clomiphene citrate
Clomiphene citrate is an oral ovulation induction drug. If an infertility problem stems from infrequent or absent ovulation, clomiphene citrate may be the first infertility treatment recommended. Because clomiphene citrate is relatively inexpensive, some physicians will go ahead and prescribe treatment after the initial battery of fertility tests. If you do not ovulate after three treatment cycles or do not become pregnant after three ovulatory cycles healthcare providers will often move on to more involved fertility tests.
If clomiphene alone is not successful, doctors might combine it with other fertility drugs. Some of these drugs, such as bromocriptine, dexamethasone (for high androgen levels), or gonadotropins might be used alone or in combination with other fertility drugs.
Before this drug therapy is prescribed, an endometrial biopsy is usually done to check for hyperplasia or cancer of the uterine lining if a woman has been anovulatory for a long time. Semen analysis is also done to check for the presence of sperm abnormalities. Tests that rule out pituitary (prolactin), thyroid or adrenal disorders are also performed.
Prior to taking the clomiphene, an ovarian ultrasound should be performed to rule out the presence of ovarian cysts. If the cycle is unsuccessful and another cycle is to be done, another ultrasound is warranted. Cyst formation after taking clomiphene can occur approximately 5% of the time.
how it works
Clomiphene stimulates the body to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the necessary hormones for ovulation. The drug behaves like an “anti-estrogen,” and convinces the body that the estrogen level is low. In response, the body will respond by secreting FSH and LH to stimulate follicular growth. Clomiphene can cause the body to produce two or three times the normal amount of estrogen. Clomiphene does not directly stimulate ovulation, but instead returns the sequence of events surrounding ovulation to a more normal state. For women who do not produce mature follicles, clomiphene can help develop mature eggs before ovulation.
The anti-estrogen effects however may affect other organs as well. Some women find that their cervical mucous does not thin as it normally would in response to estrogen around the time of ovulation. The uterine lining may not develop adequately for implantation to occur. Many women taking clomiphene will receive an injection of hCG as well to stimulate the corpus luteum, a cyst that forms on the ovary after ovulation, to produce progesterone. Others may take supplemental progesterone to ensure that the uterine lining is adequately prepared.
how to take it
Clomiphene is taken orally for 5 days, generally starting day 2-5 of your cycle (day 1 is the first day of full menstrual bleeding). Progress can be monitored at home by tracking basal body temperatures (BBT) or using an over-the-counter ovulation predictor kit, however the healthcare provider should determine the best strategy for monitoring the drug’s effect. Some prefer that their patients visit the office, because multiple follicles may develop in response to clomiphene. A transvaginal ultrasound can be performed to monitor follicular development.
Couples are advised to have intercourse every other day for one week beginning a few days after the last day of medication, because an ovulatory surge of gonadotropins can occur five to 10 days after the last day the drug is taken.
There isn’t a perfect formula to predict the proper dosage -- treatment is started at 50 milligrams daily for five days. There is a correlation between body weight and dosage. Because the pregnancy rate is no higher at twice the dosage, it makes no sense to ask for a higher dosage. However, if the first cycle does not cause ovulation, the second cycle will be at 50 milligrams higher. Dosages increase by 50 milligrams until 150 milligrams is reached. Success at 200 milligrams or 250 milligrams is rare. If ovulation is not achieved at 150 milligrams to 250 milligrams, clomiphene failure will be cited, and new options will be explored.
side effects
There are risks and side effects associated with clomiphene. Your healthcare provider will discuss important safety information with you when this product is prescribed.
results
“In properly selected patients, 80% can be expected to ovulate, and 40% become pregnant,” according to Speroff, et al, authors of Clinical Gynecologic Endocrinology and Infertility. Also from Speroff, et al: “Approximately 75% of pregnancies that do occur on clomiphene do so in the first three treatment cycles.”
The percentage of pregnancies per ovulation cycle is 20 to 25%. Almost 5% of the pregnancies are multiple pregnancies (almost all twins). The discrepancy between ovulation and pregnancy is either due to other factors or lack of persistence. In those without other factors, the pregnancy rate per ovulatory cycle approaches the normal rate of 20 to 25%.
Couples shouldn’t be discouraged if clomiphene cycles don’t result in a pregnancy, since this is the most conservative of several approaches. If treatment doesn’t result in a successful pregnancy, healthcare providers might combine clomiphene with other fertility drugs, or try a different approach altogether, such as gonadatropins.
Safety Information:
- Follistim® AQ Cartridge administered with Follistim Pen® delivers on average an 18% higher amount of follitropin beta compared to lyophilized preparations administered with a conventional syringe. A lower dose should be considered when using Follistim® AQ Cartridge.
- Follistim® AQ Cartridge, like all gonadotropins, is a potent substance capable of causing mild to severe side effects including ovarian hyperstimulation syndrome (OHSS), with or without pulmonary or vascular complications.
- Follistim® AQ Cartridge should be used only by physicians who are experienced in infertility treatment and should advise their patients of treatment risks, including OHSS and multiple births.
Please see accompanying Full Prescribing Information.