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Causes For Infertility

Causes For Infertility
There are no easy answers for infertility, and why it is so hard for some women to conceive - but there ARE some definite causes, and most couples have more than one factor.

The most important thing in beginning the process of trying to conceive, is to know your own body - and your doctor will become instrumental in helping you to do this. Recognizing the signs of ovulation, determining whether there are other obstacles preventing you and your partner from conceiving will be 2 of MANY avenues you and your physician will explore.


Ovulation Factors

Chromosomal abnormalities and endocrine dysfunctions interfering with infertility, are to be found as the leading causes of ovulatory infertility. Perhaps the three most common ones are emotional stress, strenuous exercise and excessive weight loss or weight gain. Irregular ovulation cycle, accompanied by poor cervical mucus (mentioned below) are known factors. There are replacement hormones or drugs available that can induce ovulation.

Cervical / Uterine Factors

Cervical and uterine factors usually have identifiable problems. They are physical problems or mucus related problems. The physical problems of the cervix is more related to recurrent miscarriages than a cervical evaluation. The mucus related problems usually involve three possible issues:

1. There is not enough mucus for the sperm to survive.
2. The mucus is too thick for sperm to survive.
3. The mucus contains sperm antibodies.

Tubal & Peritoneal Factors

Tubal factor infertility accounts for about 20-25% of all cases of infertility.

This category includes cases in which the woman has completely blocked fallopian tubes and also women who have either one blocked tube or no tubal blockage but tubal scarring or other tubal damage. Tubal factor infertility is usually caused by either pelvic infection, such as pelvic inflammatory disease (PID) or pelvic endometriosis. Sometimes it can be caused by scar tissue that forms after pelvic surgery.

In cases of relatively minor tubal damage it is sometimes difficult to be certain that the infertility problem is solely due to the tubal damage and there are not other significant contributing causes to the problem conceiving. In general, the standard testing is performed on all couples and if no other cause is found to explain the infertility the presumptive diagnosis can be tubal factor, or if the degree of tubal scarring is very minimal, a diagnosis of unexplained infertility may be warranted.

Peritoneal factors include endometriosis, appendicitis (especially when ruptured), abdominal or pelvic operations, infectious or non-infectious pelvic inflammatory diseases.

Immunology Factors

Anti-sperm antibodies can occur in both men and women. Antibodies are protein molecules that are attracted to a specific site on the sperm. Once attached, they may interfere with the sperm's activity in any of several ways. They may immobilize sperm, cause them to clump together, limit their ability to pass through the cervical mucus, or prevent them from binding to and penetrating the egg. Anti-sperm antibodies are frequently seen in men after vasectomy, testicular injury or infection. The cause of anti-sperm antibodies in the woman is unknown.

Researchers classify specific antibodies by type (IgA, IgG and IgM) as well as the point at which they attach to the sperm (head, midpiece, or tail). Studies indicate that IgG type antibodies are most common in men and that IgA type can be found in women's mucus and follicular fluid, but the significance of these findings is uncertain. Binding to the head is believed to interfere with attachment and penetration of the egg, while tail binding interferes with motility.
Unfortunately, testing and identification of type of antibody or the location does little to suggest who will or won't conceive. Attempts to treat the condition -- say, by lowering antibody levels with steroids or removing the antibodies from sperm -- have demonstrated limited benefit and have been fraught with disastrous complications. A trial of ovulation induction and insemination followed by in vitro fertilization with ICSI (a process that involves injecting a sperm directly into an egg) seems to be the best treatment available.

Between 20 and 25 percent of all repeated miscarriages are due to immunological problems. In some cases, the woman's immune system causes her body to reject the fetus as foreign tissue. This problem can often be solved by injecting white blood cells from the woman's partner into her body before conception, so that her body gets "used to" his cells and therefore "recognizes" the fetus later on as "friendly." Some clinics report about a 70 percent success rate using this method.

Other immunological causes involve women who produce antibodies that indirectly cause clotting in blood vessels leading to the developing fetus. The fetus is deprived of nutrients and dies in utero, which triggers an abortion. There are no definitive treatments, but some clinics are looking into combining acetylsalicylic acid (pain relievers), corticosteroids, or anticoagulants such as heparin.

Endometriosis

Many women with endometriosis have been dismissed as neurotic whiners and complainers - but the fact is - endometriosis is NOT a figment of a woman's imagination.

Endometriosis is a disease that affects millions of women. It is responsible for hundreds of thousands of missed work hours, pain ranging from mild to crippling, and, for some women, infertility.

