Clomiphene & Letrozole - Problems, risks and solutions

Problems and solutions

There aren’t any tests to predict the right dose of clomiphene or letrozole for a particular woman, so common problems are:

  • The initial dose isn’t high enough to be effective. This can be picked up by blood tests or an ultrasound scan. The solution is to increase the dose the next month.
  • The initial dose causes too many follicles to grow, increasing the risk of multiple pregnancy such as twins or triplets. This can be picked up by blood tests or an ultrasound scan. The solution is to reduce the dose the next month.
  • Clomiphene partially blocks the action of estradiol in all types of tissue, including the cervix. This means it may reduce the quality of cervical mucus around the time of ovulation which may make it harder for sperm to swim through the mucus on their way to the egg. It is hard to measure this, although some women are good at detecting their mucus around ovulation. Letrozole does not affect cervical mucus.
Risks and side effects
  • Multiple pregnancy Blood tests and ultrasound scans give a good idea about how many follicles are growing in the ovary in a particular month of treatment but they are not perfect. In addition, for many women the aim is to grow 2-3 follicles. As a consequence, Clomiphene was the original ‘fertility pill’ and is still widely used for women who don’t have regular menstrual cycles, and for women with a shorter duration of unexplained infertility. Letrozole is a new alternative to Clomiphene. about 10% of pregnancies from clomiphene treatment are twins, and about 1% are triplets. Quadruplets or more are possible but very rare. The chance of twins is lower with letrozole – below 5%. Twins are associated with 2-3 times more risk for both the mother and children for a wide range of adverse outcomes, from maternal death to cerebral palsy. See our Fertility Facts on the risk of twins.
  • Ectopic pregnancy When an embryo implants in the Fallopian tube, the cervix or the abdomen it is called an ectopic pregnancy. Ectopic pregnancies can be dangerous because the placenta can burrow into a blood vessel and cause major internal bleeding. Clomiphene or letrozole don’t increase the risk of ectopic pregnancy, but all women having fertility treatment need to be aware of the possibility of ectopic pregnancy. We can usually detect an ectopic pregnancy by the level of hCG in the pregnancy test and an early ultrasound scan, but not always. Symptoms include severe, localised abdominal pain.
Other side effects
  • Pain is your body’s way of saying that something may be wrong. We need to know about any symptoms that might be concerning you.Please tell us if you experience any of the below while on treatment. These side effects occur less often with letrozole.
  • About 10% of women using clomiphene experience hot flushes because of the way clomiphene blocks the action of estradiol.
  • Other side effects can include nausea and breast tenderness.
  • Mood swings are common but seldom severe; but if so please talk to us.
  • Headaches and blurred vision are rare side effects.
Good to know
  • Clomiphene has been used for over 40 years without any evidence of an increased risk of birth defects. It is unclear whether clomiphene could increase the risk of ovarian cancer or breast cancer – as a precaution most experts recommend that clomiphene should not be used for more than twelve months.
  • Letrozole was originally designed to help treat breast cancer and it is not yet registered to treat infertility in New Zealand. Because of this, we will ask you to sign a consent form.


Please let your medical team know if you experience any of the above or have any questions.