tumors that result in over secretion of prolactin. Cabergoline is more effective, but bromocriptine has been used longer. Once ovulation starts, women who want to become pregnant should stop cabergoline one month before attempting conception. Surgery may be needed for women who do not respond to medications or who have large tumors.
Hypogonadotropic Hypogonadism	Fertility drugs (hMG preferable to FSH alone) with or without assisted reproductive technologies.
Pelvic Inflammatory Disease	Screening high-risk women for the presence of Chlamydia trachomatis and treating the organism before it causes symptoms could reduce the risk of PID by almost 60%. If any sexually transmitted infection is detected, both partners should receive antibiotics, even if there are no symptoms. If PID symptoms develop, particularly lower abdominal pain, fertility can be preserved if women receive antibiotics within 2 days. A delay significantly increases the risk for scarring.
Polycystic Ovarian Syndrome	Lifestyle changes (weight loss and exercise in women who are overweight.) Clomiphene is the standard first-line treatment for polycystic ovarian syndrome (PCOS)-related infertility. Although some research has indicated that the diabetes drug metformin (Glucophage) might help treat infertility in women with PCOS, a 2007 study in the New England Journal of Medicine indicated that clomiphene is much more effective.
Premature Ovarian Failure	Assisted reproductive technologies with donor eggs.
Preserving fertility after cancer treatments	Removal and freezing (called cryopreservation) of ovarian tissue containing embryos or freezing immature and unfertilized eggs to use for later reimplantation. (Freezing before cancer treatment appears to offer the best chance.) Under investigation: Ovarian transplantation procedures and gonadotropin-releasing hormone analogues, which put women in a temporary pre-pubescent state during chemotherapy and may preserve fertility.
Fallopian tubal blockage	Surgical procedures (laparoscopy or salpingostomy) to clear the tubes. (Average pregnancy rate after salpingostomy is about 30%, but they can vary widely.) Flushing the tubes with an oil-based fluid (lipiodol) during hysterosalpingography (investigative). In a 2002 study, this procedure improved pregnancy rates in women with infertility of unknown causes. Assisted reproductive technologies.
Unexplained infertility	Lifestyle measures. Fertility drugs. Assisted reproductive technologies.

Lifestyle Changes

Although there are no dietary or nutritional cures for infertility, a healthy lifestyle is important. Ovulatory problems are reversible by changing behavioral patterns. Such conditions include:

Maintain a healthy weight. Women who are either over- or underweight are at risk for fertility failure, including a lower chance for achieving success with fertility procedures. Everyone should have a diet rich in fresh fruits and vegetables and whole grains and low in saturated fats.
Stop smoking. Smoking increases the risk for infertility in both men and women, and poses a future health risk for the mother and infant. Everyone should quit.
Avoid caffeine and alcohol.
Avoid excessive exercise if it causes menstrual irregularity. However, moderate and regular exercise is essential for good health. Few women exercise to the extent that their periods are affected. For those who do, one study found that simply adding calories can restore menstruation in many cases.
Don't use electric blankets. In one study, a 74% higher incidence of spontaneous abortion was associated with using an electric blanket during the month of conception. There was no association with heated waterbeds or electromagnetic waves.
Avoid any unnecessary medications.

There is no evidence of harm to a developing fetus from low exposure to microwaves or electromagnetic waves. Women who remain anxious may derive comfort by avoiding some of these devices (such as cellular phones or electric blankets) and remaining a foot or so away from others (such as computers or microwave ovens).

Both male and female hormone levels fluctuate according to the time of day, and they vary from day to day and month to month. Some timing tips might be helpful.

Male Hormone Levels and Sexual Activity. Male hormone levels are highest in the morning. (Sexual interest also tends to be higher in the morning.) In one study of men, their sexual activity was highest in October, when conception rates were also high.

Fertility and Seasonal Changes. Different studies have reported higher sperm counts in the winter than in the summer. For women, fertility rates as measured by treatment success are highest in months when days are longest.

Monitoring Basal Body Temperature. To determine the most likely time of ovulation and therefore the time of fertility, a woman is instructed to take her body temperature, called her basal body temperature. This is the body's temperature as it rises and falls in accord with hormonal fluctuations.

Each morning before rising, the woman takes her temperature with a specialized basal body thermometer and marks the result on a graph-paper chart.
The woman also notes the days of menstruation and sexual activity.
The so-called "fertile window" is 6 days long, starts 5 days before ovulation, and ends the day of ovulation.
The chances for fertility are considered to be highest between days 10 and 17 in the menstrual cycle (with day 1 being the first day of the period, and ovulation occurring about 2 weeks later). However, cycles vary from woman to woman. Researchers suggest that women track the length of their cycles, which can run anywhere from between 19 and 60 days. A long cycle, for example, suggests a delayed ovulation date.
Immediately after ovulation the body temperature increases sharply in about 80% of cases. (Some women can be ovulating normally yet not show this temperature pattern.)

By studying the temperature patterns after a few months, couples can begin to anticipate ovulation and plan their sexual activity accordingly. Couples must try to avoid becoming fixated on the chart, however, in scheduling their sexual activity. Spontaneity can be lost, and the stress on the relationship can be quite severe.

Hormone Monitoring Systems. A device called a saliva fertility monitor (Fertility Tracker) uses a microscope to view slides containing saliva and monitors estrogen levels. Home test kits that monitor reproductive hormone levels in the urine (ClearBlue) are also available. They are less costly than the saliva test but are messier. Monitoring hormones levels helps to determine when a woman is ovulating.

Frequency of Intercourse. The question of how often a couple should have intercourse is in debate. Some doctors say that having sex more than 2 days a week adds no benefits. Moreover, frequent sexual activity lowers sperm count per ejaculation. Other studies have indicated, however, that having intercourse every day, or even several times a day, before and during ovulation, improves pregnancy rates. Although sperm count per ejaculation is low, a constantly replenished semen supply is more likely to result in a fertilized egg.

