1.CLOMID HISTORY How was Clomid discovered?

Clomid is a product of Sanofi-Aventis.  

Sanofi-Aventis was formed in 2004 when Sanofi-Synthelabo merged with Aventis.

The Sanofi-Aventis Group is the world's 3rd largest pharmaceutical company, ranking number 1 in Europe. Backed by a world-class R&D organization, Sanofi-Aventis is developing leading positions in seven major therapeutic areas:

• cardiovascular disease,
• thrombosis,
• oncology,
• diabetes,
• central nervous system,
• internal medicine, and
• vaccines.

Note: World-drugs.net sells generic version of Clomid

2.CLOMID FACTS

Clomid is an oral medication commonly used in infertility treatment. Clomid is actually a trade name. The generic name is Clomiphene Citrate.

Clomid is composed of two different forms or isomers. Zuclomiphene is inert and makes up about one third of the total medication. Enclomiphene is the active part and makes up the remaining two thirds. It takes a long time for Clomid to be cleared by the body. In fact, traces of Clomid can be found several weeks later. Because of this, Clomid levels will increase in the blood over time if given over the course of a few months.

Clomid works by blocking estrogen receptors in the hypothalamus and pituitary gland. The result is that the pituitary gland is stimulated to produce more of the hormones that cause eggs to develop in the ovaries. These hormones are called gonadotropins and there are two important ones: FSH or follicle stimulating hormone and LH or luteinizing hormone. During Clomid treatment, the levels of LH and FSH both increase. It is the FSH that is initially more important to get eggs to develop.

3.ABOUT CLOMID MEDICATION

What is infertility?

Infertility is usually defined as not being able to get pregnant despite trying for one year. A broader view of infertility includes not being able to carry a pregnancy to term and have a baby. Infertility affects about 6.1 million Americans, or 10 percent of the reproductive age population, according to the American Society for Reproductive Medicine.

Pregnancy is the result of a chain of events. A woman must release an egg from one of her ovaries (ovulation). The egg must travel through a fallopian tube toward her uterus (womb). A man's sperm must join with (fertilize) the egg along the way. The fertilized egg must then become attached to the inside of the uterus. While this may seem simple, in fact many things can happen to prevent pregnancy from occurring.

Is infertility a woman's problem?

It is a myth that infertility is always a "woman's problem." About one third of infertility cases are due to problems with the man (male factors) and one third are due to problems with the woman (female factors). Other cases are due to a combination of male and female factors or to unknown causes.

Infertility in women?

The human reproductive process is complex. To accomplish a pregnancy, the intricate processes of ovulation and fertilization need to work just right. For many couples attempting pregnancy, something goes wrong in one or both of these complex processes and causes infertility. Because of the intricate series of events required to begin a pregnancy, many factors may cause a delay in starting your family.

FOLLICLE DEVELOPMENT

Every month the pituitary gland in a woman's brain sends a signal to her ovaries to prepare an egg for ovulation. The pituitary hormones — follicle-stimulating hormone (FSH) and luteinizing hormone (LH) — are involved in stimulating the ovaries to bring an egg to ovulation. A large boost in LH carries a message to the ovarian follicle to release its egg (ovulate). A woman is most fertile at the time of ovulation — around day 14 of her menstrual cycle — although the exact time of ovulation varies among women due to different lengths of menstrual cycles.

The egg is then captured by a fallopian tube and is viable for about 24 hours, but its best chance of being fertilized is within the first 12 hours following ovulation. For pregnancy to occur, a sperm must unite with the egg in the fallopian tube during this time. Sperm are capable of fertilizing the egg for up to 72 hours and must be present in the fallopian tube at the same time as the egg for conception to occur. If fertilized, the egg moves into the uterus two to four days later. There it attaches to the uterine lining and begins a nine-month process of growth.

