COMMON CAUSES OF INFERTILITY

8.1 The polycystic ovarian syndrome.

Women who have the polycystic ovarian syndrome may find that they cannot get pregnant as quickly as they would expect. However, if pregnancy does not occur within a reasonable period of time effective treatment for polycistic ovaration syndrome is available.

What is the Polycystic ovarian Syndrome?

A woman with polycystic ovarian syndrome has ovaries, which contain many small «cysts» plus some or all of the futures described below. About 20 per cent of women have polycystic ovaries, however not all of them suffer from the polycystic ovarian syndrome. Many women do not even know that they have polycystic ovaries.

Polycystic ovaries are easily diagnosed with an ultrasound scan. They contain many small cysts usually no bigger than 8mm in diameter. These small cysts usually do not get bigger and with time disappear only to be replaced by other small cysts. They do not need to be removed by surgery. Only very large cysts, more than 50mm in diameter may request surgical removal. At present the cause of polycystic ovaries is not entirely clear. There might be a kind of inheritance and may appear in women of whatever reproductive age. The ovaries do not become polycystic suddenly but the symptoms of the syndrome develop gradually.

Other Features of the polycystic ovarian Syndrome

a) Irregular Periods

Menses may be irregular, heavier than usual or prolonged. They may occur after long intervals of time or in some women may not occur at all. This is because ovulation does not occur regularly.

b) Less Frequent Ovulation

Instead of ovulating once each month, a woman with the polycyst ovarian syndrome may ovulate irregularly, not every month. This means that without treatment these women do not have as many chances of becoming pregnant. Polycystic ovaries do not respond ordinarily to the quantity of hormones, which come from the pituitary gland. However, they usually respond to additional amounts of these hormones given as treatment.

c) Miscarriage

Polycystic ovarian syndrome has been identified as the one of the conditions, which increases the risk of miscarriage. This might be due to the higher blood levels of the hormone called LH often found in these women.

d) Acne and Unwanted Body Hair

The blood level of the male hormone testosterone may be higher in women with the polycystic ovarian syndrome compared to that of other woman and this causes acne, greasy skin and unwanted hair growth of the face, chest and abdomen. The blood levels of testosterone in women with the polycystic ovarian syndrome are still much lower than the levels found in men.

e) Body Weigh

Weight gain is common in women with the polycystic ovarian syndrome, however not all these women are overweight. Some women with polycystic ovaries only develop symptoms of the syndrome when they put on weight. There are many other advantages in maintaining a normal bodyweight. Women who are overweight have an increased risk of heart disease, diabetes and arthritis later in life.

Long Term Health and the Polycystic Ovary Syndrome

Generally women with polycystic ovarian syndrome do not have an increased risk of cancer of the ovaries. Woman who do not have regular period may have a slightly increased risk of cancer of the endometrium (the internal layer of the womb). This can happen when the endometrium becomes too thick. Regular shedding of the endometrium by having regular periods prevents endometrial cancer. If the endometrium appears thick on an ultrasound or very irregular, prolonged bleeding occurs, curettage might be advised.

Treatment for Women with the Polycystic Ovary Syndrome.

As the cause of the syndrome is unclear, a radical treatment of it is not available. However the symptoms described above may be controlled with medical treatment. All women with polycystic ovaries should try to maintain a normal weight.

a) Irregular Periods

For women with polycystic ovarian syndrome who do not wish to become pregnant menstrual periods may be regulated with the administration of a low dose oral contraceptive pill. Women who cannot take the pill should try a progestogen-only treatment (for example Provera or Primolut N) for 12 days each mounth. A gynecologist should check any irregular bleeding and a smear test should be performed yearly.

b) Difficulty in Conceiving

In women with polycystic ovaries, difficulty in conceiving is most likely due to lack of regular ovulation. However, other cases of infertility such as blocked fallopian tubes or a partner with a low sperm count, may also coexist. When ovulation is irregular or entirely absent, drug or hormone treatment may be required. The most common treatment is clomiphene citrate (Clomid), which is taken as a tablet for five days early in the menstrual cycle. Therefore, although clomiphene may cause ovulation pregnancy will not always occur. Clomiphene is not always useful in women with the polycystic ovary syndrome because it may exaggerate the rise in blood levels of LH during the first part of the cycle. This reduces the chance of a successful pregnancy. A few women experience side effects with clomiphene including bloating headache stomach upset, breast discomfort, dizziness and depression. The risk of a multiple pregnancy is slightly increased with the use of clomophene. There is no increased risk of birth defects from fertility drugs.

