128 results on '"Follitropin"'
Search Results
2. Review of 2023 and outlook for 2024
- Published
- 2024
3. Dose adjustment of follicle-stimulating hormone (FSH) during ovarian stimulation as part of medically-assisted reproduction in clinical studies: a systematic review covering 10 years (2007–2017)
- Author
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Human Fatemi, Wilma Bilger, Deborah Denis, Georg Griesinger, Antonio La Marca, Salvatore Longobardi, Mary Mahony, Xiaoyan Yin, and Thomas D’Hooghe
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Follicle-stimulating hormone (FSH) ,FSH dose adjustment ,Recombinant-human FSH ,Follitropin ,Controlled ovarian stimulation (COS) ,In vitro fertilization (IVF) ,Gynecology and obstetrics ,RG1-991 ,Reproduction ,QH471-489 - Abstract
Abstract Background Individualization of the follicle-stimulating hormone (FSH) starting dose is considered standard clinical practice during controlled ovarian stimulation (COS) in patients undergoing assisted reproductive technology (ART) treatment. Furthermore, the gonadotropin dose is regularly adjusted during COS to avoid hyper- or hypo-ovarian response, but limited data are currently available to characterize such adjustments. This review describes the frequency and direction (increase/decrease) of recombinant-human FSH (r-hFSH) dose adjustment reported in clinical trials. Methods We evaluated the proportion of patients undergoing ART treatment who received ≥ 1 r-hFSH dose adjustments. The inclusion criteria included studies (published Sept 2007 to Sept 2017) in women receiving ART treatment that allowed dose adjustment within the study protocol and that reported ≥ 1 dose adjustments of r-hFSH; studies not allowing/reporting dose adjustment were excluded. Data on study design, dose adjustment and patient characteristics were extracted. Point-incidence estimates were calculated per study and overall based on pooled number of cycles with dose adjustment across studies. The Clopper–Pearson method was used to calculate 95% confidence intervals (CI) for incidence where adjustment occurred in
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- 2021
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- View/download PDF
4. Dose adjustment of follicle-stimulating hormone (FSH) during ovarian stimulation as part of medically-assisted reproduction in clinical studies: a systematic review covering 10 years (2007–2017).
- Author
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Fatemi, Human, Bilger, Wilma, Denis, Deborah, Griesinger, Georg, La Marca, Antonio, Longobardi, Salvatore, Mahony, Mary, Yin, Xiaoyan, and D'Hooghe, Thomas
- Subjects
- *
FOLLICLE-stimulating hormone , *INDUCED ovulation , *HUMAN reproductive technology , *CLINICAL trial registries , *REPRODUCTIVE technology - Abstract
Background: Individualization of the follicle-stimulating hormone (FSH) starting dose is considered standard clinical practice during controlled ovarian stimulation (COS) in patients undergoing assisted reproductive technology (ART) treatment. Furthermore, the gonadotropin dose is regularly adjusted during COS to avoid hyper- or hypo-ovarian response, but limited data are currently available to characterize such adjustments. This review describes the frequency and direction (increase/decrease) of recombinant-human FSH (r-hFSH) dose adjustment reported in clinical trials. Methods: We evaluated the proportion of patients undergoing ART treatment who received ≥ 1 r-hFSH dose adjustments. The inclusion criteria included studies (published Sept 2007 to Sept 2017) in women receiving ART treatment that allowed dose adjustment within the study protocol and that reported ≥ 1 dose adjustments of r-hFSH; studies not allowing/reporting dose adjustment were excluded. Data on study design, dose adjustment and patient characteristics were extracted. Point-incidence estimates were calculated per study and overall based on pooled number of cycles with dose adjustment across studies. The Clopper–Pearson method was used to calculate 95% confidence intervals (CI) for incidence where adjustment occurred in < 10% of patients; otherwise, a normal approximation method was used. Results: Initially, 1409 publications were identified, of which 318 were excluded during initial screening and 1073 were excluded after full text review for not meeting the inclusion criteria. Eighteen studies (6630 cycles) reported dose adjustment: 5/18 studies (1359 cycles) reported data for an unspecified dose adjustment (direction not defined), in 10/18 studies (3952 cycles) dose increases were reported, and in 11/18 studies (5123 cycles) dose decreases were reported. The studies were performed in women with poor, normal and high response, with one study reporting in oocyte donors and one in obese women. The median day that dose adjustment was permitted was Day 6 after the start of treatment. The point estimates for incidence (95% CI) for unspecified dose adjustment, dose increases, and dose decreases were 45.3% (42.7, 48.0), 19.2% (18.0, 20.5), and 9.5% (8.7, 10.3), respectively. Conclusions: This systematic review highlights that, in studies in which dose adjustment was allowed and reported, the estimated incidence of r-hFSH dose adjustments during ovarian stimulation was up to 45%. [ABSTRACT FROM AUTHOR]
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- 2021
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5. New Human Follitropin Preparations: How Glycan Structural Differences May Affect Biochemical and Biological Function and Clinical Effect
- Author
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James A. Dias and Alfredo Ulloa-Aguirre
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follitropin ,glycoprotein ,glycosylation ,pharmocodynamics ,pharmacokinetics ,therapeutics ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
It is well accepted that pituitary follitropin is secreted into the circulation as a mixture of variants, which differ not in primary structure but rather at the level of glycosylation. These glycosidic forms vary in the number of glycosylation sites filled, complexity of glycosidic chains, and sialylation and sulfation. It is generally agreed that high sialylation, 2,3 sialic acid capping of terminal N-acetyl galactosamine or galactose leads to longer circulating half-life, by blocking binding of asialoglycoprotein receptor (ASGPR) in the liver. In contrast, 2,6 sialic acid found in humans does not prevent recognition of galactose and N-acetyl galactosamine by ASGPR. Few studies on clinical outcomes comparing differences in sialylation of follitropin found in commercially available preparations are available. Thus, there is a clear need for a consortium of open data to address this unmet need. Recently, FSH glycosylation, primarily on the β-subunit, which varies as women age, has emerged as a key modifier of follitropin action, with profound biological effects in vivo in animal models. To date, limited information of recombinant follitropin hormone preparations is available. Thus, most of the studies with FSH that is well characterized biochemically have been done in vitro, with engineered non gonadal host cells bearing recombinant receptors or in animal models. Since limited studies in human granulosa cells are available, a question is whether structural differences in glycosylation in commercially available follitropin affects biological function and clinical effect in humans. The presence of fucose, for example, has not been studied greatly even though, in the case of antibody therapy it has been shown to have a large effect on antibody targeting. This review on glycosidic variability of follitropin from the biochemical/structural point of view reflects on this question and presents an assessment in the context of available published data. If clinical differences are to be expected or not, the readers will have a better understanding of the evidence for and limitations of such expectations.
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- 2021
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6. New Human Follitropin Preparations: How Glycan Structural Differences May Affect Biochemical and Biological Function and Clinical Effect.
