Ovulation Induction

What is Ovulation Induction?

Ovulation Induction (OI) is a fertility treatment which stimulates the ovaries so as to produce a single mature egg. This is typically done using one of two drugs, Clomiphene Citrate (Clomid®) also known as Serephene®, or Follicle Stimulating Hormone (FSH). Ovulation is then induced and conception is achieved through intercourse.

Clomid works by blocking oestrogen in the brain. If the brain thinks there is not enough oestrogen it creates more follicle stimulating hormone. This then causes an egg to mature so it can be released (ovulation) and fertilised by sperm following intercourse. This is often tried first as it is more straightforward and reliable (60-70% of patients will ovulate on Clomid).

FSH (gonadotrophin therapy) works in the same way as the follicle stimulating hormone made by the brain. The injected FSH causes an egg to mature so that it can be released (often requiring the use of Pregnyl (injection of hCG) and fertilised by sperm following intercourse. These are the same drugs used to stimulate egg production for IVF treatment, however in IVF the aim is to make several eggs for fertilisation. In Ovulation Induction, the aim is to make just one and hence the dose is significantly lower. FSH is more expensive than Clomid and requires more monitoring to ensure that only a single egg is matured.

Indications for Ovulation Induction

There are a number of conditions which compromise ovulation.

Hypothalamic Amenorrhoea

Some women don't ovulate because the ovaries are not exposed to enough gonadotrophins. Gonadotrophins are hormones called Luteinising Hormone (LH) and FSH, which are produced by the pituitary glands. Deficiencies of these hormones can occur because of pituitary damage but they commonly result because the body is trying to conserve energy or cope with stress. (Women with a tendency to this include those who are underweight, who exercise a lot or who are subject to a lot of stress). The condition can occur after use of the oral contraceptive pill or when puberty is delayed.

Polycystic Ovary Syndrome

Other women fail to ovulate because their ovaries produce excessive amounts of male hormone which interferes with the egg ripening process. Women with this problem are usually overweight and tend to have excessive body hair.

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 and just below a part of the brain called the hypothalamus.

Episodic activity of the hypothalamus brings about the release of two hormones from the pituitary gland – LH and FSH.

These hormones cause development of an egg in the ovary and this is accompanied by increasing oestrogen levels (E2) in the blood.

When the egg is fully developed (and the oestrogen level has risen significantly) 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 levels fall and a period comes.

Ovulation Induction Treatment Cycles

Females will be tested for Rubella immunity and blood group.

Both partners will also sign a consent form with their Clinic Doctor, which is valid for 12 months. Copies of the signed consent forms will be made available to you.

Details of the two different OI treatment options available at Flinders Reproductive Medicine are outlined below.

Ovulation Induction with Clomiphene Citrate (Clomid)

Prior to booking on for your cycle, your Doctor will provide you with a script for Clomid.

Booking on for your cycle

To book on for your ovulation induction cycle, you will need to phone the nurses on 8204 4343 when you get your period.

If you do not get regular periods, your doctor may prescribe some medication ( Provera ) to induce a period, or order a baseline blood test.

The nurses will advise you when to take Clomid, which is usually for 5 days, from days 5 to 9 of your menstrual cycle.

Cycle Monitoring

The cycle will be monitored with a vaginal ultrasound scan and a blood test to determine:

• The development of a dominant follicle which should contain an egg
• Ovulation

The ultrasound is performed using a probe which is inserted into the vagina, and requires an empty bladder.

In some cases, more than one scan and blood test may be required.

You will be advised when to have intercourse, around the time of ovulation.

A blood test for pregnancy will be taken approximately 18 days after ovulation, if you have not had a period. If the test is positive, an ultrasound scan is performed at 7 to 8 weeks of pregnancy, where we look for a fetus with a heartbeat. If this is confirmed, you will be referred to the doctor of your choice for pregnancy care.

If your period commences, please contact the Nursing Staff.

Possible Complications

Poor Response

• No dominant follicle on either ovary develops
• A follicle develops but ovulation is not confirmed

Over Response

• More than one or two dominant follicles develop, which increases the risk of a multiple pregnancy (refer to page 13 of the ovulation induction booklet for details)

Medication Side Effects

• Refer to page 11 of the ovulation induction booklet for details

Ovulation Induction with Follicle Stimulating Hormone (FSH)

Prior to booking on for your cycle, your Doctor will provide you with a script for FSH (either Puregon or Gonal F) and Pregnyl.

Booking on for your cycle

To book on for your ovulation induction cycle, you will need to phone the nurses on 8204 4343 when you get your period.

If you do not get regular periods, your doctor may prescribe some medication (Provera) to induce a period, or order a baseline blood test.

You will administer daily FSH injections, usually commencing on day 5 of your menstrual cycle. The nurses will instruct you / your partner how to administer these injections.

Cycle Monitoring with FSH

The cycle will be monitored with vaginal ultrasound scans and blood tests to determine:

• The development of a dominant follicle which should contain an egg
• Ovulation

The ultrasound is performed using a probe which is inserted into the vagina and requires an empty bladder.