If clomiphene does not help, hormones, which are injected, may be used. The hormones used, FSH and LH, are called gonadotrophins. There are pituitary hormones, which are extracted from human urine or synthesized in the laboratory. Gonadotrophins extracted from human pituitary glands are not used. FSH is mainly responsible for stimulating the growth of the follicles and LH stimulates release of the egg from the follicle. Polycystic ovaries are usually very sensitive to stimulation by these hormones and usually more than one follicle will grow when the injection are given. Because of this, courses of treatment begin with low doses and the response is carefully monitored with blood tests and ultrasound scans. If monitoring shows that too many follicles are developing, the treatment will be stopped and it may be necessary to use contraceptive measures for several days. When other treatments have not be successful in achieving pregnancy, in vitro fertilization (IVF) may be offered to women with polycentric ovarian syndrome. This treatment involves stimulation of the ovaries with gonadotrophins injections, collection of the eggs when there are mature and fertilization in the laboratory. IVF carries a risk of ovarian hyperstimulation syndrome and women with polycystic ovaries are at an increased risk of it. This condition occurs when too many follicles are stimulated resulting in abdominal swelling and nausea. Careful monitoring is essential to avoid this situation.

c) Skin Problems

Taking oral treatment may reduce acne and unwanted body hair. Oestrogen (as found in the oral contraceptive pill) is combined with an antiandrogentablet (usually spironolactone or cyproteron acetate) and the combination must be taken for many months to obtain some benefit. This therapy is of course contraceptive and therefore is of no use to those who trying to conceive, Waxing and electrolysis may be used to remove unwanted hair while waiting for the hormone treatment to work. However a trained therapist as scarring should perform these can result from unskilled treatment. If the skin problem is related to the polycystic ovary syndrome, hormone treatment is the logical solution.

8.2 Endometriosis

Endometriosis is a condition in which the endometrial cells which normally cover the cavity grows in places outside the uterus. These include the ovaries, fallopian tubes, large bowel and pelvic ligaments (figures 4 and 5). Rarely endometriosis is found in other parts of the body far away from the pelvis.

What causes endometriosis?

It is still not fully understood why endometrial tissue is found outside the uterus. One view is that fragments of endometrium are carried backwards through the fallopian tubes, intro the abdomen, where they implant (figure 4). Even outside the uterus, they can grow under the influence of female hormones just as they would in the lining of the womb. As with external wounds scar tissues can forma as a result. All these changes can irritate of interfere with the surrounding organs, leading to troublesome symptoms.1

Who gets endometriosis?

Endometriosis affects women in their reproductive years. It most often causes problems to women in there thirties and forties.

The symptoms of endometriosis:

Endometriosis does not always cause symptoms. It is sometimes found during a diagnostic procedure or operation for another condition, such as infertility. When endometriosis does cause symptoms, these vary widely in their type and severity.

Some of the most common symptoms of endometriosis are:

• Pain in the lower abdomen or lower back, during menstruality, but also at other times
  
• Pain when passing urine or opening the bowels
  
• Painful sexual intercourse
  
• Abnormal periods. For example, heavy or irregular periods.
  
• Infertility

How endometriosis diagnosed?

The symptoms of endometriosis described above can also be caused by other conditions. Your doctor will ask you about your symptoms and your general health, and then undertake a physical examination. However the only way to definitely diagnosis endometriosis is to examine the inside of the abdomen and directly see the lesions of the disease. This is done with an instrument like a telescope, called a laparoscope. The procedure is called a laparoscopy.

Laparoscopy:

Laparoscopy is done under a general anesthetic, by a specialist gynecologist. It usually doesn't require an overnight stay in hospital. The laparoscope is inserted into the abdomen through a small cut near the belly bottom a second cut near the pubic hairline is also required to insert another instrument to assist in viewing the pelvic organs through the laparoscope. This second instrument is used to move the bowel out of the way and lift up the ovaries. Endometriosis creates characteristic lesions seen through the laparoscope.

