PERGOVERIS - PERGOVERIS - CT 5472 - English version

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Introduction PERGOVERIS 150 IU/75 IU, powder and solvent for solution for injection B/1 glass vial - one 1 ml vial (CIP: 381 219-3) B/10 glass vials - ten 1 ml vials (CIP: 381 221-8) Posted on Nov 17 2009 Active substance (DCI) follitropin alfa or recombinant human follicle-stimulating hormone (r-hFSH) lutropin alfa or recombinant human luteinizing hormone (r-hLH) ENDOCRINOLOGIE - NOUVEAU MEDICAMENT ENDOCRINOLOGIE - NOUVEAU MEDICAMENT PERGOVERIS 150 UI/75 UI, association fixe de FSH et de LH recombinantesPas d’avantage clinique démontré par rapport à l’administration conjointe de ses composants L’essentiel PERGOVERIS est une association fixe de follitropine alfa ou hormone folliculo-stimulante humaine recombinante (rh-FSH) et de lutropine alfa ou hormone lutéinisante humaine recombinante (rh-LH)Cette association est indiquée dans la stimulation du développement folliculaire chez les femmes ayant un déficit sévère en LH et en FSH.Cette association fixe ne présente pas d’avantage clinique démontré par rapport à l’administration conjointe de chacun de ses composants. Par ailleurs, cette spécialité n’est pas adaptée à toutes les patientes. Stratégie thérapeutique Le but du traitement est d’obtenir une grossesse monofoetale évolutive. Il est donc indispensable d’évaluer l’ensemble des facteurs d’infertilité du couple. En cas d’anovulation d’origine hypothalamique, des mesures hygiéno-diététiques et une prise en charge psychologique sont un préalable indispensable à toute stimulation de l’ovulation ; l’administration pulsatile de GnRH, ou l’administration conjuguée de FSH et de LH ou d’HMG avec un monitorage soigneux (dosages hormonaux, échographie folliculaire) sont recommandés en première intention. A taux égal de grossesses, il y a moins d'hyperstimulations ovariennes et de grossesses multiples avec la GnRH pulsatile qu'avec les gonadotrophines.Place de la spécialité dans la stratégie thérapeutique PERGOVERIS est un traitement de première intention pour stimuler le développement folliculaire chez les femmes qui présentent un déficit sévère en LH et en FSH, défini par une concentration plasmatique de LH endogène < 1,2 UI/l.Données cliniques Efficacité Deux études ont conclu à la bioéquivalence de rh-FSH administrée seule et en association avec rh-LH d’une part, à la bioéquivalence de rh-LH administrée seule et en association avec rh-FSH d’autre part.Tolérance Il n’est pas attendu de différence entre l’administration de l’association fixe PERGOVERIS et l’administration conjointe de ses deux composantes, aux dosages correspondants et dans l’indication de l’AMM. Les gonadotrophines utilisées dans l’induction de l’ovulation augmentent le risque d’hyperstimulation ovarienne, de grossesse multiple et de fausse-couche spontanée. Conditions particulières de prescription La prescription de PERGOVERIS est réservée aux spécialistes en gynécologie