OVULATION INDUCTION

CLOMIPHENE THERAPY

Clomiphene (Serophene, Clomid) is a medication that is given orally (by mouth) for 5 days out of each menstrual cycle. It is usually taken on menstrual days 3-7 or 5-9 as determined by your physician. This medication stimulates the pituitary gland to signal the ovary to produce an egg.

Some indications for the use of clomiphene include the treatment of patients with prolonged cycles, irregular menses, or polycystic ovaries. Additionally, Clomiphene and insemination are utilized for patients with unexplained infertility or for timing donor inseminations.

Different women respond to clomiphene at different rates. The treatment plan starts with clomiphene 50-100 mg (1-2 tablets) daily for 5 days. If there is no evidence of ovulation, the dose of medication increases by 50 mg daily each cycle until ovulation occurs. If adequate ovulation has occurred, you will probably continue that dosage for 3 cycles prior to further evaluation.

Some women will time their Clomiphene cycles with temperature charts and a urine ovulation predictor kit while some women may require ultrasound monitoring of the follicles in the ovary. Ultrasound monitoring of follicular development using a vaginal probe ultrasound will usually start around day 10 of your menstrual cycle. (But this will be individualized by your physician when setting up your follicular monitoring plan.) These ultrasounds will continue until the size of the follicle(s) indicate that the egg(s) are mature.

At that point, an injection of hCG (human chorionic gonadotropin) will be given to trigger ovulation. (A teaching class to learn how to give this injection is given in the office.) Ovulation usually occurs 36-40 hours after hCG administration. Patients taking clomiphene may have intercourse at the time of ovulation or may be advised to proceed with inseminations. The choice of whether to proceed with intercourse or an insemination will depend on the diagnosis and the male partner’s semen quality.

Sometimes clomiphene has side effects which warrant discontinuing the medication these include visual disturbance and thinning of the lining of the uterus. Pregnancy rates vary from 2-25% with the use of clomiphene. Your individual pregnancy rate will be based on the diagnosis, the female partner’s age, female partner’s ovarian reserve, and whether or not inseminations were utilized.

Very often Clomiphene is used to perform a clomiphene challenge test, which is used to evaluate a woman’s egg quality (ovarian reserve). An elevated FSH is a sign of low ovarian reserve. Women with a diminished ovarian reserve may have difficulty achieving pregnancy even with fertility drugs. An evaluation of ovarian reserve is an important part of the fertility workup. Clomiphene may also be used in men to treat low sperm counts (oligospermia).

Women who conceive with Clomiphene Citrate have a 5-8% chance of becoming pregnant with twins. There is a <1% chance that a woman will conceive a high order multiple pregnancy (ie triplets or more) while taking clomiphene citrate. Clomiphene cost about $9- $60 per treatment cycle for the medication.

GONADOTROPIN THERAPY

Gonadotropins are medications that are given by injection to stimulate development of follicles (eggs) either when development of follicles is not occurring or when the production of multiple eggs and/or better timing of ovulation would be beneficial.  These hormones stimulate the ovaries and are similar to the natural hormones released by the pituitary, a small gland located at the base of the brain.  These drugs are collectively known as Human Menopausal Gonadotropins (HMG).

Different women respond to HMG at different rates, and even the same woman will not respond to HMG in the same fashion on each cycle.  Some women may need to have the dosage increased or decreased during the cycle, and some women who have responded either slower or faster than usual on previous cycles may be started on different doses.

Therefore, it is essential that your treatment be monitored closely so that the correct amount of medication is given and that ovulation is triggered when developing eggs become mature.  This monitoring involves blood testing and ultrasounds to measure the growth of the follicles in the ovary.

HMG needs to be given by an injection on a daily basis, usually over 7 to 14 days.  You will need to receive the injections at the same time each day (within 2 hours) usually between 4:00 and 9:00 pm. You will need to arrange for your husband or a friend to give you the injections unless you are using the subcutaneous medication.  At RMFC we provide an HMG Teaching Course designed to instruct persons on how to prepare the medication and give the injections.

HMG is associated with an increased risk of multiple births. The multiple gestation rate is approximately 20%, the majority of which have been twins.  About 5% of the total pregnancies result in triplets or more. Except for the increased risk of premature labor associated with multiple pregnancy, HMG does not increase the rate of premature labor or birth defects.  Since this medication is injectable, there is a risk of infection at the injection site referred to as cellulitis.

Side effects of HMG that may be observed during the cycle are breast tenderness, mood swings, bloating, tiredness, and pelvic discomfort. Many women have cysts form in the ovaries after ovulation and usually these cysts do not cause any problem other than some pelvic fullness. But sometimes these cysts do grow to considerable size and may cause significant abdominal bloating or pain (referred to as hyperstimulation).

If this occurs, it usually begins about 3 to 7 days after you receive the injection of hCG. These cysts usually start to go away after 4 to 7 days but, on rare occasions, can cause serious problems with accumulation of fluid in the abdomen that would require hospitalization. Under very rare circumstances these cysts may rupture or the ovary may twist possibly requiring surgery and possible loss of the involved ovary.

LETROZOLE

Letrozole is very similar to clomiphene in the way it works. However, letrozole is quickly cleared from the body.  It only works for the cycle in which it is taken and is less likely to adversely affect the uterine lining and cervical mucous. Letrozole is prescribed for five days each cycle, usually beginning on day three and continuing through day seven.  The usual dosage of letrozole is 2.5-5.0 mg., one- two tablets each day.