CLOMID SEROPHENE (CLOMIPHENE CITRATE) THERAPY

Clomiphene citrate has been approved for treatment of ovulation disorders since 1967. It is marketed in the US under the brand name Clomid and Serophene available in 50 mg tablets.

What are the indications for Clomiphene treatment?

Clomiphene is indicated in patients with absent or infrequent ovulation, and women with unexplained infertility. Patients with abnormal ovulation attributable to thyroid deficiency or high pituitary prolactin level may be treated with thyroid medication or prolactin lowering medication respectively. Measuring day 3 FSH (Follicle Stimulating Hormone) and estrogen levels can help your physician determine if you are a candidate for Clomiphene treatment. Generally speaking, you may be considered for treatment with Clomiphene if you experience abnormal ovulation, have normal FSH and estrogen levels or have been diagnosed with PCOS (Polycystic Ovary Syndrome).

What are the contraindications for treatment with Clomiphene?

Generally speaking, you are not a candidate for Clomiphene therapy if you have very low levels of FSH and Estrogen. In this case your doctor may recommend injectable gonadotropin therapy. Treatment with Clomiphene is not very effective for patients in their late 30’s and early 40’s; such patients may be better off with injectable gonadotropin therapy or In Vitro Fertilization (IVF). Clomiphene and gonadotropin therapy should not be utilized in cases of ovarian failure or if your day 3 FSH or estrogen level is high (diminished ovarian reserve) and your doctor may recommend donor egg IVF instead. Certainly, if you have a history of pelvic infection or endometriosis, your doctor may recommend evaluation of your fallopian tubes before considering Clomiphene treatment. Your fallopian tubes may be evaluated by tubal dye injection under x-rays (HSG) or by minimally invasive outpatient Laparoscopy. For severe tubal disease In Vitro Fertilization may be advised by your physician.

How is Clomiphene Citrate Prescribed?

It is usually prescribed at 50 mg daily starting between day 3 and day 5 of the menstrual cycle for 5 days. About 50% of the patients will ovulate and another 25% will ovulate at a dose of 100 mg daily for 5 days. In women who fail to respond to the medicine, increasing the dose of Clomiphene Citrate to above 150mg daily is not likely to be effective. In some patients a lower dose (25mg) of the fertility medication may be prescribed if too many eggs develop when treated with the standard dose.

How is the fertility medication monitored?

In some patients, all that is needed is to measure the progesterone level 7 days after ovulation to confirm that ovulation was adequate; a progesterone level above 15ng/ml is indicative of good ovulation; sometimes intrauterine insemination (IUI) is performed at the time of ovulation which can be easily pinpointed by an ovulation predictor test kit. In other patients, an ultrasound on day 12 may be recommended by your physician to follow the growth of the follicles and to measure the thickness of the lining of the uterus (endometrial thickness). Once a follicle reaches about 18 mm in diameter, another hormone (HCG) may be necessary to trigger ovulation. Ideally the lining of the uterus should be more than 8 mm thick; If no follicle over 10 mm is noted and the lining of the uterus is thin, Clomiphene Citrate can be increased by 50mg increments up to 150 mg daily. Although unlikely to be successful, some doctors recommend treatment with higher doses of Clomiphene up to 250 mg daily for 5 days

What are the treatment options if I fail to ovulate with Clomiphene?

• Injectable hormones (gonadotropin therapy) may be recommended by your physician if:

1. There is no response to Clomiphene Citrate (Clomiphene resistance)
2. The thickness of uterine lining measured by ultrasound is less than 6mm
3. If you ovulated with Clomiphene but failed to conceive.

• If you were diagnosed with Polycystic Ovary Syndrome (PCOS) and previously failed to ovulate with Clomiphene, a 5% weight loss may improve the likelihood of ovulatory response; your doctor may otherwise recommend an Insulin-Sensitizing medication such as Metformin alone or in combination with Clomiphene. Metformin alone has been shown to restore ovulation in about 50% of the patients and in 80% of patients when Metformin is combined Clomiphene.

• Some women with PCOS who had elevated male hormones (DHEAS) were treated with a combination of Clomiphene and a steroid (Dexamethasone 0.25mg daily); such treatment has been largely replaced by the more effective Clomiphene/Metformin combination.

• Laparoscopic ovarian drilling is a minimally invasive outpatient surgery utilized to induce ovulation in Polycystic Ovary Syndrome (PCOS). In this procedure approximately 10 holes are drilled into each ovary utilizing a laser beam or electrical probe resulting in restoration of ovulation in about 85% of patients and pregnancy in 50-60%. The advantage of the therapy is ovulation occurs spontaneously without the use of ovulation inducing medications and is associated with a very low risk of multiple pregnancies.

• In women who ovulate with Clomiphene but fail to conceive, other causes of infertility such as endometriosis or pelvic adhesions may be the problem. In such cases your doctor may recommend laparoscopy before pursuing a more complex treatment.

What are the risks and complications of Clomiphene therapy?

About 10% of the patients may experience hot flushes while abdominal swelling, breast tenderness, nausea, headaches and visual symptoms are infrequent. Ovarian enlargement as a result of the development of multiple follicles may occur although severe Ovarian Hyperstimulation Syndrome (OHSS) is extremely rare. Multiple pregnancies (mostly twins) occur in 7-8% of patients.

Clomiphene Citrate or injectable gonadotropin therapy should only be administered under close medical supervision. Please consult your doctor to discuss appropriate treatment options.