et/ou gynécologie-obstétrique et/ou endocrinologie et métabolisme. Ce médicament nécessite une surveillance particulière pendant le traitement.Intérêt du médicament Le service médical rendu* par PERGOVERIS est important. PERGOVERIS, association fixe de rh-FSH (150 UI) et rh-LH (75 UI) n’apporte pas d’amélioration du service médical rendu** (ASMR V) par rapport à l’utilisation conjointe de chacun de ses composants pris séparément.Avis favorable au remboursement en ville et à la prise en charge à l’hôpital.* Le service médical rendu par un médicament (SMR) correspond à son intérêt en fonction notamment de ses performances cliniques et de la gravité de la maladie traitée. La Commission de la Transparence de la HAS évalue le SMR, qui peut être important, modéré, faible, ou insuffisant pour que le médicament soit pris en charge par la collectivité.** L'amélioration du service médical rendu (ASMR) correspond au progrès thérapeutique apporté par un médicament par rapport aux traitements existants. La Commission de la transparence de la HAS évalue le niveau d'ASMR, cotée de I, majeure, à IV, mineure. Une ASMR de niveau V (équivalent de «pas d'ASMR») signifie « absence de progrès thérapeutique ». Pas d’avantage clinique démontré par rapport à l’administration conjointe de ses composants dans la stimulation du développement folliculaire PERGOVERIS est une association fixe de follitropine alfa ou hormone folliculo-stimulante humaine recombinante (rh-FSH) et de lutropine alfa ou hormone lutéinisante humaine recombinante (rh-LH)Cette association est indiquée dans la stimulation du développement folliculaire chez les femmes ayant un déficit sévère en LH et en FSH.Cette association fixe ne présente pas d’avantage clinique démontré par rapport à l’administration conjointe de chacun de ses composants. Par ailleurs, cette spécialité n’est pas adaptée à toutes les patientes.Pour en savoir plus, téléchargez la synthèse ou l'avis complet ci-dessous Pas d’avantage clinique démontré par rapport à l’administration conjointe de ses composants dans la stimulation du développement folliculaire PERGOVERIS est une association fixe de follitropine alfa ou hormone folliculo-stimulante humaine recombinante (rh-FSH) et de lutropine alfa ou hormone lutéinisante humaine recombinante (rh-LH)Cette association est indiquée dans la stimulation du développement folliculaire chez les femmes ayant un déficit sévère en LH et en FSH.Cette association fixe ne présente pas d’avantage clinique démontré par rapport à l’administration conjointe de chacun de ses composants. Par ailleurs, cette spécialité n’est pas adaptée à toutes les patientes.Pour en savoir plus, téléchargez la synthèse ou l'avis complet ci-dessous ATC Code G03GA05 G03AA07 Laboratory / Manufacturer MERCK LIPHA SANTE PERGOVERIS 150 IU/75 IU, powder and solvent for solution for injection B/1 glass vial - one 1 ml vial (CIP: 381 219-3) B/10 glass vials - ten 1 ml vials (CIP: 381 221-8) Posted on Nov 17 2009