Endometriosis (also known as lesions or implants) is found in the female pelvis. It has been found on every pelvic organ including the uterus, ovaries, tubes, ligaments, ureters, bowel, bladder, and other peritoneal surfaces.

Pain caused by endometriosis depends in part on where it is and how much a woman may have. A small spot of endometriosis may stay small and relatively inactive for many years. However, even the tiniest implant can cause incapacitating pain if it irritates a nearby nerve.

Larger implants can become locally invasive as they respond to hormone stimulation. The tissue surrounding the implant can begin to break down and bleed. The body's natural reaction is to try to cover this raw area with scar tissue (also called adhesions). But if active endometriosis becomes trapped beneath adhesions, enormous pain and pressure can result.

A large walled-off area (frequently an ovary) can lose its central blood supply. Then degeneration and destruction of the localized blood can create a cystic mass called an endometrioma. An endometrioma can be quite small, like a BB. They can also grow very large. the size of a softball.

Advanced endometriosis can result in pelvises frozen with adhesions. This means that organs designed to float freely within the pelvis are stuck together. Then, any movement of any one of those structures (such as ovarian movements during ovulation, movements during sexual intercourse, or moving material through the bowel) can result in enormous pain.

Pain is the most common symptom. Symptoms include:
• severe menstrual cramps
• pelvic pain apart from menses
• backache
• painful intercourse
• painful bowel movements
• fatigue
• bloating
• constipation
• menstrual diarrhea
• pain with exercise
• painful pelvic exams
• painful and frequent urination
There are other symptoms, but the ones listed above are the most common.

Treatment for endometriosis varies, but are usually contained to the following:

Observation

You may decide with your doctor to observe endometriosis without treatment. This decision usually takes place when endometriosis is first diagnosed. Close attention to symptoms and frequent exams by your doctor or specialist with considerable experience with endometriosis will lead to appropriate treatment at the right time. Observation is not a good option when symptoms are significant or the pelvic exam shows progressive changes.

Pregnancy

Pregnancy is not a cure for endometriosis.

During pregnancy, ovulation stops. The endometriosis implants generally become less active, and may get smaller and less tender. This seems to be the result of the hormonal changes that pregnancy brings. These include high levels of progesterone, the presence of HCG (human chorionic gonadatropin) and prolactin, among others. Menstruation stops, and many women with endometriosis feel much better while they are pregnant. However, the disease does not go away during pregnancy. After pregnancy and nursing (and sometimes before then), the symptoms return, sometimes stronger than before.

Medical suppression

Drugs do not make endometriosis disappear, but can offer temporary relief from symptoms.

• Oral contraceptives offer a regulated, low-dose combination of estrogen and progesterone to prevent ovulation. Because ovulation is difficult for many women with endometriosis, this can be a big plus for OCs.

• Progesterone is usually given in a long-acting depot form via injection (depo-provera). Progesterone can also prevent ovulation and reduce circulating estrogen levels. Side effects include irregular bleeding, bloating, weight gain, and more. Expense is reasonable.

• GNRH analogs (Synarel, Lupron, Zoladex and Danocrine) are drugs that stop virtually all ovarian activity (hormone production and ovulation

Surgery

There are four levels of a doctors surgical approach to endometriosis:

• Diagnostic surgery has diagnosis as its highest priority. That is, the whole point of the operation is to diagnose what's going on with the patient. No attempt is necessarily made to treat any disease that may be found. Conservative surgery is one in which a surgeon might treat very large, obvious, or easily treatable disease. For example, a leaking endometrioma might be drained, or an area of powder-burn implants ablated. Other areas of disease may, by design, be left untreated. Doctors who believe that endometriosis can never be controlled and will always come back often do this type of surgery.

• Aggressive conservative surgery removes all disease while preserving all organs. The emphasis is on removing all areas of endometriosis and possible endometriosis, while maintaining fertility.

• Radical surgery describes the removal of the reproductive organs. Certainly there are some women who have benefited from this approach, but the majority of women can receive long-lasting pain relief without resorting to such drastic measures. In addition, there are a host of reports of endometriosis persisting after hysterectomy. Removing a woman's uterus but leaving implants of endometriosis behind often does not relieve pain.

Pelvic Inflammatory Disease

Pelvic Inflammatory Disease or PID, is a bacterial infection of the upper female genital tract, including the uterus, fallopian tubes and ovaries.

PID can be caused by several different aerobic (oxygen requiring) and anaerobic (non-oxygen-requiring) bacteria. The two most important are the bacteria which cause Chlamydia and gonorrhea. These bacteria are usually transmitted through sexual intercourse with an infected partner.