 

 

PROCESS OF FERTILISATION

Causes of female infertility

The most common causes of female infertility include fallopian tube damage or blockage, endometriosis, ovulation disorders, elevated prolactin, polycystic ovary syndrome, early menopause, benign uterine fibroids and pelvic adhesions:

Fallopian tube damage or blockage. This condition usually results from inflammation of the fallopian tube (salpingitis). Chlamydia is the most frequent cause. Tubal inflammation may go unnoticed or cause pain and fever.

Tubal damage with scarring is the major risk factor of a pregnancy in which the fertilized egg is unable to make its way through the fallopian tube to implant in the uterus (ectopic pregnancy). One episode of tubal infection may cause fertility difficulties. The risk of ectopic pregnancy increases with each occurrence of tubal infection.

Endometriosis Endometriosis occurs when the tissue that makes up the lining of the uterus grows outside of the uterus. This tissue most commonly is implanted on the ovaries or the lining of the abdomen near the uterus, fallopian tubes and ovaries. These implants respond to the hormonal cycle and grow, shed and bleed in sync with the lining of the uterus each month, which can lead to scarring and inflammation. Pelvic pain and infertility are common in women with endometriosis.

Infertility in endometriosis also may be due to:

• Ovarian cysts (endometriomas). Ovarian cysts may indicate advanced endometriosis and often are associated with reduced fertility. Endometriomas can be treated with surgery.
• Scar tissue Endometriosis may cause rigid webs of scar tissue between the uterus, ovaries and fallopian tubes. This may prevent the transfer of the egg to the fallopian tube.

Ovulation disorders Some cases of female infertility are caused by ovulation disorders. Disruption in the part of the brain that regulates ovulation (hypothalamic-pituitary axis) can cause deficiencies in luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Even slight irregularities in the hormone system can affect ovulation.

Specific causes of hypothalamic-pituitary disorders include:

• Direct injury to the hypothalamus or pituitary gland
• Pituitary tumors
• Excessive exercise
• Anorexia nervosa

Elevated prolactin (hyperprolactinemia). The hormone prolactin stimulates breast milk production. High levels in women who aren't pregnant or nursing may affect ovulation. An elevation in prolactin levels may also indicate the presence of a pituitary tumor. In addition, some drugs can elevate levels of prolactin. Milk flow not related to pregnancy or nursing (galactorrhea) can be a sign of high prolactin.

Polycystic ovary syndrome (PCOS). An increase in androgen hormone production causes PCOS. In women with increased body mass, elevated androgen production may come from stimulation by higher levels of insulin. In lean women, the elevated levels of androgen may be stimulated by a higher ratio of luteinizing hormone (LH). Lack of menstruation (amenorrhea) or infrequent menses (oligomenorrhea) are common symptoms in women with PCOS.

 

In PCOS, increased androgen production prevents the follicles of the ovaries from producing a mature egg. Small follicles that start to grow but can't mature to ovulation remain within the ovary. A persistent lack of ovulation may lead to mild enlargement of the ovaries.

Without ovulation, the hormone progesterone isn't produced and estrogen levels remain constant. Elevated levels of androgen may cause increased dark or thick hair on the chin, upper lip or lower abdomen as well as acne and oily skin.

Early menopause (premature ovarian failure). Early menopause is the absence of menstruation and the early depletion of ovarian follicles before age 35. Although the cause is often unknown, certain conditions are associated with early menopause, including:

Autoimmune disease. The body produces antibodies to attack its own tissue, in this case the ovary. This may be associated with hypothyroidism (too little thyroid hormone).

• Radiation or chemotherapy for the treatment of cancer.
• Tobacco smoking.

Benign uterine fibroids Fibroids are benign tumors in the wall of the uterus and are common in women in their 30s. Occasionally they may cause infertility by interfering with the contour of the uterine cavity, blocking the fallopian tubes.