Informations

• Publié par: haute-autorite-sante-maladies-endocriniennes-et-metaboliques
• Publié le: 25 juin 2008
• Nombre de lectures: 30
• Licence : En savoir +
  Paternité, pas d'utilisation commerciale, partage des conditions initiales à l'identique
• Langue: English

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  The legally binding text is the original French version   TRANSPARENCY COMMITTEE

OPINION   25 June 2008     PERGOVERIS 150 IU/75 IU, powder and solvent for solution for injection B/1 glass vial - one 1 ml vial (CIP: 381 219-3) B/10 glass vials - ten 1 ml vials (CIP: 381 221-8)     Applicant: MERCK LIPHA SANTE   Follitropin alfa or recombinant human follicle-stimulating hormone (r-hFSH) / lutropin alfa or recombinant human luteinizing hormone (r-hLH)   List I Medicinal product restricted to prescription only by specialists in gynaecology and/or gynaecology-obstetrics and/or endocrinology and metabolism. Medicinal product requiring close monitoring during treatment.   Date of Marketing Authorization: 25 June 2007 (centralised procedure)   Reason for request: Inclusion on the list of medicines reimbursed by National Health Insurance and approved for use by hospitals.                                       Medical, Economic and Public Health Assessment Division

 

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CHARACTERISTICS OF THE MEDICINAL PRODUCT

  1.1. Active ingredient Follitropin alfa or recombinant human follicle-stimulating hormone (r-hFSH) / lutropin alfa or recombinant human luteinizing hormone (r-hLH)   1.2. Indication “Pergoveris is indicated for the stimulation of follicular development in women with severe luteinizing hormone (LH) and follicle-stimulating hormone (FSH) deficiency. In clinical trials, these patients were defined by an endogenous serum LH level < 1.2 IU/l.”   1.3. Dosage “Treatment with Pergoveris should be initiated under the supervision of a physician experienced in the treatment of fertility problems.   Pergoveris is intended for subcutaneous administration. The powder should be reconstituted immediately prior to use with the solvent provided.   In LH and FSH deficient women (hypogonadotrophic hypogonadism), the objective of Pergoveris therapy is to develop a single mature Graafian follicle from which the oocyte will be liberated after the administration of human chorionic gonadotropin (hCG). Pergoveris should be given as a course of daily injections. Since these patients are amenorrhoeic and have low endogenous oestrogen secretion, treatment can commence at any time.   Treatment should be tailored to the individual patient’s response as assessed by measuring follicle size by ultrasound and oestrogen response. A recommended regimen begins with one vial of Pergoveris daily. If less than one vial of Pergoveris daily is used, the follicular response may be unsatisfactory because the amount of lutropin alfa may be insufficient (see section 5.1).   If an FSH dose increase is deemed appropriate, dose adaptation should preferably be after 7-14 day intervals and preferably by 37.5-75 IU increments using a licensed follitropin alfa preparation. It may be acceptable to extend the duration of stimulation in any one cycle to up to 5 weeks.   When an optimal response is obtained, a single injection of 5,000 IU to 10,000 IU hCG should be administered 24-48 hours after the last Pergoveris injection. The patient is recommended to have coitus on the day of, and on the day following, hCG administration. Alternatively, intrauterine insemination (IUI) may be performed.   Luteal phase support may be considered since lack of substances with luteotrophic activity (LH/hCG) after ovulation may lead to premature failure of the corpus luteum.   If an excessive response is obtained, treatment should be stopped and hCG withheld. Treatment should recommence in the next cycle at a dose of FSH lower than that of the previous cycle.   In clinical trials, patients with severe FSH and LH deficiency were defined by an endogenous serum LH level <1.2 IU/l as measured in a central laboratory. However, it should be taken into account that there are variations between LH measurements performed in different laboratories. In these trials the ovulation rate per cycle was 70-75%.”    

 

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COMPARABLE MEDICINAL PRODUCTS

  2.1. ATC Classification (2008)   G03GA05 (Follitropin alfa) / G03GA07 (Lutropin alfa)   G : Genitourinary system and sex hormones G03 : Sex hormones and modulators of the genital system G03G : Gonadotropins and other ovulation stimulants G03GA : Gonadotropins G03GA05 : Follitropin alfa   G : Genitourinary system and sex hormones G03 : Sex hormones and modulators of the genital system G03G : Gonadotropins and other ovulation stimulants G03AA : Gonadotropins G03AA07 : Lutropin alfa   2.2. Medicines in the same therapeutic category   2.2.1 Closely comparable medicinal products Table 1: comparable medicinal products INN Proprietary Pharmaceutical Indication (hormonal activity - product form origin)  - Treatment of sterility, if anovulation is the only    Menotropin MENOPUR® Powder and  cause of the sterility: (FSH and LH activity – 75  vent for solution urinary origin)   IU / 75 IU  sol for injection,  h a y n p ov ot u h i l o a al t n i a   o d m n i   s u o o s r r / i d p g i i e t n r u s a it ; t   i a n ry g    i g n l   a t n h d e ;     1 ml  subcutaneous or  - ind o u v c u i l n a g t  ovulation in the course of Medically  i a n d tr m a in m is u t s r c at u i l o a n r  Assisted Procreation (IVF, GIFT, etc.);   - sterility caused by insufficient production of cervical mucus.

