Start with a daily dose of Puregon® on day 2 or 3 of the cycle
Start with daily administration of Orgalutran® 5–6 days after starting follicle stimulation with Puregon®
As soon as there is a dominant follicle of at least 18 mm and/or plasma estradiol Levels of 300–900 picograms/mL, follicle maturation should be initiated using human chorionic gonadotrophin (hCG)
GnRH antagonists/corifollitropin alfa protocol
Start with a single dose of Elonva® in the early follicular phase
Start with daily administration of Orgalutran® 5–6 days after starting follicle stimulation with Elonva®
Puregon® is given 8 days after stimulation
As soon as 3 follicles ≥ 17 mm are detected, the same day or the following day, follicle maturation should be initiated by a single dose of hCG
Utilize Puregon® for a tailored treatment approach across protocols, dosing, and responder types to help meet the individual needs of your patients.3,5
Recombinant FSH (rFSH) for daily administration with adjustable dosing in a precise drug delivery device3,4
Every patient journey is precious.
Give your patients the convenience of one, prefilled dose with proven efficacy to help meet their reproductive needs and start their families.1
SFS for single administration with the prefilled syringe at the start of the stimulation or the early follicular phase1
Choose what may be best for the needs of your patients.
Orgalutran® comes as a single, prefilled syringe used to help your patients move forward on their family journey.2
GnRH antagonist for daily administration with the single, prefilled syringe2
Contact your representative to learn more about partnering with Organon fertility.
References: 1. Elonva™ CCDS, Organon & Co., Inc., Feb 2019. 2. Orgalutran™ CCDS, Organon & Co., Inc.,
July 2020. 3. Puregon™ CCDS, Organon & Co., Inc., June 2019. 4. Puregon Pen™ CCDS, Organon & Co., Inc.,
April 2020. 5. Kettel LM, Scholl G, Bonaventura L, et al. Evaluation of a pen device for self-administration
of recombinant human FSH in clomiphene citrate-resistant anovulatory women undergoing ovulation
induction. Reprod Biomed Online. 2004;9(4):373–380.
Selected Safety Information about PUREGON®
Indications: PUREGON is indicated for the treatment of female infertility in the following clinical situations:
Anovulation (including polycystic ovarian syndrome, PCOS) in women who have been unresponsive to treatment with clomifene citrate.
Controlled ovarian hyperstimulation to induce the development of multiple follicles in medically assisted reproduction programs [eg. In vitro fertilization/embryo transfer (IVF/ET), gamete intra-fallopian transfer (GIFT) and intracytoplasmic sperm injection (ICSI)]. In the male
Deficient spermatogenesis due to hypogonadotrophic hypogonadism.
Dosage: In female: There are great inter- and intra-individual variations in the response of the ovaries to exogenous gonadotrophins. This makes it impossible to set a uniform dosage scheme. The dosage should, therefore, be adjusted individually depending on the ovarian response. This requires ultrasonography and monitoring of oestradiol levels. In comparative clinical studies with Puregon and urinary FSH it was shown that Puregon is more effective than urinary FSH in terms of a lower total dose and a shorter treatment period needed to achieve pre-ovulatory conditions. Therefore, it is considered appropriate to give a lower dosage of Puregon than generally used for urinary FSH, not only in order to optimise follicular development but also to minimise the risk of unwanted ovarian hyperstimulation. Clinical experience with Puregon is based on up to three treatment cycles in both indications. Overall experience with IVF indicates that in general the treatment success rate remains stable during the first four attempts and gradually declines thereafter.
For Anovulation, a sequential treatment scheme is recommended starting with daily administration of 50 IU Puregon. The starting dose is maintained for at least seven days. If there is no ovarian response, the daily dose is then gradually increased until follicle growth and/or plasma oestradiol levels indicate an adequate pharmacodynamic response. A daily increase of oestradiol levels of 40-100% is considered to be optimal. The daily dose is then maintained until preovulatory conditions are reached. Pre-ovulatory conditions are reached when there is ultrasonographic evidence of a dominant follicle of at least 18 mm in diameter and/or when plasma oestradiol levels of 300-900 picograms/mL (1000-3000 pmol/L) are attained. Usually, 7 to 14 days of treatment is sufficient to reach this state. The administration of Puregon is then discontinued and ovulation can be induced by administering human chorionic gonadotrophin (hCG). If the number of responding follicles is too high or oestradiol levels increase too rapidly, i.e. more than a daily doubling for oestradiol for two or three consecutive days, the daily dose should be decreased. Since follicles of over 14 mm may lead to pregnancies, multiple pre-ovulatory follicles exceeding 14 mm carry the risk of multiple gestations. In that case hCG should be withheld and pregnancy should be avoided in order to prevent multiple gestations.
