Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, The Netherlands
Before starting treatment, the couple’s infertility should be assessed as appropriate and putative contraindications for pregnancy evaluated. In particular, patients should be evaluated for hypothyroidism, adrenocortical deficiency, hyperprolactinemia and pituitary or hypothalamic tumours, and appropriate specific treatment given. There is no clinical experience with Ovitrelle in the treatment of other conditions (such as corpus luteum insufficiency or male conditions); therefore, Ovitrelle is not indicated in these conditions.
Patients undergoing ovarian stimulation are at an increased risk of developing OHSS due to multiple follicular development.
Ovarian hyperstimulation syndrome may become a serious medical event characterised by large ovarian cysts, which are prone to rupture, weight gain, dyspnoea, oliguria or the presence of ascites within a clinical picture of circulatory dysfunction. Severe OHSS could be complicated in rare cases by haemoperitoneum, acute pulmonary distress, ovarian torsion, and thromboembolism.
To minimise the risk of OHSS, ultrasonographic assessments of follicular development and/or determination of serum estradiol levels should be performed prior to treatment and at regular intervals during treatment. In anovulation, the risk of OHSS is increased by a serum estradiol level >1500 pg/mL (5400 pmol/L) and more than 3 follicles of 14 mm or more in diameter. In assisted reproductive techniques, there is an increased risk of OHSS with a serum estradiol >3,000 pg/mL (11,000 pmol/L) and 18 or more follicles of 11 mm or more in diameter.
OHSS due to excessive ovarian response can be avoided by withholding hCG administration. Therefore, if signs of ovarian hyperstimulation occur such as serum estradiol level >5,500 pg/mL (20,000 pmol/L) and/or when there are 30 or more follicles in total, it is recommended to withhold hCG administration and the patient be advised to refrain from coitus or to use barrier contraceptive methods for at least 4 days.
In patients undergoing induction of ovulation, the incidence of multiple pregnancy and births (mostly twins) is increased compared with natural conception. The risk of multiple pregnancy following assisted reproductive techniques is related to the number of embryos replaced.
Adherence to recommended Ovitrelle dose, regimen of administration and careful monitoring of therapy will minimise the risk of OHSS and multiple pregnancy. Miscarriage The rate of miscarriage, in both anovulatory patients and women undergoing assisted reproductive techniques, is higher than that found in the normal population but comparable with the rates observed in women with other fertility problems.
Since infertile women undergoing ART, and particularly IVF, often have tubal abnormalities, the incidence of ectopic pregnancies might be increased. It is important to have early ultrasound confirmation that a pregnancy is intrauterine, and to exclude the possibility of extrauterine pregnancy.
The incidence of congenital malformations after ART may be slightly higher than after spontaneous conceptions. This is thought to be due to differences in parental characteristics (e.g. maternal age, sperm characteristics) and the higher incidence of multiple pregnancies.
In women with recent or ongoing thromboembolic disease or women with generally recognised risk factors for thromboembolic events, such as personal or family history, treatment with gonadotropins may further increase the risk for aggravation or occurrence of such events. In these women, the benefits of gonadotropin administration need to be weighed against the risks. It should be noted, however, that pregnancy itself as well as OHSS also carry an increased risk of thromboembolic events, such as pulmonary embolism, ischaemic stroke or myocardial infarction.
Following administration, Ovitrelle may interfere for up to ten days with the immunological determination of serum or urinary hCG, potentially leading to a false positive pregnancy test.
Patients should be made aware of this.
During Ovitrelle therapy, a minor thyroid stimulation is possible, of which the clinical relevance is unknown.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. it is essentially “sodium-free”.
No specific interaction studies with Ovitrelle and other medicinal products have been performed; however, no clinically significant medicinal product interactions have been reported during hCG therapy.
There is no indication for the use of Ovitrelle during pregnancy. No clinical data on exposed pregnancies are available. No reproduction studies with choriogonadotropin alfa in animals were performed (see section 5.3). The potential risk for humans is unknown.
Ovitrelle is not indicated during breastfeeding. There are no data on the excretion of choriogonadotropin alfa in milk.
Ovitrelle is indicated for use in infertility (see section 4.1).
Ovitrelle is expected to have no or negligible influence on the ability to drive and use machines.
In comparative trials with different doses of Ovitrelle, the following adverse reactions were found to be associated with Ovitrelle in a dose-related fashion: OHSS, vomiting and nausea. OHSS was observed in approximately 4% of patients treated with Ovitrelle. Severe OHSS was reported in less than 0.5% of patients (see section 4.4).
The following definitions apply to the frequency terminology used hereafter: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to < 1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).
Very rare: Mild to severe hypersensitivity reactions including anaphylactic reactions and shock
Uncommon: Depression, irritability, restlessness
Common: Headache
Very rare: Thromboembolism (both in association with and separate from OHSS)
Common: Vomiting, nausea, abdominal pain
Uncommon: Diarrhoea
Very rare: Mild reversible skin reactions manifesting as rash
Common: Mild or moderate OHSS
Uncommon: Severe OHSS, breast pain
Common: Tiredness, injection site reactions.
Ectopic pregnancy, ovarian torsion and other complications have been reported in patients after hCG administration. These are considered concomitant effects related to assisted reproductive techniques.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
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