Ovitrelle (INN choreo gonadotropin alfa) is a medicinal product of choriogonadotropin alfa produced by recombinant DNA techniques. It shares the amino acid sequence with urinary hCG. Chorionic gonadotropin binds on the ovarian theca (and granulosa) cells to a transmembrane receptor shared with the luteinising hormone, the LH/CG receptor. The principal pharmacodynamic activity in women is oocyte meiosis resumption, follicular rupture (ovulation), corpus luteum formation and production of progesterone and estradiol by the corpus luteum.
In women, chorionic gonadotropin acts as a surrogate luteinising hormone surge that triggers ovulation.

Therapeutic indications
Ovitrelle is indicated in the treatment of

• Adult women undergoing superovulation prior to assisted reproductive techniques such as in vitro fertilisation (IVF): Ovitrelle is administered to trigger final follicular maturation and luteinisation after stimulation of follicular growth,

• Anovulatory or oligoovulatory adult women: Ovitrelle is administered to trigger ovulation and luteinisation in anovulatory or oligoovulatory women after stimulation of follicular growth.

Ovitrelle is used to trigger final follicular maturation and early luteinisation after use of medicinal products for stimulation of follicular growth.

Pharmacokinetic properties
Following intravenous administration, choriogonadotropin alfa is distributed to the extracellular fluid space with a distribution halflife of around 4.5 hours. The steadystate volume of distribution and the total clearance are 6 l and 0.2 l/h, respectively. There are no indications that choriogonadotropin alfa is metabolised and excreted differently than endogenous hCG.

Following subcutaneous administration, choriogonadotropin alfa is eliminated from the body with a terminal halflife of about 30 hours, and the absolute bioavailability is about 40%.
A comparative study between the freezedried and the liquid formulation showed bioequivalence between the two formulations.

Posology and method of administration
Ovitrelle is intended for subcutaneous administration. Treatment with Ovitrelle should be performed under the supervision of a physician experienced in the treatment of fertility problems.

The maximum dose is 250 micrograms. The following dose regimen should be used:
Women undergoing superovulation prior to assisted reproductive techniques such as in vitro fertilisation (IVF):
One prefilled syringe of Ovitrelle (250 micrograms) is administered 24 to 48 hours after the last administration of a follicle stimulating hormone (FSH) or human menopausal gonadotropin (hMG) preparation, i.e. when optimal stimulation of follicular growth is achieved.

Anovulatory or oligoovulatory women:
One prefilled syringe of Ovitrelle (250 micrograms) is administered 24 to 48 hours after optimal stimulation of follicular growth is achieved. The patient is recommended to have coitus on the day of, and the day after, Ovitrelle injection.

Renal or hepatic impairment
Safety, efficacy and pharmacokinetics of Ovitrelle in patients with renal or hepatic impairment have not been established.

Paediatric population
There is no relevant use of Ovitrelle in the paediatric population.

Method of administration
For subcutaneous use. Selfadministration of Ovitrelle should only be performed by patients who are adequately trained and have access to expert advice.
Ovitrelle is for single use only.

Contraindications

• Hypersensitivity to choriogonadotropin alfa or to any of the excipients of Ovitrelle

• Tumours of the hypothalamus or pituitary gland
• Ovarian enlargement or cyst due to reasons other than polycystic ovarian disease
• Gynaecological haemorrhages of unknown aetiology
• Ovarian, uterine or mammary carcinoma
• Extrauterine pregnancy in the previous 3 months
• Active thrombo-embolic disorders
• Primary ovarian failure
• Malformations of sexual organs incompatible with pregnancy
• Fibroid tumours of the uterus incompatible with pregnancy
• Postmenopausal women

Fertility, pregnancy and lactation
Pregnancy. 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.
Breast feeding. Ovitrelle is not indicated during breastfeeding.There are no data on the excretion of choriogonadotropin alfa in milk.
Fertility. Ovitrelle is indicated for use in infertility.