- Author
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Dias, James A. and Ulloa-Aguirre, Alfredo
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GALACTOSE ,FOLLICLE-stimulating hormone ,GLYCANS ,GRANULOSA cells ,TREATMENT effectiveness ,SIALIC acids ,GALACTOSAMINE - Abstract
It is well accepted that pituitary follitropin is secreted into the circulation as a mixture of variants, which differ not in primary structure but rather at the level of glycosylation. These glycosidic forms vary in the number of glycosylation sites filled, complexity of glycosidic chains, and sialylation and sulfation. It is generally agreed that high sialylation, 2,3 sialic acid capping of terminal N-acetyl galactosamine or galactose leads to longer circulating half-life, by blocking binding of asialoglycoprotein receptor (ASGPR) in the liver. In contrast, 2,6 sialic acid found in humans does not prevent recognition of galactose and N-acetyl galactosamine by ASGPR. Few studies on clinical outcomes comparing differences in sialylation of follitropin found in commercially available preparations are available. Thus, there is a clear need for a consortium of open data to address this unmet need. Recently, FSH glycosylation, primarily on the β-subunit, which varies as women age, has emerged as a key modifier of follitropin action, with profound biological effects in vivo in animal models. To date, limited information of recombinant follitropin hormone preparations is available. Thus, most of the studies with FSH that is well characterized biochemically have been done in vitro , with engineered non gonadal host cells bearing recombinant receptors or in animal models. Since limited studies in human granulosa cells are available, a question is whether structural differences in glycosylation in commercially available follitropin affects biological function and clinical effect in humans. The presence of fucose, for example, has not been studied greatly even though, in the case of antibody therapy it has been shown to have a large effect on antibody targeting. This review on glycosidic variability of follitropin from the biochemical/structural point of view reflects on this question and presents an assessment in the context of available published data. If clinical differences are to be expected or not, the readers will have a better understanding of the evidence for and limitations of such expectations. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
7. Effectiveness Assessment of a Modified Preservation Solution Containing Thyrotropin or Follitropin Based on Biochemical Analysis in Perfundates and Homogenates of Isolated Porcine Kidneys after Static Cold Storage
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Aneta Ostróżka-Cieślik, Barbara Dolińska, and Florian Ryszka
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thyrotropin ,follitropin ,Biolasol ,kidneys ,pigs ,static cold storage ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
In this paper, we assess the nephroprotective effects of thyrotropin and follitropin during ischaemia. The studies were performed in vitro in a model of isolated porcine kidneys stored in Biolasol (FZNP, Biochefa, Sosnowiec, Poland) and modified Biolasol (TSH: 1 µg/L; FSH 1 µg/L). We used the static cold storage method. The study was carried out based on 30 kidneys. The kidneys were placed in 500 mL of preservation solution chilled to 4 °C. The samples for biochemical tests were collected during the first kidney perfusion (after 2 h of storage) and during the second perfusion (after 48 h of storage). The results of ALT, AST, and LDH activities confirm the effectiveness of Biolasol + p-TSH in maintaining the structural integrity of renal cell membranes. Significantly reduced biochemical parameters of kidney function, i.e., creatinine and protein concentrations were also observed after 48 h storage. The protective effect of Biasol + p-TSH is most pronounced after 2 h of storage, suggesting a mild course of damage thereafter. A mild deterioration of renal function was observed after 48 h. The results of our analyses did not show any protective effect of Biolasol + p-FSH on the kidneys during ischaemia.
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- 2021
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8. Heterologous Production and Glycosylation of Japanese Eel Follitropin Using Silkworm.
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Hong, Sun Mee, Choi, Ji-Hyun, Jo, Sun-Jung, Min, Kwan-Sik, Kim, Dae-Jung, Lee, Jae Man, and Kusakabe, Takahiro
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ANGUILLA japonica , *BINDING site assay , *FOLLICLE-stimulating hormone , *SILKWORMS , *GLYCOSYLATION , *GONADOTROPIN - Abstract
Follitropin, an important gonadotropin hormone, participates in vitellogenesis and spermatogenesis. Equine chorionic gonadotropin (eCG) can induce gonadotropin hormone activity in non-equid species and exhibits a long biological half-life. Here, we report the production, using silkworm larval and pupal systems, of biologically active recombinant hybrid-type follitropins based on the coding sequence of the eCG C-terminal peptide (CTP) between the mature β- and α-chains of eel. The three constructs, rJeFSH, rJeFSH·eCG, and rJeFSH·2xeCG were produced and verified to be N- or O-glycosylated and secreted mature peptides. Although rJeFSH·eCG contains more elaborate O-linked carbohydrate chains than rJeFSH, it elicited no significant in vitro oocyte maturation, which may be a result of insufficient terminal sialylation of its N-and O-linked carbohydrate chains. Then, a hybrid of rJeFSH·2xeCG extended with two eCG CTP. Furthermore, the receptor binding assay revealed potency of rJeFSH and rJeFSH·2xeCG to be a few folds greater than that of rJeFSH·eCG. The findings of this study will be useful for the development of more efficient GTHs in teleosts, including eels, when various modifications with two or more extended eCG CTP produced by silkworm are included. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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9. Follitropin
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Gressner, Axel M., editor and Arndt, Torsten, editor
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- 2019
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10. The relationship between circulating anti-mullarian hormone (AMH) and superovulatory response in buffaloes
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Magdy R. Badr, Mohamed Refaai, Mohamed Atef, Adel A. Seida, and Mohamed Fathi
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Estrous cycle ,endocrine system ,education.field_of_study ,business.industry ,media_common.quotation_subject ,Population ,Embryo ,Follitropin ,Embryo transfer ,Andrology ,Follicular phase ,Medicine ,education ,business ,Ovulation ,media_common ,Hormone - Abstract
The current study aimed to investigate the effect of using the superovulatory drug ‘follitropin’ on the follicular population and number of harvested buffalo embryos. At first, all animals were exposed to AMH analysis, Estrus was synchronized either by progesterone releasing intravaginal device (PRID) for 7 days or by double doses of cloprostenol sodium 11 days interval. A total dose of 40 IU of Follitropin was injected intramuscular for each animal as superovulatory drug (5 IU am and 5 IU pm for 4 consecutive days). AI was done using double straw/time for 3 times with 12 hours interval. Seven days later (day 0=ovulation day), embryos were recovered non-surgically. The results showed that total number of follicles/ animal was significantly increased in the group synchronized by PRID (7.4 ± 0.53) than the group synchronized by cloprostenol (4.8 ± 0.18), Number of the recovered embryos was significantly higher in the group synchronized by PRID (3.2 ± 0.71) than the group synchronized by cloprostenol (2.2 ± 0.37). In conclusion, AMH analysis is a crucial issue in expecting the superovulatory response in buffaloes, injection of follitropin as a superovulatory drug during diestrus phase in buffaloes that previously synchronized by PRID leads to a higher yielded embryo
- Published
- 2021
11. Investigators from Ferring Pharmaceuticals Inc. Release New Data on Reproductive Medicine (Establishing the Follitropin Delta Dose That Provides a Comparable Ovarian Response To 150 Iu/day Follitropin Alfa)
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Follicle-stimulating hormone ,Women's health ,Follitropin ,Hormone antagonists ,Health ,Women's issues/gender studies - Abstract
2020 NOV 5 (NewsRx) -- By a News Reporter-Staff News Editor at Women's Health Weekly -- Data detailed on Health and Medicine - Reproductive Medicine have been presented. According to [...]
- Published
- 2020
12. New Findings from Merck & Company in the Area of Ovarian Hyperstimulation Syndrome Reported [The Frequency of Ovarian Hyperstimulation Syndrome and Thromboembolism with Originator Recombinant Human Follitropin Alfa (GONAL-f) for Medically ...]
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Merck & Company Inc. ,Merck KGaA ,Follicle-stimulating hormone ,Women's health ,Thromboembolism ,Medical research ,Pharmaceutical industry ,Follitropin ,Health ,Women's issues/gender studies - Abstract
2020 OCT 29 (NewsRx) -- By a News Reporter-Staff News Editor at Women's Health Weekly -- Researchers detail new data in Ovarian Diseases and Conditions - Ovarian Hyperstimulation Syndrome. According [...]
