The Drugs used in Fertility Treatment
Ovulation induction drugs
Many women do not ovulate spontaneously, and require some form of drug regime to stimulate the ovaries into producing a follicle.
In other treatments such as IVF the role of the drugs is to stimulate more than one follicle to develop.
Clomiphene as 50mg tablets, are taken for 5 days near the beginning of the menstrual cycle – commonly Days 2-6, or Days 5-9. The dose prescribed may vary between 25mg to 150mg, depending on the amount needed to induce follicle growth.
Clomiphene acts by blocking the oestrogen receptors in the hypothalamus and pituitary gland. This causes the pituitary gland to continue producing FSH in higher levels for the 5 days of medication. The effectiveness of the Clomiphene treatment is measured with estradiol blood tests, a follicular scan and a blood test for progesterone about 7 days after ovulation. The dose of the drug can then be altered in subsequent cycles, according to individual requirements.
For some women, the drug Letrozole may be used as an alternative to Clomiphene.
Other drugs used in ART
Gonadotrophin Releasing Hormone (GnRH) agonists.
Buserelin is a super-strong version of GnRH. Its initial effect is to raise the levels of FSH and LH, and after a period of time it actually blocks the release of these two hormones from the Pituitary gland. Because it blocks the release of LH, it is often used to prevent premature ovulation in IVF cycles.
It is used in 2 different regimes for IVF – on the ‘Long Course’ it is used from Day 21 of the cycle, and after a couple of weeks of injections a blood test is done to check for down-regulation. This ensures the woman’s hormones are low and ready to start the FSH injections.
In the ‘Short/ Flare Course’ it is commenced around Day 2 of the cycle, and then the FSH injections are commenced a couple of days later to take advantage of the Flare FSH production from the Pituitary gland.
Buserelin is administered by subcutaneous injection, at a similar time each day. The dose is 200-400mcg, depending on the drug regime used.
Lucrin is another version of GnRH agonist, like Buserelin.
Cetrotide or Orgalutran
These drugs are GnRH antagonists. Cetrotide and Orgalutran both work by reducing the body’s release of LH, and in doing so reduce the risk of premature LH surges that can affect IVF cycles. They are given as subcutaneous injections from around Day 6 or 7 of FSH stimulation, until trigger / ovulation time in an IVF cycle.
This is used for ‘triggering’ ovulation. The Ovidrel acts in a similar way to the natural surge of LH that triggers ovulation, by maturing the egg and causing the follicle to rupture. Egg collection in IVF or insemination in other treatments is usually timed 36 hours after the Ovidrel injection. The dose given is 250ug as a subcutaneous injection.
This is a vaginal pessary containing Progesterone. Utrogestan is used to help support the lining of the uterus when the ovaries themselves may not produce enough progesterone. The pessaries are inserted into the top of the vagina, near the cervix, to allow absorption of the hormone into the bloodstream and uterus. They are 100mg, and the usual dose is two pessaries at 8 hourly intervals, commencing soon after egg collection.
The progesterone is rapidly absorbed and metabolised by the body which is why it is important that Utrogestan given at regular intervals to maintain a constant level in the blood.
If a pregnancy occurs then Utrogestan may be continued for up to 10 weeks, or stopped earlier if the woman is producing sufficient levels of progesterone from her ovaries.
This is a progesterone gel, which is used in luteal phase support following IVF treatment. The gel comes in a pre-filled applicator, containing
90mg of Progesterone. It is given at a dose of 90mg, usually once daily but may be up to twice daily.
The applicator is inserted into the vagina, and the gel is then placed near the cervix. It is started within 4 days of the HCG trigger injection and is used until the pregnancy test.
This is an intramuscular injection of Progesterone. It is a thick oily solution that must be given into the muscle rather than the fatty layer under the skin. It is given if the woman does not absorb sufficient levels of progesterone from the Utrogestan. Its dose is usually 100mg per day, which is 1 injection each day, for a similar length of time as the Utrogestan pessaries.
Other drugs that may be used in ART
• Provera – progesterone tablets are commonly used to induce a bleed prior to treatment with stimulating drugs. The artificial hormone increases the lining of the uterus, and when the drug is stopped the drop in hormone level causes a withdrawal bleed, and the shedding of older endometrium. It may also be given in early pregnancy to supplement progesterone levels.
• Oral contraceptive – a woman may be required to take this prior to IVF treatment, to reduce the occurrence of ovarian cysts and regulate the menstrual cycle. It provides artificial Oestrogen, which inhibits the production of FSH and consequently the formation of a follicle in the ovary.
• Progynova or Estrodial Valerate – is an artificial oestrogen, which is commonly used to ‘manufacture’ artificial menstrual cycles during egg donation or the transfer of frozen embryos. It is given from day 2-4 of the cycle for a menstruating woman or at a designated date for a non-menstruating woman.
The oestrogen increases the endometrial lining of the uterus, in preparation for embryo transfer. When this drug is used in a manufactured cycle, it needs to continue for 10-12 weeks if the woman becomes pregnant. Utrogestan is used in conjunction with Progynova, and it too must continue if pregnancy occurs in a manufactured cycle.
The placenta begins production of oestrogen and progesterone after 8-10 weeks gestation, and should be able to maintain the pregnancy from 10-12 weeks.