The usual symptoms of acute PID are fever, chills, lower abdominal and pelvic pain, and vaginal discharge or bleeding. These symptoms often begin a few days after the start of your period, particularly when a STD is the cause of infection.

Infections due to Chlamydia usually progress more slowly than those caused by gonorrhea. On physical examination by a doctor, the uterus, ovaries, and fallopian tubes of the infected person are usually tender.

Complications from PID occur in one out of four infected women and include tuboovarian abscess, (inflammation surrounding the liver), chronic pelvic pain, and occasionally death. In addition, PID is the single most important risk factor for ectopic pregnancy and one of the most common causes of female infertility.

A doctor, the presence of an elevated white-blood-cell count, and a positive bacterial culture of the cervical discharge usually diagnose PID on the basis of existing symptoms, physical examination.

In some instances, PID may be confused with other illnesses, such as appendicitis and a twisted or ruptured ovarian cyst. In these situations, laparoscopy may be necessary to make the correct diagnosis. Laparoscopy is a procedure where a fiber-optic telescope is placed through a small incision made beneath the navel, enabling the doctor to view the infected pelvic organs. Ultrasound may also be used to identify a pelvic abscess.

The usual treatment for PID is antibiotics. Most women take oral antibiotics such as intramuscular ceftriaxone, and oral doxycycline and metronidazole for a period of 10 to 14 days, after which they are cured. Women who are severely ill are usually treated with intravenous antibiotic therapy in the hospital. A woman's sexual partner should also be treated with antibiotics.

Because the potential complications of PID are so dangerous, preventing its onset is of great importance. Barrier contraception with spermicidal foam and condoms provides some protection against the infectious organisms that cause PID.

Polycystic Ovarian Syndrome

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Now researchers are learning that it also has far-reaching effects on a woman's overall health. This hormonal disorder affects about 6 percent of premenopausal women, and its repercussions probably echo throughout life. During the reproductive years, the most common symptom of PCOS is irregular or infrequent menstrual periods. Other signs include prominent facial or body hair, severe acne, thinning hair on the head, and obesity. The disease gets its name from the many small cysts that build up inside the ovaries.

Many therapies target specific symptoms of PCOS, but may not address the underlying cause.

Treatments

Oral contraceptives. Traditionally, physicians have prescribed oral contraceptives (birth control pills) to regulate menstrual periods in women with PCOS. Oral contraceptives contain a combination of hormones (estrogen and progesterone). Used properly, oral contraceptives can assure that women menstruate every four weeks. Because they cause women to menstruate regularly (and, thus, shed the endometrial lining), oral contraceptives as treatment for PCOS help to reduce a woman's risk of endometrial cancer.

Anti-androgens. Anti-androgenic agents, such as spironolactone, block the effect of androgens (male hormones, including testosterone). In high doses, anti-androgens can reduce unwanted hair growth and acne.

Treating infertility. Many assisted-reproduction techniques are available for women who have difficulty conceiving because of PCOS: from oral and injectable medications that stimulate ovulation, to advanced methods of in vitro fertilization including use of donor eggs.

New Treatments

Rather than focusing on relieving specific symptoms, the newer treatments aim at what may be the root cause of PCOS, i.e. insulin resistance. Many of these new therapies are designed to lower insulin levels and, thus, reduce production of testosterone.

• Drug Therapy
New evidence suggests that using medications that lower insulin levels in the blood may be effective in restoring menstruation and reducing some of the health risks associated with PCOS. Lowering insulin levels also helps to reduce the production of testosterone, thus diminishing many of the symptoms associated with excess testosterone: hair growth on body, alopecia (hair loss on head), acne, obesity and cardiovascular risk.

• Metformin
Metformin improves both glucose tolerance and insulin sensitivity. It is approved by the FDA as a treatment for diabetes. Metformin is prescribed under the brand name Glucophage made by Bristol-Myers Squibb in 500mg, 850mg and 1000mg tablets. Glucophage is given 2-3 times daily with a meal. If a dose is missed or a meal is skipped take the next dose at the following meal. Do not double the dose at the next meal. Approximately 30 % of patients started on Glucophage will experience gastrointestinal symptoms (diarrhea, nausea, vomiting, abdominal bloating, flatulence, and loss of appetite). These symptoms are usually temporary (1-4 weeks) and will disappear during continued therapy. It is advisable for new patients to initiate therapy slowly to minimize the gastrointestinal side effects.

• Pioglitazone
Pioglitazone works primarily by improving insulin sensitivity and glucose tolerance. The FDA approved the drug in July 1999 for use in type 2 diabetes. Pioglitazone is available under the brand name ACTOS, made by Takeda Pharmaceuticals and co-marketed by Eli Lilly. ACTOS is available in 15mg, 30mg, and 45mg tablets. It is taken once daily with or without food. There were few notable side effects in clinical trials. Another added benefit seen with Pioglitazone is the reduction of triglyceride levels. Periodic liver function tests are recommended for the first year of therapy.

