Human chorionic gonadotropin (HCG) and a recombinant formulation (e.g., choriogonadotropin alfa, also known as r-hCG or the Ovidrel branded product), are a gonad-stimulating polypeptide hormone normally secreted by the placenta during pregnancy. Urinary-derived HCG products (u-HCG products) are obtained from the urine of pregnant women (e.g., Novarel, Pregnyl). Choriogonadotropin alfa (also known as recombinant-hCG) is produced via recombinant DNA techniques in Chinese Hamster Ovary (CHO) cells. The pharmacological actions of u-HCG and of r-HCG are similar and resemble those of luteinizing hormone (LH); hCG is generally used as a substitute for LH. Urinary-HCG products have been used to treat cryptorchidism or hypogonadotropic hypogonadism in males and were first introduced for the treatment of cryptorchidism in 1931. Urinary-HCG (u-HCG) remained the only hormonal agent to treat cryptorchidism until the 1970s, when gonadotropin-releasing hormone (GnRH) analogs also became a treatment option. Both urinary-derived and recombinant HCG products are used in controlled ovarian hyperstimulation protocols for infertility in females for Assisted Reproductive Technologies (ART) or ovulation induction protocols in selected patients.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 3
-NIOSH (Draft) 2020 List: Table 2
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intramuscular Administration
Urine-derived HCG products (u-HCG such as Pregnyl, Novarel)
-The FDA-approved route of administration for u-HCG is by intramuscular injection. Do not inject intravenously.
Reconstitution:
-Withdraw sterile air from the vial containing the lyophilized powder.
-Withdraw 1 mL to 10 mL of the sterile diluent provided and add to the lyophilized vial; agitate gently until powder is completely dissolved in the diluent. Do not shake. The amount of diluent to be used will be dependent on the dosage to be administered and indication for use.
-Storage of reconstituted multiple-dose vials: May be stored in the refrigerator at 2 to 8 degrees C (36 to 46 degrees F) for up to 30 days (Novarel) and up to 60 days (Pregnyl) after reconstitution. Do not freeze.
Intramuscular injection:
-Refer to the manufacturer provided "Instructions for Use".
-For adults and adolescents, inject deeply into a large muscle; the usual site is the upper outer region of the right or left buttock below the hipbone.
-For children, inject deeply into a large muscle, preferably the anterolateral aspect of the thigh.
Subcutaneous Administration
Choriogonadotropin Alfa (recombinant HCG or r-HCG) Solution for injection (Ovidrel)
-Administer by subcutaneous injection only. Do not inject intravenously or intramuscularly.
-Review the manufacturer supplied "Instructions for Use" for the prefilled syringe. The injection may be self-administered by the patient after proper training by the care team.
-Subcutaneous injection is usually made in the abdomen, at least 1 to 2 inches away from the navel.
-Inject subcutaneously taking care not to inject intradermally or into a blood vessel.
-For single-use only; promptly discard of used syringe and needle in an appropriate sharps safety container.
-Storage: Preferably store the prefilled syringe refrigerated at 2 to 8 degrees C (36 to 46 degrees F). Do not freeze. If needed, the prefilled syringe may be stored for no more than 30 days at room temperature, up to 25 degrees C (77 degrees F), but must be used within those 30 days. Protect from light. Store in original package until use.
Urine-derived HCG products (u-HCG such as Pregnyl, Novarel)
-NOTE: u-HCG products are not FDA-approved for subcutaneous administration. However, subcutaneous administration of u-HCG has been described in published literature for selected indications.
The appearance of side effects related to HCG may vary with the route of administration, dosage administered, the sex and age of the patient, and indication for therapeutic use.
The use of human chorionic gonadotropin (HCG) at therapeutic doses is generally well tolerated. Reported side effects in patients receiving HCG as part of ovulation induction protocols or Assisted Reproduction Technologies (ART) include edema or fluid retention, ectopic pregnancy (less than 2%), breakthrough bleeding (less than 2%), vaginitis (less than 2%), leukorrhea (less than 2%), and intermenstrual bleeding (less than 2%), vaginal bleeding or hemorrhage (less than 2%), hot flashes (less than 2%), genital moniliasis (genital area candidiasis, less than 2%), and cervical cancer (less than 2%) Additional adverse events that occurred in less than 2% of patients treated with HCG whether considered causally related to the product administered or not included breast pain (mastalgia).
