choriogonadotropin alfa (Rx)

1-10%

Ovidrel

• Ovarian cyst (3%)
• Ovarian hyperstimulation (2-3%)
• Abdominal pain (3-4%)
• Nausea (3%)
• Vomiting (3%)
• Injection site inflammation (<2%)

<1%

Ovidrel

• Breast pain
• Cervical lesion
• Cough
• Albuminuria
• Back pain
• Breast pain
• Cardiac arrhythmia
• Dizziness
• Emotional lability
• Genial herpes
• Hyperglycemia
• Pruritus
• Urinary tract infection
• Vaginal hemorrhage
• Vaginitis

Frequency Not Defined

Novarel, Pregnyl

• Headache
• Irritability
• Depression
• Edema
• Restlessness
• Gynecomastia
• Precocious puberty
• Fatigue
• Arterial thrombus
• Ovarian hyperstimulation syndrome
• Overian cyst rupture

Contraindications

Ovidrel

• Hypersensitivity to component
• Primary ovarian failure
• Uncontrolled thyroid or adrenal dysfunction
• Uncontrolled organic intracranial lesion such as pituitary tumor
• Undiagnosed abnormal uterine bleeding
• Ovarian cyst or enlargement of undetermined origin
• Sex hormone dependent tumor of reproductive tract and accessory organs
• Pregnancy

Novarel, Pregnyl

• Hypersensitivity to drug or components
• Precocious puberty
• Prostatic carcinoma or other androgen-dependent neoplasms
• High serum FSH, indicating primary gonadal failure in women
• Presence of uncontrolled non-gonadal endocrinopathies (eg, thyroid, adrenal, or pituitary disorders)
• Tumors of hypothalamus or pituitary gland and ovary, breast, or uterus in females and breast or prostate in males
• Malformations of reproductive organs incompatible with pregnancy
• Fibroid tumors of uterus incompatible with pregnancy
• Abnormal vaginal bleeding of undetermined origin

Cautions

Administer only after assessing adequate follicular development by serum estradiol & vaginal ultrasonography

Ovidrel

• Potent gonadotropic substance capable of causing ovarian hyperstimulation syndrome (OHSS) in women with or without pulmonary or vascular complications
• Withhold where clinically significant ovarian enlargement or excessive estradiol production to reduce risk of ovarian hyperstimulation syndrome
• Safe and effective induction of ovulation and use of prefilled syringe in women requires monitoring of ovarian response with serum estradiol and transvaginal ultrasound on a regular basis
• Ovarian hyperstimulation syndrome is characterized by mild to moderate ovarian enlargement may occur, accompanied by abdominal distension and/or abdominal pain; usually regresses without treatment in 2-3 wk; may progress rapidly to a serious medical event characterized by dramatic increase in vascular permeability, which may result in rapid fluid accumulation in peritoneal cavity, thorax and/or pericardium
• Potential for arterial thromboembolism
• Risk of enlargement of preexisting ovarian cysts or rupture of ovarian cysts with resultant hemoperitoneum
• If ovaries are abnormally enlarged on last day of FSH therapy, choriogonadotropin alfa should not be administered in this course of therapy; this will reduce risk of development of ovarian hyperstimulation syndrome
• Early warning signs of development of OHSS are severe pelvic pain, nausea, vomiting, and weight gain; symptomatology seen with cases of OHSS include abdominal pain, abdominal distension, gastrointestinal symptoms including nausea, vomiting and diarrhea, severe ovarian enlargement, weight gain, dyspnea,and oliguria
• Clinical evaluation may reveal hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic events
• Transient liver function test abnormalities suggestive of hepatic dysfunction, which may be accompanied by morphologic changes on liver biopsy, reported in association with ovarian hyperstimulation syndrome
• OHSS may be more severe and more protracted if pregnancy occurs; OHSS develops rapidly; therefore, patients should be followed for at least two weeks after hCG administration; most often, OHSS occurs after treatment has been discontinued and reaches its maximum at about seven to ten days following treatment; usually, OHSS resolves spontaneously with onset of menses; if there is evidence that OHSS may be developing prior to hCG administration hCG must be withheld
• If severe OHSS occurs, treatment with gonadotropins must be stopped and patient should be hospitalized;a physician experienced in management of this syndrome, or who is experienced in management of fluid and electrolyte imbalances should be consulted
• As with other hCG products, reports of multiple births have been associated with treatment; in ART, the risk of multiple births correlates to number of embryos transferred; multiple births were experienced by 30.9% of women receiving 250 μg in the ART studies. In the ovulation induction clinical trial, 2 of 15 live deliveries (13.3%) were associated with multiple births in women receiving therapy; the patient should be advised of potential risk of multiple births before starting treatment
• Combination of both ultrasound and serum estradiol measurement are useful for monitoring development of follicles, for timing of ovulatory trigger, as well as for detecting ovarian enlargement and minimizing risk of ovarian hyperstimulation syndrome and multiple gestation; recommended that number of growing follicles be confirmed using ultrasonography because serum estrogens do not give an indication of size or number of follicles