UTERINE FIBROIDS

 

Pelvic adhesions . Pelvic adhesions are bands of scar tissue that bind organs after pelvic infection, appendicitis, or abdominal or pelvic surgery. They may limit the functioning of the ovaries and fallopian tubes and impair fertility. Scar tissue formation inside the uterine cavity after a surgical procedure may result in a closed uterus and ceased menstruation (Asherman's syndrome). This is most common following surgery to control uterine bleeding after giving birth.

Other causes . A number of other causes can lead to infertility in women:

Medications. Temporary infertility may occur with the use of certain medications. In most cases, fertility is restored when the medication is stopped.

Thyroid problems. Disorders of the thyroid gland, either too much thyroid hormone (hyperthyroidism) or too little (hypothyroidism), can interrupt the menstrual cycle and cause infertility.

Cancer and its treatment . Certain cancers — particularly female reproductive cancers — often severely impair female fertility. Both radiation and chemotherapy may affect a woman's ability to reproduce. Chemotherapy may impair reproductive function and fertility more severely in men than in women.

Other medical conditions . Medical conditions associated with delayed puberty or amenorrhea, such as Cushing's disease, sickle cell disease, HIV/AIDS, kidney disease and diabetes, can affect a woman's fertility.

How is infertility tested?

If you have been trying to have a baby without success, you may want to seek medical help. If you are over 35, or if you have reason to believe that there may be a fertility problem, you should not wait for one year of trying before seeing a health care provider. A medical evaluation may determine the reasons for a couple's infertility. Usually this process begins with physical exams and medical and sexual histories of both partners. If there is no obvious problem, like improperly timed intercourse or absence of ovulation, tests may be needed.

For a man, testing usually begins with tests of his semen to look at the number, shape, and movement of his sperm. Sometimes other kinds of tests, such as hormone tests, are done.

For a woman, the first step in testing is to find out if she is ovulating each month. There are several ways to do this. For example, she can keep track of changes in her morning body temperature and in the texture of her cervical mucus. Another tool is a home ovulation test kit, which can be bought at drug or grocery stores.

Checks of ovulation can also be done in the doctor's office, using blood tests for hormone levels or ultrasound tests of the ovaries. If the woman is ovulating, more tests will need to be done.

Some common female tests include:

•  Hysterosalpingogram : An x-ray of the fallopian tubes and uterus after they are injected with dye. It shows if the tubes are open and shows the shape of the uterus.

•  Laparoscopy : An exam of the tubes and other female organs for disease. An instrument called a laparoscope is used to see inside the abdomen.

What is the treatment for infertility?

Depending on the test results, different treatments can be suggested. Eighty-five to 90 percent of infertility cases are treated with drugs or surgery.

Various fertility drugs may be used for women with ovulation problems. It is important to talk with your health care provider about the drug to be used. You should understand the drug's benefits and side effects. Depending on the type of fertility drug and the dosage of the drug used, multiple births (such as twins) can occur in some women.

If needed, surgery can be done to repair damage to a woman's ovaries, fallopian tubes, or uterus. Sometimes a man has an infertility problem that can be corrected by surgery.

What is assisted reproductive technology (ART)?

Assisted reproductive technology (ART) uses special methods to help infertile couples. ART involves handling both the woman's eggs and the man's sperm. Success rates vary and depend on many factors. ART can be expensive and time-consuming. But ART has made it possible for many couples to have children that otherwise would not have been conceived.

In vitro fertilization (IVF) is a procedure made famous with the 1978 birth of Louise Brown, the world's first "test tube baby." IVF is often used when a woman's fallopian tubes are blocked or when a man has low sperm counts. A drug is used to stimulate the ovaries to produce multiple eggs. Once mature, the eggs are removed and placed in a culture dish with the man's sperm for fertilization. After about 40 hours, the eggs are examined to see if they have become fertilized by the sperm and are dividing into cells. These fertilized eggs (embryos) are then placed in the woman's uterus, thus bypassing the fallopian tubes.