An injection site reaction may occur with human chorionic gonadotropin, HCG and commonly includes pain and mild localized redness or inflammation. After subcutaneous administration, 14% to 16.2% of patients experienced an injection site reaction including 7.6% to 8.1% with injection site pain, 3% to 4.7% with injection site bruising, 2% with injection site inflammation, and 3% with an unspecified injection site reaction. It has been reported that injection site reactions are more common with IM administration.
Both localized and systemic hypersensitivity reactions have been reported with human chorionic gonadotropin, HCG. Hypersensitivity reactions have included angioedema, anaphylactic shock, anaphylactoid reactions, dyspnea or shortness of breath, generalized erythema, rash (less than 2%), pruritus (less than 2%), urticaria, and fever. Postmarketing surveillance of choriogonadotropin alfa injection revealed cases of allergic reactions, including anaphylactoid reactions and mild reversible skin rashes; causal relationship is not known.
Gynecomastia has been reported as a sporadic adverse effect of use of urinary-derived human chorionic gonadotropin, HCG products in male patients. Water and sodium retention is occasionally seen after administration of high dosages of u-HCG in male patients; this is regarded as a result of excessive androgen production.
Precocious puberty can develop in prepubertal male children receiving urinary human chorionic gonadotropin, HCG products for treatment of cryptorchidism because of the induction of androgen secretion by HCG. Acne, phallic and testicular enlargement, aggressive behavior or agitation, early development of pubic hair, and rapid increase in height characterize precocious puberty. Discontinue HCG therapy if signs of precocious puberty occur.
While some side effects of human chorionic gonadotropin, HCG are dependent on the sex of the patient and the indication for use, some side effects have been reported to occur independently of these factors. Headache, irritability, restlessness, and depression have been reported in all populations of use. Headache, dizziness, malaise, emotional lability, and insomnia were each noted in less than 2% of patients receiving subcutaneous HCG for ovulation induction; fatigue, irritability, and restlessness were also reported.
In trials with recombinant human chorionic gonadotropin, HCG for ovulation induction, 3% to 4.2% of treated patients had abdominal pain, 3.4% had nausea, 2.5% had vomiting, and less than 2% had diarrhea, flatulence, back pain, or ascites. Some of these adverse events may also be signs of the ovarian hyperstimulation.
The following discusses adverse effects that are related to the use of controlled ovarian hyperstimulation protocols in which HCG may be used as an adjunct to follicle stimulating agents. Mild to moderate uncomplicated ovarian enlargement, which may be accompanied by abdominal pain and/or distension, may occur in patients treated with agent to induce ovulation. Careful monitoring of ovarian response can further minimize the risk of overstimulation. In trials, 3% had ovarian enlargement. In addition to ovarian enlargement, ovarian cyst(s) (3%) may occur. Pelvic examination and ultrasound should be performed in patients who complain of abdominal discomfort (pelvic pain) during therapy. If enlargement or cysts are present, the current fertility treatment cycle should be discontinued and further therapy withheld until resolution of the signs and symptoms and until the ovary is no longer enlarged. If substantial ovarian enlargement occurs after ovulation, sexual intercourse should be prohibited because of the risk of hemoperitoneum secondary to ruptured ovarian cysts. Human chorionic gonadotropin, HCG should be withheld if ovarian enlargement is present on the last day of FSH therapy in order to reduce the risk of ovarian hyperstimulation. Most ovarian cysts or enlargements will regress within a few days to a few weeks after discontinuation of the fertility medications. Laparoscopy is rarely needed. Ovarian cyst formation may be more likely to occur in patients with polycystic ovary syndrome. Adnexal or ovarian torsion has also been reported after treatment with gonadotropins, including HCG. Ovarian torsion may be related to other conditions, such as ovarian hyperstimulation, 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.
