Clomid (clomiphene citrate) is one of the oldest fertility drugs and is frequently prescribed to regulate or induce ovulation. Clomid is a “first line” fertility medication employed by obstetrician/gynecologists (OB/GYN) and infertility specialists.
The usual starting dose of Clomid is 50-100 mg. starting on day 3-5 of the menstrual cycle and continuing for five days. Day one of a cycle is considered the first day of good menstrual flow. If ovulation does not occur at this dose, the dosage can be increased by 50 mg. until ovulation occurs, or a maximum daily dose of 250 mg. is reached. Once ovulation occurs regularly, there is no advantage to increasing the Clomid dose. Intercourse is timed to coincide with ovulation based upon the results of an ovulation predictor kit or ultrasound.
Clomid exerts it action at the hypothalamus, a small gland at the base of the brain, where it competes with estrogen for binding sites. The hypothalamus is one of the “reproductive master glands” that controls the levels of reproductive hormones such as estrogen, luteinizing hormone, follicle stimulating hormone, and others.
When the hypothalamus senses lower estrogen levels it responds by producing gonadotropin releasing hormone (GnRH) which stimulates the pituitary to produce follicle stimulating hormone (FSH). FSH is the hormone responsible for stimulating and supporting follicular (egg) development.
Clomid binds to the sites in the hypothalamus that would normally be occupied by estrogen thus making estrogen levels “appear low”. Therefore, the hypothalamus signals the pituitary to increase FSH production which stimulates ovarian follicular recruitment and growth leading to increased estrogen production.
Clomid can also bind with the estrogen receptors in the cervical glands which can lead to inadequate or poor cervical mucus production. This potential detrimental side effect can impair the upward progression of the sperm through the female reproductive tract, especially when higher doses of Clomid are used. In a similar fashion, the uterine lining where the embryo attaches, called the endometrium, can be adversely affected in Clomid cycles. Once again, this is more common when larger doses of Clomid are needed to induce ovulation. As a result, the ultrasound is often used to look for these adverse effects, especially when the use of higher Clomid doses are needed.
Sometimes physicians will prescribe Clomid as a first line “trial” therapy without fertility testing of either partner. This plan is fine provided that the treatment with Clomid is confined to a few months. If Clomid is unsuccessful after a few months, Dr Bachus would generally recommend that a more thorough evaluation of both partners be performed to include at least a semen analysis and perhaps an ultrasound and hysterosalpingogram (HSG) study to be sure that the tubes are open.
Once Dr. Bachus identifies the cause(s) of infertility, appropriate therapies will be prescribed.
Dr. Bachus sometimes recommends transvaginal ultrasound monitoring of follicular development for Clomid patients. This allows him to assess the number and size of the follicles and to document ovulation. Some patients have poor or absent ovulation despite what appears to be normal egg development. By appropriately monitoring the dynamics of egg development with the ultrasound, ovulation can be “controlled” by the administration of a simple medication called hCG.
This medication induces ovulation in the same manner as naturally occurs by the hormone called LH. By administering hCG when the follicle is mature, ovulation can be more certain and the timing of intercourse can be more accurately determined. This simple method of treatment has resulted in many pregnancies, and has the advantage of being able to conceive at home.
The next step after the failure of Clomid alone to achieve a pregnancy is usually to combine Clomid with another stronger ovarian stimulation medication called FSH. Ultrasound monitoring along with hCG administration is then combined with intrauterine inseminations (IUIs). Sometimes FSH alone without Clomid or even in vitro fertilization (IVF) is a better option. Each couple is unique and treatments vary for a variety of reasons.
Studies demonstrate that Clomid is most likely to be effective within three to six ovulatory cycles and pregnancies beyond six cycles are uncommon. Yet, we often see patients who have been on Clomid for as long as a year without additional evaluation. This is probably not ideal, and is even more important not to delay further workup after 3-6 months of unsuccessful Clomid therapy in individuals beyond 35 years of age, or those with a limited number of eggs as determined by ultrasound.
In these individuals, time may be of greater importance and more aggressive therapies more appropriate. An infertility specialist is of even greater importance in these individuals.