Fertility drugs are extensively used in treating infertility. These include: Clomiphene, Letrozole, Bromocriptine, Danazol, Growth Hormone, HMG, HCG,FSH, GnRH analogs, GnRH anatgonists.It's a long list, and this can be quite intimidating !

They are usually the first line of therapy in treating female infertility. You must be aware of what medicines you are taking and why. It's easy for doctors to prescribe fertility drugs - but it's your responsibility to be well-informed about your medicines, so you know what to expect.

Different Fertility Drugs

Bromocriptine

This is a drug which is used specifically to treat women with hyperprolactinemia - a condition in women fail to ovulate because the pituitary is producing too much of the hormone called prolactin. Hyperprolactinemia is the cause of menstrual disturbance in about 10% of anovulatory women. Bromocriptine lowers prolactin levels to normal (the normal range in most laboratories being less than 20 ng/ml) and allows the ovary to get back to normal.

Side effects: The drug often causes nausea and dizziness during the first few days of treatment but the chances of these symptoms occurring can be reduced by starting the drug at a very low dose and gradually building up to a maintenance dose of 2 or 3 tablets daily.

Dose: A 2.5 mg tablet is available ; and the starting dose is usually 2.5 mg to 5 mg daily - taken at bedtime. After starting bromocriptine, prolactin levels can be tested (after at least one week of medication) to confirm that they have been brought down to normal. If the levels are still elevated, the dose will need to be increased. Once normal prolactin levels have been achieved (and some women need as much as 4 to 6 tablets a day to achieve this) this is then the maintenance dose.

Once your prolactin blood level is within the normal range, your periods should become more regular and you should start ovulating normally again. Remember that bromocriptine only suppresses an elevated prolactin level while you are taking it - it does not "cure" the problem.

This is why the tablets must be taken daily until a pregnancy occurs, after which they should be stopped. This is expensive medication - and some pharmaceutical companies may provide it at reduced rates if your doctor requests them to do so on your behalf.

Danazol
This is a synthetic hormone, prescribed as one type of treatment for endometriosis. It acts by suppressing the brain's production of follicle stimulating hormones and hence suppresses ovarian function. This is similar to an artificial menopause and results in the shrinking of not only the endometrium in the uterus (and hence no periods); but also hopefully the misplaced patches of endometrium outside the uterus found in patients with endometriosis, causing them to disappear.

Side Effects: Hot flushes, weight gain, acne, hirsutism (hairiness). These side effects are quite troublesome, and some women have to discontinue the drug because of these. Usually, while taking the danazol, your periods will stop completely - pseudomenopause.

Dose: The standard dose used to be 800 mg daily (4 tablets of 200 mg each). However, the side-effects at this dose are considerable, and many doctors have reported good results with doses as low as 200 mg daily. The usual course of treatment is 6-9 months and the extent of the improvement in endometriosis is then reviewed. Danazol is expensive medication, and is usually not advised for women with endometriosis who are trying to get pregnant.

Steroids

Dexamethasone, is often use as an adjunct to ovulation induction treatment, especially in patients with hirsutism who have high levels of androgens. It helps by suppressing the production of androgens by the adrenal glands. The dose is usually a 0.5 mg tablet, taken daily at bedtime. Side-effects at such a low dose are unusual.

Clomiphene

Clomiphene is the drug of first choice for inducing ovulation - growing eggs. It is cheap, effective, easily available and well tolerated. It is also used for superovulating normal women to help them grow more eggs.

Clomiphene is an antiestrogen and it acts by "fooling " the pituitary into believing that estrogen levels in the body are low as a result of which the pituitary starts producing more FSH and LH - the gonadotropin hormones which in turn leads to stimulation of the ovaries. Only women who produce estrogen will respond to clomiphene; and some doctors will test for this by seeing if they bleed in response to progestins - a progestin challenge test.

