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
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
- 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
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
Induction of ovulation (with or without