Directing the Elusive Stork

Directing the elusive stork

Infertility is defined by the World Health Organisation (WHO) as the inability of a couple to conceive after unprotected sex for two years . Interestingly, the clinical definition limits the exposure period to only 12 months . In fact, if a woman is above 35 years old, most specialists will advise her to undergo infertility evaluation after only 6 months of unprotected intercourse.

Generally, one in ten couples experience primary or secondary infertility. Primary infertility refers to couples who have never conceived while secondary infertility refers to couples who have conceived previously but are unable to do so thereafter.

The approach used in infertility treatment centres on increasing eggs, increasing sperm and reducing the distance that the sperm has to travel to reach the egg.

How babies are made

An understanding of the conception process would be useful in appreciating the various tests that may have to be taken and treatments that are available.

First, the woman's egg (oocyte) goes through a maturity process in the ovary. Then, the ovary releases the matured egg (ovum) and it will travel along the fallopian tube towards the uterus.

The man's sperms are produced and developed in the testicles. They are transported to the epididymis where they go through a maturity process. During ejaculation, the sperms are pushed into tubes called the vas deferens, which carries them to the prostate gland and into the urethra to be ejaculated into the woman's upper vagina. The sperm will then swim through the cervix, overcoming obstacles in the form of seaweed-like mucus which stretched downwards along the cervical canal. Soon after, they 'traverse' the uterine cavity to reach the opening to the fallopian tubes at the top. By now, only a few hundreds out of the millions ejaculated would survive. They then enter the fallopian tubes, swimming against the current where only a few hundred would succeed.

If the timing is right, a sperm will reach the egg and fertilization will occur in the fallopian tube. The fertilized egg travels back to the uterus to implant itself into the soft, juicy uterine wall and develops into a baby.

When there is a problem in ANY part of the conception process, the result is infertility.

The woman or the man?

Traditionally, when a couple fails to produce a baby, all eyes are cast on the woman. Some mothers-in-law go to the extent of encouraging the son to marry a second wife to ensure the continuity of the family genetic lineage, with a preference for women with big bums. However, statistic has shown that 35% of infertility cases are attributable to male factor, the same percentage as female factor. In the balance of the cases, the cause is either unknown or due to problems in both partners.

The male factor

Infertility may be caused by genetic factors and lifestyle choices like smoking and alcohol. It can also result from illnesses, infections and injuries. Consequently, these factors impact on the quality and quantity of sperm, lead to structural abnormalities, damage the reproductive organs and give rise to ejaculatory problems.

Quality and quantity of sperm

There are many ways that sperm can be affected, thus reducing a man's ability to father a child.

1. Azoospermia – the absence of sperm in the semen. This can be a result of hormonal or chromosomal deficiencies often linked to testicular failure.
2. Oligospermia – a low sperm count.
3. Asthenospermia – Loss or reduction of motility in the sperm. Motility refers to the ability to move spontaneously.
4. Teratospermia – malformed sperm.
5. Globospermia – 'round-headed' sperm.
6. Necrospermia – a rare condition where all the sperm in the ejaculate are dead or motionless.

Structural abnormalities

1. Varicocele – when the veins along the spermatic cord are dilated. The spermatic cords suspend the testicles in the scrotum. Varicocele causes the blood to flow back from the abdomen into the scrotum. This raises the temperature in the testicles and affects the production of sperm.
2. Undescended testicles (cryptorchidism) – usually diagnosed during examination for a newborn. It has been found that men who have had this condition produce lower sperm quality and lower sperm count.
3. Congenital bilateral absence of vas deferens – when the tubes that carry sperm (vas deferens) failed to developed normally, therefore, sperm cannot be transported through the male reproductive system. It is due to mutation to a specific gene.
4. Congenital absence of seminal vesicles – caused by cystic fibrosis. The seminal vesicles, together with the prostate, contributes 90% of the quantity of the ejaculate. Their absence will reduce the amount of ejaculate as well as increasing the ejaculate's acidity, a condition that is hostile to sperm.

Blockage or damage of reproductive tract

When any section of the reproductive tract is blocked or damaged, sperm transportation is therefore interrupted. The epididymis and vas deferens can be damaged or blocked by sexually transmitted diseases like gonorrhoea and chlamydia. Likewise, the ejaculatory duct will be blocked when the prostate is infected.

