Female Infertility

Infertility is a condition of the reproductive system that impairs the ability to achieve pregnancy. Primary infertility is the inability to conceive a child after regular intercourse for at least 1 year. Secondary infertility occurs in couples who have previously been pregnant at least once, but are unable to achieve another pregnancy.

Infertility affects men and women equally. About one-third of the cases are due to a male factor, one-third to the female and the remaining to the combination of both partners. Causes of infertility include a wide range of physical as well as emotional factors.

For a woman to be fertile, her reproductive organs must be healthy and functional. To conceive a child, the ovaries must release healthy eggs regularly and her reproductive tract must allow the eggs and sperm to pass into her fallopian tubes for a possible union 50% of the infertile cases are due to a problem in the woman. The problem could either be a hormonal one or an anatomical one or a pathological one. The most common causes of female infertility are listed here and each one is linked to a very simple explanation of the causes, the symptoms, the diagnostic tests and the treatment modalities. In addition we have filtered the hundreds of web sites on the related topics and have provided links to a select few.

Premature Ovarian Failure

• Poly Cystic Ovarian Disease
• Endometriosis
• Disorders of the Fallopian Tube
• Cervical Hostility
• Hyperprolactinemia
• Uterine Fibroids

What is Premature  ovarian Failure?

Every woman is born with a finite stock of oocytes (eggs) at the time of her birth. After she attains puberty, every month, some of the egg-containing follicles start growing. Some release an egg while the others die a natural death mid-way through their growth phase. Thus, this stock of eggs depletes as a woman ages and very few eggs remain in the ovary when a woman is in her forties. This is natural phenomenon of menopause also resulting in a cessation of menstruation. However, some women attain menopause much earlier in their life and this state is known as "premature ovarian failure".

How is it diagnosed?

The first indication of premature ovarian failure would be absence of menstruation for several months or several years.

In normal women in the reproductive age group, the pituitary gland in the brain secretes hormones, follicle stimulating hormone (FSH) and Luteinizing hormone (LH) which specifically binds to the receptors on the ovarian cells, stimulates them to grow and in turn produce the hormone estradiol. This estradiol enters the blood stream and as its concentration in the blood increases, it sends a message to the pituitary, preventing it from secreting any more FSH and LH.

Now, in women with premature ovarian failure, the FSH and LH cannot bind to its specific receptors in the ovary because of the diminished reserve of such cells. Therefore, there is no estradiol produced to send a negative feed-back message back to the pituitary. In the absence of any feedback from the ovary, the pituitary continues secreting large quantities of both FSH and LH.

Therefore, pituitary ovarian failure can be identified by testing the concentrations of hormones FSH and LH in the blood. Very high concentrations of these hormones in the blood similar to that found in menopausal women confirms premature ovarian failure.

What are the causes of premature ovarian failure?

In half the women with premature ovarian failure, the cause remains unclear. While in the other half, premature ovarian failure is a result of destruction of the ovaries either by chemotherapy, radiation therapy or surgery. Cancers may necessitate treatment with chemo-therapeutic agents which can damage the ovaries. Tumours of the ovaries or of other abdominal organs may need irradiation therapy which also result in the destruction of the ovarian cells. Certain infections of the ovaries may need removal of the ovary.

Damage to the ovaries results in premature ovarian failure.

Can premature ovarian failure be reversed?

Pre-mature ovarian failure is irreversible. As the cause of premature ovarian failure is unknown in more than half of such patients, the day we are able to decipher the cause, will any treatment be possible. But at the moment this disorder of the ovaries is irreversible.

Can a woman with premature ovarian failure ever be able to bear a child?

Advances in assisted reproductive technologies has made it possible even for women with premature ovarian failure to bear a child. This is possible only if woman’s general health is fine and her uterus responds to external hormones.

However, since there are no eggs in the woman’s ovaries, she would need "oocyte donation". These donated oocytes are fertilized in the laboratory with her husband’s sperms and the resultant embryo is transferred into the uterus. The patient would need to take hormone supplements daily for more than 3 months if she does conceive following embryo transfer.

The woman can have the joy of a pregnancy and giving birth to a child although the child may not have her genetic material.

What are poly cystic ovaries (PCO)?