     

 

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      2.2.2 Medicinal products in the same therapeutic class which are not closely comparable   Table 2: Medicinal products with FSH activity  dication (o I ri N g N i   n)  Pr p o r p o r d ie u t c a t r   y Pharm fo a r c m e   utical In GONAL-f ®   75 IU   Powder and solvent for solution for 450 IU/0.75 ml   injection, 1,050 IU/1.75  subcutaneous or Follitropin alfa  ml   intramuscular administration (recombinant)

GONAL-f ® 300 IU/0.5 ml   450 IU/0.75 ml   900 IU/1.5 ml  

Injectable solution in pre-filled pen, subcutaneous administration

- GONAL-f in association with a luteinizing hormone (LH) preparation is recommended for the stimulation of follicular development in women with severe LH and FSH deficiency. In clinical trials these patients were defined by an endogenous serum LH level <1.2 IU/l. - Anovulation (including polycystic ovarian disease, PCOD) in women who have been unresponsive to treatment with clomifene citrate. - Stimulation of multifollicular development in patients undergoing superovulation for assisted reproductive technologies (ART) such asin vitro  fertilization (IVF), gamete intra-fallopian transfer (GIFT) and zygote intra-fallopian transfer (ZIFT).

Puregon is indicated for the treatment of female infertility in the following clinical situations: PUREGON ®  Anovulation (including polycystic ovarian disease, - Follitropin beta  15 5 7 0 0 5       I I I U U U / / / 0 0 0 . . . 5 5 5       m m m l  l l     Injectable solution,  - t P   re C C a o O t n m D tr ) e o  i l n l n t e     d w w   it o o h v m   a c e r l i o n a   m n w i   f h h e o y n   p h e e   a r c v s it e t r i   a m b t e e ul . e   a n t   i u o n n  r t e o s  i p n o d n u s c iv e  e t   h to e     intramuscular or (recombinant)  subcutaneous  3 6 0 0 0 0     I I U U / / 0 0 . . 3 7 6 2     m m l l     administration   d a e s v si e s l t o e p d  m re e p nt r   o o d f  u m ct u i l o ti n p   l p e r  f o o g l r li a cl m e s s     [ in e   .g m .  e in d   ic vi a tr ll o y     900 IU/1.08 ml  fertilization/embryo transfer (IVF/ET), gamete intra- fallopian transfer (GIFT) and intracytoplasmic sperm injection (ICSI)]. - Anovulation (including polycystic ovarian disease, PCOD) in women who have been unresponsive to Powder and solvent treatment with clomifene citrate. Urofollitropin FOSTIMON ® avirnah pyretsmii -jn Connitlrbo lelceeda toht e ed  e olevnemp atuln io itoucnd o ge f ,     e y l r p i i n t e l d u   m s   f f i o l   l ti r c p e - d e   i m   i   n n s i   t l n e o i o c s l u l l  layl   (urinary) 150 IU / ml  subcutaneous  assisted reproduction programs [e.g.in vitro administration fertilization/embryo transfer (IVF/ET), gamete intra- fallopian transfer (GIFT) and intracytoplasmic sperm injection (ICSI)].       Table 3: Medicinal product with LH activity INN Proprietary Pharmaceutical Indication   (origin)   product   form   Powd   e s r o   l a u n ti d o  s n  o f l o v r e   nt  - h  Luveris e     i ( n F  a S s H s ) o  p ci r a e ti p o a n r   a w ti i o t n h     i a s     f r o e ll c ic o le m  s m ti e m n u d l e a d ti   n fo g r    the  Lutropin alfa LUVERIS ® for ormon injection,  s st e i v m e u r l e at L io H n     a o n f  d f   o F lli S c H ul   a d r e   f d ic e i v e e n l c o y p  ( m in e   n c t l   i i n n i   c w al o  t m ri e al n s     with  (recombinant)   75 IU   subcutaneous administration   )l.I /U neere defiitnestw htse eap l ve.2<1 LumleH res   d by an endogenous          

 

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    2.3. Medicines with a similar therapeutic aim Table 4: medicines with a similar therapeutic aim INN Proprietary Pharmaceutical form product    LUTRELEF ®  and Lyophilizate Gonadorelin 0.8mg solution for parenteral acetate use, administered   subcutaneously or LUTRELEF ®  intravenously through a 3.2mg catheter

       

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Indication

Inducing ovulation for the treatment of sterility in the event of anovulation of hypothalamic origin. According to the WHO anovulation classification, only Class I and Class IIa are appropriate for the administration of GnRH in the case of unresponsiveness to clomifene citrate.

