Clomid and Serophene for Ovulation Induction
Clomid or Serophene (generic name clomiphene citrate) is an orally administered drug used to regulate, or stimulate, ovulation. Clomid is usually started on cycle day 3, 4, or 5 and continued for five days. The dose varies based upon the cause(s) of the patient’s infertility, previous treatment results, and other factors. It's usual starting dose is 50 mg and if ovulation does not occur it can be increased up to 150 mg per day.
Clomid was originally studied as a birth control pill when researchers discovered its ovulation inducing characteristics. Contrary to follicle stimulating hormone (FSH), which stimulates the ovaries directly, Clomid’s effects are exerted at the hypothalamic gland (See the discussion on the fertility drug overview page).
Clomid works by competing, or binding, with estrogen receptors at the hypothalamus. When these receptors are occupied, the hypothalamus “measures” lower estrogen levels and thus releases GnRH, which causes the pituitary to increase FSH production. Increased FSH production leads to enhanced follicular recruitment and development.
Clomid's most significant problem is overuse. Clomid is widely used by obstetrician/gynecologists, often for longer times than recommended. Numerous studies demonstrate that Clomid is most likely to be effective in the first 3-6 ovulatory cycles and pregnancies decline dramatically after 3 cycles. If Clomid has not worked within this time frame, infertility specialists will usually move to other therapies, such as stimulated (addition of FSH) IUI or IVF.
Yet, our fertility specialists see patients who have been on Clomid for as long as a year. Continued use increases the chances of side effects and is expensive. We also see women taking Clomid whose husbands have not had a semen analysis to rule out male infertility. Clomid, or any other fertility drug, will not work unless there are “adequate”, “quality” sperm available. A semen analysis is always strongly recommended before using ovulation enhancing agents such as Clomid.
Older women, or those with declining ovarian reserve, should not "waste" valuable treatment time with Clomid. Fertility can decrease very rapidly in these women and the most effective treatments should be administered as soon as possible to maximize their chance of having a child. Older women must see an infertility specialist as quickly as possible to insure the most appropriate treatments .
A woman should also obtain a hysterosalpingogram (HSG) prior to Clomid use if she has a history of pelvic infection or pelvic surgery. If there is no history of pelvic problems, an HSG should be completed if conception has not occurred after 2-3 ovulatory cycles on Clomid. The fertility specialist can document that that the fallopian tubes are opening using the HSG.
Some infertility specialists are beginning ovulation induction treatment with drugs like Femara (letrozole) These drugs do not seem to have some of the adverse side-effects such as decreased cervical mucus, thinning of the endometrial lining or emotional irritability that are common with the use of Clomid . The incidence of twins is 2-3% with the use of Femara compared to 10% with the use of Clomid. The addition of FSH injections to either of these medications can increase the risk of multiples. These fertility drugs (aromatase inhibitors) have not been used for fertility therapy for a long time, and there may be more risks, which are not currently known. A fertility doctor should administer fertility drugs including letrozole, FSH, Clomid, and others.
Dependent upon the specific cause(s) of infertility, IUI with FSH ovulation induction may be the next step after Clomid failure. FSH causes the development of multiple follicles and increases the chances for success in the IUI cycle. However, these cycles must be monitored very carefully by an infertility specialist to reduce the chances of multiple births. Most of the high order multiples reported in the media are the result of stimulated IUI cycles often administered by general practice OB/GYNs.
There are epidemiological studies that suggest if Clomid is used longer then 12 months there may be an increase in the incidence of ovarian tumors. This is a “weak” association but should be considered when prescribing it .
Many fertility specialists monitor Clomid cycles with ultrasound, which allows visualization of follicular development and documentation of ovulation. Our infertility clinic has the specialized equipment needed to effectively monitor all types of "drug cycles" including Clomid and FSH. Our fertility doctors also physically examine patients at regular intervals to check for side effects such as ovarian enlargement.
Methods of monitoring the time of ovulation include ultrasound, urinary ovulation predictor kits, blood tests for estradiol, progesterone and luteinizing hormone (LH). Basal body temperature charts and serum progesterone levels can be used to to confirm ovulation. Sometimes an injection of hCG will be given to stimulate ovulation if follicles seen on ultrasound are of the appropriate size during monitoring.
The manufacturers Web site has a complete listing of potential side effects.
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