HCG use can result in ovarian hyperstimulation syndrome (OHSS). Do not administer HCG if the ovaries are abnormally enlarged on the last day of follicle stimulating therapy. 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 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 effusion, 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, HCG must be withheld. Cases of OHSS are more common, more severe, and more protracted if pregnancy occurs; therefore, women should be assessed for the development of OHSS for at least 2 weeks after HCG administration. If serious OHSS occurs, gonadotropins, including HCG, should be stopped and consider if hospitalization is needed. Treatment of OHSS is primarily symptomatic and overall should consist of bed rest, fluid and electrolyte management, and analgesics (if needed). Because the use of diuretics can accentuate the diminished intravascular volume, avoid diuretic use except in the late phase of resolution as described below. The management of OHSS may be divided into 3 phases as follows: ACUTE PHASE: Management should be directed at preventing hemoconcentration due to loss of intravascular volume to the third space and minimizing the risk of thromboembolic phenomena and kidney damage. Fluid intake and output, weight, hematocrit, serum and urinary electrolytes, urine specific gravity, BUN and creatinine, total proteins with albumin: globulin ratio, coagulation studies, electrocardiogram to monitor for hyperkalemia, and abdominal girth should be thoroughly assessed daily or more often based on the clinical need. Treatment, consisting of limited intravenous fluids, electrolytes, human serum albumin, is intended to normalize electrolytes while maintaining an acceptable but somewhat reduced intravascular volume. Full correction of the intravascular volume deficit may lead to an unacceptable increase in the amount of third space fluid accumulation. CHRONIC PHASE: After the acute phase is successfully managed as above, excessive fluid accumulation in the third space should be limited by instituting severe potassium, sodium, and fluid restriction. RESOLUTION PHASE: As third space fluid returns to the intravascular compartment, a fall in hematocrit and increasing urinary output are observed in the absence of any increase in intake. Peripheral and/or pulmonary edema may result if the kidneys are unable to excrete third space fluid as rapidly as it is mobilized. Diuretics may be indicated during the resolution phase, if necessary, to combat pulmonary edema. Do not remove ascitic, pleural, and pericardial fluid unless there is the necessity to relieve symptoms such as pulmonary distress or cardiac tamponade. OHSS increases the risk of injury to the ovary. Avoid pelvic examination or sexual intercourse as these may cause rupture of an ovarian cyst, which may result in hemoperitoneum. If bleeding occurs and requires surgical intervention, the clinical objective should be to control the bleeding and retain as much ovarian tissue as possible. A physician experienced in the management of OHSS, or who is experienced in the management of fluid and electrolyte imbalances, should be consulted. During trials of subcutaneous HCG use for ovulation induction, 1.7% to 3% of patients developed OHSS whereas 9% (8 of 89 patients) experienced OHSS with a 500 mcg dose. Two of the 8 patients developed severe OHSS.
Serious pulmonary conditions such as atelectasis and acute respiratory distress syndrome (ARDS) have been reported in women treated with gonadotropins such as human chorionic gonadotropin, HCG. Also, thromboembolic events such as thromboembolism both in association with and separate from the ovarian hyperstimulation syndrome (OHSS) have been reported after HCG therapy as part of ovulation induction. Intravascular thrombosis and embolism, which may originate in venous or arterial vessels, can result in reduced blood flow to critical organs or the extremities. Sequelae of such events have included venous thrombo-phlebitis, deep venous thrombosis, pulmonary embolism, pulmonary infarction, cerebral vascular occlusion (stroke), arterial occlusion resulting in loss of limb, and in rare cases myocardial infarction. In rare cases, pulmonary complications and/or thromboembolic events have been fatal.
In clinical evaluation of recombinant choriogonadotropin alfa injection (recombinant human chorionic gonadotropin, HCG) for ovulation induction, elevated hepatic enzymes were reported with both the recombinant product and the urinary-derived HCG comparator. Elevations in ALT were found in 10 (3%) of 335 patients receiving a 250 mcg dose, 9 (10%) of 89 patients receiving a 500 mcg dose, and in 16 (4.8%) of 328 patients receiving urine-derived hCG. Elevations in ALT ranged up to 1.2 times the upper limit of normal. At this time, the clinical significance of these findings is unknown. Also, transient liver function test abnormalities suggestive of hepatic dysfunction, which may be accompanied by morphologic changes on liver biopsy, have been reported in association with ovarian hyperstimulation syndrome (OHSS).
