INDICATIONS AND USAGE HCG HAS NOT BEEN DEMONSTRATED TO BE EFFECTIVE ADJUNCTIVE THERAPY IN THE TREATMENT OF OBESITY.

THERE IS NO SUBSTANTIAL EVIDENCE THAT IT INCREASES WEIGHT LOSS BEYOND THAT RESULTING FROM CALORIC RESTRICTION, THAT IT CAUSES A MORE ATTRACTIVE OR “NORMAL” DISTRIBUTION OF FAT, OR THAT IT DECREASES THE HUNGER AND DISCOMFORT ASSOCIATED WITH CALORIE-RESTRICTED DIETS.

Prepubertal cryptorchidism not due to anatomical obstruction.

In general, hCG is thought to induce testicular descent in situations when descent would have occurred at puberty.

hCG thus may help predict whether or not orchiopexy will be needed in the future.

Although, in some cases, descent following hCG administration is permanent, in most cases, the response is temporary.

Therapy is usually instituted in children between the ages of 4 and 9.

Selected cases of hypogonadotropic hypogonadism (hypogonadism secondary to a pituitary deficiency) in males.

Induction of ovulation and pregnancy in the anovulatory, infertile woman in whom the cause of anovulation is secondary and not due to primary ovarian failure, and who has been appropriately treated with human gonadotropins.

WARNINGS Use hCG in conjunction with gonadotropin therapy only if the physician is experienced with infertility problems and is familiar with the criteria for patient selection, contraindications, warnings, precautions, and adverse reactions described in the package insert for gonadotropins.

Gonadotropin therapy, including hCG, requires a certain time commitment by physicians and supportive health professionals, and requires the availability of appropriate monitoring facilities (see PRECAUTIONS/Laboratory Tests ).

Safe and effective induction of ovulation with use of PREGNYL requires monitoring of ovarian response with serum estradiol and transvaginal ultrasound on a regular basis.

Anaphylaxis Anaphylaxis has been reported with urinary-derived hCG products.

Ovarian Hyperstimulation Syndrome (OHSS) Ovarian Hyperstimulation Syndrome (OHSS) is a medical event distinct from uncomplicated ovarian enlargement and may progress rapidly to become a serious medical event.

OHSS is characterized by a dramatic increase in vascular permeability, which can result in a rapid accumulation of fluid in the peritoneal cavity, thorax, and potentially, the pericardium.

The early warning signs of the development of OHSS are severe pelvic pain, nausea, vomiting, and weight gain.

Abdominal pain, abdominal distension, gastrointestinal symptoms including nausea, vomiting and diarrhea, severe ovarian enlargement, weight gain, dyspnea, and oliguria have been reported with OHSS.

Clinical evaluation may reveal hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic reactions.

Transient liver function test abnormalities suggestive of hepatic dysfunction with or without morphologic changes on liver biopsy, have been reported in association with OHSS.

OHSS occurs after gonadotropin treatment has been discontinued and it can develop rapidly, reaching its maximum about seven to ten days following treatment.

Usually, OHSS resolves spontaneously with the onset of menses.

If there is evidence that OHSS may be developing prior to hCG administration, withhold hCG.

Cases of OHSS are more common, more severe, and more protracted if pregnancy occurs; therefore, assess women for the development of OHSS for at least two weeks after hCG administration.

Severe OHSS may be life-threatening.

Monitor women undergoing ovarian stimulation for early signs and symptoms of OHSS.

Women with known risk factors for a high ovarian response may be especially prone to the development of OHSS during or following treatment with PREGNYL.

Adherence to the recommended PREGNYL dose and treatment regimen and careful monitoring of ovarian response is important to reduce the risk of OHSS.

If serious OHSS occurs, stop gonadotropins, including hCG, and consider whether the woman should be hospitalized.

Treatment is primarily symptomatic and overall consists of bed rest, fluid and electrolyte management, and analgesics (if needed).

Because the use of diuretics can accentuate the diminished intravascular volume, avoid diuretics except in the late phase of resolution.

Initiate early consultation with a physician experienced in the management of OHSS and fluid and electrolyte imbalances.

Pulmonary and Vascular Complications Serious pulmonary conditions (e.g., atelectasis, acute respiratory distress syndrome) have been reported in women treated with gonadotropins.

