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Managing infertility with the follitropin alfa prefilled pen injector - patient considerations.

Bühler K - Ther Clin Risk Manag (2015)

Bottom Line: Accurate and easy-to-use injection devices which minimize pain, difficulty, and stress are essential for patient compliance.The efficacy in comparison to the quite more cumbersome handling with ampoules and syringes has been proven very quickly.In several studies, it has been shown that patients had a preference to the prefilled follitropin alfa pen due to the faster preparation and were more confident of accurate dosing.

View Article: PubMed Central - PubMed

Affiliation: Centre for Gynaecological Endocrinology and Reproductive Medicine, Stuttgart, Germany.

ABSTRACT
Gonadotropin treatment has been used in fertility treatment since the 1930s. First, preparations coming from animals were injected, then, gonadotropins prepared from the pituitary glands of human cadavers. A great step was achieved with the introduction of human menopausal gonadotropin extracted from the urine of postmenopausal women. When cases of Creutzfeld-Jacob disease were recognized after the use of human pituitary-derived hormone injections, urinary gonadotropins were increasingly purified and then produced by the use of recombinant DNA technology. Recombinant gonadotropins were characterized by the extreme high specificity and the nearly 100% purity. This allows for follitropin alfa, the first recombinant-human follicle stimulating hormone (r-hFSH) approved, to be quantified and filled by mass, with a small variance of only ±2% and no more with a bioassay with a variance of 45%. With recombinant preparations, it is also possible to cover the tremendous growing demand for gonadotropins. Ovarian stimulation has become a self-injecting procedure for the patients. Accurate and easy-to-use injection devices which minimize pain, difficulty, and stress are essential for patient compliance. So, two pen injectors adapted from the well-known insulin pen were introduced in fertility treatment, one as a multiple-use device rechargeable with premixed, prefilled cartridges with r-hFSH (follitropin β) and the other a disposable, prefilled drug delivery system with a liquid formulation of follitropin alfa filled by mass. The efficacy in comparison to the quite more cumbersome handling with ampoules and syringes has been proven very quickly. In several studies, it has been shown that patients had a preference to the prefilled follitropin alfa pen due to the faster preparation and were more confident of accurate dosing. The follitropin alfa (filled by mass [FbM]) prefilled pen is a move toward better quality of treatment and also better quality of life for the women within the stressful period of fertility treatment.

No MeSH data available.


Related in: MedlinePlus

Relation of frequency of OHSS and the use of recombinant hFSH.Notes: r-hFSH was introduced into the market in Germany in 1998. Data from the German IVF-Registry – D·I·R; www.deutsches-ivf-register.de.33Abbreviations: FSH, follicle stimulating hormone; OHSS, ovarian hyperstimulation syndrome; r-hFSH, recombinant-human follicle stimulating hormone.
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f1-tcrm-11-995: Relation of frequency of OHSS and the use of recombinant hFSH.Notes: r-hFSH was introduced into the market in Germany in 1998. Data from the German IVF-Registry – D·I·R; www.deutsches-ivf-register.de.33Abbreviations: FSH, follicle stimulating hormone; OHSS, ovarian hyperstimulation syndrome; r-hFSH, recombinant-human follicle stimulating hormone.

