Anne Borkowski, MD

Reproductive Endocrinologist
Infertility Specialist

4250 Dempster St.
Skokie, IL, 60076
847-763-8850

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Fertility Drugs

There are several fertility drugs available to treat female infertility. The majority induce or regulate ovulation. The medications range from oral pills such as Clomid to injections of FSH. We provide an overview of the most common fertility medications.

Clomid

Clomid is often the first ovulation inducing medication prescribed by the OB/GYN. It should never by prescribed without a semen analysis of the male partner. Treatment of the female with Clomid when an undiagnosed male infertility problem is present could waste valuable resources and, most importantly in older women, time.

Follicle stimulating hormone (FSH) is produced by the pituitary gland and directly stimulates the production of eggs within the ovarian follicles. The pituitary gland is "stimulated" by a complex interaction of chemical events controlled by the hypothalamus, a gland located at the base of the brain. The hypothalamus must stimulate the pituitary gland to release follicle stimulating hormone (FSH) and leutinizing hormone (LH) at the appropriate times for follicular recruitment, development and ovulation to occur.

Clomid acts upon the hypothalamus causing it to secrete gonadotropin-releasing hormone, which stimulates the pituitary to secrete FSH. Many factors can cause hypothalamic insufficiencies leading to ovulatory disorders including, excess exercise, stress, PCOS sudden weight lose, and some medications.

Clomid should not be used for more than three to six months. The length of treatment is dependent upon many factors including the cause(s) of infertility, the age of the patient, her laboratory values and other variables. The likelihood of success with clomiphene is highest during the first three months and diminishes thereafter.

Clomid side effects can include visual disturbances, nausea, cramping, and others. The most severe, and very unlikely, side effect is ovarian hyperstimulation which is characterized by enlarged ovaries, pain, plural effusion, possible stoke and other symptoms. Detailed information on potential side effects can be obtained from rxlist.com.

Clomid can also produce multiple births. The chance of multiple births with ovulation inducing agents is minimized when patients are carefully followed by a fertility specialist trained in the administration of infertility medications.

FSH

Gonal-F, Follistim, Menopur and other injectable FSH products stimulate the ovarian follicles directly. Clomid stimulates the ovary indirectly via the hypothalamic-pituitary interactions. Externally administered FSH is physiologically identical to the FSH produced by the pituitary. Gonal-F and Follistim are made using genetic recombinant therapy and are identical to the bodies FSH in all respects.

FSH is administered by subcutaneous injection in conjunction with assisted reproductive technologies (IVF) and intrauterine insemination (IUI) where multiple eggs are needed. Multiple egg development occurs because of the stimulatory effect of FSH on the follicles. Some women who have very low FSH levels (hypogonadotropic) and functional ovaries have an excellent response to FSH resulting in high pregnancy rates. FSH is usually administered at home by the patient or her partner.

Some products, such as Repronex and Humegon, contain FSH and small amounts of leutinizing hormone or other impurities whereas Gonal-F and Follistim are pure FSH products made with recombinant DNA technology. There is debate as to which class of these products (pure FSH vs. FSH/LH) is the most effective. Many embryologists believe higher quality eggs are obtained from pure FSH cycles.

The most serious potential side effect of the gonadotropins is ovarian hyperstimulation syndrome (OHSS). In this condition, the ovaries become enlarged and there is a "shift" of body fluid into the abdomen and pelvic cavity after ovulation. The decrease in fluid resulting from this "shift" can reduce blood perfusion and result in clots and poor circulation to the internal organs.

The best predictor of hyperstimulation is elevated estrogen levels. This is why estrogen levels must be monitored in women undergoing ovulation induction with FSH. Fortunately, the incidence of OHSS is low (approximately 5%). This potential side effect in one reason that only highly trained infertility specialists should administer FSH.

Use of gonadotropins in IVF cycles significantly increases the chances of multiple births, usually twins. The incidence of higher order births is reduced when the drugs are properly administered and monitored. The incidence of twins is higher in stimulated IUI cycles because it is difficult to control the number of eggs ovulated. In fact, most high order multiple births reported in the media are due to stimulated IUI cycles.

FSH products should only be administered by a physician specially trained in their use. Much experience is required to become familiar with variable patient responses, interpret stimulation markers, adjust dosages, and prevent unwanted side effects. Reproductive endocrinologists undergo an additional two years of fellowship training after completing their OB/GYN residency to prepare them to safely use gonadotropins.

FSH is expensive and substantial savings on some fertility drugs are offered to qualified patients by EMD Serono's Compassionate Care Program. See Details

Lupron (leuprolide acetate), Ganirelix (Ganirelix Acetate), Cetrotide (cetrorelix acetate)

GnRH agonists (Lupron), interfere with the production of FSH and LH. Lupron is a GnRH agonist which works at the hypothalamus (a small gland located at the base of the brain ) whereas Ganirelix and Cetrotide are GnRH antagonists which completely block the effect of gonadotropin releasing hormone at the pituitary gland thus creating a "more complete "down regulation" and reduction in gonadotropin levels.

