Ovulation induction is the medical treatment that aims to help the ovaries produce and release one or more eggs. The absence of regular ovulation is often resolved with individualized hormone treatment, either taken by mouth or given by injection, through which one or more eggs develop and are released.
The method is essentially one of the first approaches to the problem of infertility, increasing the chance of conception through timed intercourse or intrauterine insemination.
Which women it is for
Women with an irregular menstrual cycle, or with a regular cycle who nevertheless appear to have unexplained infertility. Drug-induced ovulation is used above all when the cause of infertility lies in the failure to release an egg, despite there being eggs in the ovaries — the classic example being women with polycystic ovary syndrome.
Methods
Ovulation is induced either with tablets, chiefly clomiphene citrate and letrozole, or with gonadotropin injections; a combination of the two classes of drug is also possible, depending on the case and on the cause of infertility.
Medication to induce ovulation usually starts on the 2nd or 3rd day of the cycle, after a transvaginal gynecological ultrasound. How long the induction lasts depends on the rate at which the follicles grow, but it usually takes 8 to 14 days.
While taking her medication the patient is monitored with ultrasound of the internal reproductive organs; depending on the case, 3 or 4 gynecological scans will be needed. On ultrasound we follow the increase in the size and number of the follicles, along with the thickening of the endometrium. When the maximum diameter of the follicles is above 17–18 millimetres, an injection of chorionic gonadotropin is recommended; this brings about the final maturation of the eggs and the subsequent release of the egg, which is followed either by timed intercourse or by intrauterine insemination (IUI).
Clomiphene citrate (Serpafar)
The drug usually used as first choice to induce ovulation is clomiphene citrate, which acts on the female endocrine axis to produce mild stimulation of the ovaries. Clomiphene citrate is usually given from the 3rd to the 7th day of the cycle, at a dose of 50 mg to 150 mg daily, depending on how the ovaries respond. Clomiphene comes in 50 mg tablets and treatment usually starts with the lowest possible dose, one tablet a day. A few days after the last tablet, the woman begins to be monitored with a series of ultrasound scans, to establish the growth of the follicle or follicles in her ovaries. Then, once the follicles have reached a satisfactory size, the day of ovulation can either be predicted by detecting a sudden rise in luteinizing hormone (LH) in the blood a few hours beforehand, or be fixed by giving chorionic gonadotropin as an injection, which brings about the final maturation of the follicles and ovulation.
Clomiphene is a drug that binds to estrogen receptors, so that a false message is sent to the brain that there is a lack of estrogen. The result is an internal rise in the hormones produced by the pituitary (FSH, LH) and therefore the production of more than one follicle by the ovaries. The maximum number of clomiphene cycles is considered to be 4 to 6, if pregnancy has not been achieved. The advantages of the treatment are its extremely low cost and how easy the medication is to take; the disadvantages are the low pregnancy rate (about 8 to 15% per cycle), the possibility of a multiple pregnancy, the possibility of ovarian hyperstimulation, and changes to the cervical mucus.
Letrozole (Femara)
This is a drug used mainly in women who have had surgery for breast cancer, to protect them from the hormones the body produces. Letrozole selectively inhibits the enzyme aromatase, which reduces the production of estrogen by the tissues.
In assisted reproduction it is used as an alternative to clomiphene, given from the 3rd to the 7th day of the cycle at a dose of 2.5 to 5 mg daily.
The advantages of the treatment are its low cost and how easy the medication is to take; the disadvantage is the low pregnancy rate (about 8 to 15% per cycle), as with clomiphene citrate. This drug appears to have an advantage over clomiphene, since it works by a different mechanism and has the theoretical advantage of avoiding the development of multiple follicles — usually a single follicle develops, so the risk of multiple pregnancy is reduced. Unlike clomiphene citrate, letrozole does not alter the cervical mucus.
Gonadotropins
Gonadotropins, as the pituitary hormones FSH and LH are called, are widely used in assisted reproduction treatments and above all in IVF. The gonadotropins (follicle-stimulating hormone FSH and luteinizing hormone LH) are the hormones released by every woman's own pituitary gland; they act directly on her follicles, ultimately causing them to grow and mature. Less often they are given for intrauterine insemination. There are various protocols for stimulating the ovaries and various gonadotropin preparations. Which preparation and which protocol are used is decided on a strictly individual basis for each case and for each of the woman's cycles.
Injectable gonadotropins are indicated in women with anovulatory cycles, whether because of polycystic ovary syndrome or hypogonadotropic hypogonadism; in women in whom ovulation induction with clomiphene or letrozole has been tried and failed; and in all IVF treatments in women with a good follicle reserve, since giving these hormone preparations yields a numerical advantage in the final harvest of eggs and ultimately of embryos compared with the woman's natural cycle.
Recombinant gonadotropins are drugs made with new technology. Two forms of the human FSH gene have now been isolated in the laboratory and inserted into genetically modified cells, so that large quantities of almost completely pure human FSH are produced.
Urinary gonadotropins are drugs made with older pharmaceutical technology. Thanks to injectable gonadotropins, whether urinary or recombinant, for nearly 30 years IVF treatment protocols have managed to increase pregnancy rates, since these hormone preparations provide a substantial number of eggs to work with and fertilize, compared with the equivalent natural cycle.