Every woman is born with millions of eggs at the time of birth. Each of these eggs is covered by specialised cells and this entire unit is called as a "follicle". After the woman attains puberty, every month a few of these follicles start growing of which one ruptures to release the egg while the others whither away. However, in some women several follicles start growing and then remain static in that state. Such ovaries which have these "cystic" follicles are termed as poly cystic ovaries.

What are the symptoms that indicate that a woman could have PCO?

Women with PCO have irregular menstrual cycles, are generally obese, have a high waist to hip ratio; excess hair growth on the face, abdomen limbs and other parts of the body. Ultra-sonographic scanning of the ovaries show the presence of several small follicles. The concentration of reproductive hormones in the blood is also altered. The hormone luteinising hormone (LH) is present in high concentration while the ratio of the hormones LH and FSH is also high. Both these hormones are produced by the pituitary gland and is responsible for the timely growth of the follicles and the release of the eggs. Some of the women may also have high concentrations of the hormone insulin in the blood and also excess of male hormones (androgens). Not all women will exhibit all these criteria associated with PCO.

How is it diagnosed?

PCO can be diagnosed by ultrasonography of the ovaries which clearly shows several hypoechogenic regions in the ovaries forming what has often been termed as "pearly necklace appearance".

Blood tests for determining the concentrations of the pituitary hormones FSH and LH, the concentration of insulin and also the androgens. These tests has to be done preferably on the second or third day after menstruation. A thorough clinical examination for any evidence of hirsuitism - excess of hair growth in the woman; a waist to hip ratio and the body mass index also has to be noted.

Does PCO affect a woman’s fertility?

The fertility of a woman with PCO is compromised especially if she has irregular menstrual cycle. These women often have anovulatory cycles (i.e., cycles where the follicles do not ovulate and release an egg.). These women also have abnormal hormone profiles and all this together results in compromised fertility.

What are the treatment options for a woman with PCO to conceive?

The first line of treatment for women with PCO would be "ovulation induction". Since these women often do not ovulate spontaneously, medications like clomiphene citrate are given to stimulate the growth of the follicle and then timing them to rupture by administering another hormone "human chorinoc gonadotropin". In case the women are resistant to clomiphene citrate and do not respond to it then they are directly injected with gonadotropins to stimulate the growth of follicles and their rupture.

One has to be extremely cautious while administering fertility drugs especially gonadotropins to women with PCO. In response to the gonadotropins, the multiple cysts present in these women can flare and lead to a condition known as "Ovarian hyperstimulation syndrome" which can become life-threatening. Careful ultrasonographic monitoring and measuring the concentration of the hormone estradiol in the blood in such women is very helpful to adjust the dose of gonadotropins being administered and minimise the risk of ovarian hyperstimulation syndrome.

Another option for women with PCO is "operative laparoscopy" where these cysts can be cauterised or burned. It is very important that this procedure is also carried out by a very experienced and skilled surgeon to ensure that no part of the ovary is damaged. Only the cysts have to be cauterised and that too till the right depth to ensure that the rest of the ovarian cells are not damaged.

There have been some recent reports on the successful use of an anti-diabetic drug, "metformin" for the treatment of PCO. This drug reduces the insulin levels and thereby may improve the hormone profile in such women. Strict monitoring is essential while the woman is on metformin and this drug should not be taken unless under medical supervision.

What is endometriosis?

The inner lining of the uterus is called as the "endometrium". Every month, in response to the hormones estradiol and progesterone produced by the ovary, this lining forms into a "bed" of cells. If the egg has been fertilized by the sperms then the resultant embryo attaches or implants on the endometrium. In case, the egg is not fertilized in that month then this lining of the uterus is shed resulting in menstrual bleeding.

In some women, the endometrium grows at places other than in the uterus. The endometrium can be present near or on the ovaries, the fallopian tubes or any other part of the abdomen. There is no outlet for the endometrium formed at locations others than within the uterus and this tissue accumulates within the body. Such a condition is called as endometriosis.

What is the cause of endometriosis ?

The exact cause of endometriosis is not yet known. There are a number of theories which have been postulated to explain this condition.

It is postulated that in women who have anomalies of the reproductive tract, retrograde menstruation occurs i.e., there is a backward flow of menstrual discharge. These endometrial cells implant on the ovaries or any part of the pelvic cavity where is grows and regresses every month in response to the menstrual changes.