ANALYSIS OF AVAILABLE DATA

  The file supplied by the laboratory includes two bioequivalence studies and three efficacy studies. One of these studies (Burguès et al.) will not be included in the efficacy analysis because although the initial daily doses of r-hFSH (GONAL-F®- 150 IU/day) and r-hLH (LUVERIS®- 150 IU/day) correspond to those in a vial of PERGOVERIS, the dose of FSH could be adjusted during the 1st cycle from the 6th day on the basis of the response obtained. The methods of this adjustment are not described in the publication, and the results presented do not indicate how many patients needed an FSH dose adjustment.   3.1. Bioequivalence studies   Two bioequivalence studies have compared the bioavailability of each active constituent, administered alone and in combination (with an r-hFSH/r-hLH ratio of 2:1). They were conducted on female volunteers pre-treated with a GnRH agonist. - Study IMP 23718 demonstrated the bioequivalence of r-hFSH (300 IU) administered alone and in combination with r-hLH (150 IU). - Study IMP 23722 demonstrated the bioequivalence of r-hLH (450 IU) administered alone and in combination with r-FSH (900 IU).   3.2. Efficacy studies 1     The applicant submitted two multicentre, randomized, open-label dose-finding studies . The studies compared several daily doses of r-hLH combined with a fixed dose of r-hFSH These two studies included women with a severe LH and FSH deficiency. All patients received a daily dose of 150 IU of r-hFSH. Each study comprised four treatment groups, according to the daily dose of r-hLH: 0, 25, 75 and 225 IU. Each cycle was not to exceed 20-21 days of treatment. Ovulation was induced by injection of hCG when a follicle≥17 mm in diameter was obtained.        

                                             1 As stated in the PERGOVERIS EPAR, the efficacy studies (GF6253 and GF6905) are those already filed for registration of LUVERIS (r-hLH). No additional evidence of efficacy was requested - www.emea.europa.eu 

 

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    Study GF 6253 - Inclusion criteria: o Women aged 18 to 35 years o level < 5IU/l and LH level <1.2 IU/l FSH ono history of ovarian hyperstimulation or systemic illness.  With   - Primary endpoint: to obtain follicular development during the first trea

tment cycle as defined by the following three parameters: o follicle≥17 mm diameter o serum oestradiol level of preovulatory≥400 pmol/L o mid-luteal phase serum progesterone level of≥25 nmol/L.

  - Results: Thirty-eight patients were included in the study and 34 in the primary endpoint analysis. During the first treatment cycle, 21 patients out of 38 did not receive the hCG injection, due to insufficient follicle development (14), risk of ovarian hyperstimulation syndrome (5), and withdrawal of consent (2). Of the 7 patients treated with doses of r-hLH and r-hFSH corresponding to the composition of Pergoveris, 4 had follicular development (excluding excessive follicular development).    Table 5 – study GF 6253 – efficacy during first treatment cycle. Daily dose of r-hLH 0 25  75 225 (no. of patients) IU/day IU/day  IU/day* IU/day p (n=10) (n=9) (n=7) (n=8) Number of patients with follicular  0/1 development 0  1/9 6/7 8/8 0.0001 Number of patients with follicular development, excluding excessive follicular 0/10  1/9 4/7 5/8 0.0124 development dose of r-hLH corresponding to the composition of PERGOVERIS *   Study GF 6905 - Inclusion criteria: o Women aged 18 to 40 years o level < 10.85 IU/l and LH level <13.3 IU/l FSH o Oestradiol level <60 pg/ml       - Primary endpoint: to obtain follicular development during the first treatment cycle, as defined by the following three parameters: o follicle≥17 mm diameter o preovulatory serum oestradiol level of≥160 pg/ml o mid-luteal phase serum progesterone level of≥10 ng/ml   - Results: Forty-three patients were included in the study and 40 in the primary endpoint