Ejaculatory problems

1. Retrograde ejaculation – where ejaculation is directed into the bladder, instead of out the penis. It can be caused by illness like diabetes.
2. Anejaculation – the absence of ejaculation caused by spinal cord injury, major lymph node surgery, diabetes or multiple sclerosis.
3. Hypospadias – a birth defect in which the male urethra is located off the tip of the penis. This causes the sperm to be deposited outside the vagina.

Diagnosis - male

A diagnosis would involve a careful evaluation of the man's medical and surgical history. Childhood diseases like mumps and current illnesses like diabetes, affect the development of sperm. In addition, the doctor would want to know of any occupational or environmental hazards such as exposure to heavy metals, radiation and pesticides. Intimate questions on sexual habits are routine. This includes frequency of intercourse and ejaculation.

The doctor will also conduct a physical examination of the reproductive organs to look for abnormalities in appearance and measurements.

A carefully performed semen analysis is a highly predictive indicator of the functionality of the man's sperm, hormonal cycle and reproductive tract. Most doctors collect at least two specimen on different days, each obtained by masturbation after 2-3 days of abstinence, on the site of analysis. The specimen has to be examined within one to two hours of collection.

Depending on the results of the semen analysis, further tests may be conducted, either to help confirm specific abnormalities or to identify other sources of problem. Examples of these tests are:
1. Antisperm antibodies – test for the existence of antibodies that bind to the sperm, reducing fertility.
2. Semen fructose – test for the existence of fructose, a sugar-like substance in the semen, the absence of which is an indication of blocked vas deferens or missing seminal vesicles.
3. Sperm penetration assay – the ability of the sperm to penetrate an egg during fertilization. Hamsters' eggs are used in the test.

Treatment – male

According to the World Health Organisation , most men who are infertile have either no demonstrable cause or suffer from conditions for which treatment is debatable. Consequently, only about 20% of these men have the potential to be treated with some degree of success.

1. Drugs and hormonal injection

Fertility drugs can be used to treat hormonal imbalance in men that is linked to low sperm count, although they have not been as successful on men as they have on women. Sometimes, a doctor may also prescribe drugs for poor sperm quality and motility.

Two of the more popular drugs are clomiphene (tablet, taken daily) and human menopausal gonadotropin (hMG) used with human chorionic gonadotropin (hCG – injection, two to three times a week). These drugs prompts the testicles to produce the male hormone, testosterone, and sperm. Of course, side effects can be expected such as breast tenderness, blurred vision and weight gain.

Sperm production is a long process, requiring 70 days for matured sperm to be produced. Hence, treatment with these hormones would take a long time too, sometimes extending over 2 years.

2. Surgery

Surgery is performed in cases of reproductive tract obstruction and varicocele. For men who has vasectomy previously, a reversal of the procedure is available where the vas deferens are rejoined. Whether or not this translate into successful pregnancy depends very much on the time lag between the original vasectomy and the reversal procedure. The longer the time, the less successful it becomes.

Blockage in the epididymis has less chance of being successfully bypassed due to the thinner and smaller veins. Surgery is also necessary when there is cyst in the prostate gland that blocks the sperms' entry into the ejaculatory duct.

Varicocelectomy is a surgical procedure to remove varicocele where the affected veins are tied-off to redirect the blood into other normal veins. Alternatively, varicocele can be treated by inserting a glue-like substance into the veins to block blood flow and thus prevents varicocele from forming, a procedure known as embolisation. It should be noted that varicocele may recur after embolisation and some studies have failed to show any benefit of having a varicocelectomy performed.

3. Medically assisted conception

There are some factors of infertility where no treatment is available. For instance, if a man suffers from congenital absence of vas deferens or seminal vesicles, reconstruction of such tract is not possible. Similarly, ejaculatory problems may be difficult to overcome. When all else have failed, medically assisted conception, which includes assisted reproduction techniques (ART) can be used to achieve prenancy.

In respect of male infertility, the most common approach is to extract sperm from the reproduction organs and use them to fertilize the female egg, either naturally or assisted. As long as sperm is produced, even if the reproductive tract is not functioning, there is still hope of bringing forth one's own child.

For men with anejaculation, they can undergo either penile vibrostimulation or electrostimulation in order to obtain an ejaculate. Electrostimulation presents some risks of hypertension and internal bleeding in the brain to men with chronic spinal cord injury.