Treatment of endometriosis:

Endometriosis varies widely from one patient to the next, regarding symptoms and severity treatment. The most suitable treatment will depend on many factors, including:

• Age
  
• Whether planning to have children or not
  
• The severity of the symptoms
  
• The extent of endometriosis seen at laparoscopy
  
• Patient preferences

a) Observation

If the symptoms of endometriosis are absent or only mild, then it may be appropriate to have no treatment at all, other than regular observation. This is especially the case if the extent of the endometriosis is minimal and pregnancy is desired. If the symptoms are more severe or troublesome, then medical or surgical treatment, or a combination of both, is available.

b) Medical treatment

Two types of drugs are available to treat endometriosis. The first one aims to reduce pain and/or inflammation, and includes drug such as paracetamol, naproxen sodium and mefenamic acid. The other type aims to suppress the growth of endometriosis by suppressing oestrogen production or having a direct effect on the endometriosis itself. This hormonal therapy can cause endometriotic lesions to shrink and possibly disappear but at the same time inhibits ovulation thus reducing fertility while treatment is given.

There are four main kinds of hormonal therapy for endometriosis:

1. Progestogens

Examples are medroxyprogesterone and dydrogesterone. With these drugs endometriosis may shrink and disappear. They can be administered as tablets or injections. Possible side effects include menstrual irregularities, weight changes, headache, weakness or fatique, abdominal pain or discomfort, dizziness, nervousness, and breast tenderness.

2. Combined oral contraceptive pill

The oral contraceptive pill, which contains both an oestrogen and a progesterone, has also been used in the treatment of endometriosis. When given for this condition, it is usually given continuously for at least 6-12 months, with the aim of suppressing ovulation and endometriosis.

3. Danazol and gestrinone

Although these are different drugs, they work in a similar way, by reducing the level of the pituitary hormones which stimulate the ovaries, and by having a direct suppressive effect on the endometriosis itself. They both administered as tablets and they have similar side effects. These may include: acne, oily skin, excessive hair growth, weight gain, hot flushes, headaches, mood changes, sweating problems, nausea, abdominal pain and menstrual irregularities.

4. GnRH agonists

This is the newest form of medical treatment for endometriosis."GnRH" stands for gonadotrofin releasing hormone. This hormone is produced in the brain, stimulates the pituitary gland in the brain to produce its hormones, which act in the ovaries, and ultimately helps regulate the amount of oestrogen produced by the ovaries. GnRH agonists are potent, synthetic versions of this hormone which act in a complex way to reduce oestrogen levels. They include nafarelin (administered as a nasal spray), and goserelin (administered as injection). Side effects may include decreased bonedenstity, hot flushes, changes in libido, dryness of the vagina, headaches, mood changes, acne, muscle pain, changes in breast size and nasal irritation (nafarelin).

c) Surgical treatment

Surgical treatment of endometriosis can range from conservative surgery, to more extensive operations. Conservative surgery can be done laparoscopically but more extensive surgery usually involves opening the abdomen in a procedure called a laparotomy.

Conservative surgery aims to:

• Destroy or remove patches of endometriosis, scar tissue and adhesions
  
• Repair damaged organs
  
• Reduce symptoms
  
• Improve fertility

More extensive surgery for severe endometriosis may involve removal of the uterus and possibly on one or both of the fallopian tubes and ovaries.

8.3 Male factor

Fertility problems concern both man and women. As many as two out of every five couples with fertility problems required treatment of both spouses, and in 25 percent of the couples the fertility problem concerns exclusively the husband.

Fertility diagnosis and treatment is time consuming and expensive. The process can frequently be eased and shortened by both partners working together with their fertility physician from the beginning. In addition to the test done in a woman, it is often necessary to perform a semen analysis to be sure that the husband has sufficient and normal sperm for fertilization.

Human conception is a difficult and complex process, even under the best conditions. Normally functioning sperm will ultimately complete the path to fertilization. This means passing through cervical mucous, traveling up the uterine

cavity and entering the fallopian tube. Once in the fallopian tube, sperm must meet an egg, penetrate the egg΄s protective coating and inner membrane, and finally fertilize the egg.