- Published
- 2020
13. An observational study «FOLLITROPIN» comparing the efficacy of follitropin alpha biosimilar: the real-world data
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E. V. Broitman, I. A. Bendusov, D. P. Kamilova, M. A. Polzikov, E. S. Tararashkina, S. V. Nikitin, M. M. Ovchinnikova, E. Sh. Ablyaeva, N. S. Stuleva, M. A. Ganikhina, K. Yu. Boyarskiy, D. T. Khetagurova, E. N. Mayasina, E. N. Ovsyannikova, M. A. Yudina, D. V. Blinov, M. M. Leviashvili, Z. B. Barakhoeva, Yu. A. Fetisova, and L. F. Iskhakova
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Embryology ,medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,Population ,Urology ,Follitropin ,Reproductive technology ,follitropin alpha ,03 medical and health sciences ,0302 clinical medicine ,ivf ,medicine ,030212 general & internal medicine ,education ,art ,education.field_of_study ,assisted reproductive technologies ,030219 obstetrics & reproductive medicine ,In vitro fertilisation ,business.industry ,Obstetrics and Gynecology ,Retrospective cohort study ,Gynecology and obstetrics ,Clinical trial ,Reproductive Medicine ,recombinant follicle-stimulating hormone ,fsh ,RG1-991 ,biosimilar ,Gonadotropin ,business ,in vitro fertilization ,Cohort study - Abstract
Introduction. The efficacy and safety of biosimilar follitropin alpha have been demonstrated in randomized blinded prospective clinical trials of phases I and III. Unfortunately, there is a gap between the clinical trials and real clinical practice data. The real-world patient data helps to create an evidence-based background for successful implementation of medicine at everyday practice in a nonselected population.Aim: to investigate the efficacy of follitropin alpha biosimilar therapy (Primapur®) in nonselected real-world population.Materials and Methods. A retrospective observational anonymized cohort study of follitropin alpha biosimilar (Primapur®) as a pre-filled pen injector with a dose adjustment of 5 IU, aimed to investigate its efficacy and safety in a nonselected population with indications to assisted reproductive technologies (ART) was carried out. The ovarian stimulation (OS) protocols included: monotherapy protocols with using only Primapur®; mixed protocols (recombinant and urinary-derived gonadotropins); short protocols with using antagonists of gonadotropin-releasing hormone (GnRH) and long protocols with GnRH agonists. The stimulation protocols were analyzed with Primapur® application for at least 5 days.Results. The overall clinical efficacy of ovarian stimulation cycles (N = 5484) was: oocytes retrieved - 9.5 ± 7.2, mature (MII) - 6.8 ± 6.6, fertilized (2PN) - 6.1 ± 5.8, clinical pregnancy per ET (PR) - 38.4 %. Mixed gonadotropin protocols (N = 2625) vs. monotherapy with Primapur® (N = 2859): oocytes retrieved - 8.6 ± 6.8 vs. 10.3 ± 7.4 (p < 0.001), mature (MII) - 6.7 ± 6.2 vs. 7.7 ± 6.9 (p < 0.001), fertilized (2PN) - 5.8 ± 5.2 vs. 7.2 ± 6.2 (p < 0.001). There were statistically significant differences between oocyte yields in mixed vs. monotherapy protocols due to subgroup differences, including age, body mass index (BMI) and IVF/ICSI attempts. No statistically significant differences were found for PR: 39.3 % vs. 37.6 % (p = 0.314). Monotherapy protocols with GnRH antagonist OS (N = 2183) vs. GnRH agonist (N = 676) revealed: oocytes retrieved - 10.5 ± 7.5 vs. 9.6 ± 7.0 (p = 0.032), mature (MII) - 7.6 ± 6.9 vs. 6.7 ± 5.7 (p < 0.001), fertilized (2PN) - 7.3 ± 6.3 vs. 5.7 ± 5.0 (p < 0.001). There were statistically significant differences between BMI and IVF/ICSI attempts. No statistically significant differences were found for PR: 37.9 % vs. 35.9 % (p = 0.482). All medicines were well tolerated and no serious adverse reactions were reported.Conclusion. This was the largest retrospective observational study conducted in the field of fertility in Russia and involved 5484 ovarian stimulation protocols at 35 IVF clinics. The obtained results demonstrated similar clinical efficacy for follitropin alpha biosimilar Primapur® in different OS protocols in real clinical practice.
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- 2021
14. Evaluation of Protocols of Controlled Ovarian Stimulation in Obtaining Mature Oocytes (MII): Retrospective Study on Assisted Reproductive Technology Procedures
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Patrícia Cordeiro Pires de Figueiredo Gomes Crisóstomo Ruivo, Denise Cristina Mós Vaz-Oliani, Cátia Manuela Ribeiro Barbosa Martins, Antonio Helio Oliani, and Renato Silva Martins
- Subjects
Infertility ,Agonist ,endocrine system ,Reproductive Techniques, Assisted ,medicine.drug_class ,medicine.medical_treatment ,Urinary system ,Follitropin ,Fertilization in Vitro ,Gonadotropin-Releasing Hormone ,Andrology ,Hormone Antagonists ,Ovulation Induction ,medicine ,Humans ,Ovarian reserve ,Retrospective Studies ,Assisted reproductive technology ,biology ,business.industry ,Anti-Müllerian hormone ,medicine.disease ,Antral follicle ,Oocytes ,biology.protein ,Follicle Stimulating Hormone ,business - Abstract
OBJECTIVE To understand which of the controlled ovarian stimulation (COS) protocols used in different patients are associated with greater amounts of oocytes retrieved. METHODS The study population was divided into three groups, considering AMH and AFC to obtain the Ovarian Response Predictor Index (ORPI); they were grouped into: G1-Low Reserve (ORPI
- Published
- 2022
15. Patent Issued for Glycoprotein Hormone Long-Acting Superagonists (USPTO 10,457,713)
- Subjects
Hormones -- Reports ,Physical fitness -- Reports ,Glycoproteins -- Reports ,Chorionic gonadotropins -- Intellectual property -- Reports ,Thyrotropin -- Reports ,Amino acids -- Intellectual property -- Reports ,Luteinizing hormone -- Reports ,Gonadotropins ,Follitropin ,Obesity ,Placental hormones ,Pituitary hormones ,Editors ,Health - Abstract
2019 NOV 16 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- From Alexandria, Virginia, NewsRx journalists report that a patent by the inventors [...]
- Published
- 2019
16. Biosimilars to recombinant human FSH medicines: comparable efficacy and safety to the original biologic.
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de Mora, Fernando and Fauser, Bart C.J.M.
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FOLLICLE-stimulating hormone , *BIOLOGICALS , *DRUG efficacy , *DRUG development , *SAFETY , *THERAPEUTICS - Abstract
Two recombinant follicle-stimulating hormone (rFSH)-bearing similar biological medicines (biosimilars) have been authorized by the European Commission. Biosimilar is a regulatory concept alluding to the evidence-based high-standard comparability studies needed to demonstrate its equivalence to a reference original biologic. Because biosimilar development represents a shift from the long-lasting existing paradigms, a thorough understanding of the science behind it will contribute to helping prescribers make informed treatment choices. Contrary to chemically-synthesized medicines, biologics are subject to an inherent molecular variability. From the experience with original biologics, regulatory authorities have accumulated a wealth of knowledge as to what minor batch-to-batch physicochemical variations may be therapeutically acceptable in a given product. Furthermore, in spite of analytically detectable differences, the two original rFSH-bearing medicines currently on the market share fundamentally the same therapeutic profile. Unlike those original medicines, a biosimilar of an rFSH product and the corresponding reference biologic share essentially the same active pharmaceutical ingredient. They are also administered via the same route, at the same dose, and for the same indications. This article revises the background evidence over which the biosimilarity principle has been built, and highlights the therapeutic potential for follitropin biosimilars in order to reassure physicians on their benefit. [ABSTRACT FROM AUTHOR]
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- 2017
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17. Évolution des préparations commercialisées à effet folliculostimulant.
