Ovitrelle

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

1. NAME OF THE MEDICINAL PRODUCT 
 
Ovitrelle 250 micrograms/0.5 mL solution for injection in pre-filled syringe 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each pre-filled syringe contains 250 micrograms choriogonadotropin alfa* (equivalent to 
approximately 6,500 IU) in 0.5 mL solution. 
 
* recombinant human chorionic gonadotropin, r-hCG produced in Chinese hamster ovary (CHO) cells 
by recombinant DNA technology 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection in pre-filled syringe. 
 
Clear, colourless to slightly yellow solution. 
The pH of the solution is 7.0 ± 0.3, its osmolality 250-400 mOsm/kg. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Ovitrelle is indicated in the treatment of 
 
• Adult women undergoing superovulation prior to assisted reproductive technologies (ART) such 

as in vitro fertilisation (IVF): Ovitrelle is administered to trigger final follicular maturation and 
luteinisation after stimulation of follicular growth, 

 
• Anovulatory or oligo-ovulatory adult women: Ovitrelle is administered to trigger ovulation and 

luteinisation in anovulatory or oligo-ovulatory women after stimulation of follicular growth. 
 
4.2 Posology and method of administration 
 
Treatment with Ovitrelle should be performed under the supervision of a physician experienced in the 
treatment of fertility problems. 
 
Posology 
 
The maximum dose is 250 micrograms. The following dose regimen should be used: 
 
• Women undergoing superovulation prior to assisted reproductive technologies (ART) such as 

in vitro fertilisation (IVF): 
 
One pre-filled 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. 

 



3 

• Anovulatory or oligo-ovulatory women:  
 
One pre-filled 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. 

 
Special populations 
 
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. Self-administration of Ovitrelle should only be performed by patients who are 
adequately trained and have access to expert advice. 
Ovitrelle is for single use only. 
 
4.3 Contraindications 
 
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 
• Tumours of the hypothalamus or pituitary gland 
• Ovarian enlargement or cyst unrelated to polycystic ovarian syndrome 
• Gynaecological haemorrhages of unknown aetiology 
• Ovarian, uterine or mammary carcinoma 
• Active thromboembolic disorders 
 
Ovitrelle must not be used in conditions when an effective response cannot be obtained, such as 
• primary ovarian failure 
• malformations of sexual organs incompatible with pregnancy 
• fibroid tumours of the uterus incompatible with pregnancy 
• postmenopausal women 
 
4.4 Special warnings and precautions for use 
 
Traceability 
 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
General recommendations 
 
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. 
 



4 

Ovarian hyperstimulation syndrome (OHSS) 
 
A certain degree of ovarian enlargement is an expected effect of controlled ovarian stimulation. It is 
more commonly seen in women with polycystic ovarian syndrome and usually regresses without 
treatment. 
 
In distinction to uncomplicated ovarian enlargement, OHSS is a condition that can manifest itself with 
increasing degrees of severity. It comprises marked ovarian enlargement, high serum sex steroids, and 
an increase in vascular permeability which can result in an accumulation of fluid in the peritoneal, 
pleural and, rarely, in the pericardial cavities. 
 
Mild manifestations of OHSS may include abdominal pain, abdominal discomfort and distension, and 
enlarged ovaries. Moderate OHSS may additionally present with nausea, vomiting, ultrasound 
evidence of ascites and marked ovarian enlargement. 
 
Severe OHSS further includes symptoms such as severe ovarian enlargement, weight gain, dyspnoea 
or oliguria. Clinical evaluation may reveal signs such as hypovolaemia, haemoconcentration, 
electrolyte imbalances, ascites, pleural effusions, or acute pulmonary distress. Very rarely, severe 
OHSS may be complicated by ovarian torsion or thromboembolic events, such as pulmonary 
embolism, ischaemic stroke or myocardial infarction. 
 
Independent risk factors for developing OHSS include young age, lean body mass, polycystic ovarian 
syndrome, higher doses of exogenous gonadotropins, high absolute or rapidly rising serum estradiol 
levels and previous episodes of OHSS, large number of developing ovarian follicles and large number 
of oocytes retrieved in ART cycles. 
 
Adherence to recommended Ovitrelle dosage and regimen of administration can minimise the risk of 
ovarian hyperstimulation. Monitoring of stimulation cycles by ultrasound scans as well as estradiol 
measurements are recommended to early identify risk factors. 
 
There is evidence to suggest that hCG plays a key role in triggering OHSS and that the syndrome may 
be more severe and more protracted if pregnancy occurs. Therefore, if signs of ovarian 
hyperstimulation occur, it is recommended that hCG be withheld and the patient be advised to refrain 
from coitus or use barrier contraceptive methods for at least 4 days. 
 
As OHSS may progress rapidly (within 24 hours) or over several days to become a serious medical 
event, patients should be followed for at least two weeks after hCG administration. 
 
Mild or moderate OHSS usually resolves spontaneously. If severe OHSS occurs, it is recommended 
that gonadotropin treatment be stopped and that the patient be hospitalised and appropriate therapy be 
started. 
 
Multiple pregnancy 
 
In patients undergoing induction of ovulation, the incidence of multiple pregnancy and births is 
increased compared with natural conception. The majority of multiple conceptions are twins. Multiple 
pregnancies, especially high order, carry an increased risk of adverse maternal and perinatal outcomes. 
 
To minimise the risk of higher order multiple pregnancy, careful monitoring of ovarian response is 
recommended. In patients undergoing ART procedures the risk of multiple pregnancy is related 
mainly to the number of embryos replaced, their quality and the patient age. 
 
Pregnancy loss 
 
The incidence of pregnancy loss by miscarriage or abortion is higher in patients undergoing 
stimulation of follicular growth for ovulation induction or ART than following natural conception. 
 



5 

Ectopic pregnancy 
 
Women with a history of tubal disease are at increased risk for ectopic pregnancy, whether the 
pregnancy is obtained by spontaneous conception or with fertility treatments. The prevalence of 
ectopic pregnancy after ART in this population was reported to be higher than in the general 
population. 
 
Congenital malformations 
 
The prevalence 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. 
 
Thromboembolic events 
 
In women with recent 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. 
 
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. It is not yet 
established whether or not treatment with gonadotropins increases the risk of these tumours in infertile 
women. 
 