Gamete intrafallopian transfer (GIFT) is similar to IVF, but used when the woman has at least one normal fallopian tube. Three to five eggs are placed in the fallopian tube, along with the man's sperm, for fertilization inside the woman's body.

Zygote intrafallopian transfer (ZIFT), also called tubal embryo transfer, combines IVF and GIFT. The eggs retrieved from the woman's ovaries are fertilized in the lab and placed in the fallopian tubes rather than the uterus.

ART procedures sometimes involve the use of donor eggs (eggs from another woman) or previously frozen embryos. Donor eggs may be used if a woman has impaired ovaries or has a genetic disease that could be passed on to her baby.

4.CLOMID EFFECTIVENESS
When is Clomid best taken?

Clomid is indicated for the treatment of ovulatory dysfunction in women desiring pregnancy. Impediments to achieving pregnancy must be excluded or adequately treated before beginning Clomid therapy. Those patients most likely to achieve success with clomiphene therapy include patients with polycystic ovary syndrome, amenorrhea-galactorrhea syndrome, psychogenic amenorrhea, post-oral-contraceptive amenorrhea, and certain cases of secondary amenorrhea of undetermined etiology.

Properly timed coitus in relationship to ovulation is important. A basal body temperature graph or other appropriate tests may help the patient and her physician determine if ovulation occurred. Once ovulation has been established, each course of Clomid should be started on or about the 5th day of the cycle. Long-term cyclic therapy is not recommended beyond a total of about six cycles.

During clinical investigations, 7578 patients received Clomid tablets USP some of whom had impediments to ovulation other than ovulatory dysfunction. In those clinical trials successful therapy characterized by pregnancy occurred in approximately 30% of these patients.

There were a total of 2635 pregnancies reported during the clinical trial period. Of those pregnancies, information on outcome was only available for 2369 of the cases.

Of the reported pregnancies, the incidence of multiple pregnancies was 7.98%, 6.9% twin, 0.5% triplet, 0.3% quadruplet, and 0.1 % quintuplet. Of the 165 twin pregnancies for which sufficient information was available, the ratio of monozygotic to dizygotic twins was about 1:5.

The overall survival of infants from multiple pregnancies including spontaneous abortions, stillbirths, and neonatal deaths is 73%.

5.CLOMID EFFECTS ON SPECIAL POPULATION
How do different people react to Clomid?

Nursing Mothers
It is not known whether Clomid is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if Clomid is administered to a nursing woman. In some patients, Clomid may reduce lactation.

Ovarian Cancer
Prolonged use of Clomid may increase the risk of a borderline or invasive ovarian tumor.  

6.CLOMID EFFECTS ON MEDICAL CONDITIONS
How does Clomid affect your existing condition/ailment?

Liver Disease Clomid therapy is contraindicated in patients with liver disease or a history of liver dysfunction.

Abnormal Uterine Bleeding . Clomid is contraindicated in patients with abnormal uterine bleeding of undetermined origin.

Ovarian Cysts . Clomid is contraindicated in patients with ovarian cysts or enlargement not due to polycystic ovarian syndrome.

Other. Clomid is contraindicated in patients with uncontrolled thyroid or adrenal dysfunction or in the presence of an organic intracranial lesion such as pituitary tumor.

7.OTHER/ALTERNATE USES OF CLOMID
What else does Clomid treat?

Clomid may also be used to diagnose certain conditions.

8.ADVERSE/SIDE EFFECTS of CLOMID
What are the side effects of Clomid?

Clomid, at recommended dosages, is generally well tolerated. Adverse reactions usually have been mild and transient and most have disappeared promptly after treatment has been discontinued.

