Pregnyl®
(chorionic gonadotropin) for injection
DESCRIPTION
Chorionic gonadotropin, a gonadotropin, is a polypeptide hormone produced by the human placenta
and obtained from the urine of pregnant persons. Chorionic gonadotropin is a purified preparation
composed of an alpha and a beta subunit. The alpha subunit is essentially identical to the alpha subunitsof the human pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone(FSH), as well as to the alpha subunit of human thyroid-stimulating hormone (TSH). The beta subunitsof these hormones differ in amino acid sequence.
PREGNYL® (chorionic gonadotropin) for injection is a sterile, dried powder for intramuscular injection
after reconstitution. Each multiple-dose vial is only for use in one patient and contains 10,000 USP
units of chorionic gonadotropin with dibasic sodium phosphate (4.4 mg) and monobasic sodium
phosphate (5 mg). If required, pH is adjusted with sodium hydroxide and/or phosphoric acid.
Each package also contains a 10-mL vial of solvent containing: water for injection with 0.56% sodium
chloride and 0.9% BENZYL ALCOHOL (preservative), WHICH IS NOT FOR USE IN NEWBORNS.
If required, pH is adjusted with sodium hydroxide and/or hydrochloric acid.
CLINICAL PHARMACOLOGY
The action of human chorionic gonadotropin (hCG) is virtually identical to that of pituitary LH,
although hCG appears to have a small degree of FSH activity as well. It stimulates production of
gonadal steroid hormones by stimulating the interstitial cells (Leydig cells) of the testis to produce
androgens and the corpus luteum of the ovary to produce progesterone.
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 isusually reversible when hCG is discontinued.
During the normal menstrual cycle, LH participates with FSH in the development and maturation of thenormal ovarian follicle, and the mid-cycle LH surge triggers ovulation. hCG can substitute for LH inthis function. During a normal pregnancy, hCG secreted by the placenta maintains the corpus luteum
after LH secretion decreases, supporting continued secretion of estrogen and progesterone andpreventing menstruation.
HCG HAS NO KNOWN EFFECT ON FAT MOBILIZATION, APPETITE OR SENSE OF HUNGER,
OR BODY FAT DISTRIBUTION.
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 INCREASESWEIGHT 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 CALORIERESTRICTED DIETS.

1. 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 isusually instituted in children between the ages of 4 and 9.
2. Selected cases of hypogonadotropic hypogonadism (hypogonadism secondary to a pituitary
deficiency) in males.
3. Induction of ovulation and pregnancy in the anovulatory, infertile woman in whom the cause ofanovulation is secondary and not due to primary ovarian failure, and who has been appropriately
treated with human gonadotropins.
CONTRAINDICATIONS• Prior hypersensitivity reactions to human gonadotropins, including hCG, or any of the excipients(see ADVERSE REACTIONS).
•High serum FSH, indicating primary gonadal failure in women.

•

Presence of uncontrolled non-gonadal endocrinopathies (e.g., thyroid, adrenal, or pituitarydisorders).

•

Tumors of the hypothalamus or pituitary gland and ovary, breast, or uterus in females and breast or
prostate in males.

•

Malformations of the reproductive organs incompatible with pregnancy.

•

Fibroid tumors of the uterus incompatible with pregnancy.

•

Abnormal vaginal bleeding of undetermined origin.

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.
1. Anaphylaxis
Anaphylaxis has been reported with urinary-derived hCG products.
2. 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 adramatic increase in vascular permeability, which can result in a rapid accumulation of fluid in theperitoneal cavity, thorax, and potentially, the pericardium. The early warning signs of the developmentof 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, pleural2

effusions, hydrothorax, acute pulmonary distress, and thromboembolic reactions. Transient liverfunction test abnormalities suggestive of hepatic dysfunction with or without morphologic changes onliver 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 withknown 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 ofovarian 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 andelectrolyte management, and analgesics (if needed). Because the use of diuretics can accentuate thediminished 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 andelectrolyte imbalances.
3. 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 theextremities. 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 vascularocclusion (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.
4. 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, pasthistory 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.
35. Multi-Fetal Gestation and BirthMulti-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.
6. Congenital Malformations