To increase a couple's chances for conception it may be necessary for the husband to undergo special sperm studies.

Sometimes a semen condition will not respond to medical treatment. In these circumstances, it may be possible to treat the sperm in the laboratory in an attempt to enhance fertilization.

In order to obtain an optimal semen specimen; the husband may be requested to refrain from ejaculation for at least 48 hours prior to providing a specimen. DO NOT ABSTAIN for longer than 5 to 7 days, as the quality of sperm decreases with prolonged storage in the body. A private room is provided for the collection of semen specimens. The wife may accompany her husband if he wishes.

Many factors affect the quality of sperm produced by an individual at any given time. These factors include: unusual stress, fever, certain medications, or any injury to the testicles. Therefore, the husband will be asked to complete a brief reproductive history as well as note any temporary condition, which may affect sperm quality. When making an appointment for semen analysis, please inform us if there has been a fever or illness within the last three months as this may affect the specimen.

If the wife's ovulatory cycle is being monitored for purposes of follicular maturation studies, artificial insemination, in vitro fertilization or gamete intra fallopian transfer, our center should be alerted if any conditions occur which may affect sperm quality, such as illness or extreme stress. This will enable us to evaluate the condition for potential adverse effects upon the husband's sperm production at the time of his wife's ovulation. During ovulation, one or more fresh semen specimens may be needed to increase chances of conception.

Since fertility problems concern the couple and not only the woman, we want to remind you that husbands are welcome, and encouraged to attend all consultations and appointments with their wives.

Semen analysis (sperm count)
Semen analysis assesses qualities such as: appearance, odour, liquefaction, viscosity, pH, volume, sperm concentration, motility, vitality, morphology, clumping, debris and description of other cellular elements, particularly leukocytes.

Semen microbiology
Sometimes, an infection in the genital tract can cause problems with sperm performance.

"Trial wash"
A trial wash is a semen-preparation method for evaluation before the assisted conception, which distinguishes suitability for intrauterine insemination (IUI), gamete intra fallopian transfer (GIFT) conventional in vitro fertilization (IVF) or intracytoplasmic insertion (ICSI).

Karyotyping and molecular genetics
Special testing is advised before assisted conception, for men with severally decreased sperm production or with bilateral congenital absence of the vas deferens. This is because there is a possibility that the condition may be the result of a chromosomal/genetic defect.

Antisperm antibodies
Antibodies against spermatozoa showing agglutinating, cytotoxic (immobilizing), or coating activity can be present in the ejaculated sperm as well as in semen, cervical mucus, or blood (male and female).

Test for agglutination or spermatotoxic antibodies can be performed on semen, cervical mucus or blood serum. A positive cytotoxicity result indicates the need for titration of specific sperm-immobilizing antibodies.

However antibodies causing neither biological action may also be present and can only be detected by tests such as the immunobead Test (IBT). To test for antisperm antibodies produced by the male partner, this test is performed directly ejaculated on spermatozoa. To test for antibodies produced by the female partner, the test is carried out indirectly, by adding the test fluid (cervical mucus or blood serum) to prepared donor spermatozoa in the lab. Unique tests are available that can test for IgG, IgA and IgM antibodies simultaneously. Isotype-specific testing is also available.

If a screening test is positive for the presence of antibodies, a sperm antibody isotyping may be performed.

Sperm-cervical mucus in-vitro interaction tests -Post -coital (Sims-Huhner test). This test investigates the compatibility of the female partner's cervical mucus with the male partner's sperm, and determines which element (if either) has a problem.

Ultrasound examination of the male genetically tracks.

Testicular Biopsy: (fine needle or open):Obtaining sperm directly from the testis for ICSI.

MESA: Microsurgical epididymal sperm aspiration. Obtaining sperm cells from the epididymis (which joins the testis to the vas) or TESA: aspirating testicular tissue by fine needle biopsy (FNA) or thru open testicular biopsy in order to recover sperm that can be subsequently used for ICSI , either immediately or after cryostorage.

Electroejaculation: Attainment of erection and ejaculation with the use of electrical stimulation.