Special Warning : אזהרת שימוש

4.4      Special warnings and precautions for use

Menogon is a potent gonadotropic substance that can have mild up to severe side effects. It should only be administered under supervision of medical doctors who are familiar with the problems and treatment of fertility disorders.

Therapies with gonadotropins require a certain expenditure of time from doctors and medical staff as well as appropriate monitoring facilities. A secure and effective use of Menogon requires regular control of the ovarian reaction by use of ultrasound, preferably in combination with measurement of serum estradiol levels. Interindividually, the reaction to the FSH administration can vary and can be very low in some patients. In order to achieve therapy aims, the lowest effective dosage in relation to the aims of treatment should be administered.

The first Menogon injection should be performed under direct medical supervision.

Women:
Prior to the treatment, the couple's infertility is to be diagnosed in an appropriate way and possible contraindications for pregnancy are to be assessed. The patients are to be examined for hypothyreosis, insufficiency of the adrenal cortex, hyperprolactinemia, and hypophysis or hypothalamus tumors and should be treated accordingly.

In patients who undergo stimulation of the follicular growth – in connection with treatment of anovulatory infertility or ART – enlargement of the ovaries or hyperstimulation may occur.
These risks can be minimised by adherence to the recommended dosage and administration regimens and through thorough monitoring of the therapy.

The assessment of the follicular development is to be performed by a medical doctor who is experienced in this context.

Ovarian hyperstimulation syndrome (OHSS)
OHSS differs from uncomplicated ovarian enlargement and can manifest with increasing grades of severity. It includes marked enlargement of the ovaries, high levels of sexual hormones and increase of the fluid permeability of the vessels. The latter can lead to fluid accumulation in the peritoneal, pleural and, in rare cases, in the pericardial cavities.

The following symptoms can be observed in severe cases of OHSS: abdominal pain, distended abdomen, excessive ovarian enlargement, increase in weight, dyspnea, oliguria, and gastrointestinal symptoms such as nausea, emesis and diarrhea. The clinical examination may reveal hypovolemia, hemoconcentration, electrolyte balance disorders, ascites, hemoperitoneum, pleural effusion, hydrothorax, acute shortness of breath, and thromboembolism.

Excessive ovarian reaction to the gonadotropin treatment rarely leads to OHSS unless the ovulation is not triggered by HCG administration. It is thus advisable not to administer HCG with ovarian hyperstimulation and to instruct the patient to renounce sexual intercourse or use nonhormonal contraceptives for at least 4 days. OHSS can progress very quickly (between 24 hours and several days) and develop to serious symptoms. Therefore patients should be controlled for a period of at least 2 weeks following the HCG administration.

Adherence to the recommended dosage and administration regimens and thorough monitoring of the therapy can minimise the appearance of ovarian hyperstimulation and multiple pregnancy (see sections 4.2 and 4.8). With ART, aspiration of all follicles prior to ovulation can reduce the risk of hyperstimulation.

OHSS can be more severe and of longer duration in cases of pregnancy. OHSS appears most frequently after completion of hormonal treatment and reaches its peak about 7 to 10 days after treatment. Normally, OHSS recedes spontaneously with the beginning of menstruation.

In cases of severe OHSS, the gonadotropin treatment should be stopped (if this has not been done yet), the patient is to be admitted to hospital, and a special OHSS treatment is to be started.

OHSS appears more frequently in women with polycystic ovarian syndrome (PCO).

Multiple pregnancy
Multiple pregnancy, particularly those of higher order, bear an increased risk of maternal and perinatal complications.

In patients who undergo an ovulation induction with Menogon, the risk of multiple pregnancy is higher in relation to natural conception. In order to minimise the risk of multiple pregnancy, thorough monitoring of the ovarian reaction is recommended.

In patients who undergo ART, the risk of multiple pregnancy mainly depends on the number of transferred embryos, their quality and the patient's age.

Prior to the treatment, the patient is to be informed about the potential risk of multiple pregnancy.
Premature birth / miscarriage
Premature birth or miscarriage are seen more frequently in patients who undergo ART or a stimulation of follicular growth for the purpose of causing ovulation than in the average population.

Ectopic pregnancy
In women with a history of tubal diseases, there is a risk of ectopic pregnancy, no matter if pregnancy has been caused by spontaneous conception or by fertility treatment. A prevalence of 2 to 5% of ectopic pregnancy after IVF has been reported, in relation to 1 to 1.5% in the normal population.

Neoplasms of the reproduction organs
In women who have undergone multiple fertilisation treatment cycles, benign and malign neoplasms of the ovaries and other reproduction organs have been reported.
It is still in question as to whether treatment with gonadotropins increases the basic risk of these tumors in infertile women.

Congenital deformations
The prevalence of congenital deformations following ART can be slightly higher than with spontaneous conception. This can probably be attributed to different parental prior encumbrance (e.g. mother's age, sperm characteristics) and multiple pregnancy.

Thromboembolism
Women with generally recognized risk factors for thromboembolic events, such as personal or family history, severe obesity (Body Mass Index > 30 kg/m2) or thrombophilia may have an increased risk of venous or arterial thromboembolic events, during or following treatment with gonadotrophins. 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.

Men:
Increased endogenous FSH levels indicate a primary testicular disorder. These patients do not respond to Menogon/HCG therapy.

Sperm analyses are to be performed 4 – 6 months after the beginning of treatment to enable assessment of the reaction to the therapy.

The use of Menogon may lead to positive results in doping tests.
The use of Menogon for doping purposes may endanger health.

Menogon contains sodium, but less than 1 mmol (23 mg) sodium per dose, i.e. essentially “sodium-free”.

Effects on Driving

4.7     Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.
However, Menogon is unlikely to have influence on the patient’s ability to drive and use machines.