Home > Resources > Ovulation Induction

Ovulation Induction

Ovulation induction is a form of treatment which involves stimulation of the ovaries to bring about development of a ripened egg which can then be fertilised by a normal act of intercourse.

Ovulation induction is used to treat women who do not ovulate or who ovulate irregularly.

'How do I know if I ovulate?'

Ovulation is usually associated with regular menstrual cycles, with periods coming every 24-35 days. Cycles outside this range maybe ovulatory, but this is less likely.

Commonly, women who ovulate may notice a change in vaginal mucus (more plentiful and more lubricating) or some localised lower abdominal pain lasting a few hours about two weeks before a period comes.

Ovulatory cycles are often associated with premenstrual symptoms such as abdominal bloating, breast swelling and tenderness or mood changes.

For those women who measure their basal temperature, there is usually a small rise (about 0.5oC) after ovulation takes place.

The best and most reliable way to check if ovulation has taken place is to measure serum progesterone. A level which is more than 20 nmol/L suggests that ovulation has occurred. Timing of the blood sample is important. It is most accurate when collected 3 to 10 days before a period.

The normal process of ovulation

For ovulation to occur, there needs to be controlled stimulation of the ovary by hormones produced in the pituitary gland. The pituitary gland is positioned just above the nose, just below a part of the brain called the hypothalamus.

Episodic activity of the hypothalamus brings about release of two hormones - luteinising hormone (LH) and follicle stimulating hormone (FSH).

These hormones cause development of an egg in the ovary. This is accompanied by increasing oestrogen levels in the blood.

When the egg is fully developed (and the oestrogen level has reached a critical level) a surge of LH occurs and the egg is released from the ovary and enters the fallopian tube. The release of the egg is ovulation.

The ovary then turns to making progesterone which is required to support a pregnancy, if it occurs. If it does not, then progesterone level falls and a period comes.

'What could be wrong if ovulation does not occur?'

The commonest problem is absence or poorly coordinated activity in the hypothalamus. Conditions that cause this are polycystic ovary syndrome, excessive exercise, under nutrition or stressful conditions.

Other less common causes are lack of pituitary hormones due to benign pituitary tumours (some of which produce large amounts of the milk hormone, Prolactin) or damage to the pituitary gland.

Early menopause, or ovarian failure, results in loss of the egg supply from the ovary.

'What are the steps before ovulation induction begins?'

First, it is important to do a complete review of history and examination and to undertake some blood tests to establish a diagnosis.

Some changes in lifestyle might be valuable. These may include diet, exercise and attention to stressful life events (see link).

Folic acid taken in early pregnancy reduces the risk of neural tube defects (spina bifida and related malformations in the baby). It is usual to prescribe folate 0.5 mg daily for this purpose. In some instances of increased risk, you may be advised by your doctor to take 5 mg daily.

Some conditions require specific treatment, for example, pituitary tumours may require surgery or a drug to reduce prolactin.

It is necessary to exclude a significant impairment in the quality of the partner's sperm. This requires examination and a sperm test.

Ovulation induction can only result in a pregnancy, if the woman's fallopian tubes are open and able to transport the ovulated egg to the uterus. Some doctors recommend laparoscopy to exclude tubal blockage before commencement of treatment. Another approach, in the absence of any symptoms or signs of pelvic disease, is to undertake treatment and only perform laparoscopy if pregnancy has not occurred after six months of treatment.

Specific treatment

Clomiphene citrate ("Clomid', "Serophene")

Clomiphene acts by stimulating the hypothalamus to provide intermittent signals for the pituitary gland. This allows episodic release of LH and FSH which are required for egg development in the ovary.

Although this stimulation is not quite the same as occurs normally, it does utilise the body's own supply of LH and FSH.

Egg development is associated with an increase in oestrogens (oestradiol; E2) and when the egg is ripe, the hypothalamus is signalled to produce a surge of LH from the pituitary. If this occurs, ovulation will take place.

Sometimes, with clomiphene, egg development occurs and E2 levels increase in the blood, but the surge of LH required for ovulation does not occur. If this happens, the ripe egg is not released and is soon absorbed. There is no rise of progesterone because ovulation does not occur.

In a subsequent cycle, this may be corrected by giving an increased dose of clomiphene and giving a timed dose of human chorionic gonadotropin (HCG) which acts like LH and which provides an artificial LH surge.

A period following clomiphene treatment is not necessarily an indication that ovulation has occurred. An appropriate increase in serum progesterone is the only proof of this (apart from pregnancy).

Sometimes clomiphene does not work because the hypothalamus is unresponsive. In this case, no increase in pituitary LH and FSH occurs, there is no egg development and no rise in E2. This might be corrected by increasing the dose of clomiphene, but it usually requires a change to gonadotropin treatment (see link).

