Vascular Complications

Thromboembolic events, both in association with and separate from OHSS, have been reported following treatment with gonadotropins, including Puregon. Intravascular thrombosis, which may originate in venous or arterial vessels, can result in reduced blood flow to vital organs or the extremities. In women with generally recognised risk factors for thromboembolic events, such as a personal or family history, severe obesity or thrombophilia, treatment with gonadotropins, including Puregon, may further increase this risk. In these women the benefits of gonadotropin administration, including Puregon, need to be weighed against the risks. It should be noted, however, that pregnancy itself also carries an increased risk of thrombosis.

Congenital Malformations

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 multiple gestations.

Ovarian Torsion

Ovarian torsion has been reported after treatment with gonadotropins, including Puregon. Ovarian torsion may be associated with other risk factors such as OHSS, pregnancy, previous abdominal surgery, past history of ovarian torsion, previous or current ovarian cyst and polycystic ovaries. Damage to the ovary due to reduced blood supply can be limited by early diagnosis and immediate detorsion.

Ovarian and other Reproductive System Neoplasms

There have been reports of ovarian and other reproductive system neoplasms, both benign and malignant, in women who have undergone multiple treatment regimens for infertility treatment. It is not established whether or not treatment with gonadotrophins increases the risk of these tumours in infertile women.

Other Medical Conditions

Medical conditions that contraindicate pregnancy should also be eva luated before starting treatment with Puregon.

In males

Primary Testicular Failure

Elevated endogeneous FSH levels in men are indicative of primary testicular failure. Such patients are unresponsive to Puregon/hCG therapy.

4.5 Interaction with other medicinal products and other forms of interaction
 Concomitant use of Puregon and clomifene citrate may enhance the follicular response. After pituitary desensitisation induced by a GnRH agonist, a higher dose of Puregon may be necessary to achieve an adequate follicular response.
4.6 Fertility, pregnancy and lactation
 Fertility

Puregon is used in the treatment of women undergoing ovarian induction or controlled ovarian hyperstimulation in assisted reproduction programmes. In males Puregon is used in the treatment of deficient spermatogenesis due to hypogonadotrophic hypogonadism. For posology and method of administration, see section 4.2.

Pregnancy

The use of Puregon during pregnancy is not indicated. In case of inadvertent exposure during pregnancy, clinical data are not sufficient to exclude a teratogenic effect of recombinant FSH. However, to date, no particular malformative effect has been reported. No teratogenic effect has been observed in animal studies.

Breast-feeding

There is no information available from clinical or animal studies on the excretion of follitropin beta in milk. It is unlikely that follitropin beta is excreted in human milk due to its high molecular weight. If foll