Leuprolide acetate is a long-acting GnRH analog. An injection of Lupron results in an initial stimulation followed by a prolonged suppression of pituitary gonadotropins. This action inhibits the release of pituitary gonadotropins and FSH, LH, and estrogen levels are lowered.

Endometrial tissue is dependent upon the presence of estrogen for growth. When endometrial tissue enters the body cavity it can attach to organs such as the tubes and ovaries thus creating endometriosis. Since Lupron lowers estrogen levels is an effective treatment for endometriosis which depends upon estrogen for support and growth.

In in vitro fertilization cycles, Lupron, Ganirelix or Cetrotide is used to lower gonadotropin levels (FSH, LH) during the stimulation cycle. External FSH is administered by injection to replace that suppressed by the GnRH agonist or antagonist allowing for precise control of the stimulation cycle.

These drugs are administered in different protocols dependent upon the patient's response. The amount of Gonal-F or Follistim required for a stimulation cycle is patient specific. In most cases more FSH is required in cycles where Ganirelix or Cetrotide is used. These drugs are administered until the eggs are mature and the retrieval is scheduled.

It is critical that ovulation not occur before egg retrieval in a stimulated IVF cycle. If ovulation does occur, the eggs cannot be retrieved and the IVF cycle is “lost”. LH is responsible for signaling the ovary to ovulate and is suppressed with Lupron, Ganirelix and Cetrotide until the physician judges that the eggs are mature. Once mature, an injection of hCG is given and the egg retrieval is scheduled.

GnRH agonists and antagonists have similar side effects and can include hot flashes, vaginal dryness, painful intercourse, headache, mood swings, fatigue, lowered libido, and insomnia. These side effects mimic the symptoms induced by the menopause.

Metformin

Glucophage (metformin) is currently being used successfully to induce ovulation in PCOS patients. Oftentimes metformin is used by reproductive specialists as a "first line" therapy or in patients who fail Clomid therapy. Metformin is sometimes used in combination with either Clomid or FSH. PCOS patients often have an exaggerated response to FSH medications and must always be monitored by a reproductive endocrinologist.

Parlodel (bromocriptine)

Prolactin is a hormone produced by the pituitary gland that stimulates the development of breast milk and inhibits ovulation. This is why menses often cease while a woman is breast-feeding. Artificially high levels of prolactin can cause anovulation (lack of ovulation) and bromocriptine is often effective in lowering prolactin.

High prolactin levels are sometimes caused by a tumor (usually benign) on the pituitary gland, which can often be treated surgically. Once prolactin levels are normalized, patients typically respond very well to treatment and subsequent pregnancy results are excellent. Parlodel can produce side effects including nausea, headache, fatigue, dizziness and others.

Progesterone

Progesterone is a hormone produced by the ovaries during the menstrual cycle and the placenta after conception to help prepare the uterus to accept and support an embryo and later the fetus. The structure on the ovary which initially produces progesterone is the corpus luteum. It is a gland composed of tissue from the ruptured follicle.

Progesterone causes the lining of the endometrium to thicken and increases its blood supply. Progesterone is administered to women undergoing assisted reproductive procedures (IVF) because drugs (FSH) used during the cycle interfere with progesterone production. After a pregnancy has been established, the placenta produces progesterone. Side effects of progesterone can include moodiness, fluid retention, depression, irritability, and hypoglycemia. We use Crinone 8% gel for progesterone supplementation or replacement as part of medicated cycles and as part of in vitro fertilization cycles. Instructions or Crinone use.

Ovidrel, Pregnyl (hCG)

Ovidrel is used to trigger ovulation in women with infertility due to anovulation and to promote final maturation of eggs in the ovaries of women undergoing assisted reproductive technologies (ART), such as in-vitro fertilization. Ovidrel is unique in that it is a pure product derived from new cellular drug DNA recombinant production techniques. Pregnyl (hCG) is a natural product derived from the urine of pregnant women and it contains impurities not found in Ovidrel. Women who are undergoing IVF with a GnRH agonist or a GnRH antagonist cannot ovulate until hCG or LH (Luveris) is administered. This prevents ovulation of the eggs before they can be retrieved and fertilized in the embryology laboratory.

Luveris (LH)

Luveris is genetically engineered pure luteinizing hormone (LH). LH is normally produced by the pituitary gland in response to stimulation by gonadotropin releasing hormone (GnRH).

Some LH is required for follicular development. Luveris may be added to stimulation cycles in an attempt to improve egg and embryo quality. LH also initiates ovulation through a "surge" in its levels" once the follicles are mature. Luveris can be used in place of hCG to initiate ovulation and in women who have severe deficiencies of FSH and LH. It is administered by subcutaneous injection.