Drugs List

Therapeutic Indications

Uses

Women undergoing superovulation prior to assisted reproductive techniques such as in vitro fertilisation (IVF).
Chorionic gonadotropin alfa is used to trigger final follicular maturation and luteinisation after stimulation of follicular growth.

Anovulatory or oligo-ovulatory women .
Chorionic gonadotropin alfa is used to trigger ovulation and luteinisation in anovulatory or oligo-ovulatory patients after stimulation of follicular growth.

Contraindications

Tumours of the hypothalamus and 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
Pregnancy (see Pregnancy)
Breastfeeding (see Lactation)

Chorionic gonadotrophin alfa injection should not be used when an effective response cannot be obtained, for example:
Primary ovarian failure
Malformation of sexual organs incompatible with pregnancy
Fibroid tumours of the uterus incompatible with pregnancy
Postmenopausal women

Precautions and Warnings

Treatment should be performed under the supervision of a physician experienced in the treatment of fertility problems.

Before starting treatment, the couple's infertility should be assessed as appropriate.
The patient should be evaluated for hypothyroidism, adrenocortical deficiency, hyperprolactinaemia and pituitary or hypothalamic tumours, and appropriate specific treatment given.

Special precautions should be taken in patients with clinically significant systemic disease where pregnancy could lead to a worsening of the condition.

Patients undergoing ovarian stimulation are at an increased risk of developing ovarian hyperstimulation syndrome (OHSS) due to multiple follicular development. This may become a serious medical event characterised by large ovarian cysts which are prone to rupture and the presence of ascites within a clinical picture of circulatory dysfunction.

To minimise the risk of OHSS and of multiple pregnancy, ultrasound scans as well as estradiol measurements are recommended for all patients. In anovulation, the risk of OHSS is increased by a serum estradiol level greater than 1500 pg/ml (5400 pmol/L) and more than 3 follicles of 14mm or more in diameter. In assisted reproductive techniques, there is an increased risk of OHSS with a serum estradiol greater than 3000 pg/ml (11,000 pmol/L) and 18 or more follicles of 11mm or more in diameter. When the estradiol level is greater than 5,500pg/ml (20,000pmol/L) and when there are 30 or more follicles in total, it may be necessary to withhold hCG administration. Patients should be advised to refrain from coitus or use barrier methods for at least 4 days.

In rare cases severe ovarian hyperstimulation syndrome may be complicated by acute pulmonary distress, haemoperitoneum, ovarian torsion and thromboembolism.

In patients 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 patients, the benefits of gonadotropin administration need to be weighed against the risks.

Adherence to the recommended dosage, regimen of administration and careful monitoring of therapy will minimise the incidence of ovarian hyperstimulation and multiple pregnancy.

Following assisted reproductive technologies the risk of multiple pregnancy is related to the number of embryos replaced. In patients undergoing induction of ovulation, incidence of multiple pregnancies and births (mostly twins) is increased compared with natural conception.

Patients receiving Assisted Reproductive Technology (ART) and particularly IVF, often have tubal abnormalities, the incidence of ectopic pregnancies might be increased. It is important to have an early ultrasound confirmation that a pregnancy is intrauterine.

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.

There is a higher miscarriage rate in both anovulatory patients and women undergoing assisted reproductive techniques. The rates are comparable to those observed in women with other fertility problems.

Self-administration should only be performed by patients who are adequately trained and have access to expert advice.

May interfere with serum/urinary determinations of hCG leading to a false positive pregnancy test for up to 10 days after administration.

Minor thyroid stimulation may occur. The clinical significance of this is unknown.

Pregnancy and Lactation

Pregnancy

Schaefer (2007) states there are no indications for using anterior pituitary hormones during an already existing pregnancy. Inadvertent use is not grounds for pregnancy termination or for invasive diagnostic procedures.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Chorionic gonadotropin alfa is contraindicated during lactation.

There is no data on the excretion of chorionic gonadotropin alfa in milk at the time of writing.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Presentation

Pre-filled syringe containing choriogonadotropin alfa 250 micrograms in 0.5ml.
Pre-filled pen containing choriogonadotropin alfa 250 micrograms in 0.5ml.

A dose of 250 micrograms is equivalent to approximately 6500 iu.

Choriogonadotropin alfa is recombinant Human Chorionic Gonadotropin produced by recombinant DNA technology using Chinese Hamster Ovary (CHO) cell lines.

Drugs List

Therapeutic Indications

Uses

Women undergoing superovulation prior to assisted reproductive techniques such as in vitro fertilisation (IVF).
Chorionic gonadotropin alfa is used to trigger final follicular maturation and luteinisation after stimulation of follicular growth.

