In cases of irregular menstrual cycle or known anovulation, we use preparations to stimulate ovulation, such as clomiphene citrate and letrozole (FEMARA). For controlled ovarian stimulation and multiple ovulation we use gonadotrophins in small doses (75-150 iu daily).
Indications
- Women with anovulation
- Mild ovarian stimulation for poor responders
- Age under 35 years old
- In cases that standard ovarian stimulation is not permitted for medical reasons
- History of breast cancer (Letrozole/ Femara)
The procedure is monitored with frequent transvaginal ultrasounds and measurement of hormone levels in the blood, in order to assess the effect of the administered hormone preparations and to adjust the dosage depending on test findings.
Clomiphene Citrate
Clomiphene citrate is the substance that binds to the oestrogen receptors in the brain, providing a false message that there is a lack of oestrogen in the blood. This message stimulates the brain to produce larger quantities of endogenous gonadotropins (FSH, LH) in the pituitary gland, compared to those produced in a normal cycle; these, in turn, stimulate the ovaries to produce more than one follicle.
It is usually administered from the 3rd until the 7th day of the cycle at a dosage of 100 mg per day, with the dosage increasing to 150 mg if the ovarian response is not appropriate. Follicles are considered mature when they measure more than 18 mm in diameter and chorionic gonadotropin (hCG) is administered to induce the final maturation of the follicle which, 32-36 hours later, will lead to spontaneous ovulation.
If a pregnancy after 4-6 cycles of treatment has not been achieved, more active treatment should be used, such as gonadotropins.
The advantages of this treatment are the low cost and ease of administration, while its disadvantages are the low pregnancy rate of 8-15% per cycle, the risk of a twin or ectopic pregnancy, ovarian overstimulation, drug failure, and other side effects such as vasomotor disturbances and alterations in the fluidity of the cervical mucus.
Letrozole (FEMARA)
This substance selectively inhibits the aromatase enzyme and radically reduces oestrogen production in the tissues.
The primary indication is supplementary administration in cases of women who have undergone surgery for breast cancer, in order to protect them from the hormones produced by the body.
Letrozole’s capacity to inhibit oestrogen production is also used in cases of infertility, to induce ovulation. The low oestrogen levels force the pituitary gland to produce greater quantities of endogenous gonadotropins (FHS, LH), compared to those produced in a normal cycle; these, in turn, stimulate the ovaries to produce more than one follicle.
It is usually administered from the 3rd until the 7th day of the cycle, at a dosage of 4 mg per day, with the dosage increasing to 6 mg per day if the ovarian response is not appropriate.
Follicles are considered mature when they exceed 18 mm in diameter and chorionic gonadotropin (hCG) is administered to induce final maturation of the follicles which, 32-36 hours later, will lead to spontaneous ovulation.
Advantages of this treatment are the low cost, ease of administration, and safety of use for women with breast cancer.
Disadvantages include the low pregnancy rate of 8-15% per cycle, the possibility of twin or ectopic pregnancy, the possibility of ovarian hyperstimulation, drug failure, and other side effects, primarily headaches and overall fatigue.
Contrary to clomiphene citrate, letrozole does not cause changes in the cervical mucus, so its use does not need to be accompanied with intrauterine insemination.
Gonadotropins
If the use of clomiphene citrate does not induce ovulation, gonadotropins (FSH, LH) are used for controlled stimulation of the ovaries and induced multiple ovulation. Administration starts on the 2nd or the 3rd day of the cycle, usually at a dosage of 75-150 iu daily, until the emergence of mature follicles. The dosage of gonadotropins is customised daily and every 3-4 days the woman is submitted to a new blood panel and ultrasounds of the ovaries and uterus, so that the administered dosage can be adjusted depending on ovarian responsiveness and test findings.
Follicles are considered mature when they exceed 18 mm in diameter and chorionic gonadotropin (hCG) is administered to induce final maturation of the follicles which, 32-36 hours later, will lead to spontaneous ovulation.
To prevent the premature rupture of the follicles and loss of the eggs due to ovarian stimulation, starting on the 6th day of stimulation antagonists are administered to assure the gradual growing of follicles until final maturation, without the risk of premature luteinisation and follicle loss. The stimulation combined with intrauterine insemination increases the pregnancy rate (10-20%), although it is still much lower than for IVF (40-50%, depending on age). As a result, in recent years the use of gonadotropins to induce ovulation is applied primarily within the framework of IVF.
The disadvantages of this stimulation include the possibility of a twin pregnancy and the possibility of ovarian hyperstimulation syndrome (OHSS), which might result in cancelling the IVF cycle.