Interference with serum or urinary testing 
 
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. 
 
Sodium content 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. it is essentially 
“sodium-free”. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
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. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There is no indication for the use of Ovitrelle during pregnancy. Data on a limited number of exposed 
pregnancies indicate no increased risks of malformation or foeto/neonatal toxicity. No reproduction 
studies with choriogonadotropin alfa in animals were performed (see section 5.3). The potential risk 
for humans is unknown. 
 



6 

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 (see section 4.1). 
 
4.7 Effects on ability to drive and use machines 
 
Ovitrelle has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
In comparative trials with different doses of Ovitrelle, OHSS was found to be associated with Ovitrelle 
in a dose-related fashion. 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). 
 
List of adverse reactions 
 
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). 
 
Immune system disorders 
Very rare: Mild to severe hypersensitivity reactions including rash, anaphylactic reactions and 

shock 
 
Nervous system disorders 
Common: Headache 
 
Vascular disorders 
Very rare: Thromboembolism (both in association with and separate from OHSS) 
 
Gastrointestinal disorders 
Common: Abdominal pain, abdominal distension, nausea, vomiting 
Uncommon: Abdominal discomfort, diarrhoea 
 
Reproductive system and breast disorders 
Common: Mild or moderate OHSS 
Uncommon: Severe OHSS 
 
General disorders and administration site conditions 
Common: Injection site reactions. 
 
Reporting of suspected adverse reactions 
 
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. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


7 

4.9 Overdose 
 
The effects of an overdose of Ovitrelle are unknown. Nevertheless, there is a possibility that OHSS 
may result from an overdose of Ovitrelle (see section 4.4). 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Sex hormones and modulators of the genital system, gonadotropins, 
ATC code: G03GA08 
 
Mechanism of action 
 
Ovitrelle 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. 
 
Pharmacodynamic effects 
 
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. 
 
Ovitrelle is used to trigger final follicular maturation and early luteinisation after use of medicinal 
products for stimulation of follicular growth. 
 
Clinical efficacy and safety 
 
In comparative clinical trials, administration of a dose of 250 micrograms of Ovitrelle was as effective 
as 5,000 IU and 10,000 IU of urinary hCG in inducing final follicular maturation and early 
luteinisation in assisted reproductive technologies, and as effective as 5,000 IU of urinary hCG in 
ovulation induction. 
 
So far, there are no signs of antibody development in humans to Ovitrelle. Repeated exposure to 
Ovitrelle was investigated in male patients only. Clinical investigation in women for the indication of 
ART and anovulation was limited to one treatment cycle. 
 
5.2 Pharmacokinetic properties 
 
Following intravenous administration, choriogonadotropin alfa is distributed to the extracellular fluid 
space with a distribution half-life of around 4.5 hours. The steady-state 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 half-life of about 30 hours, and the absolute bioavailability is about 40%. 
 
A comparative study between the freeze-dried and the liquid formulation showed bioequivalence 
between the two formulations. 
 



8 

5.3 Preclinical safety data 
 
Nonclinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity and genotoxicity. Studies on carcinogenic potential were not 
performed. This is justified, given the proteinous nature of the active substance and the negative 
outcome of the genotoxicity testing. 
 
Studies on reproduction were not performed in animals. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Mannitol 
Methionine 
Poloxamer 188 
Phosphoric acid (for pH adjustment) 
Sodium hydroxide (for pH adjustment) 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
2 years. 
After opening, the medicinal product should be used immediately. However, the in-use stability has 
been demonstrated for 24 hours at + 2°C to 8°C. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C - 8°C). Store in the original package. Within its shelf-life, the solution may 
be stored at or below 25°C for up to 30 days without being refrigerated again during this period. It 
must be discarded if not used after these 30 days. 
 
6.5 Nature and contents of container 
 
0.5 mL of solution in a pre-filled syringe (type I glass) with a plunger stopper (halobutyl rubber) and 
plunger (plastic), and with a needle for injection (stainless) – pack of 1. 
 
6.6 Special precautions for disposal and other handling 
 
Only clear solution without particles should be used. 
For single use only. 
 
Self-administration of Ovitrelle should only be performed by patients who are adequately trained and 
have access to expert advice. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 



9 

7. MARKETING AUTHORISATION HOLDER 
 
Merck Europe B.V. 
Gustav Mahlerplein 102 
1082 MA Amsterdam 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/00/165/007 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 02 February 2001 
Date of latest renewal: 02 February 2006 
 
 
10 DATE OF REVISION OF THE TEXT 
 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 

http://www.ema.europa.eu/


10 

1. NAME OF THE MEDICINAL PRODUCT 
 
Ovitrelle 250 micrograms solution for injection in pre-filled pen 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each pre-filled pen contains 250 micrograms choriogonadotropin alfa* (equivalent to approximately 
6,500 IU). 
 
* recombinant human chorionic gonadotropin, r-hCG produced in Chinese hamster ovary (CHO) cells 
by recombinant DNA technology.  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection in pre-filled pen. 
 
Clear, colourless to slightly yellow solution.  
The pH of the solution is 7.0 ± 0.3, its osmolality 250-400 mOsm/kg. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Ovitrelle is indicated in the treatment of: 
 
• Adult women undergoing superovulation prior to assisted reproductive technologies (ART) such 

as in vitro fertilisation (IVF): Ovitrelle is administered to trigger final follicular maturation and 
luteinisation after stimulation of follicular growth, 

 
• Anovulatory or oligo-ovulatory adult women: Ovitrelle is administered to trigger ovulation and 

luteinisation in anovulatory or oligo-ovulatory women after stimulation of follicular growth. 
 
4.2 Posology and method of administration 
 
Treatment with Ovitrelle should be performed under the supervision of a physician experienced in the 
treatment of fertility problems. 
 
Posology 
 
The maximum dose is 250 micrograms. The following dose regimen should be used: 
 
• Women undergoing superovulation prior to assisted reproductive technologies (ART) such as 

in vitro fertilisation (IVF): 
 
One pre-filled pen 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. 

 



11 

• Anovulatory or oligo-ovulatory women: 
 
One pre-filled pen 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. 