The female factor

Female infertility can be classified into:

1. Failure to produce eggs
1. Age - one of the most important risk factor in female infertility is age. A woman's eggs degenerate as she grows older and therefore carry a higher risk of chromosomal abnormalities. Older women are also more likely to have health problems which interfere with fertility.Men, too, experience decreasing fertility as age increases. However, in this respect, they lag behind women by approximately 10 years.
2. Weight - being overweight would cause an overload of estrogen in the body, resulting in primary ovulatory infertility. Similarly, being underweight would also throw the body's hormonal equilibrium into disarray. Lifestyle choices like smoking, alcohol, caffeine consumption and drugs are responsible for various type of female infertility.
3. Polycystic ovary syndrome (PCOS) - Women who suffers from PCOS have fluid-filled sacs in their ovaries. These are initally follicles, each with its own developing egg. Through a complex process, one of these follicles is selected to continue developing into maturity. It will then rupture and release its egg. In PCOS, the ovaries produce too much androgen (male hormones) resulting in hormonal imbalance. Consequently, the follicle is prevented from advancing into maturity, swells with fluid and forms into cyst. The ovary will then swell with each episode of trapped egg. Without ovulation, it is not possible for fertilization to occur.
4. Early menopause (premature ovarian failure) - Some women may experience early menopause when their follicles are depleted before age 40. It could be due to genetic factors, deficiency of glands and diseases.

2. Blocked passage
1. Pelvic inflammatory disease (PID) - PID is an infection of the upper genital tract caused by sexually transmitted diseases such as gonorrhoea and genital chlamydia infection. It affects the uterus, ovary, fallopian tubes and other related structures. Severe or frequent attacks of PID adversely affect a woman's fertility by scarring and damaging the fallopian tubes. Other complications include ectopic pregnancy and chronic pelvic pain.
2. Endometriosis – a condition where the tissue lining the uterus (endometrium) forms cysts in the muscle of the womb or when the lining is found outside the uterus like the ovaries, fallopian tubes, bladder, bowel and other organs. They respond to the menstrual cycle like the uterus but their shed lining is trapped in the body, causing scarring and inflammation. Endometrial growth in the fallopian tube may block the egg's passage while those in the ovary may obstruct the release of eggs. Eggs may be prevented from transferring into the fallopian tubes when there is a web of rigid scar tissue connecting the uterus, ovary and fallopian tubes.
3. Uterine fibroids – uterine fibroids are tumours or lumps made of muscle cells and other tissue that grow within the wall of the uterus. It may cause infertility by blocking the fallopian tubes, distorting the uterine cavity and altering the position of the cervix which then prevents sperm from entering the uterus.

3. Implantation problem

Immediately after ovulation, i.e when the follicle in the ovary is burst and the egg is pushed out, the now collapsed follicle along with the other few follicles that failed to make it (collectively known as corpus luteum) begin to produce the progesterone hormone. The main function of this hormone is to prepare the uterus lining for the fertilized egg to implant. It thickens the lining and induces glands to secrete a nutritious fluid, making the lining succulent.

Sometimes, a problem may occur in this process, also known as luteal phase defect. There could be inadequate progesterone due to premature failure of the corpus luteum or poor follicles being produced. On the other hand, progesterone level could be normal but the uterus lining fail to respond to it, rendering it ill-prepared for implantation.

Diagnosis – female

As in the diagnosis of male infertility, an evaluation of the medical (including menstrual) and surgical history of the woman serves to narrow down the causes of infertility.

A series of tests would be done to determine if the woman is ovulating and to look for abnormalities in her uterus and fallopian tubes.

Determining ovulation

1. Basal body temperature chart
This is an inexpensive step that can be undertaken by the woman herself. A woman's temperature is lower during the first half of a menstrual cycle. It rises around the time of ovulation and remain so for about two weeks. By using a special thermometre, the woman takes her temperature first thing in the morning and records it in a chart over several months. A rise of 0.4 degree Centigrade or higher in a 24-hour period is an indication that ovulation has occurred, after discounting for any illnesses that may cause the rise.

2. Hormone test
A urine test kit, called an ovulation predictor kit, can be used to detect if there is a surge in a hormone known as the luteinizing hormone (LH). This hormone induces one of the egg follicles to burst and expel its contained egg. Hence, a surge signifies ovulation has occurred.

Several other hormones are also routinely checked in cases of infertility. Blood test on follicle stimulating hormone (FSH), thyroid stimulating hormone, prolactin, estrogen and progesterone helps in predicting factors like premature ovarian failure, polycystic ovarian syndrome and luteal phase defect.

Determining structural abnormalities

In investigating structural abnormalities, there are several ways in which a doctor can 'look' inside a woman's body.