Once the dominant follicle is fully developed, you will have an injection of Pregnyl to induce or boost ovulation

You will be advised when to have intercourse, around the time of ovulation.

Luteal Support

You will be advised to administer luteal support after ovulation, to increase the hormone progesterone which maintains the lining of the uterus.

Luteal support will generally be two Pregnyl injections, administered on days 4 and 7 following ovulation.

A blood test for pregnancy will be taken approximately 18 days after ovulation, if you have not had a period.
If the test is positive, an ultrasound scan is performed at 7 to 8 weeks of pregnancy, where we look for a fetus with a heartbeat. If this is confirmed, you will be referred to the doctor of your choice for pregnancy care.

*If your period commences, please contact the Nursing Staff.

Possible Complications

Poor Response

• No dominant follicle on either ovary develops
• A follicle develops but ovulation is not confirmed

Over Response

• More than one or two dominant follicles develop, which increases the risk of a multiple pregnancy (refer to page 13 of the ovulation induction booklet for details)

Medication Side Effects

• Refer to page 11 of the ovulation induction booklet for details

Treatment Flow Charts

Medication

All medications can have side effects, so, from time to time concerns are raised regarding the side effects of drugs used in Ovulation Induction Treatment. Even though the majority of people do not experience the side effects of medication, the following information is provided for people contemplating or undergoing treatment.

Clomiphene Citrate (Clomid®)

Clomid® acts on the anterior pituitary gland in the brain and results in the release of hormones which stimulate ovulation.

Possible side effects include hot flushes, which are usually mild and disappear after you stop taking Clomid, and abdominal discomfort or bloating around the time of ovulation.

Less common side effects include nausea or vomiting, fatigue, dizziness or light headedness and headache.

If blurred vision, spots or flashes occur, stop taking Clomid®, and notify an FRM Nurse or Clinician.

There have also been concerns expressed that the use of Clomid® as an ovulatory stimulant may cause congenital malformations. This agent has been used for the past 30 or more years and there is no evidence that the children of mothers given Clomid have a higher incidence of congenital or pre-cancerous conditions.

Recombinant Follicle Stimulating Hormone (FSH)

Puregon® and Gonal-F® are laboratory produced products which are almost identical to FSH.

Possible side effects include nausea, abdominal cramps, bloating, breast tenderness and mood swings. These symptoms are normal, but if you are concerned, please contact the nursing staff.

hCG Chorionic Gonadotrophin (Pregnyl®)

Pregnyl® is used to mature the egg and promote ovulation, and also to stimulate progesterone production in the second half (luteal phase) of the cycle after ovulation has occurred. Pregnyl® can be self administered by subcutaneous injection.

Pregynyl can be associated with a rare condition called Ovarian Hyperstimulation Syndrome (see below).

Ovarian Hyperstimulation Syndrome (OHSS)

Ovarian Hyperstimulation Syndrome (OHSS) occurs in some women who have an over response to the stimulating medication. It is a rare but potentially serious complication, so a great deal of care is taken to avoid it. The more severe symptoms of OHSS include severe abdominal pain, nausea or vomiting, decreased urinary frequency, dark-coloured urine and shortness of breath. Therefore, it is important that you notify the clinic if you experience any of these symptoms.

Fertility Drugs and Cancer

The Fertility Society of Australia together with the National Health and Medical Research Council, has conducted a detailed study to assess whether there are links between cancer and fertility drugs. Many reproductive centres throughout Australia (including FRM) undertook the task of following up all patients attending their clinics. Non identifying data on patients was analysed, looking at where they were treated, the type and duration of any treatment, and whether the woman had subsequently developed ovarian, uterine (cervical) or breast cancer.

The study (Venn et al, Lancet 354: 1586-90, 1999) took more than 4 years to complete, with the final report being released in November 1999. The study was based on more than 20,000 women in the "treated" group and 9,000 "untreated" women who were referred, but did not have treatment. The major finding was reassuring. No more cancers were found in the treated group than the general population, when considered over a 5-10 year period.

It is important to note that, as with any drugs, it is possible there may be effects or side-effects as yet unknown. It is therefore important for follow up studies to be performed. You will be asked to consent to be contacted in the future if we have any further information for you.

Possible Complications

As with most medical procedures and fertility treatments, there are potential complications to consider with Ovulation Induction.

Multiple Pregnancy

Risks to the Mother arising from multiple pregnancy:

• High blood pressure during pregnancy
• Diabetes during pregnancy
• More physical discomfort
• Prolonged antenatal hospitalisation and surgical delivery
• Post partum haemorrhage

Potential risks for the babies:

• Low birth weight
• Premature birth
• Serious complications after birth
• Higher risk of cerebral palsy
• Increased development delays in speech and reading among "toddler" twins

Potential Social Consequences:

• Social and economic difficulties
• Psychological consequences
• Fatigue and sleep deprivation

Pregnancy Loss

As with natural conception, an Ovulation Induction pregnancy is subject to a variety of outcomes including biochemical pregnancy, ectopic pregnancy or miscarriage.