 
Special populations 
 
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. Self-administration of Ovitrelle should only be performed by patients who are 
adequately trained and have access to expert advice. 
Ovitrelle is for single use only. 
 
For instructions on the administration with the pre-filled pen, see section 6.6 and the “Instructions for 
use” provided in the carton. 
 
4.3 Contraindications 
 
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 
• Tumours of the hypothalamus or pituitary gland 
• Ovarian enlargement or cyst unrelated to polycystic ovarian syndrome 
• Gynaecological haemorrhages of unknown aetiology 
• Ovarian, uterine or mammary carcinoma 
• Active thromboembolic disorders 
 
Ovitrelle must not be used in conditions when an effective response cannot be obtained, such as 
• primary ovarian failure 
• malformations of sexual organs incompatible with pregnancy 
• fibroid tumours of the uterus incompatible with pregnancy 
• postmenopausal women 
 
4.4 Special warnings and precautions for use 
 
Traceability 
 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
General precautions 
 
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. 
 



12 

Ovarian hyperstimulation syndrome (OHSS) 
 
A certain degree of ovarian enlargement is an expected effect of controlled ovarian stimulation. It is 
more commonly seen in women with polycystic ovarian syndrome and usually regresses without 
treatment. 
 
In distinction to uncomplicated ovarian enlargement, OHSS is a condition that can manifest itself with 
increasing degrees of severity. It comprises marked ovarian enlargement, high serum sex steroids, and 
an increase in vascular permeability which can result in an accumulation of fluid in the peritoneal, 
pleural and, rarely, in the pericardial cavities. 
 
Mild manifestations of OHSS may include abdominal pain, abdominal discomfort and distension, and 
enlarged ovaries. Moderate OHSS may additionally present with nausea, vomiting, ultrasound 
evidence of ascites and marked ovarian enlargement. 
 
Severe OHSS further includes symptoms such as severe ovarian enlargement, weight gain, dyspnoea 
or oliguria. Clinical evaluation may reveal signs such as hypovolaemia, haemoconcentration, 
electrolyte imbalances, ascites, pleural effusions, or acute pulmonary distress. Very rarely, severe 
OHSS may be complicated by ovarian torsion or thromboembolic events, such as pulmonary 
embolism, ischaemic stroke or myocardial infarction. 
 
Independent risk factors for developing OHSS include young age, lean body mass, polycystic ovarian 
syndrome, higher doses of exogenous gonadotropins, high absolute or rapidly rising serum estradiol 
levels and previous episodes of OHSS, large number of developing ovarian follicles and large number 
of oocytes retrieved in ART cycles. 
 
Adherence to recommended Ovitrelle dosage and regimen of administration can minimise the risk of 
ovarian hyperstimulation. Monitoring of stimulation cycles by ultrasound scans as well as estradiol 
measurements are recommended to early identify risk factors. 
 
There is evidence to suggest that hCG plays a key role in triggering OHSS and that the syndrome may 
be more severe and more protracted if pregnancy occurs. Therefore, if signs of ovarian 
hyperstimulation occur, it is recommended that hCG be withheld and the patient be advised to refrain 
from coitus or use barrier contraceptive methods for at least 4 days. 
 
As OHSS may progress rapidly (within 24 hours) or over several days to become a serious medical 
event, patients should be followed for at least two weeks after hCG administration. 
 
Mild or moderate OHSS usually resolves spontaneously. If severe OHSS occurs, it is recommended 
that gonadotropin treatment be stopped and that the patient be hospitalised and appropriate therapy be 
started. 
 
Multiple pregnancy 
 
In patients undergoing induction of ovulation, the incidence of multiple pregnancy and births is 
increased compared with natural conception. The majority of multiple conceptions are twins. Multiple 
pregnancies, especially high order, carry an increased risk of adverse maternal and perinatal outcomes. 
 
To minimise the risk of higher order multiple pregnancy, careful monitoring of ovarian response is 
recommended. In patients undergoing ART procedures the risk of multiple pregnancy is related 
mainly to the number of embryos replaced, their quality and the patient age. 
 
Pregnancy loss 
 
The incidence of pregnancy loss by miscarriage or abortion is higher in patients undergoing 
stimulation of follicular growth for ovulation induction or ART than following natural conception. 
 



13 

Ectopic pregnancy 
 
Women with a history of tubal disease are at increased risk for ectopic pregnancy, whether the 
pregnancy is obtained by spontaneous conception or with fertility treatments. The prevalence of 
ectopic pregnancy after ART in this population was reported to be higher than in the general 
population. 
 
Congenital malformations 
 
The prevalence 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. 
 
Thromboembolic events 
 
In women with recent 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. 
 
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. It is not yet 
established whether or not treatment with gonadotropins increases the risk of these tumours in infertile 
women. 
 
Interference with serum or urinary testing 
 
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. 
 
Sodium content 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. it is essentially 
“sodium-free”. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
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. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There is no indication for the use of Ovitrelle during pregnancy. Data on a limited number of exposed 
pregnancies indicate no increased risks of malformation or foeto/neonatal toxicity. No reproduction 
studies with choriogonadotropin alfa in animals were performed (see section 5.3). The potential risk 
for humans is unknown. 
 



14 

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 (see section 4.1). 
 
4.7 Effects on ability to drive and use machines 
 
Ovitrelle has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
In comparative trials with different doses of Ovitrelle, OHSS was found to be associated with Ovitrelle 
in a dose-related fashion. 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). 
 
List of adverse reactions 
 
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). 
 
Immune system disorders 
Very rare: Mild to severe hypersensitivity reactions including rash, anaphylactic reactions and 

shock 
 
Nervous system disorders 
Common: Headache 
 
Vascular disorders 
Very rare: Thromboembolism (both in association with and separate from OHSS) 
 
Gastrointestinal disorders 
Common: Abdominal pain, abdominal distension, nausea, vomiting 
Uncommon: Abdominal discomfort, diarrhoea 
 
Reproductive system and breast disorders 
Common: Mild or moderate OHSS 
Uncommon: Severe OHSS 
 
General disorders and administration site conditions 
Common: Injection site reactions. 
 