• Rosiglitazone
made by SmithKline Beecham works in a similar fashion to Rezulin and ACTOS by improving insulin sensitivity. Avandia is available in 2mg, 4mg and 8mg tablets. Avandia is usually taken twice daily. A low incidence of side effects was noted in clinical trials. Periodic liver function tests are recommended for the first year of therapy.

How safe are these drugs?

All four drugs appear to be relatively safe for use. Fortunately, when given to non-diabetic patients, Glucophage (metformin), Rezulin (troglitazone), ACTOS(pioglitazone) nor Avandia(rosiglitazone) lowers blood sugar. This eliminates the possibility of hypoglycemia (low blood sugar).

However, Rezulin can produce a rare side effect leading to elevation of liver enzymes and possible liver damage. Your doctor should check your liver function by blood analysis for the first 8 months of drug therapy to detect any problems early on. Rezulin should not be prescribed to anyone with pre-existing liver damage.

Glucophage has been also associated with a rare condition called lactic acidosis. Reported cases have occurred primarily in diabetic patients with severe renal (kidney) insufficiency. Though neither ACTOS nor Avandia have been associated with any liver problems, the FDA is requiring monitoring of patients for any signs of liver function abnormalities during the first year of therapy. This is due to the fact that ACTOS, Avandia and Rezulin all belong to the same drug class - thiazolidinedione (TZD's).

Premature Ovarian Failure

Premature ovarian failure (POF) is defined as the cessation of menses associated with high levels of gonadotropins and low levels of estrogen before age 40. The condition has also been termed "premature menopause" or "precocious menopause." The frequency of the condition is related to the age at diagnosis. At age 30 approximately 1:1000 patients will be affected, by age 40 approximately 1:100 will be affected. Thus, this is a relatively common condition.
Prior to the onset of amenorrhea, a woman may have regular monthly menses, several months of an irregular bleeding pattern, or intermittent symptoms of irregularity. The amenorrhea may also be preceded by use of a hormonal contraceptive agent or by pregnancy. There is no evidence that either hormonal contraception or pregnancy increases the risk of POF. There may be associated complaints of hypoestrogenism, including vasomotor symptoms, vaginal dryness and dyspareunia.

POF was initially believed to be an irreversible condition, but is now known that ovarian failure is often intermittent, especially in chromosomally normal women. Case series have reported up to a 60% rate of subsequent ovarian function.
In the mid 1980's, Carolyn Coulam, M.D. published an article called Incidence of Premature Ovarian Failure, which has since remained the standard by which researchers determined the incidence rate of POF. The study followed women who lived in Rochester, Minnesota, were seen for medical care at the Mayo Clinic, and who were born around 1930. Their records were followed from 1950 through 1986 for the age at which natural menopause occurred. The study concluded that natural menopause before age 40 is unusual -- the incident rate in the 40 to 44 age group was more than 10 times larger than in the 30 to 39 year age group.

No known therapy for patients with premature ovarian failure has been proven effective. Different research articles and reports have suggested that high-dose, long-term prednisone therapy may be useful in treating autoimmune ovarian failure.

However, prednisone, when used in high-dose for a long-term has substantial side effects, including aseptic necrosisof bone requiring major surgical intervention. Despite this risk, patients with premature ovarian failure are being treated based on this anecdotal evidence.

Fibroid Tumors

Fibroid tumor diagnosis are generally made by your physician during your annual gynocological exam when your physician feels a mass, they often are found when your physician is looking for something else or may never be discovered if you do not experience symptoms. However larger fibroids may make examination of your ovaries impossible if they grow near your ovaries.

An ultrasound scan is often ordered when such masses are felt by your physician to determine the cause of the mass, however some fibroids appear on sonograms as ovarian tumors and surgery is the only way an accurate diagnosis can be made.

Although most fibroids cause no symptoms, the estimated 25% of women who do have symptoms may have abnormal bleeding, pain during menstruation , and as the fibroid tumors grow larger, women will often experience a swollen abdomen.

Larger fibroids may cause frequent urination or an inability to control your bladder, either the ability to control the urge or in severe cases, a women may find that she is unable to urinate at all. If a fibroid extends towards a woman's back it may push on the bowels, causing constipation and a backache.