For controlled ovarian hyperstimulation in medically assisted reproduction programs various stimulation protocols are applied. A starting dose of 100-225 IU is recommended for at least the first four days. Thereafter, the dose may be adjusted individually, based upon ovarian response. In clinical studies, it was shown that maintenance dosages ranging from 75-375 IU for six to twelve days are sufficient, although longer treatment may be necessary. Puregon can be given either alone, or, to prevent premature luteinisation, in combination with a GnRH agonist or antagonist. When using a GnRH agonist, a higher total treatment dose of Puregon may be required to achieve an adequate follicular response. Ovarian response is monitored by ultrasonography and measurement of plasma oestradiol levels. When ultrasonographic evaluation indicates the presence of at least three follicles of 16-20 mm, and there is evidence of a good oestradiol response (plasma levels of about 300-400 picogram/mL (1000-1300 pmol/L) for each follicle with a diameter greater than 18 mm), the final phase of maturation of the follicles is induced by administration of hCG. Oocyte retrieval is performed 34-35 hours later.
In male: Puregon should be given at a dosage of 450 IU/week, preferably divided in 3 dosages of 150 IU, concomitantly with hCG. The treatment should be continued for at least 3 to 4 months before any improvement in spermatogenesis can be expected. If a patient has not responded after this period, the combination therapy may be continued; current clinical experience indicates that treatment for up to 18 months or longer may be necessary to achieve spermatogenesis.
There is no relevant indication for use of Puregon in children.
Contraindications For males and females: Hypersensitivity to the active substance or any of the excipients. Tumours of the ovary, breast, uterus, testis, pituitary or hypothalamus. Primary gonadal failure. Additionally for females: Pregnancy or lactation. Undiagnosed vaginal bleeding. Ovarian cysts or enlarged ovaries, not related to polycystic ovarian syndrome (PCOS). Malformations of the reproductive organs incompatible with pregnancy. Fibroid tumours of the uterus incompatible with pregnancy.
Warnings and Precautions: Puregon may contain traces of streptomycin and/or neomycin. These antibiotics may cause hypersensitivity reactions in susceptible persons. Before starting treatment, the couple's infertility should be assessed as appropriate. Patients should be evaluated for hypothyroidism, adrenocortical insufficiency, hyperprolactinemia and pituitary or hypothalamic tumors, and appropriate specific treatment given. In females, Ovarian Hyperstimulation Syndrome (OHSS) may be caused by administration of hCG and by pregnancy (endogenous hCG). Women with known risk factors for a high ovarian response may be especially prone to the development of OHSS during or following treatment with Puregon. For women having their first cycle of ovarian stimulation, for whom risk factors are only partially known, close observation for early signs and symptoms of OHSS is recommended. To monitor the risk of OHSS, ultrasound assessments of follicular development should be performed prior to treatment and at regular intervals during treatment; the concurrent determination of serum estradiol levels may also be useful. Ovarian torsion has been reported after treatment with gonadotropins, including Puregon. Damage to the ovary due to reduced blood supply can be limited by early diagnosis and immediate detorsion. Women with risk factors for thromboembolic events, treatment with gonadotropins, including Puregon, may further increase this risk. In these women the benefits of gonadotropin administration, including Puregon, need to be weighed against the risks. For anovulatory women undergoing ovulation induction, monitoring follicular development with transvaginal ultrasonography and concurrent determination of serum estradiol levels is important for minimizing the risk of multi-fetal gestations. Patients should be advised of the potential risks of multiple births before starting treatment. In women undergoing ART procedures, when used for an ovulation induction cycle, appropriate FSH dose adjustment(s) should prevent multiple follicle development. Infertile women undergoing ART have an increased incidence of ectopic pregnancies. Early ultrasound confirmation that a pregnancy is intrauterine is therefore important. The incidence of congenital malformations after ART may be slightly higher than after spontaneous conceptions which is thought to be related to differences in parental characteristics and to the higher incidence of multiple gestations after ART. There have been reports of ovarian and other reproductive system neoplasms, both benign and malignant, in women who have undergone multiple treatment regimens for infertility treatment. It is not established whether or not treatment with gonadotropins increases the risk of these tumors in infertile women. Medical conditions that contraindicate pregnancy should be evaluated before starting treatment with Puregon. Rates of pregnancy loss in women undergoing assisted reproduction techniques are higher than in the normal population. In men with deficient spermatogenesis due to hypogonadotrophic hypogonadism, consider treatment with Puregon in combination with hCG only after treatment with hCG alone for at least 16 weeks has failed to restore spermatogenesis.
