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infertility

Western Fertility Drugs

The following are some of the most commonly prescribed Western Drugs in assisted reproductive technology clinics:

Pergonal

Pergonal is natural product containing both human FSH and LH, 75 or 150 international units of each per ampule, plus 10mg lactose. This material is extracted from the urine of postmenopausal women carefully purified and then freeze-dried in sterile glass ampules where it is sealed until used. Pergonal was the first drug using the hormones FSH and LH. Since then, numerous drugs similar to Pergonal have come on the market. These drugs include Metrodine, Humegon, Fertinex, Repronex, Follistom, and Gonal-F. These drugs differ in how they are made and how they are administered. However, the comments concerning monitoring, risks, and other concerns are all the same regardless of which drug in used.

Pergonal is used to either induce or correct abnormalities of ovulation in women where other methods have been ineffective. It is also used to treat those women who are infertile, who have not conceived, and for whom in vitro fertilization would be the next step. This technique, called “controlled ovarian hyper stimulation” or COH, is often effective, particularly in couples with “minimal abnormality infertility,” such as early endometriosis or similar problems.

To control ovulation in normal menstrual cycle, the pituitary gland produces two hormones: FSH and LH. Pergonal is nothing more than a mixture of those two hormones. It is the natural hormones produced by a woman’s pituitary gland. In a normal menstrual cycle, there are controls set up by the body to make sure that the number of eggs produced is limited (usually only one) and that the egg’s maturity is optimum. The administration of Pergonal bypasses your body’s natural control systems. Artificial control mechanisms must, therefore, be substituted and strict monitoring is necessary to reduce the likelihood of complications such as multiple pregnancies or hyperstimulation.

Because of the nature of the drug, it cannot be taken by mouth. The drug must, therefore, be given by injection. Pergonal injections are started on the 3rd day of the menstrual cycle. To insure maximum safety and efficiency of Pergonal, therapy must be constantly and carefully monitored. This is done using a combination of hormone levels and ultrasound examinations. In this way, the growth and development of the follicles within the ovary are monitored. Without such monitoring, Pergonal therapy can be dangerous.

There are two principal risks to Pergonal therapy. The first is “hyperstimulation syndrome.” This occurs if the follicles are overstimulated and a shot of human chorionic gonadotropin (hCG) is then given to trigger ovulation. If the hCG shot is not given, hyperstimulation will not occur. Mild forms of hyperstimulation often occur even when the follicles are not overstimulated. Hyperstimulation may also occur if conception occurs in that cycle. Very thin women are more prone to hyperstimulation than women who are normal weight or who are overweight. Women with irregular cycles. Women with Polycystic Ovarian Syndrome (PCOS) are often very sensitive and have to be monitored very carefully.

Serious hyperstimulation of the ovaries most often occurs if the estradiol (one of the subtypes of estrogen) level goes well over 2,000. If this happens, the whole cycle may be cancelled. It also depends on the reason for the Pergonal therapy. Some groups of women are more likely to “hyperstimulate” than others. Symptoms of mild hyperstimulation include lower abdominal swelling and pain or discomfort in the region of the ovaries. Ultrasound examination will show enlargement of the ovaries with multiple cysts. Therapy for mild hyperstimulation involves nothing more than rest, avoidance of strenuous activity, and mild analgesics.

Repronex

Repronex (menotropin for injection) is a purified preparation of gonadotropins extracted from the urine of postmenopausal women. Each vial of Repronex contains 75 or 150 IU of FSH activity and 75 or 150 IU of LH activity. Repronex is administered by subcutaneous or intramuscular injection. Repronex, in conjunction with hCG, is indicated for multiple follicular development (controlled ovarian stimulation) and ovulation induction in patients who have previously received pituitary suppression. Repronex is contraindicated in women who have:

  • A high FSH level indicating primary ovarian failure
  • Uncontrolled thyroid and adrenal dysfunction
  • An organic intracranial lesion such as a pituitary tumor
  • The presence of any cause of infertility other than anovulation unless they are candidates for in vitro fertilization
  • Abnormal bleeding of undetermined origin
  • Ovarian cysts or enlargement not due to polycystic ovary syndrome
  • Prior hypersensitivity to menotropins

Follistim

Follistim (follitropin beta for injection) is the first recombinant follicle-stimulating hormone (FSH) to receive FCA approval in the United States for induction of ovulation in women undergoing assisted reproductive technology (ART) procedures.

Follistim was studied in the world’s largest randomized in vitro fertilization study ever conducted. The study included 981 women undergoing IVF at 18 centres throughout Europe. The results demonstrated that Follistim is “safe and effective.” Follistim acts like naturally produced FSH by stimulation the development of follicles within the ovary. It binds to the FSH receptor located on the surface of small granulosa cells surrounding the immature follicle and oocyte. However, Follistim does not induce ovulation. For ovulation to occur, therapy with Follistim is followed by a single administration of 5,000 to 10,000 IU of human chorionic gonadotropin (hCG). The dosage range for Follistim is 75-600 IU daily depending on the patient’s response. Follistim may be administered either subcutaneously or intramuscularly. Although Follistim may cause certain adverse effects, the incidence of these events is relatively low and similar to that of other FSH-containing infertility products.

