Clomid

Clomid, Clomiphene Citrate
 
Clomiphene citrate ( Clomid, Serophene) was originally developed in 1956 as an oral contraceptive, but on the contrary, a 1960 study showed it stimulated the ovaries to produce and release eggs; it was approved for use in the United States in 1967. Since 1968, clomiphene citrate has consistently been, and still is, the most prescribed fertility medication in the world. It is a good medication, given its safety profile, effectiveness and cost.

Treatment with clomiphene is indicated to improve the timing and frequency of ovulation and to enhance the possibilities of conception for the patient who ovulates only occasionally. Clomid works at the level of the hypothalamus where it competes for estrogen binding sites. When these "receptor sites" are occupied by Clomid, the hypothalamus responds by producing more GnRH which then stimulates the pituitary to   increase the levels of FSH (follicle stimulation hormone). Higher level of FSH leads to maturation of follicles  (which contain the eggs) in the ovary.

Usually  pregnancy should occurs during the first three months of ovulation induction with Clomid and treatment beyond six months is not recommended. Clomiphene can cause side effects such as ovarian hyperstimulation (rare), visual disturbances, nausea, diminished "quality" of the cervical mucus, multiple births, and others.

How is clomiphene given?
When you are planning a clomiphene cycle, we ask that you call our office on the first or second day of your menstrual cycle. If you start on a weekend, call on Monday morning.The nurse will talk with you about the cycle, schedule an ultrasound if needed and call your prescription to the pharmacy. The usual clomiphene dose is 100mg/day for 5 days beginning on cycle day 3, 4, or 5. Ovulation usually occurs approximately 7 days after the last pill is taken.

How is treatment begun if I have no menstrual cycle?
Progesterone or a short course of birth control pills (!)  is used to induce a menses. After 5 days of progestin therapy, a period occurs, then clomiphene is started on the fifth day of bleeding. We usually start at a dose of 100 mg a day taken cycle day 5 thru 9.

How do I know when I am ovulating?
Ovulation can be predicted with the use of an ovulation predictor kit, which detects the surge of LH that occurs 1-2 days prior to ovulation . Alternatively, we use ultrasound to evaluate the growth of ovarian follicles, as well as to look at the endometrial thickness.When follicles measure 18-20 mm, and the endometrial thickness is adequate, we give an injection of hCG which triggers the ovary to release the eggs from the follicles. Intercourse and/or intrauterine insemination (IUI) can then be timed to coincide with ovulation. We obtain a progesterone level in the second half of the cycle to evaluate ovulation.

What specific findings are we looking for with ultrasound monitoring?
We are looking at the number and size of the follicles as well as the pattern and thickness of the endometrium.

When can I tell if I am pregnant?
If you have not had a period 14-16 days after ovulation, you may do a home pregnancy test. (Doing the test before 14 days may result in a false positive.) Call the nurse with the results. If it is positive, we will have you come in for a blood pregnancy test. If it is negative, we will ask you to wait a few more days, then repeat the test. If it is still negative, Dr. Ho will prescribe Provera or Aygestin to induce a period.

How long do I stay on clomiphene?
Of the women who conceive on clomiphene, approximately 90% do so within the first 3-4 cycles of taking the medication. If you are not pregnant after this time, we would schedule a consultation with Dr. Goldstein to discuss further treatment options.

What side effects can I expect from clomiphene?
For most women side effects are minimal and transient, but this is variable. The most common side effect is hot flashes during the time you are taking the medication. Other side effects can include nausea, breast tenderness, mood changes, depression and vaginal dryness. Some complaints such as visual disturbances may require that clomiphene be stopped.

Does clomiphene decrease cervical mucous and utering lining?
Estrogen is the hormone that causes the cervical mucous to increase and facilitate the passage of sperm through the cervix. It also causes the uterine lining (endometrium) to thicken in preparation for the implantation of a fertilized egg. For some women, clomiphene can have an anti-estrogenic effect on the cervical mucous and endometrium. The use of intrauterine insemination provides a way to by-pass the cervical issue by placing the sperm directly into the uterine cavity with a small catheter.

The addition of estrogen either orally or with an estrogen patch has been shown to increase the endometrium, but whether this results in improved pregnancy rates is unknown. If the endometrium is less than 8 mm at the time of ovulation, then treatments other than clomiphene should be considered.

What alternatives to clomiphene are available?
Letrozole (Femara) works in much the same way as clomiphene, but may have less of an adverse effect on the cervical mucous and endometrium. If these medications are not successful, the next form of treatment is the use of injectable medications called gonadotropins. 

What is the incidence of twins with clomiphene?
Approximately 8% of pregnancies conceived with clomiphene result in twins. Triplets, though rare, can occur. There is no increase in the incidence of congenital anomalies.