Undesirable effects Intramuscular or subcutaneous use may lead to mild and transient local reactions at the site of injection (3%). Generalised hypersensitivity reactions have been observed uncommonly (0.2%). Treatment of females: 4% in clinical trials reported signs and symptoms related to ovarian hyperstimulation syndrome (OHSS).
Undesirable effects related to this syndrome include pelvic pain and/or congestion, abdominal pain and/or distension, breast complaints and ovarian enlargement. Common side effects (≥ 1/100 to < 1/10) include headache, abdominal distension, abdominal pain, OHSS, pelvic pain, injection site reaction which include bruising, pain, redness, swelling and itching. Treatment of males: in a clinical trial in males (30 patients dosed), common side effects include headache, acne, rash, epididymal cyst, gynaecomastia, injection site induration.
Drug Interactions: Concomitant use of Puregon and clomifene citrate may enhance the follicular response. After pituitary desensitisation induced by a GnRH agonist, a higher dose of Puregon may be necessary to achieve an adequate follicular response.
Pregnancy and lactation: Use of Puregon during pregnancy and lactation is contra-indicated. In case of inadvertent exposure during pregnancy, clinical data is not sufficient to exclude a teratogenic effect of recombinant FSH. There is no information available from clinical or animal studies on the excretion of follitropin beta in milk. It is unlikely that follitropin beta is excreted in human milk due to its high molecular weight. If follitropin beta would be excreted in human milk, it would be degraded in the gastrointestinal tract of the child. Follitropin beta may affect milk production.
Before initiating therapy, please consult the full prescribing information. Full prescribing information is available upon request.
Selected Safety Information about ELONVA®
THERAPEUTIC INDICATIONS ELONVA is indicated for controlled ovarian stimulation (COS) in combination with a Gonadotropin Releasing Hormone (GnRH) antagonist for the development of multiple follicles in women participating in an Assisted Reproductive Technology (ART) program.
DOSAGE AND ADMINISTRATION Treatment with ELONVA should be initiated under the supervision of a physician experienced in the treatment of fertility problems.
On Stimulation Day 1, ELONVA should be administered as a single subcutaneous injection, preferably in the abdominal wall. The dose of ELONVA is based on weight and age in the treatment of women of reproductive age.
Subcutaneous injection of ELONVA may be carried out by the woman herself or her partner, provided the proper instructions are given by the physician. Self administration of ELONVA should only be performed by women who are well-motivated, adequately trained and with access to expert advice.
CONTRAINDICATIONS
ELONVA is contraindicated in patients with:
Hypersensitivity to the active substance or to any of the excipients.
Tumors of the ovary, breast, uterus, pituitary or hypothalamus.
Abnormal (not menstrual) vaginal bleeding without a known/diagnosed cause.
Primary ovarian failure.
Ovarian cysts or enlarged ovaries.
Fibroid tumors of the uterus incompatible with pregnancy.
Malformations of the reproductive organs incompatible with pregnancy.
Pregnancy.
Risk factors of OHSS
A history of Ovarian Hyperstimulation Syndrome (OHSS).
A previous COS cycle that resulted in more than 30 follicles ≥ 11 mm measured by ultrasound examination.
A basal antral follicle count > 20.
Polycystic ovarian syndrome (PCOS).
WARNINGS AND PRECAUTIONS
Prior to treatment, the couple’s infertility should be assessed as appropriate. In particular, the woman should be evaluated for hypothyroidism, adrenocortical insufficiency, hyperprolactinaemia and pituitary or hypothalamic tumors and appropriate specific treatment given. Medical conditions that contraindicate pregnancy should be evaluated before starting treatment with ELONVA.