The incidence of congenital malformations after ART may be slightly higher than after spontaneousconceptions. 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 associatedwith an increased risk of congenital malformations.
7. Ectopic Pregnancy
Infertile women undergoing Assisted Reproductive Technologies (ART) have an increased incidence ofectopic pregnancy. Early ultrasound confirmation that a pregnancy is intrauterine is therefore
important.
8. 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.
9. 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 notbeen established.
PRECAUTIONS
1. General
Induction of androgen secretion by hCG may cause fluid retention.
Use hCG with caution in patients with cardiac or renal disease, hypertension, epilepsy, migraine, orasthma.
Careful attention should be given to the diagnosis of infertility in candidates for hCG therapy (seeINDICATIONS AND USAGE).
Evaluate patients for uncontrolled non-gonadal endocrinopathies (e.g., thyroid, adrenal or pituitarydisorders) and provide the appropriate specific treatment.
2. Information for Patients
Prior to therapy with hCG, patients should be informed of the duration of treatment and monitoring of
their condition that will be required. The risks of Ovarian Hyperstimulation Syndrome and multiple
births in women (see WARNINGS) and other possible adverse reactions (see ADVERSE
REACTIONS) should also be discussed.
3. Laboratory Tests
In most instances, treatment of women with FSH results only in follicular recruitment anddevelopment. In the absence of an endogenous LH surge, hCG is given when monitoring of the patient
indicates that sufficient follicular development has occurred. This may be estimated by pelvic
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ultrasound alone or in combination with measurement of serum estradiol levels. The combination ofboth pelvic ultrasound and serum estradiol measurement are useful for monitoring the development offollicles, for timing of the ovulatory trigger, as well as for detecting ovarian enlargement andminimizing the risk of the Ovarian Hyperstimulation Syndrome and multiple gestation. Confirm thenumber of growing follicles using ultrasonography because serum estrogens do not give an indicationof the size or number of follicles.
Human chorionic gonadotropins can crossreact in the radioimmunoassay of gonadotropins, especiallyluteinizing hormone. Each individual laboratory should establish the degree of crossreactivity with theirgonadotropin assay. Make the laboratory aware that the patient is on hCG, if gonadotropin levels arerequested.
The clinical confirmation of ovulation, with the exception of pregnancy, is obtained by direct andindirect indices of progesterone production as well as sonographic evidence of ovulation. The indicesmost generally used are as follows:
1.
2.
3.
4.

A rise in basal body temperature
Increase in serum progesterone andMenstruation following a shift in basal body temperature
Urinary or serum luteinizing hormone (LH) rise

When used in conjunction with the indices of progesterone production, sonographic visualization of theovaries will assist in determining if ovulation has occurred. Sonographic evidence of ovulation may
include the following:
1. Fluid in the cul-de-sac
2. Collapsed follicle
3. Features consistent with corpus luteum formation (e.g., ovarian stigmata, secretory endometrium)
Accurate interpretation of the indices of ovulation requires a physician who is experienced in theinterpretation of these tests.
Sonographic evaluation of the early pregnancy is also important to rule out ectopic pregnancy.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to evaluate the carcinogenic or mutagenic
potential of chorionic gonadotropin.
Pregnancy
PREGNYL is not indicated in pregnancy. PREGNYL may be used for luteal phase support, but isdiscontinued upon confirmation of pregnancy. There are no data on the use of hCG in pregnancy.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage inclinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

5

Pediatric Use
Induction of androgen secretion by hCG may induce precocious puberty in pediatric patients treated for
cryptorchidism. Discontinue therapy if signs of precocious puberty occur.
Lactation
It is not known whether this drug is excreted in human milk. Because many drugs are excreted inhuman milk, caution should be exercised if hCG is administered to a nursing woman.
The developmental and health benefits of breastfeeding should be considered along with the mother’sclinical need for PREGNYL and any potential adverse effects on the breastfed child from PREGNYL
or from the underlying maternal condition.
Geriatric Use
Clinical studies of PREGNYL (chorionic gonadotropin) for injection did not include subjects aged 65
and over.
ADVERSE REACTIONS
For males and females
Immune system disorders
Hypersensitivity reactions, both localized and systemic in nature, including anaphylaxis have beenreported. In rare cases, generalized rash or fever may occur (see CONTRAINDICATIONS andWARNINGS). If a hypersensitivity reaction is suspected, discontinue PREGNYL and assess for otherpotential 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 anditching. 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 associatedwith severe OHSS (see WARNINGS).
Respiratory, thoracic and mediastinal disorders
Hydrothorax, as a complication of severe OHSS (see WARNINGS).