The fertility process is a roller coaster of emotions that are present throughout and in both failure and success. There are almost no sure ways to predict which couples will eventually conceive. Some couples with multiple problems will overcome great odds, while other, seemingly fertile, couples fail to conceive. Many of the new treatments are remarkable, but a live birth is never guaranteed. The emotional burden on the couple is considerable, and some planning is helpful.

Planning for Emotional Turmoil.

Decide in advance how many and what kind of procedures will be emotionally and financially acceptable and attempt to determine a final limit. Fertility treatments are expensive. A successful pregnancy often depends on repeated attempts.
Determine alternatives (adoption, donor sperm or egg, or having no children) as early as possible in the fertility process. This can reduce anxiety during treatments and feelings of hopelessness in case conception does not occur.

Managing Emotional Stress During the Process. Managing negative emotions can be viewed as important as medical treatment. The following are some ways women reduce stress while trying to conceive:

Talking to one's spouse, family, and friends is very beneficial. The best support comes from the spouse. Studies suggest that a positive attitude on the husband's part is essential for enabling his wife to deal effectively with either the success or failure of fertility treatments. Men and women may cope differently with the stress, and each should understand the other's special needs. Women tend to want greater personal space and also to want to share the burden with their husbands. Men tend to cope by seeking to improve themselves (for example being strong, or being the "best").
Almost half of women seeking fertility treatments practice good-luck rituals, including praying and wearing charms or special jewelry. No evidence exists that these practices increase fertility, but they may help reduce anxiety and enhance a sense of control.
Cognitive-behavioral therapy, which uses methods that include relaxation training and stress-management, have been associated with higher pregnancy rates. (In one study, 42% became pregnant without medical intervention.)
Attending support groups or counseling services before and after treatment helps many women endure the process and ease the grief should treatment fail. One study indicated that pregnancy rates were twice as high in women who coped with their depression by reaching out to others rather than repressing guilt or rage. (These results held only in cases in which women, not their mates, were infertile.)
Acupuncture may help some women. Some evidence suggests that this alternative treatment has beneficial effects on chemicals in the brain involved with stress and reproduction. Acupuncture is safe, but studies have been mixed on whether it can help improve pregnancy rates. One study indicated that women who received acupuncture achieved significantly higher success rates during fertility treatments (42.5%) than those who did not receive it (26.3%). Several 2006 studies suggested that acupuncture may improve pregnancy success for women who undergo in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) procedures. One of these studies found that acupuncture had a positive effect if it was given during the luteal phase (post-ovulatory period of menstrual cycle.) Another study suggested that acupuncture should be given on the day of embryo transfer.

Managing the Emotional Effects of the Outcome. After enduring the process, the couple must face the outcome, and even a positive outcome has emotional repercussions.

Effects of Failure. The emotional stress of failure can be devastating even on the most loving and affectionate relationships and even in those who have prepared for the possibility of failure. Neither the male nor female partner should hesitate to seek professional help if the emotional burdens are too heavy.
Effects of Genetic Testing. As advanced technologies allow testing and greater genetic information at the earliest stage, potential parents will have to learn to deal with the uncertainties of possible chromosomal abnormalities, which may or may not be significant.
Effects of Successful Treatments. Some studies have indicated that even if successful, some women experience higher stress and fear of failure during pregnancy. According to one study, however, women who achieved pregnancy using fertility treatments felt increasingly better and had higher self esteem and less anxiety as the pregnancy progressed than women whose pregnancies were not due to medical intervention.
Effects of Multiple Births. A successful pregnancy that results in a multiple birth introduces new complexities and emotional problems. One study reported a very high rate of depression in women with triplets, particularly if they had little help from others, and especially if their husbands weren't involved.
Effects on Parenting. Once the fertility treatment-assisted child arrives, parents (both men and women) are more likely to be anxious and to have less confidence than those who conceive naturally.

Medications

Fertility drugs are often used alone as initial treatment to induce ovulation. If they fail as sole therapy, they may be used with assisted reproductive procedures or artificial insemination to produce multiple eggs, a process called superovulation.

Clomiphene citrate (Clomid, Serophene) is usually the first fertility drug of choice for women with infrequent periods and long cycles. Unlike more potent drugs used in superovulation, clomiphene is gentler and works by blocking estrogen, which tricks the pituitary into producing

follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This boosts follicle growth and the release of the egg. Clomiphene can be taken orally, is relatively inexpensive, and the risk for multiple births (about 5%, mostly twins) is lower than with other drugs.

Women with the best chances for success with this drug are those who have the following conditions:

Polycystic ovarian syndrome (PCOS)
Ability to menstruate but irregular menstrual cycle

Women with poorer chances of success with this drug have the following conditions:

Infertility but with normal ovulation
Low estrogen levels
Premature ovarian failure (early menopause)

One or two tablets are taken each day for 5 days, usually starting 2 - 5 days after the period starts. If successful, ovulation occurs about a week after the last pill has been taken. If ovulation does not occur, then a higher dose may be given for the next cycle. If this resgimen is not successful, treatment may be prolonged or additional drugs may be added. Doctors usually do not recommend more than 6 cycles.

Clomiphene often reduces the amount and quality of cervical mucus and may cause thinning of the uterine lining. In such cases, other hormonal drugs may be given to restore thickness. Other side effects of clomiphene include ovarian cysts, hot flashes, nausea, headaches, weight gain, and fatigue. There is a 5% chance of having twins with this drug, and a slightly increased risk for miscarriage.

If clomiphene does not work or is not an appropriate choice, gonadotropin drugs are a second option. Gonadotropins include several different types of drugs that contain either a combination of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), or only FSH. Clomiphene works indirectly by stimulating the pituitary gland to secrete FSH, which prompts follicle production. In contrast, the gonadtropin hormones directly stimulate the ovaries to produce multiple follicles.

Gonadotropins are given in a shot. (Your doctor may show you how to self-administer the injection.) Gonadotropins include:

Human Menopausal Gonadtropins (hMG), also called menotropins
Human Chorionic Gonadotropins (hCG)
Urofollitropin and Follitropin, natural and synthetic forms of FSH
Gonadotropin-releasing hormone (GnRH) analogs, which include GnRH agonists and GnRH antagonists

Gonadotropin drugs are either natural compounds extracted from urine or synthetic compounds that are genetically engineered in a laboratory using recombinant DNA.