- Author
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Hugues, Jean-Nöel
- Abstract
While both FSH and LH molecules present in the gonadotropin preparations manufactured from the urines proved to be efficient, the critical role of FSH in the process of follicular growth is likely to explain why products with FSH activity only were subsequently developed. For that reason, molecules with FSH only activity were manufactured with a progressive improvement in the process of purification allowing an increase in the specific activity of the products. However, several drawbacks in the urine collection emerged when a dramatic increase in the need of products was evident further to the development of In Vitro Fertilization in the late 80s: involvement of countries where the quality control was poos regarding the sources of donors, the ways of urine storage and transportation and the risk of virus contamination. In addition, the possible advantage of the LH activity supplementation suggested by some scientists led to the production of urinary products where LH molecules were extracted and substituted with hCG in a FSH/LH ratio of 1 as done in the 60s. However, whatever the manufacture of urinary products, their low specific activity related to urinary contaminants and their poor batch to batch consistency can easily explain why they could not satisfy clinicians in their daily practice. Meanwhile, identification of FSH genes simultaneously with the emergence of DNA recombinant technologies allowed the production of recombinant FSH molecules. This was actually a major step forward in the process of gonadotropin supply: no limitation in production, an improved safety due to the traceability of the process, higher purity and bio-activity as compared to urinary products. However, the final step in the manufacture process was still dependent on the Steelman & Pohley bioassay consisting in the measurement of the rat ovarian weight. The major drawback of the bioassay was actually its imprecision. Because Follitropin alpha can be produced with a highly constant isoform profile, it can be eventually calibrated through a simple and highly precise measurement of the mass (Filled by mass process). This step was absolutely critical to improve the batch to batch consistency of the final product and, eventually, the reproducibility of the ovarian response. The technics of recombinant technology, eventually applied to gonadotropins, are clearly a new step forward at the benefit of couples. [ABSTRACT FROM AUTHOR]
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- 2017
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18. Role of cysteine residues in the carboxyl-terminus of the follicle-stimulating hormone receptor in intracellular traffic and postendocytic processing
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Brenda Melo-Nava, Patricia Casas-González, Marco Pérez-Solís, Jean Castillo-Badillo, José L. Maravillas-Montero, Eduardo Jardón-Valadez, Teresa Zariñán, Arturo Aguilar-Rojas, Nathalie GALLAY, Eric Reiter, and Alfredo Ulloa-Aguirre
- Subjects
Recycling ,internalization ,palmitoylation ,Follicle-stimulating hormone ,Follicle-stimulating hormone receptor ,Follitropin ,Biology (General) ,QH301-705.5 - Abstract
Posttranslational modifications occurring during the biosynthesis of G protein-coupled receptors include glycosylation and palmitoylation at conserved cysteine residues located in the carboxyl-terminus (Ctail) of the receptor. In a number of these receptors, these modifications play an important role in receptor function and particularly, in intracellular trafficking. In the present study, the three cysteine residues present in the carboxyl-terminus of the human FSHR were replaced with glycine by site-directed mutagenesis. Wild-type and mutant (Cys627/629/655Gly) FSHRs were then transiently expressed in HEK-293 cells and analyzed for cell-surface plasma membrane expression, agonist-stimulated signaling and internalization, and postendocytic processing in the abscence and presence of lysosome and/or proteasome inhibitors. Compared with the wild-type FSHR, the triple mutant FSHR exhibited ~70% reduction in plasma membrane expression as well as a profound attenuation in agonist-stimulated cAMP production and ERK1/2 phosphorylation. Incubation of HEK-293 cells expressing the wild-type FSHR with 2-bromopalmitate (palmitoylation inhibitor) for 6 h, decreased plasma membrane expression of the receptor by ~30%. The internalization kinetics and β-arrestin 1 and 2 recruitment were similar between the wild-type and triple mutant FSHR as disclosed by assays performed in non-equilibrium binding conditions and by confocal microscopy. Cells expressing the mutant FSHR recycled the internalized FSHR back to the plasma membrane less efficiently than those expressing the wild-type FSHR, an effect that was counteracted by proteasome but not by lysosome inhibition. These results indicate that replacement of the cysteine residues present in the carboxyl-terminus of the FSHR, impairs receptor trafficking from the endoplasmic reticulum/Golgi apparatus to the plasma membrane and its recycling from endosomes back to the cell surface following agonist-induced internalization. Since in the FSHR these cysteine residues are S-palmitoylated, the data presented emphasize on this posttranslational modification as an important factor for both upward and downward trafficking of this receptor.
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- 2016
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19. Fully human glyco-optimized recombinant FSH (follitropin epsilon) – a randomized, comparator-controlled phase II clinical trial
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Kelvin Eckert, Bruno Dietrich, Georg Griesinger, Steffen Goletz, Lars Stöckl, and Andreas Tandler-Schneider
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Adult ,0301 basic medicine ,Agonist ,endocrine system ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,Follitropin ,Context (language use) ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Ovarian Follicle ,Ovulation Induction ,Internal medicine ,Humans ,Medicine ,Inhibins ,Progesterone ,Ivf treatment ,030219 obstetrics & reproductive medicine ,Dose-Response Relationship, Drug ,Estradiol ,business.industry ,Standard treatment ,Ovary ,Dose-finding ,Obstetrics and Gynecology ,Recombinant Proteins ,Clinical trial ,Recombinant fsh ,030104 developmental biology ,Endocrinology ,Reproductive Medicine ,Follitropin epsilon ,Female ,Follicle Stimulating Hormone, Human ,Ovarian stimulation ,business ,Human glyco-optimized recombinant FSH ,Recombinant FSH ,Developmental Biology ,Hormone - Abstract
Research question The study aimed to determine the standard treatment dose of follitropin epsilon for ovarian stimulation in the context of IVF treatment. Design A total of 247 women aged 18-37 years were treated with either 52.5, 75, 112.5 or 150 IU follitropin epsilon daily, or 150 IU every other day, or 150 IU follitropin alfa daily in a long gonadotrophin-releasing hormone agonist protocol. The study was performed as a randomized, assessor-blinded, comparator-controlled, six-armed phase II trial in eight fertility clinics in two European countries. Results The primary results were as follow. First, none of the doses of follitropin epsilon showed superiority for the main outcome measure, i.e. number of follicles ≥12 mm in size. Follitropin epsilon 75 IU produced results most similar to those of follitropin alfa 150 IU. In terms of secondary results, stronger effects of follitropin epsilon 112.5 IU compared with follitropin alfa 150 IU were seen for secondary outcome measures such as hormone concentrations (oestradiol, inhibin B and progesterone) and oocyte number. Conclusions Follitropin epsilon 75 IU daily results in a similar ovarian response to a standard dose of 150 IU follitropin alfa. This dose could be tested in a phase III trial.
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- 2020
20. Efficacy of Follitropin-A (Gonal-F) Versus Follitropin-B (Puregon) for Controlled Ovarian Stimulation in Women Undergoing IVF
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Mohammed Khudhair Hasan, Najlaa Saadi Ismael, Yazan A. Bataineh, Qutaiba Ahmed Al Khames Aga, Myasar Jasim Mohammed Al Taie, Hayder Abdulhafedh Kurji, and Ahmed Hazem Abdulkareem
- Subjects
Infertility ,endocrine system ,Pregnancy ,In vitro fertilisation ,business.industry ,medicine.medical_treatment ,Embryo ,Follitropin ,medicine.disease ,Oocyte ,Andrology ,Pregnancy rate ,Human fertilization ,medicine.anatomical_structure ,medicine ,business ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) - Abstract
The purpose of this study was to compare the efficacy of two recombinant FSH on pregnancy rates in infertile patients. Material and Methods: between 2015-2017, 387 females intended to have in vitro fertilization (IVF) for infertility treatment (226 patients use Gonal-F and 161 using Puregon. Results: Serum E2 concentration at hCG time was higher with Follitropin-a treated patients, and a larger number of retrieved oocyte result in a large number of the transferred embryo, and high pregnancy rate than Follitropin-b treated patients. Conclusions: Gonal-F (Follitropin-a) is associated with a potential stimulatory effect on ovaries. Puregon (Follitropin-b) was associated with a lower clinical pregnancy rate (PR). E2 level 5-7 days after stimulation can be used as an indicator of the success of IVF.