Treatment of Fibroids


If your fibroid tumors are severe enough that they cause certain symptoms, surgery is often, the required treatment. Symptoms which justify surgery include: extremely heavy bleeding during your menstrual cycle, which causes anemia that does not respond to treatment; pain, which has become intolerable to the woman or discomfort caused by the pressure of the fibroids on another organ; or when the location of the tumors is likely to cause further problems.
Surgery for fibroid tumors includes, myomectomy and hysterectomy.

Myomectomy is the surgical removal of each individual tumor without damage to the uterus, preserving a woman's ability to conceive. However, fibroids will often grow back and although it is possible to have a myomectomy repeated, multiple myomectomies can cause other problems such as the walls of the uterus sticking together due to scarring.
Women should also consider uterine artery embalization. Uterine artery embalization leaves the uterus intact in a non-surgical procedure. Polyvinyl particles are placed into the uterine artery at a point just before the nexis of vessels spread out into the uterine tissue. The particles flow into the vessels and clog them. This prevents the fibroids from receiving the constant blood supply they require and causes the fibroids shrink overtime. However, almost immediately the symptoms of heavy bleeding and pelvic pain are significantly reduced.

The sad fact is that because fibroids do grow back, most women will eventually have to face a hysterectomy. Removing the uterus is the only permanent way to effectively relieve most women of fibroids.

Other Causes of Infertility

Luteal Phase Defect (or deficiency) (LPD):

A condition that occurs when the uterine lining does not develop adequately because of inadequate progesterone stimulation; or because of the inability of the uterine lining to respond to progesterone stimulation. LPD may prevent embryonic implantation or cause an early abortion.

More simply stated - LPD is a hormonal imbalance, effecting ovulatory function and uterine endometrial lining, which can increase a woman's risk of both conception difficulties and early miscarriage.

Hyperprolactinerma

Hyperprolactinemia is a common clinical problem. It is found in up to one-third of patients with absence of menstruation and in up to 90 percent of women.

Hyperprolactinemia is a condition in which excess prolactin circulates in the bloodstream of nonpregnant women. Hyperprolactinemia can produce a variety of reproductive dysfunctions including inadequate progesterone production during the luteal phase after ovulation, irregular ovulation and menstruation, absence of menstruation, and galactorrhea (breast milk production by a woman who is not nursing). Prolactin levels should be measured in women who experience these conditions. In men, hyperprolactinemia may be associated with impotence and can affect fertility.

Prolactin secretion may increase mildly with sleep, stress, coitus, exercise, nipple stimulation, ingestion of certain foods, and pregnancy. If a woman's prolactin level is elevated the first time it is tested, a second sample should be checked when she is fasting and non-stressed. Confirmed elevations of prolactin need to be evaluated.

Diabetes

It is thought that type 1 diabetes associated with accelerated aging may contribute to premature ovarian failure. It is also thought that early menopause is a previously unknown complication of diabetes, rather than a result of existing diabetic complications.

Thyroid Disease

Research indicates that IVF failure also occurs in women who produce antithyroid antibodies to their thyroid glands, regardless of whether or not there are clinical symptoms or signs of reduced thyroid hormone activity (hypothyroidism). Many women, especially those who have a family history thyroid disease, will manifest these antibodies.
The presence of these antibodies is associated with a variety of manifestations of poor reproductive performance, says Dr. Geoffrey Sher, author of In Vitro Fertilization, The Art Of Making Babies. He goes on to say, "These range from infertility, through early miscarriage to prematurity, intrauterine growth retardation, other serious complications of late pregnancy, and even fetal death." These complications he said, often occur when there is no clinical suggestion of hypothyroidism.

Lupus

If you have Lupus, it is important that you have the best information from a rheumatologist and obstetrician (preferably a team), who familiar with high-risk pregnancies. Most lupus patients can have successful pregnancies, and normal babies. However, it's important to be aware of the times when lupus can increase the risks.
Even under the best of circumstances. In SLE (Systemic Lupus Erythematosus), certain conditions can affect fertility.
If you have lupus, the body minimizes your ability to take on new work, for example, the work of getting pregnant. This means you may have irregular periods, or none at all. Although it is possible to ovulate without having a period, it is much less common. Avoid conceiving until the disease has settled down for a few months.

Scarring in the pelvic region.

Childbirth may put you at risk for a bacterial infection, causing PID. The bacteria can enter your pelvic region through the dilated cervix.

Stress.

This can affect ovulation. After having one child, a couple's "workload" and exhaustion level can increase enormously.

Strenuous exercise and weight loss.

Many women will overdo it in the gym in a mad scramble to reclaim their figures after childbirth. This can affect ovulation. Whatever the cause, couples with secondary infertility will need to consider the same options as couples dealing with primary infertility.



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