Human Menopausal Gonadotropin (hMG). HMG drugs, also called menotropins, contain a mixture of both FSH and LH. These drugs (Pergonal, Repronex, Metrodin, Humegon) are all derived from the urine of postmenopausal women. HMG is administered as a series of injections 2 - 3 days after the period starts. Injections are usually given for 7 - 12 days, but the time may be extended if ovulation does not occur. In such cases, a shot of human chorionic gonadotropin (hCG) may trigger ovulation.

Human Chorionic Gonadotropin (hCG). Human chorionic gonadotropin (hCG) is similar to LH. It mimics the LH surge, which stimulates the follicle to release the egg. Natural hCG drugs, derived from the urine of pregnant women, include Pregnyl, Profasi, Novarel, APL, Chorex, and Follutein. Ovidrel is the only available genetically modified hCG drug. Ovidrel has fewer side effects at the injection site, and its quality can be better controlled than the natural drugs. It is generally used after hMG or FSH to stimulate the final maturation stages of the follicles. Ovulation, if it occurs, does so about 36 - 72 hours after administration.

Urofollitropin and Follitropin. Urofollitropin (Bravelle, Fertinex) is a purified form of FSH, derived from the urine of postmenopausal women. Follitropin drugs (Gonal-F, Follistim) are synthetic versions of FSH. These FSH drugs are sometimes given in combination with an hCG drug.

GnRH Analogs (Agonists or Antagonists). Gonadotropin-releasing hormone (GnRH) is a hormone produced in the hypothalamus part of the brain. GnRH stimulates the pituitary gland to produce LH and FSH. GnRH analogs are synthetic drugs that are classified as either agonists or antagonists. They are similar to natural GnRH but have very different actions. While natural GnRH stimulates LH and FSH, these drugs actually prevent the LH and FSH surge that occurs right before ovulation. This action helps prevent the premature release of the eggs before they can be harvested for assisted reproductive technologies.

GnRH agonists include leuprolide (Lupron), nafarelin (Synarel), and goserelin (Zoladex).
GnRH antagonists include ganirelix (Antagon) and cetrorelix (Cetrotide). GnRH antagonists suppress FSH and LH more than GnRH agonists, and they may require fewer injections.

Women with endometriosis often have an especially hard time getting pregnant. A 2006 review suggested that GnRH agonists may help women with endometriosis quadruple their chances of becoming pregnant when the drug is used 3 - 6 months prior to in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). [See In-Depth Report #74: Endometriosis.]

Multiple Births. Overproduction of follicles can lead to ovarian enlargement. This event increases the risk for multiple births. There is a 25% chance of multiple births (about 17% for twins and 8% for triplets and or more).

Ovarian Hyperstimulation Syndrome. The most serious complication with superovulation is ovarian hyperstimulation syndrome (OHS), which is associated with the enlarged ovary (although the precise cause is unknown). This can result in dangerous fluid and electrolyte imbalances and endanger the liver and kidney. OHS is also associated with a higher risk for blood clots. In rare cases, it can be fatal. Symptoms include abdominal bloating, nausea, vomiting, and shortness of breath.

Bleeding and Rupture of Ovarian Cysts. Overproduction of follicles, if unchecked, may result in bleeding and rupture of ovarian cysts.

Cancer Concerns. There has been concern that clomiphene and gonadotropins may increase the risks for ovarian and breast cancer. Most evidence to date does not indicate that ovulation-stimulating drugs increase the risks for these types of cancers. However, more research needs to be done. Some studies suggest that clomiphene, which is chemically related to the breast cancer drug tamoxifen, may actually decrease the risk for breast cancer.

Progesterone. Progesterone is a hormone that is produced by the body during the menstrual cycle. Progesterone drugs are sometimes given to women who have experienced frequent miscarriages (a possible sign of progesterone deficiency). A progesterone drug may also be given after egg retrieval during an in vitro fertilization (IVF) cycle to help thicken the uterine lining (endometrium) so it can better hold the egg following implantation.

Aromatase Inhibitors. Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many major body tissues. These drugs include anastrozole (Arimidex) and letrozole (Femara). These drugs are used for treating breast cancer and are being investigated for stimulating ovulation in infertile women. Although letrozole is not approved for treatment of infertility, it has become widely used for this purpose in recent years. Some doctors were concerned that letrozole could increase the risk of birth defects. However, a major 2006 study indicated that letrozole does not increase risk to the fetus. The study compared the rate of birth defects among babies whose mothers conceived with letrozole and those who used clomiphene (the standard first-line fertility drug). Researchers found no differences in birth outcomes between the two groups.

Tamoxifen. Tamoxifen (Nolvadex) is a drug known as a selective estrogen-receptor modulator (SERM). It is used to prevent breast cancer in high-risk women. Studies suggest that it may equal clomiphene in its ability to induce ovulation. It may be especially useful when used along with IVF for preserving fertility in breast cancer patients. This drug is less expensive than clomiphene, but it poses some health hazards, including a risk for blood clots and uterine cancer.

Glucocorticoids. Glucocorticoids are steroid hormones that are sometimes used in combination with IVF and intracytoplasmic sperm injection (ICSI). It is thought that anti-inflammatory effect of these drugs can help make the lining of the uterus more responsive to egg implantation. However, a 2007 review indicated that glucocorticoids do not help improve pregnancy success rates and should not be used routinely with assisted reproductive technologies.