Gonal-F

Gonal-F (follitropin alpha for injection) is a highly pure and consistent FSH produced by rDNA technology. Gonal-F acts directly on the ovaries to help stimulate the development of follicles. It is administered daily, and the length of treatment per cycle varies from patient to patient dependent on individual patient response to this drug. Gonal-F comes in an ampule that contains powder which needs to be mixed with sterile water. This medication is administered by easy subcutaneous injection, thus allowing for self-administration.

Clomid

Clomid (clomiphene citrate, serophene) is synthetic drug which stimulates the hypothalamus to release more GnRH. This, in turn, prompts the pituitary to release more LH and FSH and thus increases the stimulation of the ovary to begin to produce a mature egg. Clomid is a good first choice drug when a woman’s ovaries are capable of functioning normally and when her hypothalamus and pituitary are also capable of producing their hormones. Structurally similar to estrogen, Clomid binds to the sites in the brain where estrogen normally attaches, called estrogen receptors. Once these receptor sites are filled up with clomiphene, they cannot bind with natural estrogen circulating in the blood and they are fooled into thinking that the amount of estrogen in the blood is too low. In response, the hypothalamus releases more GnRH, causing the pituitary to pump out more FSH which then causes a follicle to grow to produce more estrogen and start maturing an egg to prepare for ovulation. Typically, a woman taking Clomid produces double or triple the amount of estrogen in that cycle compared to pre-treatment cycles.

If a woman is menstruating, even if irregularly, Clomid is usually effective, particularly if she develops follicles that are not reaching normal size. Usually, a mature follicle is about 20 millimetres in diameter or about the size of a small grape just before it ruptures and releases its egg. Clomid may help small, immature follicles grow to maturity. Clomid is also often effective for a woman with luteal phase defect (LPD). A woman with LPD may begin the ovulation process properly, but her ovarian function becomes disrupted, resulting in low production of the hormone progesterone in the luteal phase of the menstrual cycle. Following ovulation, the ovary produces progesterone, the hormone needed to prepare the uterine lining for implantation of the fertilized egg which has divided and entered the uterine cavity. A fall in progesterone levels in the blood during this critical time can interfere with early embryo implantation or, even if a fertilized egg has already implanted, cause a woman to menstruate too early and end pregnancy within a few days after implantation.

If a woman responds to Clomid and develops a mature follicle (determined by adequate estrogen production and ultrasound examination) but has no LH surge by cycle day 15, then injection of hCG, which acts like LH, can be given to stimulate final egg maturation and follicle rupture, thus releasing the egg. The woman tends to ovulate about 36 hours after the LH surge or hCG injection. This can be confirmed by further ultrasound scans. If a woman does not ovulate after taking one Clomid tablet for five days, then her doctor will usually double the daily dose to two tablets (100mg) in her next cycle, and, if she still does not respond, then triple the daily dose to 150mg a day, but this is not recommended by either of the drug’s two manufacturers. Women tend to have side effects much more frequently at higher doses. If the dose of clomiphene is too high, the uterine lining may not respond completely to estrogen and progesterone stimulation and may not develop properly. As a result, a woman’s fertilized egg may not be able to implant in her uterus.

Because Clomid binds to estrogen receptors, including the estrogen receptors in the cervix, it can interfere with the ability of the cervical mucus glands to be stimulated by estrogen to produce fertile mucus. Only “hostile” or dry cervical mucus may develop in the days preceding ovulation. If this occurs, adding a small amount of estrogen beginning on cycle day 10 and continuing until the LH surge may enhance cervical mucus production. Some women taking Clomid experience hot flashes and premenstrual-type symptoms, such as migraines and breast discomfort (particularly if they have fibrocystic disease of the breasts). Visual symptoms, such as spots, flashes, or blurry vision, are less common and indicate that treatment should stop.

Lupron

Lupron (leuprolide) is a synthetic version of the naturally occurring gonadotropin-releasing hormone (GnRH) which is a hormone normally released from the hypothalamus. Lupron may be used for a number of different medical problems. These include treatment for prevention of premature LH surges with assisted reproductive technologies (ART); anemia caused by bleeding of uterine myomas; central precocious puberty (CPP); and pain due to endometriosis. About 1-2 weeks after receiving her first dose, one enters a pseudo-menopausal state with low levels of estrogen, hot flushes, and other such menopausal side effects.

hCG

hCG stand for human chorionic gonadotropin, a polypeptide hormone produced by the human placenta. It is composed of an alpha and a beta subunit. The alpha subunit is essentially identical to the alpha subunits of the human pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (TSH). The beta subunits of these hormones differ in amino acid sequence. Chorionic gonadotropin is obtained from the human pregnancy urine. It is used in fertility clinics to help stimulate the release of the egg. hCG is contraindicated in precocious puberty, prostatic carcinoma, or other androgen-dependent neoplasms, or in those with a prior allergic reaction to hCG. One well-known brand of hCG in the U.S is Novarel which is given by injection.