Reporting of suspected adverse reactions 
 
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. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


15 

4.9 Overdose 
 
The effects of an overdose of Ovitrelle are unknown. Nevertheless, there is a possibility that OHSS 
may result from an overdose of Ovitrelle (see section 4.4). 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Sex hormones and modulators of the genital system, gonadotropins, 
ATC code: G03GA08 
 
Mechanism of action 
 
Ovitrelle 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. 
 
Pharmacodynamic effects 
 
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. 
 
Ovitrelle is used to trigger final follicular maturation and early luteinisation after use of medicinal 
products for stimulation of follicular growth. 
 
Clinical efficacy and safety 
 
In comparative clinical trials, administration of a dose of 250 micrograms of Ovitrelle was as effective 
as 5,000 IU and 10,000 IU of urinary hCG in inducing final follicular maturation and early 
luteinisation in assisted reproductive technologies, and as effective as 5,000 IU of urinary hCG in 
ovulation induction. 
 
So far, there are no signs of antibody development in humans to Ovitrelle. Repeated exposure to 
Ovitrelle was investigated in male patients only. Clinical investigation in women for the indication of 
ART and anovulation was limited to one treatment cycle. 
 
5.2 Pharmacokinetic properties 
 
Following intravenous administration, choriogonadotropin alfa is distributed to the extracellular fluid 
space with a distribution half-life of around 4.5 hours. The steady-state 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 half-life of about 30 hours, and the absolute bioavailability is about 40%. 
 
A comparative study between the freeze-dried and the liquid formulation showed bioequivalence 
between the two formulations. 
 



16 

5.3 Preclinical safety data 
 
Nonclinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity and genotoxicity. Studies on carcinogenic potential were not 
performed. This is justified, given the proteinous nature of the active substance and the negative 
outcome of the genotoxicity testing. 
 
Studies on reproduction were not performed in animals. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Mannitol 
Methionine 
Disodium phosphate dihydrate 
Sodium dihydrogen phosphate monohydrate 
Poloxamer 188 
Phosphoric acid (for pH adjustment) 
Sodium hydroxide (for pH adjustment) 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
2 years. 
After opening, the medicinal product should be used immediately.  
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C - 8°C). Do not freeze. 
 
6.5 Nature and contents of container 
 
3 mL cartridge (type I glass, with a bromobutyl rubber plunger stopper and an aluminium crimp cap 
with bromobutyl rubber) preassembled in a pre-filled pen. Each pre-filled pen contains 0.5 mL of 
solution for injection. 
Pack of 1 pre-filled pen and 1 injection needle. 
 
6.6 Special precautions for disposal and other handling 
 
See the “Instructions for use” provided in the carton. 
 
Only clear solution without particles should be used. Use each needle and pen only once. 
 
Self-administration of Ovitrelle should only be performed by patients who are adequately trained and 
have access to expert advice. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 



17 

7. MARKETING AUTHORISATION HOLDER 
 
Merck Europe B.V. 
Gustav Mahlerplein 102 
1082 MA Amsterdam 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/00/165/008 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 02 February 2001 
Date of latest renewal: 02 February 2006 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
  

http://www.ema.europa.eu/


18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE 

AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE  
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND 
USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE 

AND EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 



19 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer of the biological active substance 
 
Merck Serono S.A. 
Zone Industrielle de l’Ouriettaz 
1170 Aubonne 
Switzerland 
 
Name and address of the manufacturer responsible for batch release 
 
Merck Serono S.p.A. 
Via delle Magnolie 15 
70026 Modugno (Bari) 
Italy 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of 
Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 
and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk management plan (RMP) 
 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 
activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 
marketing authorisation and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
  



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



22 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
BOX OF 1 PRE-FILLED SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ovitrelle 250 micrograms/0.5 mL solution for injection in pre-filled syringe 
choriogonadotropin alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled syringe contains 250 micrograms (6,500 IU) choriogonadotropin alfa. 
 
 
3. LIST OF EXCIPIENTS 
 
Mannitol, methionine, poloxamer 188, phosphoric acid (for pH adjustment), sodium hydroxide (for pH 
adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
1 pre-filled syringe with 0.5 mL solution for injection 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For single use only. 
Read the package leaflet before use. 
Subcutaneous use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Store in the original package. May be stored at or below +25°C for up to 
30 days without being refrigerated again during this period and must be discarded if not used during 
these 30 days. 
 
 



23 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Merck Europe B.V. 
Gustav Mahlerplein 102 
1082 MA Amsterdam 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/00/165/007 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
ovitrelle 250/0.5 ml 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



24 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED SYRINGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Ovitrelle 250 micrograms/0.5 mL solution for injection 
choriogonadotropin alfa 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Batch 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
250 micrograms/0.5 mL 
 
 
6. OTHER 
 



25 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
BOX OF 1 PRE-FILLED PEN 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ovitrelle 250 micrograms solution for injection in pre-filled pen 
choriogonadotropin alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled pen contains 250 micrograms (approximately 6,500 IU) choriogonadotropin alfa. 
 
 
3. LIST OF EXCIPIENTS 
 
Mannitol, methionine, disodium phosphate dihydrate, sodium dihydrogen phosphate monohydrate, 
poloxamer 188, phosphoric acid (for pH adjustment), sodium hydroxide (for pH adjustment), water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 pre-filled pen of 0.5 mL solution 
1 injection needle 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For single use only. 
Read the package leaflet before use. 
Subcutaneous use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze. 
 



26 

 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Merck Europe B.V. 
Gustav Mahlerplein 102 
1082 MA Amsterdam 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/00/165/008 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
ovitrelle 250 pen 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 
  



27 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED PEN LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Ovitrelle 250 micrograms solution for injection 
choriogonadotropin alfa 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Batch 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
250 micrograms/0.5 mL 
 
 
6. OTHER 
 
  



28 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



29 

Package leaflet: Information for the user 
 

Ovitrelle 250 micrograms/0.5 mL solution for injection in pre-filled syringe 
choriogonadotropin alfa 

 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Ovitrelle is and what it is used for 
2. What do you need to know before you use Ovitrelle 
3. How to use Ovitrelle 
4. Possible side effects 
5. How to store Ovitrelle 
6. Contents of the pack and other information 
 
 
1. What Ovitrelle is and what it is used for  
 
What Ovitrelle is 
 
Ovitrelle contains a medicine called ‘choriogonadotropin alfa’, made in a laboratory by a special 
recombinant DNA technique. Choriogonadotropin alfa is similar to a hormone found naturally in your 
body called ‘chorionic gonadotropin’, which is involved in reproduction and fertility. 
 