There have been infrequent reports of new primary malignancy (ovarian neoplasm), both benign and malignant, in women who have had multiple drug therapy for controlled ovarian stimulation; however, a causal relationship has not been established.
Human chorionic gonadotropin, HCG is contraindicated for use in any patient with a prior history of HCG hypersensitivity. Anaphylaxis has been reported with the use of urinary-derived hCG products (e.g., Novarel, Pregnyl). The diluents supplied for these products contain benzyl alcohol and should be used with caution in those with benzyl alcohol hypersensitivity. Use the choriogonadotropin alfa (r-HCG) (Ovidrel) product with caution in patients with hamster protein hypersensitivity as the product is manufactured using Chinese hamster ovary cells.
Human chorionic gonadotropin (HCG) may induce precocious puberty in patients treated for cryptorchidism; discontinue HCG therapy if signs of precocious puberty occur. The Novarel product contains a specific contraindication against use in patients with precocious puberty.
HCG use requires an experienced clinician who specializes in endocrine conditions and/or infertility treatments. Before use, perform a complete gynecologic and endocrinologic evaluation and diagnose the cause of infertility; the diagnosis should include an evaluation of the fertility of the partner. HCG use is contraindicated in patients with an uncontrolled non-gonadal endocrinopathies (e.g., thyroid, adrenal, or pituitary disorders). Those with primary ovarian failure (as indicated by high levels of FSH) will not respond to treatment. Patients with pituitary adenoma or other pituitary or hypothalamic tumors will also not respond to HCG treatment. HCG treatment is also contraindicated in patients with uncontrolled thyroid disease or untreated adrenal insufficiency.
Because endocrine treatment plans and fertility protocols that include human chorionic gonadotropin, HCG may stimulate the growth of hormonally-dependent tissues, HCG use is contraindicated in patients with abnormal or dysfunctional uterine bleeding of undetermined origin or sex-hormone dependent neoplasms of the reproductive tract and accessory organs, such as ovarian cancer, breast cancer, uterine cancer, or prostate cancer. There have been infrequent reports of ovarian neoplasms, both benign and malignant, in patients who have had multiple drug therapy for controlled ovarian stimulation; however, a causal relationship has not been established. Patients with anatomical or tissue malformations of the reproductive organs that are incompatible with pregnancy, such as selected fibroid tumors of the uterus incompatible with pregnancy (selected cases of uterine leiomyomata), should not receive HCG treatment.
Human chorionic gonadotropin, HCG use is contraindicated in patients with ovarian cyst or enlargement of undetermined origin. Abnormal ovarian enlargement may occur with HCG therapy. Careful monitoring of ovarian response can further minimize the risk of overstimulation. Use of ultrasound monitoring of ovarian response and/or measurement of serum estradiol levels is important before HCG administration to minimize the risk of ovarian hyperstimulation syndrome (OHSS). If the ovaries are abnormally enlarged on the last day of the use of a follicle stimulating agent, HCG should not be administered in order to reduce the chance of developing OHSS. Prohibit intercourse in patients with significant ovarian enlargement because of the danger of hemoperitoneum resulting from rupture of ovarian cysts. 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 2 weeks after HCG administration.
Serious pulmonary and thromboembolic reactions both in association with, and separate from ovarian hyperstimulation ayndrome (OHSS) have been reported following gonadotropin therapy. Patients with generally recognized risk factors for thrombosis, such as personal or family history of thromboembolic disease, severe obesity, or thrombophilia, may have an increased risk of venous or arterial thromboembolic events during or following treatment with gonadotropins such as human chorionic gonadotropin, HCG. In those with recognized risk factors, the benefits of ovulation induction and ART need to be weighed against the risks. Intravascular thrombosis and embolism, which may originate in venous or arterial vessels, can result in reduced blood flow to critical organs or the extremities and in rare cases have resulted in death.