Mentions: Gonadotropin injections for ovarian stimulation were introduced in modern fertility treatment in the 1930s and were first prepared from different animal sources: pregnant mare serum gonadotrophin and swine and ovine pituitaries extractions. These drugs continued to be used until the early 1960s. But all these animal preparations had to be withdrawn from the market because of the detected antibody formation against natural human pituitary gonadotropin.6 Since 1958, gonadotropins were extracted from pituitary glands of human cadavers – human pituitary gonadotropin (hPG). But they had to be withdrawn when cases of iatrogenic Creutzfeld-Jacob disease were detected. A milestone in the gonadotropin treatment was the introduction of the two-step protocol in the 1940s: first, stimulation of follicular growth and then induction of final oocyte maturation and ovulation with human chorionic gonadotropin (hCG) – first extracted from human placentas, then, as today, from urine of pregnant women.6 Even 75 years later, this principle is still carried out. The first human menopausal gonadotropin (hMG) preparation, produced by isolation and purification from crude extracts of large urine pools of postmenopausal women, finally resulted in a relatively simple procedure7 that was registered in 1950, and in 1963, was introduced into clinical use as “Pergonal 75”, a preparation with 75 IU follicle stimulating hormone (FSH) and 75 IU luteinizing hormone (LH), with tolerated variance of −20% to +25% measured by a standard bioassay. The first pregnancy with this compound was reported by Lunenfeld.8 While in the early hMG preparations >95% were impurities, in the highly purified (HP) preparations of today the rate of impurities is only about 30%.9 But during the purification process, natural LH activity disappears so that >95% of the biological LH activity in the purified preparations result from spiking with hCG. After the disaster with hPG, every endeavor has been made to purify urinary gonadotropins in order to achieve a greater safety for the patients. FSH HP achieved the highest degree in purity, >95%. But in all urinary preparations, u-hMG and u-hCG, recently, human prion proteins with all their theoretical risks have been detected.10 Therefore, it seems logical that several committees all over the world, like in Australia or UK, have published the recommendation to replace such drugs with recombinant products with likely higher standards of purity and safety.11 The first “pure” hFSH, follitropin alfa – Gonal-F® (Merck Senoro, Darmstadt, Germany), produced in 1988 by recombinant DNA technology, using a cell culture system with Chinese hamster ovary cells, was licensed in Europe in 1996. A quite similar recombinant-human follicle stimulating hormone (r-hFSH) (follitropin β – Puregon®/Follistim® [Merck Sharpe & Dohme, Kenilworth, NJ, USA]) was approved 1 year later.12 During the ensuing period, the efficacy of r-hFSH was proven by countless studies.13 Due to the higher bioavailability of the recombinant FSH, a higher number of oocytes – which represents a robust surrogate outcome for clinical success – is retrieved in IVF treatment with a lower dose and lower rate of ovarian hyperstimulation syndrome (OHSS) as compared to urinary gonadotropins (Figure 1).14 Even when in randomized controlled studies no statistically significant differences between hMG and r-hFSH with regard to live birth rate could be found, there exists clinical evidence of differences between hMG and r-hFSH concerning dose variability and purity.15–18


Managing infertility with the follitropin alfa prefilled pen injector - patient considerations.

Bühler K - Ther Clin Risk Manag (2015)

Relation of frequency of OHSS and the use of recombinant hFSH.Notes: r-hFSH was introduced into the market in Germany in 1998. Data from the German IVF-Registry – D·I·R; www.deutsches-ivf-register.de.33Abbreviations: FSH, follicle stimulating hormone; OHSS, ovarian hyperstimulation syndrome; r-hFSH, recombinant-human follicle stimulating hormone.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492655&req=5