Anovulatory or oligo-ovulatory women .
Chorionic gonadotropin alfa is used to trigger ovulation and luteinisation in anovulatory or oligo-ovulatory patients after stimulation of follicular growth.

Dosage

Treatment with chorionic gonadotropin alfa should be performed under the supervision of a physician experienced in the treatment of fertility problems.

The maximum dose is 250 micrograms.

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Contraindications

Tumours of the hypothalamus and 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
Pregnancy (see Pregnancy)
Breastfeeding (see Lactation)

Chorionic gonadotrophin alfa injection should not be used when an effective response cannot be obtained, for example:
Primary ovarian failure
Malformation of sexual organs incompatible with pregnancy
Fibroid tumours of the uterus incompatible with pregnancy
Postmenopausal women

Precautions and Warnings

Treatment should be performed under the supervision of a physician experienced in the treatment of fertility problems.

Before starting treatment, the couple's infertility should be assessed as appropriate.
The patient should be evaluated for hypothyroidism, adrenocortical deficiency, hyperprolactinaemia and pituitary or hypothalamic tumours, and appropriate specific treatment given.

Special precautions should be taken in patients with clinically significant systemic disease where pregnancy could lead to a worsening of the condition.

Patients undergoing ovarian stimulation are at an increased risk of developing ovarian hyperstimulation syndrome (OHSS) due to multiple follicular development. This may become a serious medical event characterised by large ovarian cysts which are prone to rupture and the presence of ascites within a clinical picture of circulatory dysfunction.

To minimise the risk of OHSS and of multiple pregnancy, ultrasound scans as well as estradiol measurements are recommended for all patients. In anovulation, the risk of OHSS is increased by a serum estradiol level greater than 1500 pg/ml (5400 pmol/L) and more than 3 follicles of 14mm or more in diameter. In assisted reproductive techniques, there is an increased risk of OHSS with a serum estradiol greater than 3000 pg/ml (11,000 pmol/L) and 18 or more follicles of 11mm or more in diameter. When the estradiol level is greater than 5,500pg/ml (20,000pmol/L) and when there are 30 or more follicles in total, it may be necessary to withhold hCG administration. Patients should be advised to refrain from coitus or use barrier methods for at least 4 days.

In rare cases severe ovarian hyperstimulation syndrome may be complicated by acute pulmonary distress, haemoperitoneum, ovarian torsion and thromboembolism.

In patients 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 patients, the benefits of gonadotropin administration need to be weighed against the risks.

Adherence to the recommended dosage, regimen of administration and careful monitoring of therapy will minimise the incidence of ovarian hyperstimulation and multiple pregnancy.

Following assisted reproductive technologies the risk of multiple pregnancy is related to the number of embryos replaced. In patients undergoing induction of ovulation, incidence of multiple pregnancies and births (mostly twins) is increased compared with natural conception.

Patients receiving Assisted Reproductive Technology (ART) and particularly IVF, often have tubal abnormalities, the incidence of ectopic pregnancies might be increased. It is important to have an early ultrasound confirmation that a pregnancy is intrauterine.

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.

There is a higher miscarriage rate in both anovulatory patients and women undergoing assisted reproductive techniques. The rates are comparable to those observed in women with other fertility problems.

Self-administration should only be performed by patients who are adequately trained and have access to expert advice.

May interfere with serum/urinary determinations of hCG leading to a false positive pregnancy test for up to 10 days after administration.

Minor thyroid stimulation may occur. The clinical significance of this is unknown.

Pregnancy and Lactation

Pregnancy

Schaefer (2007) states there are no indications for using anterior pituitary hormones during an already existing pregnancy. Inadvertent use is not grounds for pregnancy termination or for invasive diagnostic procedures.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Chorionic gonadotropin alfa is contraindicated during lactation.

There is no data on the excretion of chorionic gonadotropin alfa in milk at the time of writing.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Shelf Life and Storage

Store between 2 degrees C and 8 degrees C
Store in original package

The solution may be stored at or below 25 degrees C for up to 30 days without being refrigerated again during that period.
Discard if not used in this period.

Reference Sources

British National Formulary, 63rd Edition (2011) Pharmaceutical Press, London.

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Ovitrelle 250 micrograms/0.5ml prefilled syringe. Merck Serono. Revised June 2011.

Summary of Product Characteristics: Ovitrelle 250 micrograms/0.5ml prefilled pen. Merck Serono. Revised June 2011.