Dose- The starting dose is one tablet (50 mg.) a day for five consecutive days. The first tablet can be taken on day 2, 3, 4 or 5 of the cycle - this is usually decided by your doctor and depends on the length of your menstrual cycle. It is not enough to just take clomiphene - it is equally important to monitor the response as well. This is best done by serial daily vaginal ultrasound scans. The ovulation induced by clomiphene occurs about 5 to 7 days after the course of tablets is completed - that is, day 12-16 of your cycle.

If ovulation fails to occur, the dose can be increased for subsequent cycles, till upto 200 mg per day. Often human chorionic gonadotrophin (HCG) is given to trigger ovulation to mimic the woman's natural LH surge. Ultrasound and blood oestrogen levels may be used to determine the best day to administer HCG. If ovulation does not occur - the patient becomes a candidate for HMG or FSH (see below).Usually blood testing of progesterone levels (done 7 days after ovulation) accompanies clomiphene treatment to help identify the correct dosage needed. Clomiphene induces ovulation in approximately 70% of appropriately selected patients and has a 30-40% pregnancy rate.

Clomiphene increases a woman's risk of twin pregnancy by approximately 10%. However, the risk of having more than two babies is 1 %. Occasionally ovarian cysts occur following clomiphene administration. These usually disappear when the drug is stopped.

Side Effects

Side effects can include hot flushes and mood swings early in the cycle,; and depression, nausea and breast tenderness later in the cycle. Severe headaches or visual problems, though rare, are indications to stop the medication.

As clomiphene works as an "antioestrogen" it can have an adverse effect on cervical mucus making it thicker than usual. It is therefore important to check on sperm/mucus survival with a post coital or post insemination test. If this is consistently negative due to poor mucus, a change of medication may be advised. Alternatively, low-dose estrogens may be added to your treatment.

Long term effects

As the drug is only given for 5 days early in the cycle it does not have any long term effect on future ovulations or on hormone levels; or on pregnancy. Some doctors were worried that the prolonged use of clomiphene would increase the risk of the patient developing ovarian cancer. However, extensive research has shown that this worry is unfounded.

Gonadotropins

Gonadotropin treatment is "big-gun " therapy, and is usually reserved for difficult anovulatory problems. The two gonadotropin hormones, Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) are produced in the pituitary and their secretion is controlled by a third hormone, Gonadotropin Releasing Hormone (GnRH), released by the hypothalamus.

At the start of a new cycle, the hypothalamus begins to release GnRH. GnRH then acts on the pituitary gland to release FSH and LH. These two hormones stimulate the ovary, causing follicles to develop (as the name suggests, this is the primary action of the FSH - to stimulate follicular growth). When it is time for ovulation, a sudden burst of LH is released from the pituitary (the LH surge) which causes the egg to be released from the mature follicle in the ovary.

How does Nature ensure that only one egg is released every cycle?

About 30-40 follicles will start growing in response to the FSH produced by the pituitary. However, of these follicles, only one is destined to grow (become dominant) and rupture to release its mature egg. The others will die - a process called atresia. The dominant follicle releases increasing amounts of estrogen as it grows bigger.

This estrogen in turn decreases the production of FSH by the pituitary (in a negative feedback control loop), so that without high levels of FSH, the smaller follicles no longer have a stimulus to grow; and they gradually die. The dominant follicle by now has become so big, that it can grow by itself, and doesn't need the additional FSH stimulation.

FSH

This represents a more recent purified form of HMG which contains mostly FSH and negligible amounts of LH. The indications for use, administration and ovarian response are almost identical to HMG. However, as FSH contains almost no LH, it has a theoretical advantage for women with PCO ( polycystic ovarian syndrome) who characteristically have an elevated LH level. However, it is also more expensive than HMG.