f1-tcrm-11-995: Relation of frequency of OHSS and the use of recombinant hFSH.Notes: r-hFSH was introduced into the market in Germany in 1998. Data from the German IVF-Registry – D·I·R; www.deutsches-ivf-register.de.33Abbreviations: FSH, follicle stimulating hormone; OHSS, ovarian hyperstimulation syndrome; r-hFSH, recombinant-human follicle stimulating hormone.
Mentions: Gonadotropin injections for ovarian stimulation were introduced in modern fertility treatment in the 1930s and were first prepared from different animal sources: pregnant mare serum gonadotrophin and swine and ovine pituitaries extractions. These drugs continued to be used until the early 1960s. But all these animal preparations had to be withdrawn from the market because of the detected antibody formation against natural human pituitary gonadotropin.6 Since 1958, gonadotropins were extracted from pituitary glands of human cadavers – human pituitary gonadotropin (hPG). But they had to be withdrawn when cases of iatrogenic Creutzfeld-Jacob disease were detected. A milestone in the gonadotropin treatment was the introduction of the two-step protocol in the 1940s: first, stimulation of follicular growth and then induction of final oocyte maturation and ovulation with human chorionic gonadotropin (hCG) – first extracted from human placentas, then, as today, from urine of pregnant women.6 Even 75 years later, this principle is still carried out. The first human menopausal gonadotropin (hMG) preparation, produced by isolation and purification from crude extracts of large urine pools of postmenopausal women, finally resulted in a relatively simple procedure7 that was registered in 1950, and in 1963, was introduced into clinical use as “Pergonal 75”, a preparation with 75 IU follicle stimulating hormone (FSH) and 75 IU luteinizing hormone (LH), with tolerated variance of −20% to +25% measured by a standard bioassay. The first pregnancy with this compound was reported by Lunenfeld.8 While in the early hMG preparations >95% were impurities, in the highly purified (HP) preparations of today the rate of impurities is only about 30%.9 But during the purification process, natural LH activity disappears so that >95% of the biological LH activity in the purified preparations result from spiking with hCG. After the disaster with hPG, every endeavor has been made to purify urinary gonadotropins in order to achieve a greater safety for the patients. FSH HP achieved the highest degree in purity, >95%. But in all urinary preparations, u-hMG and u-hCG, recently, human prion proteins with all their theoretical risks have been detected.10 Therefore, it seems logical that several committees all over the world, like in Australia or UK, have published the recommendation to replace such drugs with recombinant products with likely higher standards of purity and safety.11 The first “pure” hFSH, follitropin alfa – Gonal-F® (Merck Senoro, Darmstadt, Germany), produced in 1988 by recombinant DNA technology, using a cell culture system with Chinese hamster ovary cells, was licensed in Europe in 1996. A quite similar recombinant-human follicle stimulating hormone (r-hFSH) (follitropin β – Puregon®/Follistim® [Merck Sharpe & Dohme, Kenilworth, NJ, USA]) was approved 1 year later.12 During the ensuing period, the efficacy of r-hFSH was proven by countless studies.13 Due to the higher bioavailability of the recombinant FSH, a higher number of oocytes – which represents a robust surrogate outcome for clinical success – is retrieved in IVF treatment with a lower dose and lower rate of ovarian hyperstimulation syndrome (OHSS) as compared to urinary gonadotropins (Figure 1).14 Even when in randomized controlled studies no statistically significant differences between hMG and r-hFSH with regard to live birth rate could be found, there exists clinical evidence of differences between hMG and r-hFSH concerning dose variability and purity.15–18

Bottom Line: Accurate and easy-to-use injection devices which minimize pain, difficulty, and stress are essential for patient compliance.The efficacy in comparison to the quite more cumbersome handling with ampoules and syringes has been proven very quickly.In several studies, it has been shown that patients had a preference to the prefilled follitropin alfa pen due to the faster preparation and were more confident of accurate dosing.

View Article: PubMed Central - PubMed

Affiliation: Centre for Gynaecological Endocrinology and Reproductive Medicine, Stuttgart, Germany.

ABSTRACT
Gonadotropin treatment has been used in fertility treatment since the 1930s. First, preparations coming from animals were injected, then, gonadotropins prepared from the pituitary glands of human cadavers. A great step was achieved with the introduction of human menopausal gonadotropin extracted from the urine of postmenopausal women. When cases of Creutzfeld-Jacob disease were recognized after the use of human pituitary-derived hormone injections, urinary gonadotropins were increasingly purified and then produced by the use of recombinant DNA technology. Recombinant gonadotropins were characterized by the extreme high specificity and the nearly 100% purity. This allows for follitropin alfa, the first recombinant-human follicle stimulating hormone (r-hFSH) approved, to be quantified and filled by mass, with a small variance of only ±2% and no more with a bioassay with a variance of 45%. With recombinant preparations, it is also possible to cover the tremendous growing demand for gonadotropins. Ovarian stimulation has become a self-injecting procedure for the patients. Accurate and easy-to-use injection devices which minimize pain, difficulty, and stress are essential for patient compliance. So, two pen injectors adapted from the well-known insulin pen were introduced in fertility treatment, one as a multiple-use device rechargeable with premixed, prefilled cartridges with r-hFSH (follitropin β) and the other a disposable, prefilled drug delivery system with a liquid formulation of follitropin alfa filled by mass. The efficacy in comparison to the quite more cumbersome handling with ampoules and syringes has been proven very quickly. In several studies, it has been shown that patients had a preference to the prefilled follitropin alfa pen due to the faster preparation and were more confident of accurate dosing. The follitropin alfa (filled by mass [FbM]) prefilled pen is a move toward better quality of treatment and also better quality of life for the women within the stressful period of fertility treatment.

No MeSH data available.


Related in: MedlinePlus