Regimens to induce ovulation vary widely according to individual need. A typical procedure, involving superovulation and in vitro fertilization (IVF) may be as follows:

Doctors make sure that the patient is not pregnant or in the luteal phase of her menstrual cycle (the premenstrual period).
Injections of either human menopausal gonadtropins, which contains luteinizing hormone (LH) and follicle-stimulating hormone (FSH) or pure FSH are administered daily 2 - 4 days after day 1 of the next cycle. Either drug may be used.
After 4 - 8 days of treatment, estrogen levels are monitored. Increasing levels on the fourth day of treatment may be strong indicators of success. If estrogen levels indicate that ovaries are responding, ultrasound is then performed to detect possible overproduction of follicles. Such evaluation should then be conducted every 1 - 2 days and dosages adjusted accordingly.
Gonadotropin-releasing hormone analogs are used to prevent a premature release of LH hormone (and therefore ovulation). GnRH agonists are typically administered either early on or a few days after ovulation in the cycle previous to the one planned for IVF. This approach is referred to as the long protocol, and it serves to suppress the pituitary gland and allows time for the eggs to mature before harvesting. Other protocols using GnRH antagonists are under investigation, but to date the long protocol has the best pregnancy rates.
When at least three follicles have reached a diameter of 18 mm, human chorionic gonadotropins (hCG) is typically administered to release the egg. It is not given if there are signs of overproduction of follicles, which suggests a risk for ovarian hyperstimulation syndrome (OHS), a dangerous complication. (One study reported that giving high doses of progesterone to high-risk women the day of hCG administration may prevent OHS.)
Egg retrieval may be performed about 36 hours following hCG administration, with the transfer of the embryo (the fertilized egg) back into the woman 2 - 3 days after retrieval.
Embryos are transferred to the uterus through a small tube. This process does not require an anesthetic, although the procedure can cause cramping.

Natural (Unstimulated) In Vitro Fertilization Cycles. An alternative to superovulation for some couples is natural in vitro fertilization (IVF) cycles. It allows multiple, consecutive cycles of treatment. Natural IVF is far less expensive than standard hyperstimulation methods and avoids their risks, including multiple births and ovarian hyperstimulation syndrome (OHS).

The process involves ultrasound and hormonal monitoring starting 5 days before the estimated ovulation day.
No superovulation drugs are used, such as follicle-stimulating hormone (FSH) and human menopausal gonadtropins (hMG). The doctor, however, may administer an injection of human chorionic gonadotropins (hCG) to stimulate the luteinizing hormone (LH) surge.
The egg retrieval timing is based on detecting LH surge.
A single egg is retrieved. The procedure that follows is similar to other IVF cycles.

The basic disadvantage to this approach is that the eggs may be released before there is a chance for them to be harvested. Women report far lower stress levels with this approach, however, even though it requires more treatment cycles. In one study, the live-birth rate was 32%. Not all women are appropriate candidates, however. Women should have regular menstrual cycles and infertility of unknown cause or associated with problems in the fallopian tubes. Pregnancy rates are still very low in older women.

Clomiphene. Another gentler alternative to superovulation is the use of clomiphene before IVF, which works slightly better than unstimulated IVF.

Assisted Reproductive Technologies

Assisted reproductive technologies (ART) are medical techniques that help couples conceive. These procedures involve either:

A couple’s own eggs or sperm
Donor eggs, sperm, or embryos

Fertilization may occur either in the laboratory or in the uterus. In the U.S., the number of live birth deliveries from ART increased by 128% between 1996 and 2002. More than 45,000 babies are now born in the U.S. each year using assisted reproductive technologies.

ART includes fertility drug treatments, artificial insemination (AI), in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and other procedures.

Artificial insemination (AI) is the least complex of the assisted reproductive technologies and is often tried first in uncomplicated cases of infertility. AI either involves placing the sperm directly in the cervix (called intracervical insemination) or into the uterus (called intrauterine insemination, or IUI). IUI is the standard AI procedure.

It is useful under the following circumstances:

When the woman's cervical mucus is unreceptive
When donor sperm are required
If the man's sperm count is very low
When unexplained infertility exists in both partners

Those in whom AI fails, couples with specific fertility defects, or older women may be candidates for more advanced reproductive technologies.

Pregnancy Rates. A review of 45 studies reported that in unexplained infertility cases, the per-cycle pregnancy rates were 4% for intrauterine insemination (IUI) alone and 8 - 17% per cycle for IUI combined with superovulation, a procedure that uses fertility drugs to bolster egg recovery.

Researchers in one study suggested IUI as a reasonable first option for many women under age 43. It is less expensive and poses less risk for multiple births than the more advanced assisted reproductive technologies (ART), such as in vitro fertilization. Although IVF procedures are more effective per cycle, couples tend to be able to afford more IUI cycles, so the pregnancy rates over time are very similar.

The Artificial Insemination Procedure. The AI procedure is as follows:

A woman usually (but not always) takes fertility drugs in advance.
The man must produce sperm at the time the woman is ovulating.
The sperm are subjected to certain so-called "washing" procedures. They are then inserted into the uterine cavity through a long, thin catheter.

The administration of fertility drugs and sperm retrieval is timed so that the process can coincide with ovulation.

About 71% of assisted reproductive technologies (ART) procedures now use in vitro fertilization (IVF) with the woman's own eggs. An in vitro procedure is one that is performed in the laboratory. Advances in these procedures have dramatically increased the rate of live births.

The best candidates for IVF are women with damaged fallopian tubes, and some experts believe it is a better option than attempting surgical repair. IVF is also used when infertility is unexplained or when the male partner has the infertility problem. A typical IVF procedure is as follows:

The doctor first induces superovulation using fertility drugs so that several eggs can be harvested from the ovary before they have been released from the follicles. Higher doses of fertility drugs for subsequent cycles do not appear to add any advantage in women who have a poor response the first time.
To harvest eggs, the doctor generally inserts a probe into the vagina and is guided by ultrasound. A needle is then used to drain the liquid from the follicles, and several eggs are retrieved.
The eggs and sperm are combined in a Petri dish. Between 48 - 72 hours later the eggs are usually fertilized.
The resulting embryos (the first stage toward the development of the fetus) are reimplanted into the woman's uterus.
It takes about 2 weeks to determine if the process is successful.

IVF success rates for the first three cycles of treatment are about equal. They then decline modestly for the fourth cycle and drop significantly after the fifth cycle.