It has also been thought that endometriosis may have a genetic origin as women whose mothers or sisters who suffer from endometriosis are more prone to it.

What are the symptoms ?

Many women with endometriosis may not have any symptoms. The type of symptoms and their intensity depends upon the location of the endometriotic tissue and the extent to which the disease has spread. However, the most common symptoms associated with endometriosis are:

• severe cramps during or prior to menstruation.

• pain during intercourse

• some women with endometriosis may complain of vaginal bleeding at irregular intervals.

• Infertility could be a result of endomtroisis.

How is it diagnosed?

The diagnosis of endometriosis cannot be made on the basis of the patients symptoms alone and needs to be confirmed by a diagnostic laparoscopy.

Laparoscopy is a minor surgical procedure by which a laparoscope (a thin telescope) is inserted into the abdomen through the navel. This enables the surgeon to directly visualize the reproductive organs. The presence of endometriosis and the extent to which it has spread can be gauged by the surgeon. Whether the endometriosis is deep or superficial and the extent of adhesions it has caused is determined and the endometriosis is scored as minimal, mild, moderate or severe.

Can it cause infertility?

Endometriosis on its own does not necessarily cause infertility. However, the endometriotic tissues can hinder conception. Endometriosis may cause adhesions around the ovary and the fallopian tube. These adhesions may interfere with the release of the eggs from the ovary; they may interfere with the capturing of the eggs by the fallopian tube. In such instances, endometriosis may be a cause of infertility.

Can it be treated with medications ?

Three different types of medications are available for the treatment of endometriosis. Endometrial tissue, be it at its natural site in the uterus, or the extra-uterine location of endometrial tissue in patients with endometriosis, is under the control of the hormones produced by the ovary. The aim of medical treatment is to prevent the secretion of hormones by the ovaries or negate their effect. In all these three types of medical treatment of endometriosis, menstruation ceases as long as the woman is on medication and the symptoms of endometriosis can be overcome. The three types of medications currently available are:

• Oral contraceptive pills can be taken continuously without waiting for a withdrawal bleed.

• Danazol. This drug leads to a drop in the levels of the hormone estradiol in the blood and prevents the proliferation of the endometrial implants. Small patches of endometriosis can be treated successfully with Danazol.

• Gonadotropin releasing Hormone analogs (GnRHa). These are the newest class of hormones that have been used to treat endometriosis. This drug creates a pseudo-state of menopause and as long as the woman is on GnRHa treatment, she produce negligible amounts of reproductive hormones. In the absence of reproductive hormones in the body, the endometrial lining becomes very thin.

All these medications have several side effects and need to be taken only under the supervision of a doctor.

Can endometriosis be treated surgically?

Endometriosis can also be surgically treated. If the endometrial implants are very large then it is advisable to surgically remove these implants. This is generally done under laparoscopic visualisation. The endometrial implants are "cauterised" or "ablated" with a mild degree of electrical current. This procedure should be performed only by a well trained endoscopic surgeon so that no part of the reproductive tract is damaged.

What are the other options of treating infertility in spite of endometriosis.

In women who have endometriosis and are infertile but do not suffer from any other symptoms of endometriosis then their problem can be treated by any of the assisted reproductive technologies. If her fallopian tubes are not blocked then she can be treated by intra-uterine insemination or gamete intra-fallopian transfer. If the tubes are blocked or are unhealthy then she can be treated by in vitro fertilization and embryo transfer.

What is a fallopian tube ?

The fallopian tubes emerge from each side of the uterus and extend to the surface of the ovary. The ovarian end of each of the tubes is funnel-like which surrounds the ovary. The funnel-like end comprises many fine, delicate finger-like projections called "fimbriae". These fimbriae "capture" the egg as soon as it is released from the ovary. If this egg meets the sperms, it gets fertilized in the tube and the early stages of embryo development takes place in the Fallopian tube. The cells of the Falopian tube provide all the nutrition needed by the egg, the sperms and the embryos.

What can go wrong with a woman’s fallopian tube ?