- Published
- 2019
21. P–669 'Follitropin': A retrospective, observational study comparing the efficacy of follitropin alpha biosimilar therapy in different ovarian stimulation protocols: real-world data
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D Kamilova, D. T. Khetagurova, Z Barakhoeva, E Mayasina, T Ushakova, D Blinov, M Ganikhina, K Boyarsky, M Ovchinnikova, M Polzikov, E Ablyaeva, S Nikitin, E Osina, and I Bendusov
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Oncology ,medicine.medical_specialty ,business.industry ,Rehabilitation ,Obstetrics and Gynecology ,Retrospective cohort study ,Biosimilar ,Follitropin ,Follitropin alpha ,Biosimilar Pharmaceuticals ,Reproductive Medicine ,Internal medicine ,medicine ,Menotropins ,business ,Real world data ,Unexplained infertility - Abstract
Study question To investigate the therapeutic efficacy of follitropin alpha biosimilar therapy in nonselected patients undergoing IVF. Summary answer This large retrospective study demonstrated similar therapeutic efficacy for follitropin alpha biosimilar therapy in women who underwent ovarian stimulation (OS) using different protocols. What is known already Based on data from the last meta-analyses (Budani et al., 2020), follitropin alpha biosimilars showed similar efficacy and safety in randomized controlled trials aimed at proving the therapeutic equivalence in terms of oocytes retrieved in women undergoing OS. In most cases, normogonadotrophic patients were enrolled in such studies without any endocrine or ovarian disturbances. The absence of real-world data can be compensated by additional post-marketing studies aimed at investigating the efficacy of biosimilars in different OS protocols using antagonists and agonists of GnRH and OS with mixed gonadotropins. Study design, size, duration A retrospective, observational, anonymized cohort study conducted at 35 IVF clinics in Russia, named “FOLLITROPIN”, compared the efficacy of OS in 2020. The OS protocols analysed where follitropin alpha biosimilar (Primapur®) was applied for at least 5 days. All of the analysed subjects underwent OS using GnRH antagonist/agonist protocols, with no restrictions on the OS protocol or food supplements/vitamins. No inclusion or exclusion criteria were applied. Overall, 5484 OS protocols were analysed. Participants/materials, setting, methods The efficacy of 5484 OS protocols was calculated, and two subgroups were extracted: (1) mixed gonadotropin OS protocols (N = 2625) vs monotherapy with Primapur® (N = 2859); (2) GnRH antagonist OS (N = 2183) vs GnRH agonist (N = 676) using only Primapur®. Demographic and clinical characteristics: (1) Age 34.9±4.8 vs 32.9±4.7 (p Main results and the role of chance The total efficacy of OS with Primapur®: oocytes retrieved: 9.5±7.2, MII: 6.8±6.6, 2PN: 6.1±5.8, clinical pregnancy per ET (PR) 6 weeks after ET: 38.4%. Subgroup 1 analysis: oocytes retrieved: 8.6±6.8 vs 10.3±7.4 (p Limitations, reasons for caution The real-world patient data analysed in this study were representative, showing the ability of follitropin biosimilars to develop both folliculogenesis and clinical pregnancy in a nonselected population. Additional comparative studies are needed to confirm the efficacy of the biosimilars in patients with classified types of infertility causes, including unexplained infertility. Wider implications of the findings: In this study, we demonstrated the therapeutic efficacy of biosimilars in terms of oocyte yield and clinical pregnancy development in women undergoing different OS protocols. Further large-scale studies with known hormonal levels before and during OS, as well as the micro- and macronutrient status of both parents, are needed. Trial registration number None
- Published
- 2021
22. P–637 Development and validation of an Artificial Intelligence algorithm that matches a clinician ability to select the best follitropin dose for ovarian stimulation
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J Cerquides, N. Corre Mañas, R Vassena, F Rodríguez, and J L Arcos
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Reproductive Medicine ,business.industry ,Computer science ,Rehabilitation ,Obstetrics and Gynecology ,Follitropin ,Stimulation ,Artificial intelligence ,business - Abstract
Study question Is it possible for an Artificial Intelligence (AI) model to match the performance of clinicians in prescribing the first dose of follitropin? Summary answer The AI based Decision Support System (DSS) we developed identifies accurately the optimal starting dose range of follitropin and prospectively matches the clinicians’ performance. What is known already Most patients treated by IVF undergo Controlled Ovarian Stimulation (COS). Based on their ovarian markers, demographic characteristics, and clinical history, an initial dose of follitropin is prescribed. Failing to tailor correctly this dose can result in a suboptimal ovarian response, leading on the one hand to low and ineffective response or, on the other, to excessive and dangerous stimulation. AI methods can learn from large databases of COS results and generate predictive models to assist the clinicians in optimizing this decision. Study design, size, duration A database of 2713 first IVF cycles from 5 clinics, from 2011 to 2019 was used to develop the model. Predictor variables included: age, BMI, AMH, FSH, LH, estradiol, Antral Follicular Count (AFC), infertility etiology, and previous live births. 80% of the database was used to train the algorithm, and 20% to test the DSS. Additional 524 cycles from a different period (2020–2021) were used for prospective validation. Participants/materials, setting, methods Follitropin dosage was divided in 4 categories: 100–150IU, 151–200IU, 201–250IU, and >250IU. An optimal ovarian response is defined as retrieving 10–15 MII, whenever the patient ovarian reserve allows it. To predict the optimal dose range personalized to each patient, the DSS uses a Random Forest model learned with training cycles. To evaluate the DSS performance, a score for each dose range and each patient was defined given the prescribed doses and the corresponding ovarian responses. Main results and the role of chance The cycles included in the database were from women 37.2±4.9 years old [18–45], with a BMI of 23.7±4.2, AMH of 2.4±2.3, AFC of 11.8±7.7; the average number of oocytes and MII obtained was 10.1±7.1 and 7.2±5.3, respectively. The DSS achieved a performance mean score of 0.88 in the testing database, a value significantly better than the one calculated for the doses prescribed by the clinicians, which had a mean score of 0.83 (p-value Limitations, reasons for caution The DSS prospective validation should be extended to more clinical cases to ensure higher reliability. Hyper-responders were underrepresented in the database which can lead to less accurate recommendation in some of these women. As all AI models, the DSS should be tested prospectively before clinical application. Wider implications of the findings: The AI based clinical Decision Support System that we developed could be deployed as a training and learning tool for new clinicians and serve as quality control for experienced ones; further, it can be used as an electronic second opinion, for instance by providing information in peer-to-peer case discussions. Trial registration number Not applicable
- Published
- 2021
23. Effectiveness Assessment of a Modified Preservation Solution Containing Thyrotropin or Follitropin Based on Biochemical Analysis in Perfundates and Homogenates of Isolated Porcine Kidneys after Static Cold Storage
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Barbara Dolińska, Florian Ryszka, and Aneta Ostróżka-Cieślik
- Subjects
0301 basic medicine ,kidneys ,endocrine system ,endocrine system diseases ,QH301-705.5 ,Swine ,Organ Preservation Solutions ,Ischemia ,Cold storage ,Renal function ,Thyrotropin ,030209 endocrinology & metabolism ,Follitropin ,Kidney ,Catalysis ,Article ,static cold storage ,Inorganic Chemistry ,Andrology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Animals ,Biology (General) ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Spectroscopy ,Kidney perfusion ,Creatinine ,Chemistry ,Organic Chemistry ,pigs ,General Medicine ,Organ Preservation ,Biolasol ,medicine.disease ,In vitro ,Computer Science Applications ,Cold Temperature ,030104 developmental biology ,Follicle Stimulating Hormone ,Perfusion ,follitropin ,hormones, hormone substitutes, and hormone antagonists - Abstract
In this paper, we assess the nephroprotective effects of thyrotropin and follitropin during ischaemia. The studies were performed in vitro in a model of isolated porcine kidneys stored in Biolasol (FZNP, Biochefa, Sosnowiec, Poland) and modified Biolasol (TSH: 1 µg/L, FSH 1 µg/L). We used the static cold storage method. The study was carried out based on 30 kidneys. The kidneys were placed in 500 mL of preservation solution chilled to 4 °C. The samples for biochemical tests were collected during the first kidney perfusion (after 2 h of storage) and during the second perfusion (after 48 h of storage). The results of ALT, AST, and LDH activities confirm the effectiveness of Biolasol + p-TSH in maintaining the structural integrity of renal cell membranes. Significantly reduced biochemical parameters of kidney function, i.e., creatinine and protein concentrations were also observed after 48 h storage. The protective effect of Biasol + p-TSH is most pronounced after 2 h of storage, suggesting a mild course of damage thereafter. A mild deterioration of renal function was observed after 48 h. The results of our analyses did not show any protective effect of Biolasol + p-FSH on the kidneys during ischaemia.