Gamete/Zygote Intrafallopian Transfer. Gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT) are adaptations of IVF. GIFT and ZIFT are used in unexplained female infertility and in mild male infertility. The success rates are similar to those of IVF, but a woman must have at least one functioning fallopian tube.

GIFT: The procedure is as follows:

The eggs are harvested as in IVF.
They are mixed with the sperm but not actively fertilized.
They are immediately injected back into the woman. Laparoscopy, a technique that employs a miniature viewing device, is used with this procedure to guide the placement of the embryos or egg through a long, thin catheter into the fallopian tubes.
The sperm and egg are placed exactly where they would be in natural fertilization.

ZIFT: The procedure is as follows.

The eggs are harvested as in IVF.
They are then mixed with the sperm and, in this case, are fertilized in the laboratory.
They are then implanted in the fallopian tubes as in GIFT. (The advantage of this procedure over GIFT is that the doctor and couple are assured that fertilization has taken place, and the eggs can be examined for defects before implantation.)

In 2002, more than 45,000 American babies were born using in vitro fertilization (IVF). Success rates have increased in all age groups (although they are still considerably lower in older than in younger women). Chances for assisted reproductive technologies (ART) success are also greater among women who do not have uterine abnormalities and have had previous successful pregnancies.

Success rates are also higher or lower depending on whether the woman uses her own eggs or whether they are donated and also whether the eggs are fresh or frozen. The highest live birth rates are with donated fresh eggs (an average of 50% per transfer). The lowest rates are when a woman uses her own frozen eggs (an average of 29% per transfer). However, using frozen eggs is less expensive than fresh eggs, so a couple may be able to afford more cycles with frozen eggs.

Use of Donor Eggs. Older women are more likely to use donor eggs. In a 2002 study, success rates were the same for women who used donors with an age range of 20 - 40. There were also no differences in delivery rates for recipients up to age 45. Women over 45, however, increasingly had problems with implantation, pregnancy, and delivery.

Use of Frozen Eggs. Frozen eggs tend to have lower success rates because of toxins released by cells damaged in the freezing and thawing tissues.

Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology used for couples when male infertility is the main problem. It involves injecting a single sperm into an egg obtained from in vitro fertilization (IVF). The procedure is very simple:

A tiny glass tube (called a holding pipet) stabilizes the egg.
A second glass tube (called the injection pipet) is used to penetrate the egg's membrane and deposit a single sperm into the egg.
The egg is released into a drop of cultured medium.
If fertilized, the egg is allowed to develop for 1 - 2 days, then it is either frozen or implanted.

The greatest concern with this procedure has been whether it increases the risk for birth defects. However, several studies have reported no higher risks of birth defects in children born using ICSI procedures. While some studies have shown a higher number of birth defects in children conceived with ICSI, experts think that this may have more to do with the genetic background of the parents than ICSI itself. Recent research suggests that ICSI children develop normally. A 2006 study of 8-year-old children conceived with ICSI found no important differences between these children and children who were conceived naturally.

A 2007 study in the New England Journal of Medicine indicated that ICSI use has increased 5-fold over the past decade, even though the proportion of men receiving treatment for male infertility has remained the same. In 1995, 11% of IVF cycles used ICSI. By 2004, 57.5% of IVF cycles used ICSI. Doctors caution that while ICSI is an important assisted reproductive technology for male infertility, it may be overused. Some doctors recommend ICSI for women who have failed prior IVF attempts or who have few or poor-quality eggs, even if their male partners have normal semen measurements. There is little evidence that ICSI helps improve pregnancy success for couples who do not have a problem with male factor infertility, according to the Society for Assisted Reproductive Technology.

In Vitro Maturation. A technique called in vitro maturation allows fertilization without the use of fertility drugs. In this process, follicles are harvested a few days before ovulation. In such cases, up to 50 have already begun to mature. At this time, about 15 of these maturing follicles can be removed, out of which 2 or 3 can produce healthy embryos.

Blastocyst Transfer. Blastocyst transfer is very promising. Instead of implanting the standard 2- or 3-day-old embryos in the uterus, the procedure implants blastocysts, which are more complex, 5-day-old embryos. Fewer blastocysts than embryos need to be implanted, reducing the risk for multiple births. (There is, however, a higher risk for identical twins compared to other procedures.) Offspring may be more likely to be males than females. Pregnancy rates are about 36% with a first attempt but then drop significantly. The procedure is more likely to be successful in younger than older women.

Ooplasmic Transfer. Ooplasmic transfer is a controversial experimental procedure that uses the woman's own egg and a female donor's egg and the male sperm for fertilization. Genetic material from the donor's egg plus the sperm are added to the woman's own egg. This has been successful in a few cases, but studies are very early and long-term effects are unknown. Research on this and similar procedures is currently conducted outside the U.S.

Complications of Assisted Reproductive Technologies

Since assisted reproductive technology (ART) procedures have become more widespread since 1980, multiple births have significantly increased. About 35% of all ART births are multiple ones, with 4.3% being triplets or more. Multiple births increase the risk of complications, for both the mother and the child.

Assisted reproductive technology (ART), and multiple births, increase the risks for pregnancy complications. According to a 2005 study, the type of complications may depend on the infertility treatment:

Fertility drugs. Increase risks of the placenta becoming detached from the uterus (“placental abruption”), third trimester miscarriage, and gestational diabetes.
In vitro fertilization. Increase risks of placental abruption, the placenta developing in the lower section of the uterus (“placenta previa”), dangerously high blood pressure during pregnancy (“pre-eclampsia”), and Caesarean sections.

Multiple births can also increase the risk of pregnancy death. A 2006 study indicated that women who carry multiple fetuses have a 3.6 times greater risk of dying from pregnancy complications than women with singleton pregnancies. The leading causes of death were blood clot (embolism), high blood pressure complications, excessive bleeding (hemorrhage), and infections.

