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Ovulation disorders are some of the main causes of infertility in women. These are usually caused by an imbalance of hormones.
The most common causes of failure to ovulate are stress, weight fluctuations and Polycystic Ovarian Syndrome (PCOS). Other causes may include disorders of the pituitary gland, thyroid gland and raised prolactin levels.
Before any treatment can be offered, it’s important to perform certain tests in order to establish the actual cause. These tests include an ultrasound scan of the ovaries and womb, and blood tests to measure a range of hormones including thyroid, prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone and other androgens (male hormones). In some cases failure of ovulation is due to ovarian failure. This may occur following treatment for cancer or may be the start of the menopause (premature ovarian failure). In this case drug treatment will not help, and your doctor will discuss alternative options.
We may advise a test of your fallopian tubes before ovulation induction treatment. This will be discussed with you depending on your symptoms and risk factors.
Ovulation induction medications, often referred to as fertility drugs, are used to stimulate the follicles in your ovaries resulting in the production of multiple eggs in one cycle. The medications also control the time that you release the eggs, or ovulate, so sexual intercourse or intrauterine insemination (IUI) can be scheduled at a time that is most likely to achieve a pregnancy.
The main types of drugs used in ovulation induction are:
- Clomifene Citrate (Clomifene) – This medication comes in a tablet form and is used for women who have infrequent periods or long menstrual cycles. It increases the production of follicle stimulating hormone (FSH) by the pituitary gland, thereby stimulating follicles and hence egg growth. This tablet is normally given in a starting dose of 50 mgs (1 tablet) taken from the second to the sixth day of the period. If the periods are very infrequent then it may be necessary to induce a period-like bleed by giving a different type of tablet called Norethisterone. Common side effects include headaches, blurred vision, hot flushes and multiple pregnancy.
- Gonadotropins (Menopur, Bemfola and Gonal F) – This is an injected medication that is used to induce the release of the egg once the follicles are developed and the eggs are mature. Their main active ingredient is the follicle stimulating hormone (FSH). These injections are given on a daily basis. Side effects may include abdominal distention/discomfort, bloating sensation, mood swings, fatigue or restlessness. There is a risk of multiple pregnancy if more than 1 ovarian follicle develops. If 3 or more follicles develop we advise cycle cancellation and abstinence from intercourse to prevent a multiple pregnancy.
- Metformin is given to some patients with PCOS. It is usually prescribed in combination with other medications to help ovulation. It can cause nausea, abdominal cramps and upset stomach. These side effects can be reduced by taking the drug with food and gradually building up to the full dose.
- Aromatase Inhibitors (such as letrozole) – Theses are tablets that are an alternative to Clomifene for women with polycystic ovaries. Ovulation induction treatment, using either tablets or injections, causes the woman to release an egg and so have the chance of conceiving naturally. Timing of intercourse is therefore very important and monitoring is vital. This monitoring is carried out using ultrasound scans in women receiving FSH injections, as well as blood tests to check the hormone levels. The ultrasound scans will monitor the development of follicles and thereby reduce both the chance of a multiple pregnancy and also ovarian hyper-stimulation (OHSS). When follicles have reached an appropriate size, intercourse is advised. An injection of hCG may be given to ensure the egg is released from the follicle and facilitate the timing of intercourse or IUI. Alternatively at this point the sperm may be inserted in the uterus using a vaginal catheter (IUI).
Individual responses to treatment can be unpredictable and if, during the monitoring, the response is insufficient or too strong, the cycle may have to be cancelled and restarted as appropriate. If the response to the drugs is satisfactory, treatment usually continues for six cycles; treatment cycles can be carried out consecutively without a break.
What are the side effects?
Potential side effects are mainly related to the drugs.
Multiple pregnancies are a risk of ovulation induction treatments. Twins can result in up to 10% of cases with Clomifene treatment, and 20% with Gonadotropins. Triplets may also occur in around 1% of cases. With careful monitoring the risk of multiple pregnancy is reduced but not eliminated.
A rare side effect that can occur is ovarian hyper stimulation syndrome (OHSS). Symptoms include severe pain in the pelvis, abdomen and chest, nausea, vomiting, bloating, weight gain and difficulty breathing. Hospitalisation may be needed.
The risk of ovarian cancer was previously reported to be increased in women who were prescribed Clomifene over prolonged periods. The risk, if any, is thought to be small and recent data indicates that there is no increased risk, However, the Committee on Safety of Medicines (CSM) recommend that no more than 12 cycles of Clomifene citrate should be administered.