- Published
- 2021
24. Heterologous Production and Glycosylation of Japanese Eel Follitropin Using Silkworm
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Kwan Sik Min, Jae Man Lee, Sun Jung Jo, Dae-Jung Kim, Takahiro Kusakabe, Ji Hyun Choi, and Sun Mee Hong
- Subjects
0106 biological sciences ,endocrine system ,Glycosylation ,medicine.drug_class ,Biomedical Engineering ,Heterologous ,Bioengineering ,Follitropin ,Biology ,01 natural sciences ,Applied Microbiology and Biotechnology ,03 medical and health sciences ,chemistry.chemical_compound ,010608 biotechnology ,medicine ,Japanese eel ,Equine chorionic gonadotropin ,030304 developmental biology ,0303 health sciences ,Hormone activity ,fungi ,biology.organism_classification ,chemistry ,Biochemistry ,Vitellogenesis ,Gonadotropin ,Biotechnology - Abstract
Follitropin, an important gonadotropin hormone, participates in vitellogenesis and spermatogenesis. Equine chorionic gonadotropin (eCG) can induce gonadotropin hormone activity in non-equid species and exhibits a long biological half-life. Here, we report the production, using silkworm larval and pupal systems, of biologically active recombinant hybrid-type follitropins based on the coding sequence of the eCG C-terminal peptide (CTP) between the mature β- and α-chains of eel. The three constructs, rJeFSH, rJeFSH·eCG, and rJeFSH·2xeCG were produced and verified to be N- or O-glycosylated and secreted mature peptides. Although rJeFSH·eCG contains more elaborate O-linked carbohydrate chains than rJeFSH, it elicited no significant in vitro oocyte maturation, which may be a result of insufficient terminal sialylation of its N-and O-linked carbohydrate chains. Then, a hybrid of rJeFSH·2xeCG extended with two eCG CTP. Furthermore, the receptor binding assay revealed potency of rJeFSH and rJeFSH·2xeCG to be a few folds greater than that of rJeFSH·eCG. The findings of this study will be useful for the development of more efficient GTHs in teleosts, including eels, when various modifications with two or more extended eCG CTP produced by silkworm are included.
- Published
- 2019
25. Major results of a phase III comparative multicenter study on the follitropin alfa biosimilar (Primapur®) and the original follitropin alfa (Gonal-f®)
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M. M. Ovchinnikova, R. I. Shalinа, A. V. Kolotovkina, L. G. Sichinava, V.P. Apryshko, Z. B. Barakhoeva, N. A. Marilova, Yu. V. Sherbatyuk, Irina Zorina, G. V. Kasyanova, A. A. Miskun, N. Yu. Belousova, T. A. Teterina, M. A. Tishenko, S.A. Yakovenko, L. A. Vovk, E. G. Morozova, Yu. A. Fetisova, and M. A. Polzikov
- Subjects
Infertility ,Embryology ,medicine.medical_specialty ,medicine.medical_treatment ,Urology ,Follitropin ,Reproductive technology ,law.invention ,Randomized controlled trial ,law ,medicine ,assisted reproductive technologies ,In vitro fertilisation ,business.industry ,Obstetrics and Gynecology ,Biosimilar ,Gynecology and obstetrics ,medicine.disease ,Follitropin alfa ,follitropin alfa ,Reproductive Medicine ,Multicenter study ,recombinant follicle-stimulating hormone ,RG1-991 ,biosimilar ,business ,in vitro fertilization - Abstract
A clinical study on the efficacy and safety of follitropin alfa has been conducted. The aim of the study was to confirm the therapeutic equivalence between the follitropin alfa biosimilar (Primapur®) and the reference medication (Gonal-f®) in controlled induction of superovulation within the assisted reproductive technologies (ART) programs. Materials and methods. This multicenter, randomized, blind at the embryological stage, in parallel groups, comparative study of phase III (RCT 754 from 26.10.16/NCT03088137) involved 110 women aged 20-35 years with established causes of infertility (tubal factor, male factor). The patients were randomized into 2 equal groups of 55 participants each. The primary end-point for assessing the therapeutic equivalence was the number of aspirated oocytes. The secondary end-points included the number of fertilized oocytes, the number of days of stimulation, the total dose of the injected drug, the occurrence rate of biochemical and clinical pregnancies. Results. In this study, the follitropin alfa biosimilar was shown to be equivalent to the original follitropin in terms of the number of aspirated oocytes. Also, no statistically significant differences were found in the number of mature and fertilized oocytes, the days of stimulation, the dose of the drug administered during the treatment, and the rate of the onset of biochemical or clinical pregnancy. Conclusion. The therapeutic equivalence between the follitropin alfa containing Primapur® and Gonal-f® has been demonstrated.
- Published
- 2018
26. New Human Follitropin Preparations: How Glycan Structural Differences May Affect Biochemical and Biological Function and Clinical Effect
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Alfredo Ulloa-Aguirre and James A. Dias
- Subjects
0301 basic medicine ,glycoprotein ,Male ,Glycan ,endocrine system ,Glycosylation ,Acetylgalactosamine ,Endocrinology, Diabetes and Metabolism ,pharmocodynamics ,Follitropin ,Context (language use) ,Review ,Asialoglycoprotein Receptor ,CHO Cells ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Endocrinology ,Cricetulus ,Polysaccharides ,therapeutics ,Animals ,Humans ,Protein Isoforms ,Glycoproteins ,chemistry.chemical_classification ,lcsh:RC648-665 ,030219 obstetrics & reproductive medicine ,biology ,N-Acetylneuraminic Acid ,Recombinant Proteins ,Sialic acid ,Rats ,030104 developmental biology ,chemistry ,Biochemistry ,Liver ,Galactosamine ,biology.protein ,Asialoglycoprotein receptor ,Female ,Follicle Stimulating Hormone, Human ,Follicle Stimulating Hormone ,Glycoprotein ,follitropin ,pharmacokinetics - Abstract
It is well accepted that pituitary follitropin is secreted into the circulation as a mixture of variants, which differ not in primary structure but rather at the level of glycosylation. These glycosidic forms vary in the number of glycosylation sites filled, complexity of glycosidic chains, and sialylation and sulfation. It is generally agreed that high sialylation, 2,3 sialic acid capping of terminal N-acetyl galactosamine or galactose leads to longer circulating half-life, by blocking binding of asialoglycoprotein receptor (ASGPR) in the liver. In contrast, 2,6 sialic acid found in humans does not prevent recognition of galactose and N-acetyl galactosamine by ASGPR. Few studies on clinical outcomes comparing differences in sialylation of follitropin found in commercially available preparations are available. Thus, there is a clear need for a consortium of open data to address this unmet need. Recently, FSH glycosylation, primarily on the β-subunit, which varies as women age, has emerged as a key modifier of follitropin action, with profound biological effects in vivo in animal models. To date, limited information of recombinant follitropin hormone preparations is available. Thus, most of the studies with FSH that is well characterized biochemically have been done in vitro, with engineered non gonadal host cells bearing recombinant receptors or in animal models. Since limited studies in human granulosa cells are available, a question is whether structural differences in glycosylation in commercially available follitropin affects biological function and clinical effect in humans. The presence of fucose, for example, has not been studied greatly even though, in the case of antibody therapy it has been shown to have a large effect on antibody targeting. This review on glycosidic variability of follitropin from the biochemical/structural point of view reflects on this question and presents an assessment in the context of available published data. If clinical differences are to be expected or not, the readers will have a better understanding of the evidence for and limitations of such expectations.
