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Pergoveris contains potent gonadotrophic substances capable of causing mild to severe adverse reactions, and should only be used by physicians who are thoroughly familiar with infertility problems and their management.
Gonadotrophin therapy requires a certain time commitment by physicians and supportive health professionals, as well as the availability of appropriate monitoring facilities. In women, safe and effective use of Pergoveris calls for monitoring of ovarian response with ultrasound, alone or preferably in combination with measurement of serum oestradiol levels, on a regular basis. There may be a degree of interpatient variability in response to FSH/LH administration, with a poor response to FSH/LH in some patients and exaggerated response in others. The lowest effective dose in relation to the treatment objective should be used.
Self-administration of Pergoveris should only be performed by patients who are well motivated, adequately trained and with access to expert advice. The 1st injection of Pergoveris should be performed under direct medical supervision. Patients with porphyria or a family history of porphyria, Pergoveris may increase the risk of an acute attack. Deterioration or a 1st appearance of this condition may require cessation of treatment. Pergoveris contains <1 mmol sodium (23 mg) per dose ie, essentially sodium-free.
Pergoveris contains sucrose 30 mg/dose. This should be taken into account in patients with diabetes mellitus.
Before starting treatment, the couple's infertility should be assessed as appropriate. In particular, patients should be evaluated for the following: Hypothyroidism, adrenocortical deficiency, hyperprolactinemia and pituitary or hypothalamic tumours.
Appropriate specific treatment should be given.
Patients undergoing stimulation of follicular growth are at an increased risk of developing hyperstimulation in view of possible excessive oestrogen response and multiple follicular development.
In clinical trials, lutropin α in combination with follitropin α has been shown to increase the ovarian sensitivity to gonadotropins. If an FSH dose increase is deemed appropriate, dose adaptation should preferably be at 7-14 day intervals and preferably with 37.5-75 IU increments using a licensed follitropin α preparation.
Ovarian hyperstimulation syndrome (OHSS) is a medical event distinct from uncomplicated ovarian enlargement. OHSS is a condition that can manifest itself with increasing degrees of severity. It comprises marked ovarian enlargement, high serum sex steroids, and an increase in vascular permeability which can result in an accumulation of fluid in the peritoneal, pleural and rarely, in the pericardial cavities.
Mild manifestations of OHSS include abdominal pain, abdominal discomfort and distension, and enlarged ovaries. Moderate OHSS may additionally present with nausea, vomiting, ultrasound evidence of ascites and marked ovarian enlargement.
Severe OHSS further includes symptoms eg, severe ovarian enlargement, weight gain, dyspnoea or oliguria. Clinical evaluation may reveal signs eg, hypovolaemia, haemoconcentration, electrolyte imbalances, ascites, pleural effusions, or acute pulmonary distress and thromboembolic events, haemoperitonium, hydrothorax.
Very rarely, severe OHSS may be complicated by ovarian torsion or thromboembolic events eg, pulmonary embolism, ischemic stroke and myocardial infarction.
Excessive ovarian response seldom gives rise to significant hyperstimulation unless hCG is administered to induce ovulation. Therefore, if signs of ovarian hyperstimulation occur, it is recommended that hCG be withheld and advise the patient to refrain from coitus or use barrier methods for at least 4 days.
OHSS may progress rapidly (within 24 hrs to several days) to become a serious medical event; therefore, patients should be followed for at least 2 wks after hCG administration.
To minimize the risk of OHSS or of multiple pregnancy (see texts on Multiple Pregnancies as follows), monitoring of stimulation cycles by ultrasound scans as well as oestradiol measurements are recommended to early identify risk factors. In anovulation, the risk of OHSS is increased by a serum oestradiol level >900 pg/mL (3300 pmol/L) and by the presence of >3 follicles of ≥14 mm in diameter.
Adherence to recommended Pergoveris and FSH dosage and regimen of administration can minimize the risk of ovarian hyperstimulation (see Dosage & Administration).
OHSS may be more severe and more protracted if pregnancy occurs. Most often, OHSS occurs after hormonal treatment has been discontinued and reaches its maximum at about 7-10 days following treatment. Usually, OHSS resolves spontaneously with the onset of menses.
If severe OHSS occurs, it is recommended that gonadotrophin treatment be stopped if still ongoing. The patient should be hospitalized and specific therapy for OHSS started.
This syndrome occurs with higher incidence in patients with polycystic ovarian disease.
Multiple Pregnancies: In patients undergoing induction of ovulation, the incidence of multiple pregnancies is increased compared with natural conception. The majority of multiple conceptions are twins. To minimize the risk of multiple pregnancy, careful monitoring of ovarian response is recommended.
The patients should be advised of the potential risk of multiple births before starting treatment.
Pregnancy Loss: The incidence of pregnancy loss by miscarriage or abortion is higher in patients undergoing stimulation of follicular growth for ovulation induction than following natural conception. When risk of OHSS or multiple pregnancies is assumed, treatment discontinuation should be considered.
Ectopic Pregnancy: Women with a history of tubal disease are at risk of ectopic pregnancy, whether the pregnancy is obtained by spontaneous conception or with fertility treatments. The prevalence of ectopic pregnancy after ART was reported to be higher than in the general population.
Reproductive System Neoplasms: There have been reports of ovarian and other reproductive system neoplasms, both benign and malignant, in women who have undergone multiple drug regimens for infertility treatment. It is not yet established whether or not treatment with gonadotrophins increases the risk of these tumours in infertile women.
Congenital Anomalies: The prevalence of congenital anomalies after the use of assisted reproductive technology (ART) may be slightly higher than after spontaneous conceptions although it is unclear whether this is related to factors inherent to the couple's infertility or the ART procedures. Based on clinical trials and post-marketing data, there is no evidence that gonadotropin use increase the risk of congenital anomalies in the offspring of the patients receiving infertility treatments.
Thromboembolic Events: In women with recent or ongoing thromboembolic disease or women with generally recognized risk factors for thromboembolic events eg, personal or family history, treatment with gonadotrophins may further increase the risk for aggravation or occurrence of such events. In these women, the benefits of gonadotrophin administration need to be weighed against the risks. It should be noted however, that pregnancy itself also carries an increased risk of thromboembolic events.
Effects on Ability to Drive and Operate Machinery: No studies on the effects on the ability to drive and use machines have been performed.
Use in pregnancy & lactation: Pergoveris should not be used during pregnancy or lactation.