1. Hysterosalpingogram – this is performed to check for possible blockage of the fallopian tubes and abnormalities in the uterine cavity. A special oil or water-based dye is injected through the cervix into the uterus. A series of x-ray is taken as the dye fills the cavity and moves up to the tubes. If the tubes are 'open', the dye will spill out at their ends into the peritoneal cavity. One study has shown that flushing the tubes with oil-based dye may improve fertility. Side effects include cramping, allergy to the dye and pelvic infection. Abnormalities that may be detected are endometriosis growth, fibroids, polyps (mass of tissue projecting outwards from the surrounding tissue), pelvic scar tissue and blockage in fallopian tubes.
2. Hysteroscopy – instead of viewing using x-ray, a telescope attached to a light source called hysteroscope is inserted through the cervix into the uterus to gain insights of the uterus and fallopan tubes. A gas (carbon dioxide) or liquid (saline) is used to inflate the cavity for a better view. Very often, some conditions are treated during the procedure like cutting away scar tissue and removing endometrial implants. Hysteroscopy is usually carried out in conjunction with a laparoscopy.
3. Laparoscopy – a laparoscope is a narrow surgical telescope much like the hysteroscope but usually wider in diameter. It is inserted into the abdomen, instead of the cervix, through a very small incision below the navel, providing a view outside the uterus. Carbon dioxide is blown into the abdomen to ensure space exist between the organs. A small video camera is usually attached to the outer end of the scope so that the image may be viewed on a TV monitor. It allows the doctor to scan the pelvic cavity for endometriosis, adhesions, scarring or fibroids.
4. Ultrasound – high frequency sound waves are used to create a moving image (sonogram) on a television screen. Conditions like the shape, status and position of the reproductive organs can be seen. It can also be used to measure the thickness of the uterus lining to determine if it is ready for embryo implantation.

Apart from viewing the reproductive organs to check for abnormalities, an endometrial biopsy may be carried out. A swap of the tissue from the uterus lining is taken to be examined if the corpus luteum is producing progesterone adequately or if the uterine lining responds normally to progesterone. Tissue sample of the cervix may also be evaluated to rule out infection.

A post-coital test can provide insights into unsuccessful fertilization. Cervical mucus is collected a few hours after the couple has intercourse at home. Then, it is examined to check adequacy of the woman's cervical mucus production, the amount of sperm movement and the ability of the sperm to penetrate the mucus.

In order to provide guidance on the appropriate treatment, sometimes, a chomiphene citrate challenged test (CCCT) is conducted to evaluate a woman's ovarian reserves, i.e the number of remaining eggs and their quality.

Treatment - female

1. Drugs

The use of fertility drugs is typically the first step in the treatment. They are used to:

· correct specific hormonal imbalances to induce ovulation; or
· enhance the normal ovulation process where several eggs are produced in a cycle, compared to the usual one egg, to be used with assisted reproduction techniques (ART). This is known as super-ovulation.

Fertility drugs are broadly categorised as oral and injectable:

1. Clomiphene citrate – taken orally, it acts by misleading the brain into believing that the level of estrogen is very low. This causes the pituitary gland to release more FSH and LH, which stimulate the growth of an ovarian follicle containing an egg. There is a 5% risk of multiple births in women treated with clomiphene per se, primarily twins. There is also a possibility of developing ovarian hyperstimulating syndrome (OHSS) in which the ovarian is greatly enlarged, a condition that can be life-threatening. Side effects include hot flashes, mood swings, depression and weight gain.
2. hMG (human menopausal gonadotrophin) - this injectable is used when clomiphene has been unsuccessful. It contains either FSH and LH or just LH alone. Unlike clomiphene which acts indirectly, HMG stimulates the ovaries directly to produce more follicles, and therefore more eggs. It is popular for women with polycystic ovarian syndrome. The main risks are multiple births, OHSS and ectopic pregnancy.
3. hCG (human chorionic gonadotrophin) – Both clomiphene and hMG cause eggs to grow but do not trigger ovulation. This is where hCG is injected to stimulate the follicles to release the eggs. Ocassionally, it is also used to support the second half of the stimulation cycle since a sequential low dose will promote the production of progesterone that is required to prepare the uterine lining for embryo implantation. In men, hCG can be used to enhance sperm production.
4. GnRH (Gonadotrophin releasing hormone) analogues – commonly employed with in-vitro fertilization, these are given to 'turn off' a woman's own production of FSH and LH so as not to interfere with the hormonal treatment prescribed by the doctor. This gives the doctor more control on the stimulation that is achieved by preventing premature ovulation. Other than that, it is used to treat endometriosis. They are two types of medicines under this class of drugs – the GnRH agonist and GnRH antagonist, the choice of which is dependent on the doctor's evaluation of the patient's condition.
5. Progesterone – this is necessary to ensure the uterine lining is ready for implantation and to maintain the pregnancy should one occur. Supplementation of progesterone is typically performed with ART.
6. Bromocriptine – inhibits the production of prolactin, the hormone that stimulates milk production, thus allowing normal ovulation to take place.