What Ovitrelle is used for 
 
Ovitrelle is used together with other medicines: 
• To help develop and ripen several follicles (each containing an egg) in women undergoing 

assisted reproductive technologies (procedure that may help you to become pregnant) such as 
‘in vitro fertilisation’. Other medicines will be given first to bring about the growth of several 
follicles. 

• To help release an egg from the ovary (ovulation induction) in women who cannot produce eggs 
(‘anovulation’), or women who produce too few eggs (‘oligo-ovulation’). Other medicines will 
be given first to develop and ripen the follicles. 

 
 
2. What do you need to know before you use Ovitrelle 
 
Do not use Ovitrelle 
 
• if you are allergic to choriogonadotropin alfa or any of the other ingredients of this medicine 

(listed in section 6). 
• if you have a tumour in your hypothalamus or pituitary gland (both are parts of the brain). 
• if you have large ovaries or sacs of fluid within the ovaries (ovarian cysts) of unknown origin. 
• if you have unexplained vaginal bleeding. 
• if you have cancer of your ovaries, womb or breast. 
• if you have severe inflammation of your veins or blood clotting in your veins (active 

thromboembolic disorders). 



30 

• if you have any condition that usually makes a normal pregnancy impossible, such as 
menopause or early menopause (ovarian failure), or malformations of sexual organs. 

 
Do not use Ovitrelle if any of the above applies to you. If you are not sure, talk to your doctor before 
using this medicine. 
 
Warnings and precautions 
 
Before the treatment is started, your and your partner's fertility should be evaluated by a doctor 
experienced in the treatment of fertility problems. 
 
Ovarian hyperstimulation syndrome (OHSS) 
 
This medicine may increase your risk of developing OHSS. This is when your follicles develop too 
much and become large cysts. 
 
If you get lower abdominal pain, gain any weight rapidly, feel sick or are vomiting, or have difficulty 
in breathing, do not give yourself the Ovitrelle injection and talk to your doctor straight away (see 
section 4). If you are developing OHSS, you may be told not to have sex or to use a barrier 
contraceptive method for at least four days. 
 
The risk of OHSS is reduced if the usual dose of Ovitrelle is used, and if you are monitored closely 
throughout your treatment cycle (e.g. blood tests for estradiol levels and ultrasound). 
 
Multiple pregnancy and/or birth defects 
 
When using Ovitrelle, you have a higher risk of being pregnant with more than one child at the same 
time (‘multiple pregnancy’, usually twins) than if you conceived naturally. Multiple pregnancy may 
lead to medical complications for you and your babies. When undergoing assisted reproductive 
technologies, the risk of having a multiple pregnancy is related to your age, the quality and the number 
of fertilised eggs or embryos placed inside you. Multiple pregnancies and specific characteristics of 
couples with fertility problems (e.g. age) may also be associated with an increased chance of birth 
defects. 
 
The risk of multiple pregnancy is reduced if you are monitored closely throughout your treatment 
cycle (e.g. blood tests for estradiol levels and ultrasound). 
 
Ectopic pregnancy 
 
Pregnancy outside of the womb (an ectopic pregnancy) may occur in women with damaged fallopian 
tubes (the tubes which carry the egg from the ovary to the womb). Therefore, your doctor should 
perform an early ultrasound examination to rule out the possibility of pregnancy outside the womb. 
 
Miscarriage 
 
When undergoing assisted reproductive technologies or stimulation of your ovaries to produce eggs, 
you are more likely to have a miscarriage than the average woman. 
 
Blood clotting problems (thromboembolic events) 
 
Talk to your doctor before using Ovitrelle if you or a member of your family have ever had blood clots 
in the leg or in the lung, or a heart attack or stroke. You may be at a higher risk of serious blood clots 
or existing clots might become worse with Ovitrelle treatment. 
 



31 

Tumours of sexual organs 
 
There have been reports of tumours in the ovaries and other sex organs, both benign and malignant, in 
women who have undergone multiple regimens for infertility treatment. 
 
Pregnancy tests 
 
If you do a pregnancy test with serum or urine after use of Ovitrelle, and up to ten days later, it may 
happen that you get a false positive test result. If you are not sure, talk to your doctor. 
 
Children and adolescents 
 
Ovitrelle is not for use in children and adolescents. 
 
Other medicines and Ovitrelle 
 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
 
Pregnancy and breast-feeding 
 
Do not use Ovitrelle if you are pregnant or breast-feeding. 
If you are pregnant or breast-feeding, ask your doctor for advice before taking this medicine. 
 
Driving and using machines 
 
It is not expected that Ovitrelle will affect your ability to drive and use machines. 
 
Ovitrelle contains sodium 
 
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium-
free”. 
 
 
3. How to use Ovitrelle  
 
Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if 
you are not sure. 
 
How much to use 
 
• The recommended dose is 1 pre-filled syringe (250 micrograms/0.5 mL) given as a single 

injection. 
• Your doctor will have explained exactly when to give the injection. 
 
Using this medicine 
 
• Ovitrelle is intended for subcutaneous use that means given by injection under the skin. 
• Each pre-filled syringe is for single use only. Only clear solution without particles should be 

used. 
• Your doctor or nurse will show you how to use the Ovitrelle pre-filled syringe to inject the 

medicine.  
• Inject Ovitrelle as your doctor or nurse taught you. 
• After the injection, dispose of the used syringe safely. 
 
If you administer Ovitrelle to yourself, please carefully read the following instructions: 
 
1. Wash your hands. It is important that your hands and the items you use are as clean as possible. 



32 

 
2. Assemble everything you need. Please note that alcohol swabs are not contained in the package. 

Find a clean area and lay out everything: 
- two alcohol swabs, 
- one pre-filled syringe containing the medicinal product. 

 
3. Injection: 

 

Immediately inject the solution: Your doctor or nurse will have 
already advised you where to inject (e.g. tummy, front of thigh). 
Wipe the chosen area with an alcohol swab. Firmly pinch the skin 
together and insert the needle for injection at a 45° to 90° angle using 
a dart-like motion. Inject under the skin, as you were taught. Do not 
inject directly into a vein. Inject the solution by pushing gently on 
the plunger. Take as much time as you need to inject all the solution. 
Immediately withdraw the needle and clean the skin with an alcohol 
swab using a circular motion. 