 

 

analysis. During the first treatment cycle, 5 patients out of 40 did not receive the hCG injection due to ovarian hyperstimulation syndrome. Only 15 of the 40 patients included in the analysis had an LH level <1.2 IU/l, corresponding to the indication of PERGOVERIS. Of these 15 patients, 3 were treated with doses of r-hLH and r-hFSH corresponding to the composition of this product.

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Table 6 – study GF 6905 – efficacy Daily dose of r-hLH

 

0 25  75 225 IU/day IU/day  IU/day* IU/day  p Total number of patients n=11 n=9  n=11 n=9 d N e u v m el b o e p r  men o t f    patients with follicular  7/11 9/9  8/11 6/9 NS  Number of patients with LH < 1.2IU** n=3 n=5  n=3 n=4   d N e u v m el b o e p r  men o t f *   * patients with follicular  0/3 5/5  2/3 3/4 p=0.04**    * dose of r-hLH corresponding to the composition of PERGOVERIS; **:a posteriorianalysis   3.3. Adverse effects   Two adverse events were observed in study GF 6253: a shock secondary to an injection and a miscarriage. The most frequent other adverse effects observed in the studies listed above are those cited in the SPC: - very common (≥1/10): o headache oinjection site reaction (pain, redness, bruising, swelling and/or to severe  mild irritation at the site of injection) o cysts ovarian - common (≥1/100, <1/10)  o somnolence o abdominaland gastrointestinal symptoms such as nausea, vomiting, pain diarrhoea, abdominal cramps and bloating o breast pain, pelvic pain, mild to moderate ovarian hyperstimulation syndrome (OHSS)  uncommon (≥1/1,000, <1/100) - o OHSS severe The PERGOVERIS SPC also states the known complications of gonadotropins used to induce ovulation: risk of OHSS, multiple pregnancy or miscarriage.   3.4. Conclusion   Two studies (IMP 23722 et IMP 23718) concluded that r-hFSH (300 IU) was bioequivalent when administered alone and in combination with r-hLH (150 IU), and r-hLH (450 IU) was bioequivalent when administered alone and in combination with r-hFSH (900 IU).   Two open-label dose-finding studies (GF 6253 and GF 6905) compared four daily doses of r- hLH (0, 25, 75 or 225 IU) associated with a fixed daily dose of 150 IU r-hFSH. Their primary endpoint was to obtain follicular development during the first treatment cycle.   Study GF 6253, which included women with an LH level of under 1.2 IU/l, showed a significant difference between the four treatment groups (34 patients were included in the analysis). Follicular development (excluding excessive developments) was found in 4 of the 7 patients treated with 75 IU/day of r-hLH (dose corresponding to that of PERGOVERIS).   Study GF 6905, which included women with an LH level of under 13.3 IU/l, showed no significant difference between the groups. Of the 40 patients analysed, only 15 had an LH level of under 1.2 IU/ml, 3 of whom were treated with 75 IU/day of r-hLH (dose corresponding to that of PERGOVERIS).  

 

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    No difference in safety is expected between the administration of the fixed combination of PERGOVERIS and combined administration of its two constituents, at the corresponding doses and for the indication specified in the Marketing Authorization.  