HCG

HCG is produced by the placenta during pregnancy. Because it is very similar biologically to LH it is used to trigger ovulation by mimicking the natural LH surge at mid cycle. It can be used in combination with Clomid and also HMG/FSH to induce ovulation. It is isolated and purified from the urine of pregnant women. It is available in ampoules as a sterile white powder containing 5000 IU or 10000 IU. This powder is dissolved in a diluent and administered by IM injection.

Synthetic GnRH

Synthetic GnRH stimulates the pituitary gland to secrete LH and FSH. It is used to induce ovulation in selected women with hypothalamic dysfunction. The hormone has to be given in a manner which mimics the natural secretion of LHRH, i.e. in "pulses" approximately 90 minutes apart. This is given by means of a small pump placed under the skin of the arm or abdomen. This treatment is now given instead of HMG at certain specialist centres. It has the advantage over HMG that it produces an ovulation cycle which is similar to the natural cycle and multiple ovulation is very unusual.

GnRH Analogues

These drugs may be used for the treatment of endometriosis and fibroids. They work by initially stimulating, then switching off ( down-regulating) the pituitary gland, and are administered intranasally or by injection. They thus induce a "menopausal" state, allowing the endometriosis and fibroids to shrink, since there is no further production of estrogens.

GnRH analogs are most commonly used today as adjunctive therapy in order to enhance induction of ovulation with HMG, especially for IVF ( in vitro fertilization) treatment. Your own gonadotropins (FSH and LH) are turned off by the GnRH analogues ( this is called pituitary downregulation) , so that your physician has a clean slate to work with when administering exogenous gonadotropins to induce superovulation.

GnRH antagonists

Currently, most in-vitro fertilization (IVF) centres use pituitary down-regulation with gonadotrophin-releasing hormone (GnRH) agonists to prevent premature luteinization. However, this requires at least 7-14 days of GnRH agonist pretreatment. A more rational approach would be to use the newer GnRH antagonists, which cause an immediate blockage of the GnRH receptors on the pituitary gland.

Thus , treatment with the antagonist can be limited to only those 2-3 days when high oestradiol levels may induce an LH surge. Clinical experience with GnRH antagonists in IVF treatment thus far has been encouraging and demonstrates a high efficacy in preventing the LH surge.

Growth Hormone

Some women will respond very poorly to HMG injections. They grow few or no follicles, inspite of being given large doses. In some of these "poor responders" synthetic growth hormone (HGH, human growth hormone) has been used to try to enhance the response of the ovary to the HMG. However, the response to this very expensive drug has been quite disappointing, and it is no longer used.

Medicines Used In Male Infertility Treatments : HMG and HCG

These are useful in stimulating sperm production in men with hypogonadotropic hypogonadism (men with low FSH and LH levels, because of hypothalamic or pituitary malfunction), but this is a rare condition.

Treatment often takes many months to restore the sperm quality to fertile levels. Combination treatment is required, with HCG stimulating testosterone production; and FSH stimulating sperm production. Initially, the man takes HCG injections thrice a week for about 6 months. This normally causes the size of the testes to increase and the testosterone to reach normal levels. HMG injections are then added.

These can be mixed with the HCG and are also given thrice a week. Once sperm production has been achieved, the HMG can be stopped; and HCG treatment continued alone. While sperm counts achieved are usually low (less than 10 million per ml), a successful pregnancy can be achieved in 50 % of correctly diagnosed patients.

Unfortunately, these expensive injections are often misused as "empiric" therapy in men with low sperm counts - with expectedly disappointing results.

Read more-Male Infertility Treatment - and why it does not work

Bromocryptine
As in the female, this is used to lower unusually elevated levels of prolactin.

Testosterone

This is given to suppress sperm production in the hope that when medication is stopped (usually after 5-6 months), then the sperm production will "rebound " to higher levels than originally (testosterone rebound). This form of treatment is now seldom used as it may further impair fertility and is hazardous.

Testosterone is also be used for the treatment of impotence or diminished libido when blood testosterone levels are low. Testosterone is available as an oily injection and is given intramuscularly, usually once a week. Oral preparations are also available now, but these are more expensive and may not be as effective.