 
4. Dispose of all used items: 

Once you have finished your injection, immediately discard the empty syringe in a sharps 
container. Any unused solution must be discarded. 

 
If you use more Ovitrelle than you should 
 
The effects of an overdose of Ovitrelle are unknown, nevertheless there is a possibility that ovarian 
hyperstimulation syndrome (OHSS) may occur, which is further described in section 4. 
 
If you forget to use Ovitrelle 
 
If you forget to use Ovitrelle, please talk to your doctor as soon as you notice. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Stop using Ovitrelle and see a doctor straight away if you notice any of the following serious side 
effects – you may need urgent medical treatment: 
• Allergic reactions such as rash, fast or uneven pulse, swelling of your tongue and throat, 

sneezing, wheezing, or serious breathing difficulty are very rare (may affect up to 1 in 
10,000 people). 

• Lower abdominal pain, abdominal distension or abdominal discomfort together with nausea 
(feeling sick) or vomiting may be the symptoms of ovarian hyperstimulation syndrome (OHSS). 
This may indicate that the ovaries over-reacted to the treatment and that large ovarian cysts 
developed (see also in section 2. under “Ovarian hyperstimulation syndrome”). This event is 
common (may affect up to 1 in 10 people). 

• The OHSS may become severe with clearly enlarged ovaries, decreased urine production, 
weight gain, difficulty in breathing and possible fluid accumulation in your stomach or chest. 
This event is uncommon (may affect up to 1 in 100 people). 

• Serious blood clotting complications (thromboembolic events) sometimes independent of OHSS 
may be found very rarely. This could cause chest pain, breathlessness, stroke or heart attack (see 
also in section 2. under “Blood clotting problems”). 

 



33 

Other side effects 
 
Common (may affect up to 1 in 10 people) 
• Headache. 
• Local reactions at the injection site, such as pain, redness or swelling. 
 
Uncommon (may affect up to 1 in 100 people) 
• Diarrhoea. 
 
Reporting of side effects 
 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Ovitrelle  
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The 
expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C - 8°C). Store in the original package. Ovitrelle 250 micrograms solution 
for injection may be stored at room temperature (at or below +25°C) for up to 30 days without being 
refrigerated again during this period, and must be discarded if not used during these 30 days. 
 
Do not throw away any medicine via wastewater or household waste. Ask your pharmacist how to 
throw away medicines no longer used. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Ovitrelle contains 
 
• The active substance is choriogonadotropin alfa, produced by recombinant DNA technology. 
• Each pre-filled syringe contains 250 micrograms / 0.5 mL (equivalent to 6500 IU). 
• The other ingredients are mannitol, methionine, poloxamer 188, phosphoric acid, sodium 

hydroxide, water for injections. 
 
What Ovitrelle looks like and contents of the pack 
 
Ovitrelle is provided as solution for injection. It is available as a single pre-filled syringe (pack of 1). 
 
Marketing Authorisation Holder 
 
Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, The Netherlands 
 
Manufacturer 
 
Merck Serono S.p.A., Via delle Magnolie 15, 70026 Modugno (Bari), Italy 
 
 
This leaflet was last revised in 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


34 

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 



35 

Package leaflet: Information for the user 
 

Ovitrelle 250 micrograms solution for injection in pre-filled pen 
choriogonadotropin alfa 

 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
-  If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Ovitrelle is and what it is used for 
2. What do you need to know before you use Ovitrelle 
3. How to use Ovitrelle 
4. Possible side effects 
5. How to store Ovitrelle 
6. Contents of the pack and other information 
 
 
1. What Ovitrelle is and what it is used for 
 
What Ovitrelle is 
 
Ovitrelle contains a medicine called ‘choriogonadotropin alfa’, made in a laboratory by a special 
recombinant DNA technique. Choriogonadotropin alfa is similar to a hormone found naturally in your 
body called ‘chorionic gonadotropin’, which is involved in reproduction and fertility. 
 
What Ovitrelle is used for 
 
Ovitrelle is used together with other medicines: 
• To help develop and ripen several follicles (each containing an egg) in women undergoing 

assisted reproductive technologies (procedure that may help you to become pregnant) such as 
‘in vitro fertilisation’. Other medicines will be given first to bring about the growth of several 
follicles. 

• To help release an egg from the ovary (ovulation induction) in women who cannot produce eggs 
(‘anovulation’), or women who produce too few eggs (‘oligo-ovulation’). Other medicines will 
be given first to develop and ripen the follicles. 

 
 
2. What do you need to know before you use Ovitrelle 
 
Do not use Ovitrelle 
 
• if you are allergic to choriogonadotropin alfa or any of the other ingredients of this medicine 

(listed in section 6). 
• if you have a tumour in your hypothalamus or pituitary gland (both are parts of the brain). 
• if you have large ovaries or sacs of fluid within the ovaries (ovarian cysts) of unknown origin. 
• if you have unexplained vaginal bleeding. 
• if you have cancer of your ovaries, womb or breast. 
• if you have severe inflammation of your veins or blood clotting in your veins (active 

thromboembolic disorders). 



36 

• if you have any condition that usually makes a normal pregnancy impossible, such as 
menopause or early menopause (ovarian failure), or malformations of sexual organs. 

 
Do not use Ovitrelle if any of the above applies to you. If you are not sure, talk to your doctor before 
using this medicine. 
 
Warnings and precautions 
 
Before the treatment is started, your and your partner's fertility should be evaluated by a doctor 
experienced in the treatment of fertility problems. 
 
Ovarian hyperstimulation syndrome (OHSS) 
 
This medicine may increase your risk of developing OHSS. This is when your follicles develop too 
much and become large cysts.  
 
If you get lower abdominal pain, gain any weight rapidly, feel sick or are vomiting, or have difficulty 
in breathing, do not give yourself the Ovitrelle injection and talk to your doctor straight away (see 
section 4). If you are developing OHSS, you may be told not to have sex or to use a barrier 
contraceptive method for at least four days. 
 