4. TRANSPARENCY COMMITTEE CONCLUSIONS

    4.1. Actual benefit   Infertility is not severe, but radically alters a couple’s quality of life.   The proprietary drug is intended to provide curative treatment.   Its efficacy/adverse event ratio is high.   Public health benefit Infertility associated with severe LH and FSH deficiency in women represents a low public health burden in view of the small number of patients concerned. Improving the treatment of this deficiency does not constitute a public health priority. Several hormone treatments are already available. Having regard to the available data and the conditions of use, which do not allow dose adjustment,improve morbidity or quality of life comparedPERGOVERIS is not expected to with the free combination of its two constituents, LH and FSH. Consequently, PERGOVERIS is not expected to have an impact on public health.   This proprietary drug is used for first-line therapy.   There are alternative drugs available.   The actual benefit of PERGOVERIS is substantial.   4.2.Improvement in actual benefit    The proprietary product PERGOVERIS, a fixed combination of r-hFSH (150 IU) and r-hLH (75 IU), does not provide any improvement in actual benefit (IAB V) compared with the combined use of each of its constituents considered separately.   4.3. Therapeutic use   2 4.3.1 Reference treatment strategy   Summary:   The aim of the treatment is to achieve a viable single-embryo pregnancy. It is therefore essential to evaluate all the couple’s infertility factors.   The treatment strategy should take account of the woman’s age, the duration of the infertility, associated factors and previous responses (Grade A).   Handling of ovulation inducers requires specific medical training and suitable experience (expert consensus). All ovulation inducers, apart from clomifene citrate, are available only on prescription by the specialists listed in the Marketing Authorization.

                                             2 Ovulation inducers: gonadotropins - Recommendations - Afssaps - 2007 update.  

 

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          An etiological assessment of infertile couples is required before a treatment strategy is decided on. This report involves at least a check on fallopian tube permeability, basic hormone assays, semen analysis and tests for thromboembolism risk factors (expert consensus).    It is recommended that preventive measures should be promoted in general: prevention and treatment of sexually transmissible diseases for both partners, recommending that both partners should give up smoking, nutritional management of the female patient so that she achieves the ideal weight, and reducing the age of first pregnancy by providing information about the reduction of fertility with age (Grade C).   There is no point in offering ovulation induction treatment if the basic endogenous FSH level is markedly and constantly elevated, whatever the woman’s age (Grade A)   Anovulation of hypothalamic origin: Diet and lifestyle measures and psychological counselling are an essential pre-requisite for the stimulation of ovulation (Grade B).   Pulsatile administration of GnRH, or combined administration of FSH and LH or HMG, with careful monitoring (hormone assays, follicular ultrasonography) are recommended as first- line treatment (Grade A).   The rate of pregnancies being equal, there is a lower rate of ovarian hyperstimulation and multiple pregnancies with pulsatile GnRH than with gonadotropins.   4.3.2 Therapeutic use:   Pergoveris is a first-line medicine which stimulates follicular development in women with a severe LH and FSH deficiency. In clinical trials, these patients were defined by an endogenous serum LH concentration < 1.2   IU/l. The usefulness of this fixed combination for the treatment of patients compared with separate administration of its two ingredients has not been established. Moreover, this product is not suitable for the treatment of all patients.   4.4. Target population According to the available epidemiological data 3 , 60,000 couples a year consult a doctor due to infertility which has lasted for more than a year. 74% of the women in those 60,000 couples are diagnosed as infertile. Hypothalamus/pituitary gland insufficiency only represents 1.2% of the causes of infertility, ie. approximately 500 women.   In view of these factors, the target population of PERGOVERIS is a maximum of 500 women in France, especially as in practice, daily doses of FSH lower than the dose contained in PERGOVERIS may be suitable for some patients. Moreover, some patients treated with PERGOVERIS will require a dose adjustment.      

                                             3 Thonneau P, Patureau J, Moyse C, Marchand S, Tallec A, Ferial MLet al.L’infécondité en France : résultats d’une étude multicentrique dans trois départements français (1988-1989). Contracept Fertil  Sex 1992 ; 20 (1) : 27-32

 

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    4.5. Transparency Committee recommendations   The Transparency Committee recommends inclusion on the list of medicines reimbursed by National Insurance and on the list of medicines approved for use by hospitals and various public services for the indication and at the dosage specified in the Marketing Authorization.   4.5.1 Packaging: appropriate for the prescription conditions   4.5.2 Reimbursement rate: 100%  

 

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