The main risks for children conceived with assisted reproductive technology (ART) are complications associated with pregnancy problems and multiple births. Children conceived with ART are more likely to be born premature and to have extremely low birth weight. These conditions increase the risk for heart and lung problems, as well as learning and developmental disabilities. Premature delivery is also associated with cerebral palsy, a brain injury condition that affects muscle coordination. A 2006 study indicated that children born after in vitro fertilization have an increased risk for cerebral palsy.

However, studies suggest that ART does not increase the risk for chromosomal damage or other major birth defects. Couples undergoing ART may have other factors, such as older age or genetic predispositions, which make complications more likely. Infertility itself, even without ART, can pose a risk factor for birth defects. Children conceived naturally by couples with infertility problems tended to have more disorders of the nervous system, digestive system, and musculoskeletal system than children born to fertile couples, according to a 2006 study in the British Medical Journal. Children born to couples treated for infertility with ART may also have a slightly increased risk for these problems, as well as genital organ malformations, but the overall risk for birth defects appears to be very small.

ART remains a good option for many infertile couples. The likelihood of having a healthy single child of normal birth weight using ART is about 94%. The likelihood of having a child free of major birth defects is about 91%. Frozen eggs do not appear to pose any higher risk for developmental problems.

Preimplantation genetic diagnosis (PGD) is now available in some fertility centers. It can help identify genetic defects in the offspring and may help parents determine future problems. Such testing, however, also raises significant emotional issues that should be addressed beforehand.

Given the hazards of multiple births, parents must make some hard decisions if the treatment produces multiple embryos. The choices are limited:

Carry all of them to term, which increases health risks for both the mother and the developing fetuses
Complete abortion
Embryo reduction, in which the doctor removes one or more embryos (possibly endangering the remaining embryos)

At this time, the best approach is to limit the number of implanted embryos in the first place. Researchers are attempting to develop methods to reduce the risk for multiple births:

Most centers now implant two to three embryos at a time, and the remainder can be frozen for future use. (Frozen eggs do not appear to pose a risk for developmental problems in children conceived using them.) This limits the chance for success, but implanting more than three embryos only increases success rates very slightly, whereas the risk for multiple births increases significantly.
Reducing the dosage of fertility drugs also reduces the risk for multiple births, but not significantly, and it also reduces the chance for successful outcome.
Blastocyst transfer may help reduce the chances for multiple births.

Resources

www.resolve.org -- National Infertility Association
www.asrm.org -- American Society for Reproductive Medicine
www.theafa.org -- American Fertility Association
www.endometriosisassn.org -- The Endometriosis Association
www.acog.org -- American College of Obstetricians and Gynecologists
www.endo-society.org -- The Endocrine Society
www.aace.com -- American Association of Clinical Endocrinologists
www.cdc.gov/reproductivehealth/index.htm -- Centers for Disease Control: Assisted Reproductive Technology Reports

References

Boomsma CM, Keay SD, Macklon NS. Peri-implantation glucocorticoid administration for assisted reproductive technology cycles. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD005996.

Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Iron intake and risk of ovulatory infertility. Obstet Gynecol. 2006 Nov;108(5):1145-52.

Dieterle S, Ying G, Hatzmann W, Neuer A. Effect of acupuncture on the outcome of in vitro fertilization and intracytoplasmic sperm injection: a randomized, prospective, controlled clinical study. Fertil Steril. 2006 May;85(5):1347-51.

Hvidtjorn D, Grove J, Schendel DE, Vaeth M, Ernst E, Nielsen LF, et al. Cerebral palsy among children born after in vitro fertilization: the role of preterm delivery--a population-based, cohort study. Pediatrics. 2006 Aug;118(2):475-82.

Jain T, Gupta RS. Trends in the use of intracytoplasmic sperm injection in the United States. N Engl J Med. 2007 Jul 19;357(3):251-7.

Jensen A, Sharif H, Svare EI, Frederiksen K, Kjaer SK. Risk of breast cancer after exposure to fertility drugs: results from a large Danish cohort study. Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1400-7. Epub 2007 Jun 21.

Lee SJ, Schover LR, Partridge AH, Patrizio P, Wallace WH, Hagerty K, et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol. 2006 Jun 20;24(18):2917-31.

Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA, et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007 Feb 8;356(6):551-66.

Mackay AP, Berg CJ, King JC, Duran C, Chang J. Pregnancy-Related Mortality Among Women With Multifetal Pregnancies. Obstet Gynecol. 2006 Mar;107(3):563-568.

Ombelet W, Martens G, De Sutter P, Gerris J, Bosmans E, Ruyssinck G, et al. Perinatal outcome of 12,021 singleton and 3108 twin births after non-IVF-assisted reproduction: a cohort study. Hum Reprod. 2006 Apr;21(4):1025-32.

Sallam HN, Garcia-Velasco JA, Dias S, Arici A. Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004635.

Shevell T, Malone FD, Vidaver J, Porter TF, Luthy DA, Comstock CH, et al. Assisted reproductive technology and pregnancy outcome. Obstet Gynecol. 2005 Nov;106(5 Pt 1):1039-45.

Smith C, Coyle M, Norman RJ. Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer. Fertil Steril. 2006 May;85(5):1352-8.

Terry KL, Willett WC, Rich-Edwards JW, Michels KB. A prospective study of infertility due to ovulatory disorders, ovulation induction, and incidence of breast cancer. Arch Intern Med. 2006 Dec 11-25;166(22):2484-9.

Tulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari J, et al. Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril. 2006 Jun;85(6):1761-5.

Westergaard LG, Mao Q, Krogslund M, Sandrini S, Lenz S, Grinsted J. Acupuncture on the day of embryo transfer significantly improves the reproductive outcome in infertile women: a prospective, randomized trial. Fertil Steril. 2006 May;85(5):1341-6.

Zhu JL, Basso O, Obel C, Bille C, Olsen J. Infertility, infertility treatment, and congenital malformations: Danish national birth cohort. BMJ. 2006 Sep 30;333(7570):679. Epub 2006 Aug 7.