The risk of OHSS is reduced if the usual dose of Ovitrelle is used, and if you are monitored closely 
throughout your treatment cycle (e.g. blood tests for estradiol levels and ultrasound). 
 
Multiple pregnancy and/or birth defects 
 
When using Ovitrelle, you have a higher risk of being pregnant with more than one child at the same 
time (‘multiple pregnancy’, usually twins) than if you conceived naturally. Multiple pregnancy may 
lead to medical complications for you and your babies. When undergoing assisted reproductive 
technologies, the risk of having a multiple pregnancy is related to your age, the quality and the number 
of fertilised eggs or embryos placed inside you. Multiple pregnancies and specific characteristics of 
couples with fertility problems (e.g. age) may also be associated with an increased chance of birth 
defects. 
 
The risk of multiple pregnancy is reduced if you are monitored closely throughout your treatment 
cycle (e.g. blood tests for estradiol levels and ultrasound). 
 
Ectopic pregnancy 
 
Pregnancy outside of the womb (an ectopic pregnancy) may occur in women with damaged fallopian 
tubes (the tubes which carry the egg from the ovary to the womb). Therefore, your doctor should 
perform an early ultrasound examination to rule out the possibility of pregnancy outside the womb. 
 
Miscarriage 
 
When undergoing assisted reproductive technologies or stimulation of your ovaries to produce eggs, 
you are more likely to have a miscarriage than the average woman. 
 
Blood clotting problems (thromboembolic events) 
 
Talk to your doctor before using Ovitrelle if you or a member of your family have ever had blood clots 
in the leg or in the lung, or a heart attack or stroke. You may be at a higher risk of serious blood clots 
or existing clots might become worse with Ovitrelle treatment. 
 



37 

Tumours of sexual organs 
 
There have been reports of tumours in the ovaries and other sex organs, both benign and malignant, in 
women who have undergone multiple regimens for infertility treatment. 
 
Pregnancy tests 
 
If you do a pregnancy test with serum or urine after use of Ovitrelle, and up to ten days later, it may 
happen that you get a false positive test result. If you are not sure, talk to your doctor. 
 
Children and adolescents 
 
Ovitrelle is not for use in children and adolescents. 
 
Other medicines and Ovitrelle 
 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
 
Pregnancy and breast-feeding 
 
Do not use Ovitrelle if you are pregnant or breast-feeding.  
If you are pregnant or breast-feeding, ask your doctor for advice before taking this medicine. 
 
Driving and using machines 
 
It is not expected that Ovitrelle will affect your ability to drive and use machines. 
 
Ovitrelle contains sodium 
 
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium-
free”. 
 
 
3. How to use Ovitrelle  
 
Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if 
you are not sure.  
 
How much to use 
 
• The recommended dose is 1 pre-filled pen (250 micrograms/0.5 mL) given as a single injection. 
• Your doctor will explain to you exactly when to give the injection. 
 
Using this medicine 
 
• If you administer Ovitrelle to yourself, please carefully read and follow the separate 

“Instructions for use” provided in the carton. 
• Ovitrelle is intended to be given by injection under the skin (subcutaneously). 
• Each pre-filled pen is for single use only. 
• Your doctor or nurse will show you how to use the Ovitrelle pre-filled pen to inject the 

medicine. 
• Inject Ovitrelle as your doctor or nurse taught you. 
• After the injection, dispose of the used needle safely, and discard the pen. 
 



38 

If you use more Ovitrelle than you should 
 
The effects of an overdose of Ovitrelle are unknown, nevertheless there is a possibility that ovarian 
hyperstimulation syndrome (OHSS) may occur, which is further described in section 4. 
 
If you forget to use Ovitrelle 
 
If you forget to use Ovitrelle, please talk to your doctor as soon as you notice. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Stop using Ovitrelle and see a doctor straight away if you notice any of the following serious side 
effects – you may need urgent medical treatment: 
• Allergic reactions such as rash, fast or uneven pulse, swelling of your tongue and throat, 

sneezing, wheezing, or serious breathing difficulty are very rare (may affect up to 1 in 
10,000 people). 

• Lower abdominal pain, abdominal distension or abdominal discomfort together with nausea 
(feeling sick) or vomiting may be the symptoms of ovarian hyperstimulation syndrome (OHSS). 
This may indicate that the ovaries over-reacted to the treatment and that large ovarian cysts 
developed (see also in section 2. under “Ovarian hyperstimulation syndrome”). This event is 
common (may affect up to 1 in 10 people). 

• The OHSS may become severe with clearly enlarged ovaries, decreased urine production, 
weight gain, difficulty in breathing and possible fluid accumulation in your stomach or chest. 
This event is uncommon (may affect up to 1 in 100 people). 

• Serious blood clotting complications (thromboembolic events) sometimes independent of OHSS 
may be found very rarely. This could cause chest pain, breathlessness, stroke or heart attack (see 
also in section 2. under “Blood clotting problems”). 

 
Other side effects 
 
Common (may affect up to 1 in 10 people) 
• Headache. 
• Local reactions at the injection site, such as pain, redness or swelling. 
 
Uncommon (may affect up to 1 in 100 people) 
• Diarrhoea. 
 
Reporting of side effects 
 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Ovitrelle  
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The 
expiry date refers to the last day of that month. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


39 

Store in a refrigerator (2°C-8°C). Do not freeze. 
 
Do not use Ovitrelle if you notice any signs of deterioration, if the liquid contains particles or is not 
clear. 
 
Do not throw away any medicine via wastewater or household waste. Ask your pharmacist how to 
throw away medicines no longer used. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Ovitrelle contains 
 
• The active substance is choriogonadotropin alfa, produced by recombinant DNA technology. 
• Each pre-filled pen contains 250 micrograms choriogonadotropin alfa in 0.5 mL (equivalent to 

approximately 6,500 International Units, IU). 
• The other ingredients are mannitol, methionine disodium phosphate dihydrate, sodium 

dihydrogen phosphate monohydrate, poloxamer 188, phosphoric acid (for pH adjustment), 
sodium hydroxide (for pH adjustment) and water for injections.  

 
What Ovitrelle looks like and contents of the pack 
 
• Ovitrelle comes as a clear, colourless to slightly yellow liquid for injection in a pre-filled pen. 
• Each pen contains 0.5 mL of solution. 
• It is supplied in packs of 1 pre-filled pen and 1 injection needle. 
 