ELONVA is intended for single subcutaneous injection only. Additional injections of ELONVA should not be given with the same treatment cycle.
After administration of ELONVA, no additional FSH-containing product should be administered prior to stimulation day 8.
The use of ELONVA in women with renal insufficiency is not recommended as excretion of corifollitropin alfa may be reduced.
There are limited data on the use of ELONVA in combination with a GnRH agonist. Therefore, the use of ELONVA is not recommended in combination with a GnRH agonist.
Women with known risk factors for a high ovarian response may be especially prone to the development of ovarian hyperstimulation syndrome (OHSS) during or following treatment with ELONVA. For women having their first cycle of ovarian stimulation, for whom risk factors are only partially known, close observation for early sign and symptoms of OHSS is recommended.
OHSS is a medical event distinct from uncomplicated ovarian enlargement. Severe OHSS may be life-threatening and in rare instances, venous or arterial thromboembolism may occur.
Signs and symptoms of OHSS may be caused by administration of human chorionic gonadotropin (hCG) and by pregnancy (endogenous hCG). Therefore, patients should be monitored for at least two weeks after hCG administration.
To minimize the risk of OHSS, ultrasonographic assessment of follicular development and/or determination of serum estradiol levels should be performed prior to treatment and at regular intervals during treatment.
Adherence to the recommended ELONVA dose and treatment regimens and careful monitoring of ovarian response is important to minimize the risk of OHSS.
Ovarian torsion has been reported after treatment with gonadotropin. This may be related to other conditions such as OHSS, pregnancy, previous abdominal surgery, past history of ovarian torsion and previous or current ovarian cysts. Damage to ovary can be limited by early diagnosis and immediate detorsion.
Multiple pregnancies and births have been reported for all gonadotropin treatments. The women and her partner should be advised of the potential risks for the mother (pregnancy and delivery complications) and the neonate (low birth weight) before starting treatment. In women undergoing ART procedures, the risk of multiple pregnancies is mainly related to the number of embryos transferred.
Infertile women undergoing ART, have an increased incidence of ectopic pregnancies. Thus, it is important to have an early ultrasound confirmation that a pregnancy is intrauterine, and to exclude the possibility of extrauterine pregnancy.
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 have been reports of ovarian and other reproductive system neoplasms, in women who have undergone multiple treatment regimens for infertility. It is not established whether or not treatment with gonadotropins increases the risk of these tumors in infertile women.
In women with generally recognized risk factors for thromboembolic events, such as a personal or family history, severe obesity or thrombophilia, treatment with gonadotropins may further increase this risk. In these women the benefits of gonadotropin administration need to be weighed against the risks. It should be noted that pregnancy itself also carries an increased risk of thrombosis.
ADVERSE EVENTS The most frequently reported adverse drug reactions during treatment with ELONVA in clinical trials are pelvic discomfort, OHSS, headache, pelvic pain, nausea, fatigue and breast tenderness. For additional adverse experience information, see the product circular.
DRUG INTERACTIONS No interaction studies with ELONVA and other medicines have been performed. Since corifollitropin alfa is not a substrate of cytochrome P450 enzymes, no metabolic interactions with other medicinal products is anticipated. ELONVA may cause a false positive hCG pregnancy test if the test is administered during the ovarian stimulation portion of the ART cycle. This may be due to cross-reactivity of some hCG pregnancy tests with the carboxy-terminal peptide of the beta subunit of ELONVA.
PREGNANCY AND LACTATION The use of ELONVA during pregnancy is contraindicated. In case of inadvertent exposure to ELONVA during pregnancy, clinical data are not sufficient to exclude an adverse outcome of pregnancy. Reproductive toxicity has been observed in animal studies.
The use of ELONVA during breast-feeding is not indicated.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES No studies on the ability to drive and use machines have been performed. ELONVA may cause dizziness. Women should be advised that if they feel dizzy, they should not drive or use machines.
Selected Safety Information about ORGALUTRAN®
THERAPEUTIC INDICATIONS The prevention of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation (COH) for assisted reproduction techniques (ART).