Damage to the fimbriae can result in them not being able to "capture" the egg and direct it into the tube. Damage to the inner linings of the cells of the tube can prevent fertilization; development of the embryo and in some instances the movement of the embryo towards the uterus resulting in an "ectopic pregnancy". The tubes may be blocked because of a pelvic infection and this will prevent the sperm from fertilizing an egg. Endometriosis may also result in tubal blockage. The fallopian tubes are surgically severed and the ends sewn up to prevent pregnancy.

What tests can be done to determine whether a woman’s fallopian tubes are normal ?

Three types of tests are now available for evaluating the status of the fallopian tubes. These are :

Hysterosalpingography: A radio-opaque dye is injected into the uterus through the vagina and then X-rays are taken. If the tube is not blocked then the dye can be seen emerging /spilling out of the fallopian tube. If no dye emerges out of the tube then one can conclude that it is blocked.

Hysterosonosalpingography: Where large amounts of fluid is injected into the uterus through the vagina. If the tubes are not blocked then this fluid emerges out of the fimbrial end of the fallopian tubes. The entire procedure is performed under ultrasound guidance and the fluid that comes out can be seen ultra-sonographically.

Diagnostic Laparoscopy: In this procedure, a fibre-optic telescope, a laparoscope, is inserted into the abdomen through the navel. With the laparoscope, the surgeon can directly visualise the status of the fallopian tube. One can see the position of the fimbriae and also whether the tubes are open or blocked. Then a coloured dye such as methylene blue is injected through the vagina. If the tubes are open (patent) then the dye spills out of the fimbrial end of fallopian tube immediately. No dye will spill out of the fallopian tube if it is blocked. And if there is some damage to tube then the dye will spill out slowly.

Can abnormalities of the fallopian tube be corrected ?

If the fallopian tube is blocked because of tubal ligation as in cases of tubal sterilisation then it can be surgically reversed. However, whenever the blockage of the tube is a result of pelvic infection then surgical correction may not be possible. No medical therapy is known as yet to correct damaged fallopian tubes.

What are the options available for women with damaged fallopian tubes to bear a child ?

In women where there is a pathological damage to the fallopian tube then surgical correction of the tube is not possible. In such women the best option for bearing a child is in vitro fertilization and embryo transfer.

What is the role of the cervix in a normal conception ?

The cervix acts a "sentry" restricting the entry of "poor quality" sperms, cells other than sperms present in semen and the seminal plasma from entering into the uterus. It acts as a natural filter and only the highly motile sperms enter into the upper reproductive tract of the women. It also acts as a store house where the sperms are stored in the cervical mucus.

How can one diagnose whether the cervix is hostile to sperms ?

The Post-Coital Test is the most apt test to detect whether the cause of infertility in a couple is a "hostile cervix".

What is the post-coital test ?

For this test, secretions of the cervix are studied under the microscope few hours after a couple has been advised sexual intercourse. It is very important to perform this test during the middle of the menstrual cycle. The specific detailed instructions for this test would be given to you by your doctor.

What are the reasons why a cervix can be hostile to sperms ?

In some women, the cervix "overdoes its sentry duty" and in such women the cervix not only prevents but may also damage the sperms which are trying to gain entry into the uterus.

The different reasons as to why a cervix can be hostile to sperms are:

• The woman’s lower reproductive tract may be infected with microorganisms which may produce substances which are toxic to the sperms.
• Some women may produced anti-sperm antibodies which bind to the sperms; immobilize them and prevent them from passing through the cervix.
• The cause of cervical hostility remains unknown but a post-coital test shows the presence of non-motile sperms.

What are the treatment options available for a woman with a hostile cervix ?

It is important to identify the cause for the cervical hostility. If it is due to a microbial infections then the same can be treated with appropriate antibiotics. If it is due to anti-sperm antibodies or if the cause of a poor post-coital test is unknown then the best treatment option for infertility in such women would be intra-uterine insemination.

Hyperprolactinemia

What is hyperprolactinemia ?

Prolactin is one of the hormones produced by the pituitary gland located in the brain. This hormone stimulates lactation in women and its presence in concentrations higher than normal in non-lactating women is termed as "hyperprolactinemia".

What is the normal function of the hormone prolactin ?