Human chorionic gonadotropin, HCG products are contraindicated for use during pregnancy due to a potential for fetal harm. HCG may be used for luteal phase support, but is discontinued upon confirmation of pregnancy. Intrauterine death and impaired parturition were observed in pregnant rats given a dose of urinary-hCG (500 IU) equivalent to 3 times the maximum human dose of 10,000 USP, based on body surface area. When administered to mice, animal-derived formulations of gonadotropin mixtures have induced a high incidence of external congenital anomalies. While animal data are not always indicative of the response in human gestation, the potential for serious fetal harm cannot be excluded. If the patient becomes pregnant while receiving this drug, apprise the patient of the potential hazard to a fetus. The incidence of congenital malformations after some assisted reproductive technologies [specifically in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)] may be slightly higher than after spontaneous conception. This slightly higher incidence is thought to be related to differences in parental characteristics (e.g., maternal age, maternal and paternal genetic background, sperm characteristics) and to the higher incidence of multi-fetal gestations after IVF or ICSI. Inform the individual and their partner of the potential risks of multi-fetal gestation and birth. There are no indications that the use of gonadotropins during IVF or ICSI in order to produce pregnancy is associated with an increased risk of congenital malformations. 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.
Human chorionic gonadotropin, HCG should be used with caution during breast-feeding. Most endogenous gonadotropins are found in breast milk or tissues to some degree. The effect on breast milk and the effect on a breastfed child are not known.
Adnexal or ovarian torsion has been reported after treatment with gonadotropins such as human chorionic gonadotropin, HCG. This may be related to patient risk factors such as ovarian hyperstimulation syndrome (OHSS), previous abdominal surgery, past history of ovarian torsion, previous or current ovarian cyst, and polycystic ovary syndrome (PCOS). Damage to the ovary due to reduced blood supply can be limited by early diagnosis and immediate detorsion.
Since infertile patients undergoing ovarian stimulation for assisted reproduction technologies (ART) often have tubal abnormalities, the incidence of ectopic pregnancy may be increased. Early ultrasound confirmation that a pregnancy is intrauterine is therefore important.
Due to the lack of therapeutic effect and potential risks of therapy, human chorionic gonadotropin, HCG is not to be used for obesity treatment. Claims that HCG increases weight loss beyond that from calorie 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 are not supported by substantial evidence. Numerous data to date suggest the agent is not effective in assisting weight loss.
Tobacco smoking is a lifestyle choice that may decrease fertility or the effectiveness of fertility treatments in some women and/or men. Patients should be encouraged to avoid tobacco consumption and pursue smoking cessation while pursuing fertility therapies such as the use of human chorinonic gonadotropin, hCG.
The recommended diluent for reconstitution of urinary human chorionic gonadotropin (u-HCG) injections (e.g., Pregnyl, Novarel, generic u-HCG products) is Bacteriostatic Water for Injection, which is preserved with benzyl alcohol. Benzyl alcohol has been reported to be associated with a fatal "gasping syndrome" in neonates and premature infants.
The induction of androgen secretion by HCG may cause fluid retention. Use HCG with caution in male patients with cardiac disease, renal disease, hypertension, a seizure disorder, migraine, or asthma.
For the treatment of male infants and children with prepubertal cryptorchidism not caused by anatomical obstruction:
NOTE: HCG appears to be more effective at inducing testicular descent in those infants and children with palpable testes in the high scrotal, prescrotal, or inguinal regions. Intra-abdominal testes are especially refractory to HCG treatment. While hormonal therapy is traditionally instituted after the age of 4 years, there are several studies that include male children of younger ages, and there is some evidence that treatment prior to age 2 years may be beneficial in terms of long-term outcomes. Consult specialized references for the most current recommendations.
Intramuscular dosage:
Children (males) >= 6 years: The International Health Foundation has advocated a dosage of 1000 USP units IM 2 times per week for a total of 5 weeks. NOTE: various dosage regimens have been advocated for male children >= 4 years old. The following alternative regimens have been employed; however, the total dosage and length of the treatment course may vary widely: 1) 4000 USP units IM 3 times per week for 3 weeks; 2) 5000 USP units IM every other day for 4 doses; 3) 15 doses of 500-1000 USP units IM given over a period of 6 weeks; or 4) administer 500 USP units IM 3 times per week for 4-6 weeks. If not successful, then another course of HCG 1 month later may be administered at doses of 1000 USP units IM 3 times per week for 4-6 weeks.
Children (males) 1-5 years: The International Health Foundation has advocated a dosage of 500 USP units IM 2 times per week for a total of 5 weeks.
