FertinexTM (urofollitropin for injection, purified) should only be used by physicians who are thoroughly familiar with infertility problems and their management. It is a potent gonadotropic substance capable of causing mild to severe adverse reactions. Therefore, the lowest dose consistent with the expectation of good results should be used. Gonadotropin therapy requires a certain time commitment by physicians and supportive health professionals, and its use requires the availability of appropriate monitoring facilities (see
PRECAUTIONS: Laboratory Tests). Safe and effective use of Fertinex (urofollitropin) TM requires monitoring of ovarian response with, serum estradiol and vaginal ultrasound, on a regular basis.
Overstimulation of the Ovary During FertinexTM (urofollitropin for injection, purified) Therapy
Ovarian Enlargement: Mild to moderate uncomplicated ovarian enlargement which may be accompanied by abdominal distension and/or abdominal pain occurs in approximately 20% of those treated with urofollitropin and hCG, and generally regresses without treatment within two or three weeks. Careful monitoring of ovarian response can further minimize the risk of overstimulation.
If the ovaries are abnormally enlarged on the last day of Fertinex (urofollitropin) TM therapy, hCG should not be administered in this course of therapy. This will reduce the chances of development of the Ovarian Hyperstimulation Syndrome.
The Ovarian Hyperstimulation Syndrome (OHSS): OHSS is a medical event distinct from uncomplicated ovarian enlargement. Severe OHSS may progress rapidly (within 24 hours to several days) to become a serious medical event. It is characterized by an apparent 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 development of OHSS are severe pelvic pain, nausea, vomiting, and weight gain. The following symptomatology has been seen with cases of OHSS: abdominal pain, abdominal distension, gastrointestinal symptoms including nausea, vomiting and diarrhea, severe ovarian enlargement, weight gain, dyspnea, and oliguria. Clinical evaluation may reveal hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic events (see Pulmonary and Vascular Complications - below). 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 the Ovarian Hyperstimulation Syndrome (OHSS).
Severe OHSS occurred in approximately 6.0% of patients treated with urofollitropin therapy in the initial clinical trials, in patients treated for anovulation due to polycystic ovarian syndrome. In these studies, prospective monitoring of ovarian response using serum estradiol determination or ultrasonographic visualizations was not routinely employed. In more recent clinical trials in oligo-anovulatory and infertile women in which both estradiol and ultrasound measurements were utilized to monitor follicular development, the incidence of severe OHSS was 0.6%. During studies for in vitro fertilization, four cases of OHSS were reported following 1,586 treatment cycles (0.25%). OHSS may be more severe and more protracted if pregnancy occurs. OHSS develops rapidly; therefore, patients should be followed for at least two weeks after hCG administration. Most often, OHSS occurs after treatment has been discontinued and reaches its maximum at about seven to ten days following treatment. Usually, OHSS resolves spontaneously with the onset of menses. If there is evidence that OHSS may be developing prior to hCG administration (see
PRECAUTIONS: Laboratory Tests), the hCG must be withheld.
If severe OHSS occurs, treatment must be stopped and the patient should be hospitalized.
A physician experienced in the management of this syndrome, or who is experienced in the management in fluid and electrolyte imbalances should be consulted.
Pulmonary and Vascular Complications
The following paragraph describes serious medical events reported following gonadotropin therapy.
Serious pulmonary conditions (e.g., atelectasis, acute respiratory distress syndrome) have been reported. In addition, thromboembolic events both in association with, and separate from the Ovarian Hyperstimulation Syndrome have been reported. Intravascular thrombosis and embolism can result in reduced blood wflow to critical organs or the extremities. Sequelae of such events have included venous thrombophlebitis, pulmonary embolism, pulmonary infarction, cerebral vascular occlusion (stroke), and arterial occlusion resulting in loss of limb. In rare cases, pulmonary complications and/or thromboembolic events have resulted in death.
Reports of multiple births have been associated with urofollitropin-hCG treatment including triplet and quintuplet gestations. In clinical studies with Fertinex (urofollitropin) TM 79.2% of the pregnancies following ovulation induction therapy resulted in single births and 20.8% in multiple births. The risk of multiple births in patients undergoing ART procedures is related to the number of embryos replaced. The patient and her husband should be advised of the potential risk of multiple births before starting treatment.