Prolactin stimulates production of breast milk in women after the delivery of a child. This hormone prevents the secretion of hormones, follicle stimulating hormone and Luteinising hormone which are essential for normal growth of egg-containing follicles in the ovaries. Therefore, lactating women do not ovulate or menstruate. Presence of higher than normal concentrations of prolactin in the blood of non-lactating women affects normal ovulation in these women and can be one of the causes of infertility.

What are the tests performed to diagnose hyperprolactinemia ?

Hyperprolactinemia can be detected by estimating the concentration of the hormone "prolactin" in the blood. This blood test need not be done on an empty stomach. In cases where the concentration of prolactin in the blood is in the borderline state, it is advisable to repeat the test and see what is the average concentration of the hormone before embarking on any treatment.

Some of the women who have hyper-prolactinemia may have some breast secretions. Observations of these secretions under the microscope show the presence of fat globules.

What are the causes of hyperprolactinemia ?

High prolactin levels in the blood in non-lactating women may be due to several factors:

• The prolactin producing cells in the pituitary may be hyperactive.

• Certain drugs such as tranquilizers, pain killers and alcohol may cause a rise in prolactin levels.

• Stress also induces hyperprolactinemia.

• Prolactin producing cells in the pituitary form a cluster – a benign (non canerous) tumour resulting in excess production of prolactin. In cases of very high concentrations of prolactin in non-lactating women, a computed tomography scan needs to be carried out to rule out a pituitary adenoma.

Can hyperprolactinemia affects a woman’s fertility ?

Lactating women do not ovulate. Therefore women with hyperprolactinemia also have ovulatory disorders and therefore compromised fertility.

UTERINE FIBROIDS

What are fibroids ?

The outer wall of the uterus (the womb) in the woman is covered by a thick muscular layer. The presence of abnormal masses of smooth muscle tissue on the uterine wall is termed as fibroids. There may be one large fibroid or several small ones. These fibroids generally form in women who are in their 30s or 40s and regress with menopause. These fibroids may result in excessive uterine bleeding, abdominal pain, a feeling of great pressure in the lower abdomen, infertility, miscarriages or premature delivery while some women may have no symptoms associated with the fibroid. Fibroids are also termed as leimyomas or myomas.

Are there different types of fibroids ?

Fibroids are termed as "sub-serous", "intramural" or submucous" depending upon their location in the uterine cavity. Sub-serous and intramural are the most common types of fibroids and are located beneath the outer peritoneal covering of the uterus and in the muscular uterine wall respectively. The sub-mucous fibroids are present in the uterine cavity.

How can these fibroids be detected ?

Large fibroids are easily visualized by ultra-sonography. The high frequency waves create an image of the pelvic organs and presence of an abnormal mass in the abdomen clearly indicate the presence of fibroids.

The presence of the fibroids can be confirmed by a diagnostic laparoscopy and a diagnostic hysteroscopy.

Are these fibroids cancers ?

These fibroids are not cancerous.

Can these fibroids affect a woman’s chance of conceiving ?

The presence of a fibroid by itself may not necessarily interfere with the chances of a woman conceiving but will depend upon the location and the size of the fibroid.

Can fibroids be treated with medications ?

The size of the fibroid can be temporarily reduced by the administration of a drug called gonadotropin releasing hormone analogue (GnRHa). Long term administration of this drug stops the pituitary from secreting hormones which in turn prevents the ovaries from secreting its hormones. The absence of ovarian hormones results in the shrinkage of the uterine fibroids. These medication cannot be used for extended periods of time and therefore GnRHa is used primarily to decrease the size of fibroid prior to surgery and in women who have become anemic due to excessive bleeding and cannot be operated to remove the fibroid.

Should these fibroids be removed ?

It is not always necessary to remove the fibroids. If a woman is not having excessive bleeding, or abdominal pain i.e., if the fibroid is not bothering her then it is not important to remove the fibroid. The decision on whether to remove the fibroid or not depends upon the location and size of the fibroid and if the woman has had any history miscarriage.

Depending upon the location of the fibroid, it can be removed either laparoscopically or hysteroscopically.

If a woman is pregnant, can the fibroid interfere with her pregnancy ?

The fibroid does not always interfere with pregnancy. However, if the fibroid is present very close to the fetus or the embryo then it can lead to a miscarriage or abortion.