Review Date:
10/29/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

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Aging changes in the heart and blood vessels

admin — Thu, 04 Sep 2008 19:18:30 -0700

Overview

Alternative Names
Information

Illustrations

Taking your carotid pulse

Circulation of blood through the heart

Radial pulse

Normal heart anatomy (cut section)

Effects of age on blood pressure

HEALTH GUIDE REFERENCE FROM A.D.A.M

Alternative Names

Heart disease - aging; Atherosclerosis - aging

Information

Some changes in the heart and blood vessels normally occur with age, but many others are modifiable factors that, if not treated, can lead to heart disease.

BACKGROUND

The heart has two sides. The right side pumps blood to the lungs to receive oxygen and get rid of carbon dioxide. The left side pumps oxygen-rich blood to the body.

Blood flows out of the heart through arteries, which branch out and get smaller and smaller as they go into the tissues. In the tissues, they become tiny capillaries.

Capillaries are where the blood gives up oxygen and nutrients to the tissues, and receives carbon dioxide and wastes back from the tissues. Then, the vessels begin to collect together into larger and larger veins, which return blood to the heart.

Aging causes changes in the heart and in the blood vessels. Heart and blood vessel diseases are some of the most common disorders in the elderly.

AGING CHANGES

Heart

Normal changes in the heart include deposits of the "aging pigment," lipofuscin. The heart muscle cells degenerate slightly. The valves inside the heart, which control the direction of blood flow, thicken and become stiffer. A heart murmur caused by valve stiffness is fairly common in the elderly.
The heart has a natural pacemaker system that controls heartbeat. Some of the pathways of this system may develop fibrous tissue and fat deposits. The natural pacemaker (the SA node) loses some of its cells. These changes may result in a slightly slower heart rate.
Heart changes cause the ECG of a normal, healthy aged person to be slightly different than the ECG of a healthy younger adult. Abnormal rhythms (arrhythmias) such as atrial fibrillation are common in older people, which may be caused by heart disease.
A slight increase in the size of the heart, especially the left ventricle, is not uncommon. The heart wall thickens, so the amount of blood that the chamber can hold may actually decrease despite the increased overall heart size. The heart may fill more slowly.

Blood vessels

The main artery from the heart (aorta) becomes thicker, stiffer, and less flexible. This is probably related to changes in the connective tissue of the blood vessel wall. This makes the blood pressure higher and makes the heart work harder, which may lead to hypertrophy (thickening of the heart muscle). The other arteries also thicken and stiffen. In general, most elderly people experience a moderate increase in blood pressure.
Receptors, called baroreceptors, monitor the blood pressure and make changes to help maintain a fairly constant blood pressure when a person changes positions or activities. The baroreceptors become less sensitive with aging. This may explain the relatively common finding of orthostatic hypotension, a condition in which the blood pressure falls when a person goes from lying or sitting to standing, resulting in dizziness.
The wall of the capillaries thickens slightly. This may cause a slightly slower rate of exchange of nutrients and wastes.

Blood

The blood itself changes slightly with age. Aging causes a normal reduction in total body water. As part of this, there is less fluid in the bloodstream, so blood volume decreases.
The number of red blood cells (and correspondingly, the hemoglobin and hematocrit levels) are reduced. This contributes to fatigue. Most of the white blood cells stay at the same levels, although certain white blood cells important to immunity (lymphocytes) decrease in number and ability to fight off bacteria. This reduces the ability to resist infection.

EFFECT OF CHANGES

Under normal circumstances, the heart continues to adequately supply all parts of the body. However, an aging heart may be slightly less able to tolerate increased workloads, because changes reduce this extra pumping ability (reserve heart function).

Some of the things that can increase heart workload include illness, infections, emotional stress, injuries, extreme physical exertion, and certain medications.

COMMON PROBLEMS

Heart and blood vessel diseases are fairly common in older people. Common disorders include high blood pressure and orthostatic hypotension.
Arteriosclerosis (hardening of the arteries) is very common. Fatty plaque deposits inside the blood vessels cause it to narrow and can totally block blood vessels.
Coronary artery disease is fairly common.
Angina (chest pain caused by temporarily reduced blood flow to the heart muscle), shortness of breath with exertion and heart attack can result from coronary artery disease.
Abnormal heart rhythms (arrhythmias) of various types can occur.
Heart failure is also very common in the elderly. In people older than 75, heart failure occurs 10 times more often than in younger adults.
Valve diseases are fairly common. Aortic stenosis, or narrowing of the aortic valve, is the most common valve disease in the elderly.
Anemia may occur, possibly related to malnutrition, chronic infections, blood loss from the gastrointestinal tract, or as a complication of other diseases or medications.
Transient ischemic attacks (TIA) or strokes can occur if blood flow to the brain is disrupted.

Other problems with the heart and blood vessels include the following:

Peripheral vascular disease, resulting in claudication (intermittent pain in the legs with walking)
Varicose veins
Blood clots
- Thrombophlebitis
- Deep vein thrombosis

PREVENTION

You can help your circulatory system (heart and blood vessels). Heart disease risk factors that you have some control over include high blood pressure, cholesterol levels, diabetes, obesity, and smoking.

Eat a heart-healthy diet with reduced amounts of saturated fat and cholesterol, and control your weight. Follow your health care provider's recommendations for treatment of high blood pressure, high cholesterol or diabetes. Minimize or stop smoking.
Moderate exercise is one of the best things you can do to keep your heart, and the rest of your body, healthy. Consult with your health care provider before beginning a new exercise program. Exercise moderately and within your capabilities, but do it regularly.
People who exercise usually have less body fat and smoke less than people who do not exercise. They also tend to have fewer blood pressure problems and less heart disease.
Exercise may help prevent obesity and helps people with diabetes control their blood sugar.
Exercise may help you maintain your maximum abilities as much as possible and reduces stress.

Corns and calluses

admin — Wed, 03 Sep 2008 17:55:18 -0700

Overview

Definition
Alternative Names
Causes, incidence, and risk factors
Symptoms
Signs and tests
Treatment
Expectations (prognosis)
Complications
Calling your health care provider
References

Illustrations

Corns and calluses

Skin layers

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Corns and calluses are thickened layers of skin caused by repeated pressure or friction.

