small uncontrolled study suggest a higher ovarian response than in combination with a GnRH antagonist. Therefore, the use of Elonva is not recommended in combination with a GnRH agonist (see also section 4.2).
Ovarian hyperstimulation syndrome (OHSS)
OHSS is a medical event distinct from uncomplicated ovarian enlargement. Clinical signs and symptoms of mild and moderate OHSS are abdominal pain, nausea, diarrhoea, mild to moderate enlargement of ovaries and ovarian cysts. Severe OHSS may be life-threatening. Clinical signs and symptoms of severe OHSS are large ovarian cysts, acute abdominal pain, ascites, pleural effusion, hydrothorax, dyspnoea, oliguria, haematological abnormalities and weight gain. In rare instances, venous or arterial thromboembolism may occur in association with OHSS. Transient liver function test abnormalities suggestive of hepatic dysfunction with or without morphologic changes on liver biopsy have also been reported in association with OHSS.
OHSS may be caused by administration of hCG and by pregnancy (endogenous hCG). Early OHSS usually occurs within 10 days after hCG administration and may be associated with an excessive ovarian response to gonadotropin stimulation. Late OHSS occurs more than 10 days after hCG administration, as a consequence of the hormonal changes with pregnancy. Because of the risk of developing OHSS, patients should be monitored for at least two weeks after hCG administration.
Women with known risk factors for a high ovarian response may be especially prone to the development of OHSS following treatment with Elonva. For women having their first cycle of ovarian stimulation, for whom risk factors are only partially known, close observation for early signs and symptoms of OHSS is recommended.
To reduce the risk of OHSS, ultrasonographic assessments of follicular development should be performed prior to treatment and at regular intervals during treatment. The concurrent determination of serum oestradiol levels may also be useful. In ART there is an increased risk of OHSS with 18 or more follicles of 11 mm or more in diameter. When there are 30 or more follicles in total it is advised to withhold hCG administration.
Depending on the ovarian response, the following measures can be considered to reduce the risk of OHSS:
- withhold further stimulation with a gonadotropin for a maximum of 3 days (coasting);
- withhold hCG and cancel the treatment cycle;
- administer a dose lower than 10,000 IU of hCG for triggering final oocyte maturation, e.g. 5,000 IU hCG or 250 micrograms rec-hCG (which is equivalent to approximately 6,500 IU);
- cancel the fresh embryo transfer and cryopreserve embryos;
- avoid administration of hCG for luteal phase support.
Adherence to the recommended Elonva dose and treatment cycle and careful monitoring of ovarian response is important to reduce the risk of OHSS. If OHSS develops, standard and appropriate management of OHSS should be implemented and followed.
Ovarian torsion
Ovarian torsion has been reported after treatment with gonadotropins, including Elonva. 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.
Multiple pregnancy
Multiple pregnancies and births have been reported for all gonadotropin treatments, including Elon |