6

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 (seeWARNINGS).
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
DOSAGE AND ADMINISTRATION
For intramuscular use only. Each multiple-dose vial is to be used for one patient. The dosage regimen
employed in any particular case will depend upon the indication for the use, the age and weight of thepatient, and the physician’s preference. The following regimens have been advocated by various
authorities:
Prepubertal cryptorchidism not due to anatomical obstruction. Generally, institute therapy in children
between the ages of 4 and 9.
1. 4000 USP units 3 times weekly for 3 weeks.
2. 5000 USP units every second day for 4 injections.
3. 15 injections for 500 to 1000 USP units over a period of 6 weeks.
4. 500 USP units 3 times weekly for 4 to 6 weeks. If this course of treatment is not successful, anotherseries is begun 1 month later, giving 1000 USP units per injection.
Selected cases of hypogonadotropic hypogonadism in males.
1. 500 to 1000 USP units 3 times a week for 3 weeks, followed by the same dose twice a week for 3
weeks.
2. 4000 USP units 3 times weekly for 6 to 9 months, following which the dosage may be reduced to2000 USP units 3 times weekly for an additional 3 months.
Induction of ovulation and pregnancy in the anovulatory, infertile woman in whom the cause ofanovulation is secondary and not due to primary ovarian failure and who has been appropriately
treated with gonadotropins. (See also prescribing information for gonadotropins for dosage andadministration for that drug product.)7

5000 to 10,000 USP units 1 day following the last dose of gonadotropins. (A dosage of 10,000 USP
units is recommended in the labeling for gonadotropins.)
Directions for Reconstitution
Withdraw sterile air from vial with lyophilized powder and inject into vial with solvent. Remove 1 to
10 mL of solvent and add to vial with lyophilized powder; agitate gently until powder is completely
dissolved in solution. Do not shake.
PREGNYL is a white, dry powder / cake. The solvent is a clear and colorless aqueous solution.
Visually inspect parenteral drug products for particulate matter and discoloration prior toadministration, whenever solution and container permit. If there is a discoloration or particulates, do not
use.
IMPORTANT: IF NEEDED, THE RECONSTITUTED SOLUTION IS STABLE FOR 60 DAYS
WHEN REFRIGERATED. DO NOT FREEZE. USE THE RECONSTITUTED SOLUTIONWITHIN 60 DAYS OF RECONSTITUTION. IF THE RECONSTITUTED SOLUTION IS NO
LONGER NEEDED, DISCARD UNUSED PORTION.
HOW SUPPLIED
Two-vial package containing:
One 10 mL multiple-dose vial for administration by one patient, containing lyophilized powder of
10,000 USP units of chorionic gonadotropin per vial, NDC 78206-150-01.
One 10 mL multiple-dose vial of solvent containing: water for injection with sodium chloride 0.56%
and benzyl alcohol (preservative) 0.9%, NDC 78206-151-89.
Storage: Store unopened vial at controlled room temperature 15°C to 25°C (59°F to 77°F).
If reconstituted solution in vial is not used immediately, then store refrigerated [2°C to 8°C (36°F to46°F)] until use and discard after 60 days. Do not shake. Do not freeze.
PREGNYL manufactured by:

U.S. License No. 2331
PREGNYL Solvent manufactured by:
Baxter Pharmaceutical Solutions LLC
Bloomington, IN 47403, USA
For patent information: www.organon.com/our-solutions/patent/© 2024 Organon group of companies. All rights reserved.
Revised: 06/2024
uspi-og8829-pwi-2406r001
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