Novarel, Pregnyl

• To be used in conjunction with human menopausal gonadotropins only by physicians experienced with infertility problems who are familiar with criteria for patient selection, contraindications, warnings, precautions, and adverse reactions described in package insert for menotropins
• Use with caution in cardiovascular disease, asthma, history of migraines, renal impairment, seizure disorders
• Not effective in treatment of obesity
• May induce precocious puberty in children being treated for cryptorchidism (discontinue if signs of precocious puberty occur
• Safety and efficacy not established in children <4 years of age
• Anaphylaxis reported with urinary-derived HCG products
• Principal serious adverse reactions during this use are ascites with or without pain, and/or pleural effusion, rupture of ovarian cysts with resultant hemoperitoneum, multiple births, and arterial thromboembolism
• For pediatric use, induction of androgen secretion by HCG may induce precocious puberty in pediatric patients treated for cryptorchidism; therapy should be discontinued if signs of precocious puberty occur
• 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 (eg, 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
• Infertile women undergoing assisted reproductive technologies (ART) have increased incidence of ectopic pregnancy; early ultrasound confirmation that a pregnancy is intrauterine is therefore important
• 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
• 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
• Induction of androgen secretion by hCG may cause fluid retention; use hCG with caution in patients with cardiac or renal disease, hypertension, epilepsy, migraine, or asthma
• Evaluate patients for uncontrolled non-gonadal endocrinopathies (eg, thyroid, adrenal or pituitary disorders) and provide the appropriate specific treatment
• Gonadotropin therapy, including hCG, requires certain time commitment by physicians and supportive health professionals, and requires the availability of appropriate monitoring facilities; safe and effective induction of ovulation with use of this drug requires monitoring of ovarian response with serum estradiol and transvaginal ultrasound on a regular basis
• Ovarian torsion has been reported after treatment; 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 ovary due to reduced blood supply can be limited by early diagnosis and immediate detorsion

• Ovarian hyperstimulation syndrome

  • 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, 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 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 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 development of OHSS during or following therapy
  • Adherence to recommended dose and treatment regimen and careful monitoring of ovarian response is important to reduce risk of OHSS; if serious OHSS occurs, stop gonadotropins, including hCG, and consider whether 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 diminished intravascular volume, avoid diuretics except in the late phase of resolution; initiate early consultation with a physician experienced in management of OHSS and fluid and electrolyte imbalances

• Pulmonary and vascular complications

  • Serious pulmonary conditions (eg, atelectasis, acute respiratory distress syndrome) reported in women treated with gonadotropins; in addition, thromboembolic reactions both in association with and separate from OHSS 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 or against risks; pregnancy itself also carries an increased risk of thrombosis

Pregnancy

Intrauterine death and impaired parturition observed in pregnant rats given a dose of urinary-hCG (500 IU) equivalent to three times maximum human dose of 10,000 USP, based on body surface area

Lactation

Not known whether this drug is excreted in human milk; because many drugs are excreted in human milk, exercise caution if hCG administered to a nursing woman

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed child from therapy or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Ovidrel

• Produced by recombinant DNA techniques: human chorionic gonadotropin; stimulates late follicular maturation & resumption of oocyte meiosis & initiates rupture of pre-ovulatory ovarian follicle

Novarel, Pregnyl

• Obtained from the urine of pregnant women; stimulates production of gonadal steroid hornones by causing production of androgen by the testes
• Stimulates ovulation by acting as a substitute for luteinizing hormone

Pharmacokinetics

Ovidrel

• Vd: 21.4 L
• Time to peak: 12-24 hr
• Bioavailability: 40%
• Half-life: 4 hr
• Time to peak: 12-24 hr
• Excretion: Urine (10%)

Novarel, Pregnyl

• Half-life: 11 hr intial; 23 hr terminal
• Excretion: Urine