Infertility In Women - Medications

Other Agents Used or Under Investigation

Tamoxifen. Tamoxifen (Nolvadex) is a drug known as a selective estrogen-receptor modulators (SERM). It is used to prevent breast cancer in high-risk women. Studies are also now suggesting that it may equal clomiphene in its ability to induce ovulation. It may be especially useful when used along with IVF for preserving fertility in breast cancer patients. This drug is less expensive than clomiphene and but poses some health hazards, including a risk for blood clots and uterine cancer.

Aromatase Inhibitors.Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many major body tissues. These agents include anastrozole (Arimidex) and letrozole (Femara). Like tamoxifen, they are used for treating breast cancer and are being investigated for infertility in women. They do not appear to have the severe side effects of tamoxifen, however. In a 2002 comparison study between letrozole and clomiphene, the women who took letrozole had lower estrogen levels than those taking clomiphene. Evidence is suggesting that high estrogen levels may be harmful to the developing embryo. Therefore, letrozole may be more protective of the developing embryo than clomiphene.

Typical Regimen for Hyperstimulation and In Vitro Fertilization

Regimens to induce ovulation vary widely according to individual need. A typical procedure, involving superovulation and in vitro fertilization (IVF) may be as follows:

Doctors make sure that the patient is not pregnant or in the luteal phase of her menstrual cycle (the premenstrual period).
Injections of either hMG (which contains LH and FSH) or pure FSH are administered daily two to four days after day 1 of the next cycle. Either drug may be used.
After four to eight days of treatment, estrogen levels are monitored. Increasing levels on the fourth day of treatment may be strong indicators of success. If estrogen levels indicate that ovaries are responding, ultrasound is then performed to detect possible overproduction of follicles. Such evaluation should then be conducted every one to two days and dosages adjusted accordingly.
GnRH analogs are used to prevent a premature release of LH hormone (and therefore ovulation). GnRH agonists are typically administered either early on or a few days after ovulation in the cycle previous to the one planned for IVF. This approach is referred to as the long protocol and it serves to suppress the pituitary gland and allows time for the eggs to mature before harvesting. Other protocols using GnRH antagonists are under investigation, but to date the long protocol has the best pregnancy rates.
When at least three follicles have reached a diameter of 18 mm, hCG is typically administered to release the egg. It is not given if there are signs of overproduction of follicles, which suggests a risk for ovarian hyperstimulation syndrome (OHS), a dangerous complication. (One study reported that administering high doses of progesterone in high-risk women the day of hCG administration may prevent OHS.)
Egg retrieval may be performed about 36 hours following hCG administration, with the transfer of the embryo (the fertilized egg) back into the woman two or three days after retrieval.
Embryos are transferred to the uterus through a small tube. This process does not require an anesthetic, although the procedure can cause cramping.

Gentler Alternatives to Superovulation

Natural (Unstimulated) In Vitro Fertilization Cycles. An alternative to superovulation for some couples is natural IVF cycles. It allows multiple, consecutive cycles of treatment. Natural IVF is far less expensive than standard hyperstimulation methods and avoids their risks, including multiple births and ovarian hyperstimulation syndrome (OHS).

The process involves ultrasound and hormonal monitoring starting five days before the estimated ovulation day.
No superovulation agents are used, such as FSH and hMG. The doctor, however, may administer an injection of hCG to stimulate the LH surge.
The egg retrieval timing is based on detecting LH surge.
A single egg is retrieved. The procedure that follows is similar to other IVF cycles.

The basic disadvantage to this approach is that the eggs may be released before there is a chance for them to be harvested. Women report far lower stress levels with this approach, however, even though it requires more treatment cycles. In one 2001 study, the live-birth rate was 32%. Not all women are appropriate candidates, however. Women should have regular menstrual cycles and infertility of unknown cause or associated with problems in the fallopian tubes. Pregnancy rates are still very low in older women.

Clomiphene. Another gentler alternative to superovulation is the use of clomiphene before IVF, which works slightly better than unstimulated IVF.