Anovulatory failure (a menstrual cycle during which the ovaries do not release an egg) or ovulation disorders are some of the main causes of infertility in the female. 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.
Treatment for these conditions is relatively simple and effective at restoring normal ovulation. Before any treatment can be offered, it’s very 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 if the hormone, FSH level is high (more than 20 mIU/mL when measured at the start of a period), and AMH level is low (less than 1pmol/l), ovarian failure is likely. In this case drug treatment will not help, and your doctor will discuss alternative options.
If there are no indications in the medical history of any problems with the fallopian tubes (eg, no history of abdominal surgery, pelvic inflammation and/or history of Chlamydia infection), a test for tubal patency (to check that the fallopian tubes and open) may be deferred until ovulatory cycles have been achieved for three months.
If, however, injections of gonadotropins are required, assessment of the tubes by either X-ray examination (HSG) or ultrasound test (Hycosy) would be carried out.
If you are not ovulating, then drugs may be administered with the onset of menstruation to stimulate egg production. This would initially be in tablet form, but if this is not effective then more powerful fertility injections may be necessary to stimulate egg production in the ovaries.
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, intrauterine insemination (IUI), and in vitro fertilisation (IVF) procedures can be scheduled at a time that is most likely to achieve a pregnancy.
The main types of drugs used in ovulation induction are:
- Clomiphene Citrate (Clomid) – 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 by giving a different type of tablet called Norethisterone. Common side effects include headaches, blurred vision and hot flushes.
- Gonadotropins (Menopur, Puregon and GonalF) – This is an injectable medication that is used to induce the release of the egg once the follicles are developed and the eggs are mature. Their active ingredient is the follicle stimulating hormone (FSH). These injections are given on a daily basis and start at a dose of 75 i.u. each day. Side effects may include abdominal distention/discomfort, bloating sensation, mood swings, fatigue or restlessness.
- Glucophage (Metformin) – Metformin is given to patients as an insulin lowering medication. Most commonly used in patients with PCOS, the medication has been shown to reverse the endocrine abnormalities seen with polycystic ovary syndrome within two or three months. The use of Metformin can result in decreased hair loss, diminished facial and body hair growth, and normalization of elevated blood pressure, regulation of periods, weight loss and normal fertility.
- Aromatase Inhibitors such as Letrazole and Anastrazole are not yet licensed to be used in the UK for ovulation induction.
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 (except with clomid), 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 clomiphene 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 is essential should these symptoms occur.
The risk of ovarian cancer was previously reported to be increased in women who have taken ovulation induction drugs over prolonged periods. The risk, if any, is thought to be small and the link is related to infertility and not to the medication. Clomiphene has been most closely associated with this risk and the vast majority of reported tumours have been of borderline in nature. Most 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 Clomiphene citrate should be administered.