In clinical trials Orgalutran was used with recombinant follicle stimulating hormone (FSH).
DOSAGE AND ADMINISTRATION Orgalutran should only be prescribed by a specialist experienced in the treatment of infertility.
Orgalutran is used to prevent premature LH surges in patients undergoing COH. Controlled ovarian hyperstimulation with FSH may start at day 2 or 3 of menses. Orgalutran (0.25 mg) should be injected subcutaneously once daily, starting in general on day 6 of FSH administration. In high responders an early LH rise may be prevented by starting Orgalutran treatment on day 5. The start of Orgalutran may be delayed in absence of follicular growth.
Orgalutran and FSH should be administered approximately at the same time. However, the preparations should not be mixed and different injection sites are to be used.
FSH dose adjustments should be based on the number and size of growing follicles, rather than on the amount of circulating oestradiol. Daily treatment with Orgalutran should be continued up to the day that sufficient follicles of adequate size are present. Final maturation of follicles can be induced by administering human chorionic gonadotrophin (hCG). Because of the half-life of ganirelix, the time between two Orgalutran injections as well as the time between the last Orgalutran injection and the hCG injection should not exceed 30 hrs, as otherwise a premature LH surge may occur. Therefore, when injecting Orgalutran in the morning, treatment with Orgalutran should be continued throughout the gonadotrophin treatment period including the day of triggering ovulation. When injecting Orgalutran in the afternoon the last Orgalutran injection should be given in the afternoon prior to the day of triggering ovulation.
Orgalutran has shown to be safe and effective in patients undergoing multiple treatment cycles. Luteal phase support should be given according to the reproductive medical center's practice.
Method of administration: Orgalutran should be administered subcutaneously, preferably in the upper leg. The injection site should be varied to prevent lipoatrophy. The patient or her partner may perform the injections of Orgalutran themselves, provided that they are adequately instructed and have access to expert advice.
CONTRAINDICATIONS Hypersensitivity to the active substance, any of the excipients, gonadotropin-releasing hormone (GnRH) or any other GnRH analogue. Moderate or severe impairment of renal or hepatic function. Pregnancy or lactation.
WARNINGS AND PRECAUTIONS Special care should be taken in women with signs and symptoms of active allergic conditions. If a hypersensitivity reaction is suspected, Orgalutran should be discontinued and appropriate treatment administered. In the absence of clinical experience, Orgalutran treatment is not advised in women with severe allergic conditions.
Ovarian hyperstimulation syndrome (OHSS) may occur during or following ovarian stimulation. OHSS must be considered an intrinsic risk of gonadotrophin stimulation and should be treated symptomatically.
Since infertile women undergoing assisted reproduction, and particularly IVF, often have tubal abnormalities the incidence of ectopic pregnancies might be increased. Early ultrasound confirmation that a pregnancy is intrauterine is therefore important.
The incidence of congenital malformations after Assisted Reproductive Technologies (ART) may be slightly higher than after spontaneous conceptions. This slightly higher incidence is thought to be related to differences in parental characteristics (e.g., maternal age, sperm characteristics) and to the higher incidence of multiple gestations after ART. There are no indications that the use of GnRH antagonists during ART is associated with an increased risk of congenital malformations.
The safety and efficacy of Orgalutran have not been established in women weighing less than 50kg or more than 90kg.
ADVERSE EVENTS Orgalutran may cause a local skin reaction at the site of injection (predominantly redness, with or without swelling). In clinical studies, one hour after injection, the incidence of at least one moderate or severe local skin reaction per treatment cycle, as reported by patients, was 12% in Orgalutran treated patients and 25% in patients treated subcutaneously with a GnRH agonist. The local reactions generally disappear within 4 hours after administration. For additional adverse experience information, see the product circular.
DRUG INTERACTIONS Interactions of Orgalutran with other medicines have not been investigated; interactions with commonly used medicinal products can therefore not be excluded.
PREGNANCY AND LACTATION No clinical data on exposed pregnancies are available.
In animals, exposure to ganirelix at the time of implantation resulted in litter resorption. The relevance of these data for humans is unknown.
It is not known whether ganirelix is excreted in breast milk.
The use of Orgalutran is contraindicated during pregnancy and lactation.
Before initiating therapy, please consult the full prescribing information. Full prescribing information is available upon request.