Read more-Is Your IVF Treatment Reducing Your Libido?

Clomiphene

This is the most commonly prescribed medicine for infertile men. Its use is largely empirical and very controversial as the results are not predictable. This is usually prescribed as a 25 mg tablet, to be taken once a day, for 25 days per month, for a course of 3 to 6 months. It acts by increasing the levels of FSH and LH, which stimulate the testes to produce testosterone and sperm. The group of men who seem to benefit the most from clomiphene have low sperm counts, with low or low-normal gonadotropin levels. However, while clomiphene may increase sperm counts in selected men, it hasn't been proven effective in increasing pregnancy rates.

Antibiotics

Just as in the female, antibiotics can resolve a chronic infection in the reproductive tract in the male. Often no specific organism is isolated but improvement in the numbers of normal sperm as well as the reduction in white cells in semen can be seen in some men following several weeks of antibiotics.

Vitamins

No supportive evidence that they work but sometimes they are worth a try.

Ayurvedic treatment and other magic potions
Everyone seems to have a "magic potion" to cure low sperm counts - the trouble is that no one has ever proven that anything works! Take all claims with a liberal pinch of salt.

The problem with the medical treatment of a low sperm count is that for most people it simply doesn't work. After all, if the reason for a low sperm count is a microdeletion on the Y-chromosome, then how can medication help ?

The very fact that there are so many ways of "treating" a low sperm count itself suggests that there is no effective method available. This is the sad state of affairs today and much needs to be learnt about the causes of poor production of sperm before we can find effective methods of treating it.

A Treatment for Everything?

However, patients want treatment, so there is pressure on the doctor to prescribe, even if he knows the therapy may not be helpful . When most patients go to a doctor, they expect that the doctor will prescribe a medicine and treat their problem.

Since most people still believe there is a "pill for every ill", they expect that the doctor will give them a medicine ( or an injection) which will increase their sperm count. No patient ever wants to hear the truth that there is really no effective treatment available today for increasing the sperm count.

Doctors Being Pressurized

Since most doctors know this, they are pressurised into prescribing medicines for these patients, because they do not want the patient to be unhappy with them. They are worried that if they do not fulfill the patient's expectation of a prescription, the patient will desert them, and go elsewhere, which is why they often do not tell the patient the complete truth.

The doctor also remembers the occasional anecdotal successes (who come back for followup , while the others desert the doctor and are lost to followup) is why patients with low sperm counts are put on every treatment imaginable - with little rational basis - Vitamin E, Vitamin C, high-protein diets, hoemeopathic pills and ayurvedic churans. However, the very fact that there are hundreds of medicines itself proves that there is no medicine which works !

The Justification

Many doctors justify their prescriptions by saying - " Anyway it can't hurt - and in any case, what else can we do? " However, this attitude can be positively harmful. It wastes time, during which the wife gets older, and her fertility potential decreases. Patients are unhappy when there is no improvement in the sperm count and lose confidence in doctors.

It also stops the patient from exploring effective modes of alternative therapy - such as IVF and ICSI . Today empiric therapy should be criticised unless it is used as a short term therapeutic trial with a defined end-point.

Be Cautious

A word of warning. Medical treatment for male infertility does not have a high success rate and has unpleasant side effects, so don't take it unless your doctor explains his rationale. The treatment is best considered "experimental" and can be tried as a therapeutic trial. Make sure, however, that semen is examined for improvement after three months and then decide whether you want to press on regardless.

It is worth emphasising how small the list for male infertility treatment is - especially as compared to female treatment. This simply reflects our ignorance about male infertility - we know very little about what causes it, and our knowledge about how to treat it is even more pitiable!

Summary

Fertility drugs are extensively used in treating infertility. They are usually the first line of therapy in treating female infertility. You must be aware of what medicines you are taking and why