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- 2021
27. Receptors | Thyroid-Stimulating Hormone/Luteinizing Hormone/Follicle-Stimulating Hormone Receptors
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Combarnous, Yves, Crépieux, Pascale, Reiter, Eric, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Dynamiques de populations multi-échelles pour des systèmes physiologiques (MUSCA), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE), Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE)
- Subjects
LH ,Gonadotropin ,Thyroid ,endocrine system ,0303 health sciences ,TSH ,[SDV]Life Sciences [q-bio] ,Lutropin ,Ovary ,Thyrotropin ,Follitropin ,TSHR ,03 medical and health sciences ,Thyrotropin receptor autoantibodies TRAbs ,0302 clinical medicine ,FSHR ,030220 oncology & carcinogenesis ,FSH ,LHCGR ,Glycoprotein hormone ,G protein-coupled receptor ,Testes ,hormones, hormone substitutes, and hormone antagonists ,030304 developmental biology - Abstract
International audience; The thyroid-stimulating hormone receptor (TSHR), luteinizing hormone receptor (LHCGR), and follicle-stimulating hormone receptor (FSHR) are collectively referred to as the glycoprotein hormone receptors because they bind structurally similar glycoprotein hormones. The glycoprotein hormones consist of the pituitary thyroid-stimulating hormone (thyrotropin, TSH), luteinizing hormone (lutropin, LH), and follicle-stimulating hormone (follitropin, FSH) as well as the chorionic gonadotropin (choriogonadotropin, CG) placental hormone. The glycoprotein hormones are each composed of two dissimilar subunits (α and β) that are noncovalently associated. Within a given species, the α-subunit is identical and the β-subunits are distinct but homologous. Due to the largely similar nature of LHβ and CGβ, the LHCGR binds either LH or CG. The binding specificity of LH/CG to the LHCGR, FSH to the FSHR, and TSH to the TSHR is fairly strict. However, in some cases, extremely high levels of hormone can cause activation of the inappropriate receptor. Because the LHCGR and FSHR are localized primarily to the gonads, these two receptors are also referred to as the gonadotropin receptors. The glycoprotein hormone receptors belong to the family A (rhodopsin-like) of G protein-coupled receptors (GPCRs). However, they share the relatively unique feature of having a large extracellular domain that mediates high affinity binding of the hormone. In spite of their different physiological roles, the glycoprotein hormone receptors share a similar structural organization and mechanism of action.
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- 2021
28. Short anogenital distance is associated with testicular germ cell tumour development
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Moreno-Mendoza D., Casamonti E., Riera-Escamilla A., Pietroforte S., Corona G., Ruiz-Castañe E., and Krausz C.
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Male ,Anal Canal ,cancer risk ,penis ,single nucleotide polymorphism ,androgen receptor ,AR protein, human ,Cryptorchidism ,Testis ,genetics ,cryptorchism ,Prospective Studies ,pathophysiology ,scrotum ,Hypospadias ,adult ,seminoma ,risk assessment ,Neoplasms, Germ Cell and Embryonal ,priority journal ,spermatozoon count ,Receptors, Androgen ,non seminomatous germinoma ,luteinizing hormone ,Androgens ,follitropin ,carcinogenesis ,prospective study ,hormone determination ,phenotype ,androgen ,sperm ,Polymorphism, Single Nucleotide ,Article ,semen analysis ,histology ,Testicular Neoplasms ,Semen ,Humans ,controlled study ,anogenital distance ,human ,gonadotropin ,testis tumor ,spermatozoon motility ,case control study ,major clinical study ,human tissue ,sensitivity and specificity ,Spain ,testosterone ,physiology ,metabolism ,neoplasm ,anatomy and histology - Abstract
Background: Testicular germ cell tumour is a multifactorial disease in which various genetic and environmental factors play a role. Testicular germ cell tumour is part of the testicular dysgenesis syndrome which includes also cryptorchidism, hypospadias, oligo/azoospermia and short anogenital distance. Objectives: The primary objective was to examine anogenital distance in testicular germ cell tumour cases and healthy fertile controls. The secondary objective was to assess the (CAG)n polymorphism of the Androgen Receptor gene in relationship with anogenital distances and testicular germ cell tumour development. Material and Methods: 156 testicular germ cell tumour patients and 110 tumour-free normozoospermic controls of Spanish origin. All subjects underwent full andrological workup (including semen and hormone analysis) and genetic analysis (Androgen Receptor (CAG)n). The main outcome measures were the anopenile distance (AGDap), the anoscrotal distance (AGDas) and AR(CAG)n. Result: We observed significantly shorter anogenital distances in the group of testicular germ cell tumour patients in respect to controls (P
- Published
- 2020
29. Cell-free nucleic acids and melatonin levels in human follicular fluid predict embryo quality in patients undergoing in-vitro fertilization treatment
- Author
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Ismail Abdur Rahman Khan Sherwani, Sana Abbas, Zaid Munir, Yousaf Latif Khan, Hikmet Hakan Aydin, Zahira Hassan, Shahzad Bhatti, Samina Suhail, Haroon Latif Khan, and Ege Üniversitesi
- Subjects
antral follicle count ,Male ,ovary follicle ,Embryo quality ,medicine.medical_treatment ,cell free nucleic acid ,Chorionic Gonadotropin ,male infertility ,thyrotropin ,0302 clinical medicine ,Ovarian Follicle ,follitropin blood level ,Pregnancy ,Follicular phase ,Prospective Studies ,Melatonin ,receiver operating characteristic ,030219 obstetrics & reproductive medicine ,predictive value ,Estradiol ,copy number variation ,Obstetrics and Gynecology ,clinical trial ,Embryo ,recombinant follitropin ,transvaginal echography ,chemiluminescence immunoassay ,real time polymerase chain reaction ,IVF ,030220 oncology & carcinogenesis ,mammalian embryo ,luteinizing hormone ,Circulating cell-free nucleic acids ,blood sampling ,tertiary care center ,Female ,follitropin ,in vitro fertilization ,Cell-Free Nucleic Acids ,Infertility, Female ,prospective study ,medicine.drug ,Adult ,Infertility ,DNA Copy Number Variations ,female infertility ,embryo ,hormone blood level ,gene dosage ,DNA Fragmentation ,Fertilization in Vitro ,Follicular fluid ,progesterone ,purigon ,chemistry ,recombinant chorionic gonadotropin ,Article ,menstrual cycle ,Andrology ,03 medical and health sciences ,Follicle ,Ovulation Induction ,blood ,medicine ,Humans ,human ,procedures ,oocyte ,Infertility, Male ,embryo transfer ,pregnancy outcome ,In vitro fertilisation ,ovary follicle fluid ,business.industry ,endometrial thickness ,triptorelin ,DNA ,progesterone blood level ,Embryo, Mammalian ,medicine.disease ,major clinical study ,oocyte maturation ,pregnant woman ,thyrotropin blood level ,ROC Curve ,Reproductive Medicine ,estradiol blood level ,Oocytes ,luteinizing hormone blood level ,Follicle Stimulating Hormone ,business ,Muellerian inhibiting factor - Abstract
Despite many advances in assisted reproductive technology (ART), the most viable embryo selection remains a challenge for infertility treatment. This study was designed to investigate whether intrafollicular circulating cell-free DNA (cfDNA) fragments and Melatonin levels predict embryo quality in patients undergoing IVF treatment. A total of eight hundred and ninety-five follicular fluid (ff) samples were collected from 325 infertile patients undergoing IVF treatment. Patients were enrolled from August 2017 to December 2018 in the infertility center of a tertiary care hospital. A clear non-hematic follicular fluid was aspirated after the removal of eggs from the dominant follicles (>18 mm) of each patient. Melatonin and E-2 levels in each follicular sample were estimated by immune-chemiluminescence using commercially available kits. ALU-qPCR evaluated cfDNA levels in individual follicular fluid samples. Our study presented a significant and negative relationship between intra-follicular cfDNA and melatonin concentration (-0.541: P = 25%) than embryos with low fragmentation rate (, Lahore institute of Fertility and Endocrinology, Hammed Latif Hospital, Lahore institute of Fertility and Endocrinology, Hammed Latif Hospital.