A typical cycle of treatment with Clomiphene:

Clomiphene comes in 50 mg tablets. It is usually taken in a dose of 25-150 mg a day for 5 days commencing on the fifth day after the start of a period.

Clomiphene may be used with minimal monitoring, but each cycle should at least be checked with a serum progesterone to determine if ovulation has been achieved.

A fully monitored cycle gives the best indication of response to clomiphene and at the same time it indicates if additional or alternative treatment is required.

Typical monitored cycle of Clomiphene treatment:

* Ultrasound

Side effects and complications of treatment with Clomiphene

Side effects of clomiphene are not common, but larger doses can be associated with episodic flushing, mild nausea and visual disturbance, flashing, or spots in the eye.

If ovulation occurs, there may be abdominal bloating, lower abdominal discomfort or urinary symptoms (frequency or discomfort when passing urine).

When properly monitored, hyperstimulation (see link) should not occur.

Clomiphene has been used for 40 years. Concerns have been expressed about an association between long term use of clomiphene and the incidence of ovarian and breast cancer. A large study has failed to find a statistically significant correlation, but this remains under consideration (see link).

It seems sensible to exercise caution with long term use of clomiphene, hence the advantage of monitoring ovulation and changing treatment which if not effective.

No increased risk of fetal abnormalities have been reported with clomiphene.

Women who ovulate on clomiphene treatment are less likely to become pregnant than that women who ovulate spontaneously. (There is no chance of conception if ovulation does not occur.) Clomiphene has an anti-oestrogen effect which may impair the production of mucus and a transport of sperm.

Gonadotropin

Gonadotropins contain FSH ("Gonal-F", "Puregon") or HCG ("Profasi", "Pregnyl").

FSH is manufactured synthetically, but HCG, as available at present, is extracted and purified from human urine.

The purpose of FSH is to directly stimulate the ovary resulting in the development and maturation of eggs. Once matured, the eggs are released (ovulated) by giving an injection of HCG.

The aim is to develop a single ripe egg before the HCG is given. If more than two eggs develop, it is usual in our clinic to advise against unprotected intercourse and having the HCG injection. This advice is given to minimise the risk of multiple pregnancy.

Development of the egg is monitored by intermittent blood tests and ultrasound.

A typical Gonadotropin stimulation cycle

FSH is given as a subcutaneous injection beginning approximately 5 days after a period.

The dose prescribed depends on the woman's age, weight and underlying medical condition resulting in loss of ovulation. The usual dose starts from 50 - 100 IU a day.

* ultrasound

Side effects of treatment with Gonadotropins

After injection, there may be stinging or redness at the site.

As oestrogen levels increase, some women notice breast tenderness and mood change.

Sometimes, the ovaries are very sensitive to FSH and multiple eggs develop. If HCG is given there is a chance of multiple pregnancy occurring. This complication can be largely avoided by ceasing FSH and not giving HCG. Barrier contraception (condoms) are used during intercourse for two weeks after FSH is ceased.

Rarely, after FSH and HCG treatment, the ovaries enlarge and produce high levels of a substance which causes leakage of protein into the abdominal cavity. This may be associated with nausea, lower abdominal pain and swelling. In extreme circumstances large amounts of fluid accumulate in the abdomen and sometimes the lung cavities, causing shortness of breath and major discomfort.

The aim of the treatment is to develop one or two eggs and the cycle should be cancelled if more follicles develop, hence reducing the chance of the above complication.

'What is the chance of a successful pregnancy with this treatment?'

As with all fertility treatment, the success rate depends on a large number of factors including:

Age of the woman. Success is reduced with age > 40 years

Underlying medical condition. Pregnancy rate is less with polycystic ovaries than some other conditions.

Weight of the woman. Miscarriage rate is higher when weight is greater than 100 kg or BMI >25.

Quality of sperm. This can be variable for a number of reasons.

We have been treating women with ovulation induction for more than 15 years and currently treat approximately 5-10 patients each week.

We have recently reviewed our figures for women on gonadotropin treatment. These women have been trying to conceive for at least twelve months, most had polycystic ovary syndrome and did not respond to clomiphene.

The women were treated for varying durations from 1-9 cycles between 1998 and 2000.

The results were as follows:

Costs of treatment

Ovulation induction requires careful monitoring, but is relatively "low-tech" compared with other forms of fertility treatment.

At present, ovulation induction is a service provided to patients at Flinders Medical Centre by specialists paid by the hospital and by Flinders Reproductive Medicine Pty Ltd.

There are no out of pocket costs for laboratory tests or ultrasounds.

Clomiphene, FSH and HCG are available at a standard prescription cost (around $25) either as a PBS item or through the hospital's Pharmacy.

top of page | home | disclaimer | sitemap | contact us | site by thefactory