Infants (males) 6-12 months: The International Health Foundation has advocated a dosage of 250 USP units IM 2 times per week for a total of 5 weeks.
For treatment of selected cases of hypogonadotropic hypogonadism (HH) in males:
Intramuscular dosage:
Adults and Adolescents: NOTE: The following regimens have been employed; however, the total dosage and duration of treatment may vary widely and are individualized: 1) 500 to 1,000 USP Units IM 3 times per week for 3 weeks, followed by the same dose twice per week for 3 weeks; 2) 4,000 USP Units IM 3 times per week for 6 to 9 months, then reduced to 2,000 USP Units IM 3 times a week for an additional 3 months.
-for selected men with HH to treat oligospermia* and to induce fertility:
NOTE: In selected men with HH and low sperm counts not due to primary testicular failure, HCG has been used along with r-FSH or menotropins to induce spermatogenesis following primary treatment for HH.
Subcutaneous dosage*:
Adults: 500 to 1,500 USP Units subcutaneously 3 times weekly; dosage may vary widely and is individualized to the patient response, such as serum testosterone levels and sperm counts. FSH or FSH analogs may be added to optimize sperm production.
For induction of ovulation and pregnancy to treat infertility and anovulation in patients in whom the cause of anovulation is secondary and not due to primary ovarian failure, including in patients undergoing Assisted Reproductive Technology (ART):
NOTE: HCG should not be administered until adequate follicular development is indicated by serum estradiol and vaginal ultrasonography. HCG must be withheld if there is an excessive ovarian response. Consult specialized references.
-for final follicular maturation and early luteinization in patients who have undergone pituitary desensitization and have been appropriately pretreated with follicle stimulating hormones as part of an ART (e.g., in vitro fertilization and embryo transfer):
Subcutaneous dosage (choriogonadotropin alfa, also known as recombinant hCG or r-hCG):
Adults: 250 mcg subcutaneously as a single dose 1 day after the last dose of following the last dose of the follicle stimulating agent.
-for use in infertile patients undergoing ovulation induction:
Subcutaneous dosage (choriogonadotropin alfa, also known as recombinant hCG or r-hCG):
Adults: 250 mcg subcutaneously as a single dose 1 day after the last dose of the follicle stimulating agent.
Intramuscular dosage (urine-derived products):
Adults: 5,000 to 10,000 USP Units IM as a single dose 1 day after the last dose of the follicle stimulating agent. The labeling for the particular follicle stimulating agent should also be consulted. The labeling for menotropins recommends an HCG dosage of 10,000 USP units.
For luteal phase support* of embryo implantation and early pregnancy by treating corpus luteum insufficiency*, as part of an Assisted Reproductive Technology (ART) program:
Intramuscular dosage (urine-derived products):
Adults: Use not definitively established; evidence is largely empirical. Low-dose hCG (500 USP Units IM every other day for 5 doses), initiated 24 to 48 hours after the induction of ovulation with a GnRH agonist, has been used. Other dosage regimens have been used, but higher dosages may be more likely to cause ovarian hyperstimulaton syndrome (OHSS). Progesterone is usually preferred over hCG due to a lower risk for side effects such as OHSS and a larger body of evidence for use.
Maximum Dosage Limits:
Dosage regimens of urine-derived human chorionic gonadotropin (u-HCG products) depend upon the patient's age, sex, weight, condition being treated, product chosen, and the prescribing clinician's judgment. Therefore, u-HCG doses may vary widely and must be carefully individualized. The higher dosage regimens of the manufacturer labeling are represented here as a basic reference.
-Adults
For infertility treatment to trigger ovulation: 250 mcg/dose subcutaneously for choriogonadotropin alfa (Ovidrel). 10,000 USP Units/dose IM for u-HCG products (e.g., Novarel, Pregnyl)
For male hypogonadotropic hypogonadism: 4,000 units/dose IM.
-Geriatric
Safety and efficacy have not been established; clinical studies have generally excluded those 65 years of age and older.
-Adolescents
Up to 5,000 USP Units/dose IM for u-HCG for treating prepubertal cryptorchidism not due to anatomical obstruction.