In addition, thromboembolic reactions both in association with, and separate from OHSS have been reported following gonadotropin therapy.

Intravascular thrombosis, which may originate in venous or arterial vessels, can result in reduced blood flow to vital organs or the extremities.

Women with generally recognized risk factors for thrombosis, such as a personal or family history, severe obesity, or thrombophilia, may have an increased risk of venous or arterial thromboembolic events, during or following treatment with gonadotropins.

Sequelae of such reactions have included venous thrombophlebitis, pulmonary embolism, pulmonary infarction, cerebral vascular occlusion (stroke), and arterial occlusion resulting in loss of limb and rarely in myocardial infarction.

In rare cases, pulmonary complications and/or thromboembolic reactions have resulted in death.

In women with recognized risk factors, the benefits of ovulation induction, in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment need to be weighed against the risks.

Pregnancy itself also carries an increased risk of thrombosis.

Ovarian Torsion Ovarian torsion has been reported after treatment with gonadotropins, including PREGNYL.

Ovarian torsion may be related to other conditions, such as OHSS, pregnancy, previous abdominal surgery, past history of ovarian torsion, and previous or current ovarian cysts.

Damage to the ovary due to reduced blood supply can be limited by early diagnosis and immediate detorsion.

Multi-Fetal Gestation and Birth Multi-fetal gestation and births have been reported with all gonadotropin therapy including hCG.

Advise women of the potential risk of multiple births before starting treatment with gonadotropins including PREGNYL.

Congenital Malformations The incidence of congenital malformations after ART may be slightly higher than after spontaneous conceptions.

This slightly higher incidence is thought to be related to differences in parental characteristics (e.g., maternal age, sperm characteristics) and to the higher incidence of multiple gestations after ART.

There are no indications that the use of gonadotropins during ART is associated with an increased risk of congenital malformations.

Ectopic Pregnancy Infertile women undergoing Assisted Reproductive Technologies (ART) have an increased incidence of ectopic pregnancy.

Early ultrasound confirmation that a pregnancy is intrauterine is therefore important.

Spontaneous Abortion The risk of spontaneous abortion (miscarriage) is increased with gonadotropin products.

However, causality has not been established.

The increased risk may be a factor of the underlying infertility.

Ovarian Neoplasms There have been infrequent reports of ovarian neoplasms, both benign and malignant, in women who have undergone multiple drug therapy for ovarian stimulation; however, a causal relationship has not been established.

ADVERSE REACTIONS For males and females: Immune system disorders Hypersensitivity reactions, both localized and systemic in nature, including anaphylaxis have been reported.

In rare cases, generalized rash or fever may occur (see CONTRAINDICATIONS and WARNINGS ).

If a hypersensitivity reaction is suspected, discontinue PREGNYL and assess for other potential causes for the event.

Psychiatric disorders Irritability Restlessness Depression Nervous system disorders Headache General disorders and administration site conditions PREGNYL may cause reactions at the site of injection, such as bruising, pain, redness, swelling and itching.

Occasionally, allergic reactions have been reported, mostly manifesting as pain and/or rash at the injection site (see CONTRAINDICATIONS and WARNINGS ).

Edema Fatigue In the female: Vascular disorders In rare instances, thromboembolism has been associated with FSH/hCG therapy, usually associated with severe OHSS (see WARNINGS ).

Respiratory, thoracic and mediastinal disorders Hydrothorax, as a complication of severe OHSS (see WARNINGS ).

Gastrointestinal disorders Abdominal pain and gastrointestinal symptoms such as nausea and diarrhea, related to mild OHSS.

Ascites, as a complication of severe OHSS (see WARNINGS ).

Reproductive system and breast disorders Unwanted ovarian hyperstimulation, mild or severe Ovarian Hyperstimulation Syndrome (see WARNINGS ).

Mild to moderate enlargement of ovaries and ovarian cysts related to mild OHSS.

Large ovarian cysts (prone to rupture), usually associated with severe OHSS (see WARNINGS ).

Painful breasts Investigations Weight gain as a characteristic of severe OHSS (see WARNINGS ).

In the male: Metabolism and nutrition disorders Water and sodium retention is occasionally seen after administration of high dosages; this is regarded as a result of excessive androgen production.

Reproductive system and breast disorders HCG treatment may sporadically cause gynecomastia.

Precocious puberty