Adverse experiences reported in patients treated with Clomid during clinical studies are shown in the table below

Incidence of Adverse Events In Clinical Studies (Events Greater than 1%) (n = 8029)
Adverse Event	%
Ovarian Enlargement	13.6
Vasomotor Flushes	10.4
Abdominal-Pelvic     Discomfort/     Distention/Bloating	5.5
Nausea and Vomiting	2.2
Breast Discomfort	2.1
Visual Symptoms     Blurred vision, lights, floaters, waves,     unspecified visual     complaints, photophobia,     diplopia, scotomata, phosphenes	1.5
Headache	1.3
Abnormal Uterine Bleeding     Intermenstrual spotting, menorrhagia	1.3

The following adverse events have been reported in fewer than 1% of patients in clinical trials: Acute abdomen, appetite increase, constipation, dermatitis or rash, depression, diarrhea, dizziness, fatigue, hair loss/dry hair, increased urinary frequency/volume, insomnia, light-headedness, nervous tension, vaginal dryness, vertigo, weight gain/loss.

Patients on prolonged Clomid therapy may show elevated serum levels of desmosterol. This is most likely due to a direct interference with cholesterol synthesis. However, the serum sterols in patients receiving the recommended dose of Clomid are not significantly altered. Ovarian cancer has been infrequently reported in patients who have received fertility drugs. Infertility is a primary risk factor for ovarian cancer; however, epidemiology data suggest that prolonged use of clomiphene may increase the risk of a borderline or invasive ovarian tumor.

Postmarketing Adverse Events

The following adverse experiences were reported spontaneously with Clomid. The cause and effect relationship of the listed events to the administration of Clomid is not known.

Dermatologic : Acne, allergic reaction, erythema, erythema multiforme, erythema nodosum, hypertrichosis, pruritus

Central Nervous System: Migraine headache, paresthesia, seizure, stroke, syncope

Psychiatric : Anxiety, irritability, mood changes, and psychosis

Visual Disorders : Abnormal accommodation, cataract, eye pain, macular edema, optic neuritis, photopsia, posterior vitreous detachment, retinal hemorrhage, retinal thrombosis, retinal vascular spasm, temporary loss of vision

Cardiovascular: Arrhythmia, chest pain, edema, hypertension, palpitation, phlebitis, pulmonary embolism, shortness of breath, tachycardia, thrombophlebitis

Musculoskeletal: Arthralgia, back pain, myalgia

Hepatic : Transaminases increased, hepatitis

Neoplasms : Liver (hepatic hemangiosarcoma, liver cell adenoma, hepatocellular carcinoma); breast (fibrocystic disease, breast carcinoma); endometrium (endometrial carcinoma); nervous system (astrocytoma, pituitary tumor, prolactinoma, neurofibromatosis, glioblastoma multiforme, brain abcess); ovary (luteoma of pregnancy, dermoid cyst of the ovary, ovarian carcinoma); trophoblastic (hydatiform mole, choriocarcinoma); miscellaneous (melanoma, myeloma, perianal cysts, renal cell carcinoma, Hodgkin's lymphoma, tongue carcinoma, bladder carcinoma); and neoplasms of offspring (neuroectodermal tumor, thyroid tumor, hepatoblastoma, lymphocytic leukemia)

Genitourinary : Endometriosis, ovarian cyst (ovarian enlargement or cysts could, as such, be complicated by adnexal torsion), ovarian hemorrhage, tubal pregnancy, uterine hemorrhage

Body as a Whole : Fever, tinnitus, weakness

Other : Leukocytosis, thyroid disorder

Fetal/Neonatal anomalies. The following fetal abnormalities have also been reported during postmarketing surveillance: delayed development; abnormal bone development including skeletal malformations of the skull, face, nasal passages, jaw, hand, limb (ectromelia including amelia, hemimelia, and phocomelia), foot, and joints; tissue malformations including imperforate anus, tracheoesophageal fistula, diaphragmatic hernia, renal agenesis and dysgenesis, and malformations of the eye and lens (cataract), ear, lung, heart (ventricular septal defect and tetralogy of Fallot), and genitalia; as well as dwarfism, deafness, mental retardation, chromosomal disorders, and neural tube defects (including anencephaly).