2. Surgery

Surgery is an option when infertility is due to blockage and abnormal growth in the organs. Unblocking the fallopian tubes or removing fibroids, endometriosis, pelvic adhesions caused by sexually transmitted disease and ovarian cysts can increase the chances of conception. The types of surgery normally conducted are laparoscopy, hysteroscopy and laparotomy.

Laparotomy is an open exploration of the abdomen and pelvis. It requires anaesthesia and the incision is similar to a caesarean section.

For a woman who suffers from hydrosalpinx, a condition where there is buildup of fluid at the end of fallopian tubes near the ovaries, surgical removal of that part that generates the fluid will improve fertility.

Although not recommended as the first course of treatment, 'ovarian drilling' is an alternative treatment for women with PCOS. During a laparoscopy, the surgeon punctures 4 to 10 holes in the ovary by using a laser fibre or electrosurgical needed. Visually, it is like puncturing a throw-pillow. Amazingly, this treatment can reduce the male hormone level and restore ovulation, albeit only for a few months. There is a risk of developing scar tissue on the ovary.

3. Medically assisted conception

While ovulation disorder is basically treated with drugs, structural abnormalities that persist even after surgery and other methods, may be indicated for assisted conception. As a matter of fact, assisted conception is frequently combined with a drug regimen.

Absence of cervical mucus may be overcome with artificial insemination or in-vitro fertilization cum embryo transfer (IVF-ET), so too is the presence of antisperm antibodies in the cervix. For other conditions like irreversible tubal damage and absence of fallopian tubes, IVF-ET may be the only option.

Seek counselling

Infertility touches many aspects of a person's life. It affects one's perspective on life, how one feels about self and the relationship with spouse and others. Owing to the fact that it can be an extremely lonely journey, many people will benefit from support of professional counsellors. Seeking the help of professional counsellors should not be construed as failure on one's part. Rather, it is very much an essential element in a holistic approach to rise above the problem.

By Quah Kim Lan

Disclaimer

This article is intended for general use only. Please consult your doctor before deciding on any of the above methods.

Side bar 1: Speak like the doctors do – egg terms

1. Oocyte – an egg cell that has not developed completely.
2. Ovum – The egg cell, which is matured and is ready to be expelled from the ovary.
3. Ova - the plural form of ovum.
4. Zygote – the first 3 to 5 days of fertilized egg when it travels along the fallopian tube to go to the uterus.
5. Blastocyst – the fertilized egg in the uterus that has developed into a hollow ball of cells where the shell (zona pellucida) has dissolved.
6. Embryo – the product of conception from the time of fertilization until the beginning of of the 8th week. During this short period almost all the major structures have formed.
7. Foetus – the product of conception from the end of the 8th week until birth, at whatever period of the pregnancy this may be.
8. Gamete – a reproductive cell, whether egg or sperm.

Side bar 2 : Interesting Egg Facts

A baby girl is born with egg cells (oocytes) in her ovaries. These oocytes were developed very early in life and by the 22nd week of pregnancy, numbered 7 million. They waste away leaving 2 million present at birth. No oocyte is developed after birth.

During childhood, many more oocytes are destroyed and by puberty only 200,000 remain. Each month, between puberty and menopause, 12 – 30 oocytes develop further, one of which will outdo the rest in growth and be expelled from the ovary. This is the ovum which may be fertilized.

In the whole of a woman's reproductive life, only 400 eggs are released. Thousands of oocyte that do not mature, degenerates, more rapidly in the 10 to 15 years before menopause. All oocytes are gone by menopause.

Side bar 3: What not to say to those who are trying to conceive

1. You need to relax and go on a holiday. That'll help you.
2. Maybe you are not meant to have a child.
3. I would have quit long time ago.
4. All that money spent on treatment could be used for something that's more certain.
5. I would be planning on my retirement if I were you.
6. You should be happy with the one you have (secondary infertility).