Alternative Names

Calluses and corns

Causes, incidence, and risk factors

Corns and calluses are caused by pressure or friction on skin. A corn is thickened skin on the top or side of a toe, usually from shoes that do not fit properly. A callus is thickened skin on your hands or the soles of your feet.

The thickening of the skin is a protective reaction. For example, farmers and rowers get callused hands that prevent them from getting painful blisters. People with bunions often develop a callus over the bunion because it rubs against the shoe.

Neither corns nor calluses are serious conditions.

Symptoms

Thick and hardened skin
May be flaky and dry
Located on hands, feet, or other areas that may be rubbed or pressured

Signs and tests

Your health care provider will make the diagnosis after observing the skin. In most cases tests are not necessary.

Treatment

Usually, preventing friction is the only treatment needed. If a corn is the result of a poor-fitting shoe, changing to shoes that fit properly will usually eliminate the corn within a couple of weeks. Until then, protect the skin with donut-shaped corn pads, available in pharmacies. If desired, use a pumice stone to gently wear down the corn.

Calluses on the hands can be treated by wearing gloves during activities that cause friction, such as gardening and weight lifting.

If an infection or ulcer occurs in an area of a callus or corn, unhealthy tissue may need to be removed by a health care provider and treatment with antibiotics may be necessary.

Calluses often reflect undue pressure placed on the skin because of an underlying problem such as bunions. Proper treatment of any underlying condition should prevent the calluses from returning.

Expectations (prognosis)

Corns and calluses are rarely serious. If treated properly, they should improve without causing long-term problems.

Complications

Complications of corns and calluses are rare. People with diabetes are prone to ulcers and infections and should regularly examine their feet to identify any problems right away. Such foot injuries need medical attention.

Calling your health care provider

Very closely check your feet if you have diabetes or numbness in the feet or toes. If you have diabetes and notice problems with your feet, contact your health care provider.

Otherwise, simply changing to better-fitting shoes or wearing gloves should resolve most problems with corns and calluses.

If you suspect that your corn or callus is infected or is not getting better despite treatment, contact your health care provider. Also call your health care provider if you have continued symptoms of pain, redness, warmth, or drainage.

References

Boulton AJ. Pressure and the diabetic foot: clinical science and offloading techniques. Am J Surg. 2004; 187(5A): 17S-24S.

Freeman DB. Corns and calluses resulting from mechanical hyperkeratosis. Am Fam Physician. 2002; 65(11): 2277-2280.

Pinzur MS. Guidelines for diabetic foot care: recommendations endorsed by the Diabetes Committee of the American Orthopaedic Foot and Ankle Society. Foot Ankle Int. 2005; 26(1): 113-119.

Review Date: 5/6/2007

Reviewed By: Thomas N. Joseph, MD, Private Practice specializing in Orthopaedics, subspecialty Foot and Ankle, Camden Bone & Joint, Camden, SC. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Source Doc: 1_001232

Lichen simplex chronicus

admin — Wed, 03 Sep 2008 17:52:41 -0700

Overview

Definition
Causes, incidence, and risk factors
Symptoms
Signs and tests
Treatment
Expectations (prognosis)
Complications
Calling your health care provider

Illustrations

Lichen simplex chronicus on the ankle

Lichen simplex chronicus

Lichen simplex chronicus on the back

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Lichen simplex chronicus is a skin disorder characterized by chronic itching and scratching. The constant scratching causes thick, leathery, brownish skin.

Causes, incidence, and risk factors

This is a skin disorder characterized by a self-perpetuating scratch-itch cycle:

It may begin with something that rubs, irritates, or scratches the skin, such as clothing.
This causes the person to rub or scratch the affected area. Constant scratching causes the skin to thicken.
The thickened skin itches, causing more scratching, causing more thickening.
The skin may become leathery and brownish in the affected area.

This disorder may be associated with atopic dermatitis (eczema) or psoriasis. It may also be associated with nervousness, anxiety, depression, and other psychologic disorders.

It is common in children, who chronically scratch insect bites and other areas. It can also be common in mentally retarded children who have chronic repetitive movements.

Symptoms

Itching of the skin
- May be chronic
- May be intense
- Increases with nervous tension, stress
Skin lesion, patch, or plaque
- Exaggerated skin lines over the lesion
- Circumscribed lesion with distinct borders
- Skin lesion becomes leathery textured (lichenification)
- Darkened (hyperpigmented) or reddened skin
- Excoriation, raw areas
- Scratch marks
- Scaling
- Commonly located on the ankle, wrist, neck, rectum/anal area, forearms, thighs, lower leg, back of the knee, inner elbow

Signs and tests

The diagnosis is primarily based on the appearance of the skin and a history of chronic itching and scratching. A skin lesion biopsy may be needed to confirm the diagnosis.

Treatment

The primary treatment is to stop scratching the skin. This may include counseling to become aware of the importance of not scratching, stress management, or behavior modification.

The itching and inflammation may be treated with a lotion or steroid cream applied to the affected area of the skin. Peeling ointments, such as those containing salicylic acid, may be used on thickened lesions. Soaps or lotions containing coal tar may be recommended.

Dressings that cover and protect the area may be used with or without topical medications. They are left in place for a week or more at a time.

Antihistamines, sedatives, or tranquilizers may be needed to reduce itching and to reduce stress. Steroids may be injected directly into lesions to reduce itching and inflammation.

Antidepressants and tranquilizers may be needed in those patients who have an emotional component to their lichen simplex chronicus.

Expectations (prognosis)

Lichen simplex chronicus may be controlled by reducing stress and scratching. It may return or change sites.

Complications

Secondary bacterial skin infection
Permanent scar formation
Permanent changes in skin color

Calling your health care provider

Call your health care provider if symptoms worsen or new symptoms develop, especially signs of skin infection such as pain, redness or drainage from the lesion, or fever.

Review Date: 10/16/2006

Reviewed By: Michael S. Lehrer, M.D., Department of Dermatology, University of Pennsylvania Medical Center, Philadelphia, PA. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

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Source Doc: 1_000872