-Children
4 to 12 years: Up to 5,000 USP Units/dose IM for u-HCG for treating prepubertal cryptorchidism not due to anatomical obstruction.
1 to 3 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established; off-label use has been described in the literature.
-Neonates
Safety and efficacy have not been established; off-label use has been described in the literature.
Patients with Hepatic Impairment Dosing
The safety and efficacy of HCG has not been established in patients with hepatic impairment.
Patients with Renal Impairment Dosing
The safety and efficacy of HCG has not been established in patients with renal impairment.
*non-FDA-approved indication
There are no drug interactions associated with Human Chorionic Gonadotropin, HCG products.
The action of human chorionic gonadotropin (HCG) is virtually identical to that of pituitary luteinizing hormone (LH), although HCG appears to have a small degree of FSH activity as well. The mechanism of action of HCG depends upon the purpose for which it is being used, the sex of the patient, and the level of maturity of the patient to whom it is administered.
HCG stimulates the interstitial cells (Leydig cells) of the testis to produce androgens. Androgen stimulation in the male leads to the development of secondary sex characteristics and may stimulate testicular descent when no anatomical impediment to descent is present. This descent is usually reversible when HCG is discontinued. Because of these actions, HCG is most commonly used in males for the treatment of prepubertal cryptorchidism and for selected cases of hypogonadotropic hypogonadism.
During the normal menstrual cycle, LH participates with FSH in the development and maturation of the normal ovarian follicle, and the mid-cycle LH surge triggers ovulation. HCG can substitute for LH in this function. In pregnancy, HCG, secreted by the placenta, maintains the viability of the corpus luteum to provide the continued secretion of estrogen and progesterone necessary to support the first trimester of pregnancy and prevent menstruation. The administration of exogenous HCG in fertility protocols allows for final maturation of the oocytes and either ovulation can ensue or oocyte retrieval can take place for assisted reproductive technology (ART) procedures.
HCG has no known effects on appetite, or on mobilization or distribution of body fat.
Human chorionic gonadotropin is administered subcutaneously and intramuscularly, dependent on the product chosen for use. Similar to other polypeptides, gonadotropins are almost completely degraded in the gastrointestinal tract; therefore, parenteral administration is required.
-Urine-derived products (u-hCG): In the body, endogenous human chorionic gonadotropin primarily distributes into the testes in males and into the ovaries in females. In the ovaries, hCG is concentrated in the fluid of the developing follicles. The metabolic fate of u-hCG has not been elucidated, but it is eliminated in a biphasic manner. The terminal half-life is approximately 23 hours. After a single IM injection, roughly 10% to 12% of a dose is excreted unchanged in the urine within 24 hours and can be detected for up to 3 to 4 days.
-Recombinant hCG (r-hCG): The metabolic fate of r-hCG, also known as choriogonadotropin alfa, has not been elucidated, but it is eliminated in a biphasic manner. Recombinant-hCG is eliminated from the body with a mean terminal half-life of roughly 29 hours (range 23 to 35 hours), which is similar to urine-derived hCG. After a single subcutaneous injection, roughly 10% of the dose is excreted unchanged in the urine within 24 hours.
-Route-Specific Pharmacokinetics
Intramuscular Route
-Urine-derived products: Urinary-derived human chorionic gonadotropin (u-hCG) is administered by the intramuscular (IM) route. Serum concentrations of hCG are detectable within 2 hours of IM administration; peak concentrations are attained within 6 hours and persist for roughly 36 hours.
Subcutaneous Route
-Recombinant hCG (r-hCG): Recombinant hCG, also known as choriogonadotropin alfa, is administered subcutaneously. Following a 250 mcg subcutaneous dose, Cmax is achieved within 12 to 24 hours, with an absolute bioavailability of roughly 40%.
-Urine-derived products (u-hCG): Subcutaneous administration of u-hCG products has been studied.
-Special Populations
Hepatic Impairment
The pharmacokinetics of human chorionic gonadotropin and choriogonadotropin alfa (r-hCG) have not been established in patients with hepatic impairment; no data are available.
Renal Impairment
The pharmacokinetics of human chorionic gonadotropin and choriogonadotropin alfa (r-hCG) have not been established in patients with renal impairment; no data are available.