Prednisolone

Prednisolone is a cortisone-like drug which is sold in North America under a wide variety of names as well as being available as a generic in the U.S and Canada. It is effective for relief of a wide variety of inflammatory and allergic disorders and is also effective in suppressing immunity. In the fertility clinic, it is used to suppress the immune system and, therefore, increase implantation as long as there is no antibody problem.

Estradiol

Estradiol is one of the estrogens or female sex hormones. Some of its common prescription names in the U.S include Estrace, Etraguard, Estratab, Gynetone, PMS-Estradiol, and Premarin. In the fertility clinic, estradiol is used to help the endometrium become thicker for implantation and for the prevention of miscarriage, especially in women using an egg donor.

Progesterone

Progesterone is one of the steroid hormones. It is secreted by the corpus luteum and by the placenta and is responsible for preparing the body for pregnancy and, if pregnancy occurs, maintaining it until birth. Like all steroids, it is a small hydrophobic molecule. Thus I diffuses freely through the plasma membrane of all cells. However, in target cells, like those of the endometrium, it becomes tightly bound to a cytoplasmic protein, the progesterone receptor. Then the complex of receptor and its hormone moves into the nucleus where it binds to a progesterone response element. The progesterone response element is a specific sequence of DNA in the promoters of certain genes that is needed to turn those genes on (or off). Thus, the complex progesterone with its receptor forms a transcription factor. In the fertility clinic, exogenous or supplemental progesterone is delivered by intramuscular (IM) injection or by vaginal suppository.

Progesterone is an important hormone in preventing miscarriage. Without adequate progesterone, the uterine lining will remain rigid, thereby, making pregnancy difficult to achieve. The lack of normal progesterone production by the ovaries in the second half of the menstrual cycle is called luteal phase defect. Women who have this defect either are unable to have their fertilized eggs implant in their uterine lining or, if the egg is implanted, it is so weak that miscarriage is certain outcome.

To lessen the possibility of miscarriage, women who have luteal phase defect use progesterone supplements after ovulation to help maximize the chance of carrying a pregnancy to full term. Progesterone supplements are also prescribed to women who are undergoing IVF and other methods of assisted reproductive technology. Progesterone supplements are given to women following an egg transfer in certain types of fertilization methods. Treatment for all women using progesterone supplements continues for at least 14 days following ovulation. If pregnancy occurs in a woman who is taking progesterone supplements, her doctor may decide to continue the treatment for another 8-10 weeks until placental autonomy occurs. Placental autonomy occurs when the placenta manufactures sufficient progesterone itself to support the pregnancy.

Antagon

Antagon Injection (ganirelix acetate) is used to inhibit premature ovulation in women undergoing fertility procedures. It prevents the premature rise in levels of luteinizing hormone in women undergoing ovarian hyperstimulation as a part of specific infertility treatments such as IVF and ICSI (intracytoplasmic sperm injection). During stimulation of the growth of multiple follicles with gonadotropins, such as follicle-stimulating hormone (FSH), a rise in LH at too early time may have unfavorable effects on the eggs and the possibility of getting pregnant. In general, there are two types of treatment regimens used to avoid an early rise in LH: GnRH-agonists and GnRH-antagonists. Antagon is a GnRH-antogonist that has the ability to rapidly inhibit LH release instantaneously. It achieves quickly what GnRH-agonists can take 2-3 weeks to do and is, therefore, only required during the final days of stimulation. However, women who have experienced a hypersensitivity reaction to gonadotropin-releasing hormone (GnRH) or any other GnRH-type drug and/or women who suspect or know they are pregnant should not use Antagon. The most frequent side effects of Antagon are abdominal pain, foetal death, and headache.

Baby Aspirin

A study, which was conducted by following the history of over 1,000 women, has indicated that women who suffer unexplained late recurrent miscarriages may benefit from a daily, low dose aspirin (acetylsalicylic acid, 75mg tablet). The birth rate in this group was 65% compared with 49% in the women who did not take aspirin. Antiphospholipid antibody syndrome is a clinical sequence of events that affects clotting and may cause recurrent pregnancy loss and low platelets. Two autoantibodies are involved in this condition: the lupus anticoagulant (LAC) and anticardiolipin antibody (ACA). Some clinicians are convinced that antiphospholipid antibodies are associated with infertility as well and, in some cases, women are treated with heparin to improve the rate of pregnancy. In the treatment of recurrent miscarriage, where ACA and/or LAC is suspected, it has been found that heparin plus low dose aspirin (80-100mg per day) is beneficial. Moderate severity of disease is more responsive to aspirin therapy than are the more severe cases. Baby aspirin is used because of its smaller dosage.

Safety

The information contained herein is for educational purposes only. Please consult your doctor for further information on western fertility drugs and how they may assist in IVF and pregnancy. It is not recommended that pregnant women take Aspirin without first consulting their Doctor.