Hormonal therapy is taken for two reasons:
- Ovulation Induction
In ovulation induction, hormone therapy is used to bring about or induce ovulation in women who are not ovulating normally (these are usually women with irregular or infrequent menstruations). The goal in ovulation induction is the release of one mature egg.
Most often fertility pills such as Clomiphene Citrate (Clomid) or Letrozole, are used for ovulation induction. If these two medications are not effective, injections of gonadotropins (hormones that act on the ovary to promote egg development) may be necessary.
- Ovarian Stimulation
Hormone therapy can also be helpful for couples with unexplained or mild male factor infertility. In this case, ovarian stimulation is used to stimulate the ovaries to guarantee ovulation and to produce up to three eggs. The medications used for ovarian stimulation are Clomiphene Citrate tablets or gonadotropins (hormone injections).
Ovarian stimulation is usually prescribed in combination with Intrauterine Insemination (IUI).
Most women who take gonadotropins do not have serious side effects but those who do, report temporary side effects that include inflammation at the injection site, mood swings, breast tenderness, abdominal bloating/discomfort, and headache.
The main risk of treatment with gonadotropins is the risk of multiple pregnancy (approximately 25% of pregnancies are multiple pregnancies). An additional risk of treatment is the rare occurrence (~ 1%) of ovarian hyper-stimulation syndrome (OHSS). Although the incidence may be up to 6% in young women who have polycystic ovaries which are very sensitive to hormonal stimulation. While rare, OHSS is a serious condition that requires close monitoring and treatment of symptoms.
Medications used for ovulation induction and ovarian stimulation
- Clomiphene Citrate
- Letrozole
- Gonadotropins
- Human Chorionic Gonadotropin (HCG) or Ovidrel
Clomiphene Citrate (Clomid, Serophene)
Clomiphene is an “anti estrogen” that blocks the effect of estrogen on the brain. This causes the brain to produce more of its own “gonadotropin” hormones that stimulate the ovary to produce eggs. When used in women who do not ovulate naturally, Clomiphene is successful in inducing ovulation in approximately 60% of women. Clomiphene Citrate is taken orally and is prescribed for five consecutive days at the beginning of a menstrual cycle. Most women who take Clomiphene do not report side effects but those who do may have headaches, hot flushes, breast tenderness, visual disturbances, abdominal discomfort, and/or nausea. The main risk of treatment with Clomiphene is the risk of a multiple pregnancy (more than one fetus) - about 8% of pregnancies will be multiple pregnancies. An additional risk of treatment is the rare occurrence (less than 1%) of ovarian hyper-stimulation syndrome (OHSS). While rare, OHSS is a serious condition that requires close monitoring and treatment of symptoms. Use of Clomiphene for more than 12 cycles has been suggested to be associated with a possible (unproven) increased risk of ovarian tumours. For this reason, we recommend use of Clomiphene for up to six cycles of treatment only.
Letrozole (Femara)
Letrozole is an estrogen-lowering compound that has recently been found to induce ovulation (its effect is similar to that of Clomiphene). Like Clomiphene, Letrozole is an oral medication that is taken for five days at the beginning of a menstrual cycle. Side effects with Letrozole are rare.
Gonadotropins
The gonadotropins are the hormones produced by the brain that signal or stimulate the ovaries to produce eggs. There are two gonadotropin hormones: Follicle Stimulating Hormone (FSH) that stimulates the development of eggs, and Luteinizing Hormone (LH), which is important in egg maturation. Gonadotropins are prescribed when Clomiphene and/or Letrozole have been ineffective or when a stronger stimulation of the ovaries is needed. The gonadotropins that are used in treatment may be natural human hormones that have been purified, or they may be manufactured. Gonadotropins must be taken by injection, usually subcutaneous (under the skin) injection, and are usually taken for several days at the beginning of a menstrual cycle. Because gonadotropins are stronger than Clomiphene and Letrozole, and are likely to produce a greater number of eggs, closer monitoring with ultrasound is necessary.
Human Chorionic Gonadotropin (HCG) or Ovidrel
HCG is a hormone that is naturally produced in pregnancy. It is used in fertility treatment because it is known to bring about the final maturation and release or “ovulation” of mature egg(s). hCG is used to provoke ovulation only and does not cause more eggs to develop. hCG is given at the end of the treatment cycle once eggs are judged to be mature. Like the gonadotropins, hCG is available in the form of purified natural human hormone and manufactured hormone, and like the gonadotropins, HCG is given by subcutaneous injection. Side effects after HCG injection are extremely rare and include inflammation of the injection site and “ovulation- like” cramping.
Monitoring
All women on hormone therapy are monitored carefully with vaginal ultrasound scans throughout the treatment cycle. It is not possible to see individual eggs with ultrasound pictures, but it is possible to see the sac or follicle in which each egg grows. Growing follicles are monitored during the treatment cycle and when the largest follicle(s) reaches maturity, the egg(s) is considered ready for release (ovulation) and fertilization.
Treatment cycles are cancelled when ultrasound monitoring shows that the risk of multiples is high because too many eggs have been produced, or when no follicles have developed despite treatment.
With intrauterine insemination (IUI), a soft, flexible plastic catheter is used to inject a sample of prepared(washed) sperm directly into the uterine cavity (inside of the uterus). This bypasses the cervix and brings sperm closer to the fallopian tubes where fertilization occurs, increasing the chance of pregnancy. IUI is usually recommended as "first line" treatment for infertile couples with unexplained infertility or mild male-factor infertility.
Intra-uterine insemination (IUI) and hormone therapy are usually recommended for a maximum 3 cycles of treatment after which, if no pregnancy is achieved, in vitro treatment (IVF or IVM) would be considered.
The MUHC Reproductive Centre is recognized as a world-class centre for Reproductive Surgery and particularly, Laparoscopic Surgery. Surgery plays an important role in the management of infertility. There are many situations where there are structural barriers to fertility that can be remedied by surgery. For example, approximately 35 to 40% of infertility is due to “tubal damage” (of the fallopian tubes) that is, partial or complete blockage by scar tissue that prevents or reduces the chances of conception.
Decreased fertility may also be caused by endometriosis, a condition that causes the formation of scar tissue around the outside of the reproductive organs; Implantation can also be affected by scar tissue, fibroids or other growths in the uterus. All of these and other conditions may be successfully treated with reproductive surgery on an outpatient basis.
At the MUHC Reproductive Centre, Laparoscopic Surgery is preferred because it is less invasive. Laparoscopy is a highly specialized technique that employs tiny instruments guided by a small camera. The use of laparoscopic surgery results in the need for only a very small incision and allows a much faster recovery.
The Endocrinology Clinic at the MUHC Reproductive Centre is an important complement to our program of treatment options for infertility. Our Endocrinologist will treat and monitor patients with various Metabolic and Endocrinological problems related to infertility, including:
Polycystic Ovarian Syndrome
Insulin Resistance
Diabetes
Thyroid Dysfunction
Pituitary Dysfunctions (Prolactinomas, Hypogonadotropic Hypogonadism)
Premature Ovarian Failure
Disorders of androgen secretion (acne, hirsutism, seborrhea, and alopecia)
Our patients are asked to undergo a series of investigations so that any of these related disorders can be identified and treated before infertility treatment is started.