Marketing Authorisation Holder 
 
Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, The Netherlands 
 
Manufacturer 
 
Merck Serono S.p.A., Via delle Magnolie 15, 70026 Modugno (Bari), Italy 
 
 
This leaflet was last revised in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 



40 

Instructions For Use 
OVITRELLE 250 micrograms solution for injection in pre-filled pen 

Choriogonadotropin alfa 
 
CONTENTS 
1. How to use your Ovitrelle pre-filled pen 
2. Before you start using your Ovitrelle pre-filled pen 
3. Getting your Ovitrelle pre-filled pen ready for injection 
4. Setting the dose – “How to set the dose to 250” 
5. Injecting the dose 
6. After the injection 
 
Warning: Please read these instructions for use before using your Ovitrelle pre-filled pen. Follow the 

procedure exactly, as it may differ from your past experience. 
 
 
1. How to use your Ovitrelle pre-filled pen 
 
• The pen is for subcutaneous injection only. 
• Inject Ovitrelle as your doctor or nurse taught you. 
• This pen is for single use only. Do not share the pen. 
 
 
2. Before you start using your Ovitrelle pre-filled pen 
 
• Wash your hands with soap and water. 
 
• Find a clean area and a flat surface. 
 
• Verify the expiration date on the pen label. 
 
• Gather everything you need and lay it out: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1. dose setting knob 
2. dose display 
3. plunger piston 
4. reservoir holder 
5. threaded needle connector 
6. pen cap 

7. peel-off seal tab 
8. removable needle  
9. inner needle shield 
10. outer needle cap  
11. alcohol swabs 
12. sharps disposal container 

 
Please note: alcohol swabs and sharps disposal container are not provided in the pack. 



41 

 
 
3. Getting your Ovitrelle pre-filled pen ready for injection 
 
3.1 Take off the pen cap 
 

 
 
3.2 Prepare your needle for injection 
• Get a new needle - only use the ‘single use’ needle supplied. 
• Hold the outer needle cap firmly. 
 
• Check that the peel-off seal on the outer needle cap is not 

damaged or loose. 

 
 

• Remove the peel-off seal. 

 
 

 
CAUTION: 
If the peel-off seal is damaged or loose, do not use the needle. Throw it away in a sharps disposal 
container. Ask your doctor or pharmacist how to get a new needle. 
 



42 

3.3. Attach the needle 
 
• Screw the threaded tip of the Ovitrelle pre-filled pen into the 

outer needle cap until you feel a light resistance. 
Warning: Do not attach the needle too tightly; the needle could 

be difficult to remove after the injection. 

 
 

 
• Remove the outer needle cap by pulling it gently.  

 
 
 
 
 
Put it aside for later use. 

 

 
 

• Hold the Ovitrelle pre-filled pen with the needle pointing 
upward. 
 

• Carefully remove and discard the green inner shield. 
 

 
 
 
3.4. Look closely at the tip of the needle for tiny drop(s) of fluid 
 
• If you see a tiny drop(s) of fluid proceed to Section 4: 

Setting the dose to 250. 

 
 
CAUTION: 
If you do not see a tiny drop(s) at or near the needle tip, you must perform the steps on the next page.  
 



43 

If you do not see a tiny drop(s) of fluid at or near the tip: 

 
1. Gently turn the dose setting knob clockwise until you see a dot (●) in the dose display. If you 

pass this position, simply turn the dose setting knob back to the dot (●). 
2. Hold the pen with the needle pointing upward. 
3. Tap the reservoir holder gently. 
4. Press the dose setting knob as far as it will go. A tiny drop of liquid will appear at the top of the 

needle; this shows that your pre-filled pen is ready for injection. 
 

  
5. If you do not see any liquid, you may try a second time (you may do this a maximum of two 

times) starting from step 1 of section “If you do not see a tiny drop(s) of fluid at or near the tip” 
above. 

 
4. Setting the dose to 250 
• Gently turn the dose setting knob clockwise. The dose display will show a straight line and you 

have to keep turning until you can read the number ‘250’. 
• Do not push or pull the dose setting button while you turn it. 

 



44 

 
 
• The dose display should show ‘250’, shown in the figure below. 
 

 
 
5. Injecting the dose 
 
5.1 Choose the injection site in the area your doctor or nurse has told you to give the injection. 
 
5.2 Clean the skin at the injection site by wiping with an alcohol swab. 
 
5.3 Verify once more that the number in the dose display reads ‘250’. If it is not, you must adjust it 

(see step “4. Setting the dose to 250”). 
 



45 

5.4 Inject the dose as you were trained to do by your doctor or nurse 
 
• Slowly push the needle into the skin entirely (1). 
 
• Press the dose knob down as far as it will go and hold it to 

complete the full injection. 

 
 

• Hold the dose knob down for a minimum of 5 seconds to ensure 
you inject the full dose (2). 

 
• The dose number shown in the dose display will turn back 

to ‘0’. This shows that the complete dose was delivered. 
 
 
 
 

 

• After a minimum of 5 seconds, pull the needle out of the skin 
while keeping the dose setting knob pressed down (3). 

 
• Release the dose setting knob. 

 
6. After the injection 
 
6.1 Check that the dose display shows ‘0’ 
• This confirms that the dose has been fully delivered. Do not attempt to inject a second time. 
• In case the dose display doesn’t show ‘0’, please contact your doctor or pharmacist. 
 

 
 

6.2 Removing the needle after injection 
• Hold the pre-filled pen firmly by the reservoir holder. 
• Carefully put the outer needle cap onto the needle. 
 



46 

  
 

• Then grip the outer needle cap and unscrew the needle. 
 

 
 

• Be careful not to prick yourself with the needle. 
• Now put the pen cap back onto the pen. 
 
6.3 Disposal 
• Use the needle and pen only once.  
 
• Once you have finished your injection, dispose of the used needle 

safely. 
 

• Discard the pen. It is best to put it back into its original package. 
 
• When the pen is empty, ask your pharmacist how to dispose of it. 
 
 
Warning:  Do not throw away any medicine via wastewater or household waste. 
 
 
These instructions for use were last revised in: 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET