Pregnyl

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 subunits of 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 subunits of these hormones differ in amino acid sequence.

PREGNYL

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.

• 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 pituitary disorders).
• 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.

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.
  
  
  
  

• 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 pituitary disorders).
• 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.

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.
  
  
  
  

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.
  
  
  
  

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.
  
  
  
  

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.
  
  
  
  

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.
  
  
  
  

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.
  
  
  
  

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.