- Published
- 2020
30. Stężenia gonadotropin i α podjednostki w surowicy krwi u pacjentów z gruczolakami gonadotropowymi przysadki w zależności od immunoreaktywności guza
- Author
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Maciej Radek, Katarzyna Winczyk, Maria Jaranowska, Jacek Świętosławski, Jolanta Kunert-Radek, Marek Pawlikowski Łódź, and Jolanta Fryczak
- Subjects
endocrine system ,medicine.medical_specialty ,Α subunit ,Adenoma ,medicine.drug_class ,business.industry ,Endocrinology, Diabetes and Metabolism ,Follitropin ,medicine.disease ,Endocrinology ,Blood serum ,Pituitary adenoma ,Internal medicine ,medicine ,In patient ,Gonadotropin ,business ,hormones, hormone substitutes, and hormone antagonists ,Immunostaining - Abstract
Introduction: Although active gonadotropin-secreting pituitary adenomas are considered very rare, the vast majority of pituitary tumours diagnosed as “non-functioning” express gonadotropins or their free β or α subunits. However, systemic investigations comparing the serum concentrations of follitropin (FSH), lutropin (LH), and α–subunit (αSU) before surgery with the immunoreactivity of the respective substances in the excised tumours are still lacking. Material and methods: Immunostaining of FSH, LH, and αSU was compared in 43 surgically removed gonadotropin — expressing pituitary adenomas with serum concentrations of the above-mentioned substances before surgery in the same patients. Results: The serum concentrations of FSH were elevated (> 11.6 mU/mL) in 8/12 (66.7%) cases of FSH-positive adenomas. By contrast, in FSH–negative tumours the elevation of FSH is absent. Moreover, only 1/25 (4%) patients with LH–positive adenoma had the elevated serum concentration of LH (51.5 mU/mL). The overproduction of LH was not observed in adenomas expressing free β LH or in LH-negative tumours. In patients with αSU-positive adenomas elevated serum levels of αSU were observed in 3/15 (20%) cases. No αSU elevations were observed in patients with αSU–negative adenomas. The mean serum FSH, LH, and αSU concentrations were higher in patients with FSH, LH, and/or αSU immunopositive tumours in comparison with immunonegative. However, the differences are not statistically significant. Conclusions: Although “silent” gonadotropinomas constitute a frequent subtype of pituitary adenomas, the “active” subtype (i.e. manifesting by gonadotropin excess) are rare (approx. 4% of all pituitary adenomas). Gonadotropinomas are difficult to diagnose before surgery. The measurement of gonadotropins including αSU is needed but often not sufficient for presurgical diagnosis.
- Published
- 2018
31. Evidence summaries and recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome: Assessment and treatment of infertility.
- Abstract
STUDY QUESTION: What is the recommended assessment and management of infertile women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertize and consumer preference? SUMMARY ANSWER: International evidence-based guidelines, including 44 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of infertile women with PCOS. WHAT IS KNOWN ALREADY: Previous guidelines on PCOS lacked rigorous evidence-based processes, failed to engage consumer and multidisciplinary perspectives or were outdated. The assessment and management of infertile women with PCOS are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist. PARTICIPANTS/MATERIALS, SETTING, METHODS: Governance included a six continent international advisory and a project board, a multidisciplinary international guideline development group (GDG), consumer and translation committees. Extensive health professional and consumer engagement informed the guideline scope and priorities. The engaged international society-nominated panel included endocrinology, gynaecology, reproductive endocrinology, obstetrics, public health and other experts, alongside consumers, project management, evidence synthesis and translation experts. Thirty-seven societies and organizations covering 71 countries engaged in the process. Extensive online communication and two face-to-face meetings over 15 months addressed 19 prioritized clinical questions involving nine evidence-based reviews and 10 narrative reviews. Evidence-based recommendations (EBRs) were formulated prior to consensus voting within the guideline panel. STUDY DESIGN, SIZE, DURATION: International evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. A (AGREE) II-compl
- Published
- 2019
32. The effects of intrauterine insemination and single embryo transfer or modified natural cycle in vitro fertilization on offspring's health-Follow-up of a randomized clinical trial.
- Abstract
Objective: Does ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction affect neurodevelopmental and physical health of the offspring? Study design: Infertile couples were randomly allocated to intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH), modified natural cycle in vitro fertilization (IVF-MNC) or single embryo transfer IVF (IVF-SET). We compared neurodevelopmental and physical health in childhood (4-7 years). We used age-appropriate questionnaires to assess behavioral problems (Child Behavior Check List (CBCL)) and executive functioning (Behavior Rating Inventory of Executive Function (BRIEF)). We measured body mass index Z-score, waist- and hip-circumference, body fat percentage, blood pressure Z-scores, pulse wave velocity, glucose, insulin, insulin resistance, total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides, and high sensitivity c-reactive protein. We compared groups by analysis of variance. Result(s): We examined 191 (57%) of the 333 children born in the study at a mean age of 5.5 years (range 4.0-7.6 years). We found no statistically significant differences between randomization groups in children's neurodevelopmental or physical health indices (all p-values > 0.05). Comparing the outcomes between actual method of conception, including a naturally conceived group, also did not show statistically significant differences. Conclusion(s): Although this follow-up study was not powered on childhood outcomes and limited power due to attrition may have hampered detection of subtle effects, we found no indications of differences in neurodevelopmental and physical health between ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction. Future trials should be powered on child outcomes, and aim to optimize follow-up rates to provide answers that are more definitive.Copyright © 2019 Elsevier B.V.
- Published
- 2019
33. Evidence summaries and recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome: Assessment and treatment of infertility.
- Abstract
STUDY QUESTION: What is the recommended assessment and management of infertile women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertize and consumer preference? SUMMARY ANSWER: International evidence-based guidelines, including 44 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of infertile women with PCOS. WHAT IS KNOWN ALREADY: Previous guidelines on PCOS lacked rigorous evidence-based processes, failed to engage consumer and multidisciplinary perspectives or were outdated. The assessment and management of infertile women with PCOS are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist. PARTICIPANTS/MATERIALS, SETTING, METHODS: Governance included a six continent international advisory and a project board, a multidisciplinary international guideline development group (GDG), consumer and translation committees. Extensive health professional and consumer engagement informed the guideline scope and priorities. The engaged international society-nominated panel included endocrinology, gynaecology, reproductive endocrinology, obstetrics, public health and other experts, alongside consumers, project management, evidence synthesis and translation experts. Thirty-seven societies and organizations covering 71 countries engaged in the process. Extensive online communication and two face-to-face meetings over 15 months addressed 19 prioritized clinical questions involving nine evidence-based reviews and 10 narrative reviews. Evidence-based recommendations (EBRs) were formulated prior to consensus voting within the guideline panel. STUDY DESIGN, SIZE, DURATION: International evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. A (AGREE) II-compl
- Published
- 2019
34. The effects of intrauterine insemination and single embryo transfer or modified natural cycle in vitro fertilization on offspring's health-Follow-up of a randomized clinical trial.
- Abstract
Objective: Does ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction affect neurodevelopmental and physical health of the offspring? Study design: Infertile couples were randomly allocated to intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH), modified natural cycle in vitro fertilization (IVF-MNC) or single embryo transfer IVF (IVF-SET). We compared neurodevelopmental and physical health in childhood (4-7 years). We used age-appropriate questionnaires to assess behavioral problems (Child Behavior Check List (CBCL)) and executive functioning (Behavior Rating Inventory of Executive Function (BRIEF)). We measured body mass index Z-score, waist- and hip-circumference, body fat percentage, blood pressure Z-scores, pulse wave velocity, glucose, insulin, insulin resistance, total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides, and high sensitivity c-reactive protein. We compared groups by analysis of variance. Result(s): We examined 191 (57%) of the 333 children born in the study at a mean age of 5.5 years (range 4.0-7.6 years). We found no statistically significant differences between randomization groups in children's neurodevelopmental or physical health indices (all p-values > 0.05). Comparing the outcomes between actual method of conception, including a naturally conceived group, also did not show statistically significant differences. Conclusion(s): Although this follow-up study was not powered on childhood outcomes and limited power due to attrition may have hampered detection of subtle effects, we found no indications of differences in neurodevelopmental and physical health between ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction. Future trials should be powered on child outcomes, and aim to optimize follow-up rates to provide answers that are more definitive.Copyright © 2019 Elsevier B.V.
- Published
- 2019
35. Medicines (follitropin Alpha Lutropin Alpha)
- Subjects
Follitropin ,Luteinizing hormone ,Business, international - Abstract
Tenders are invited for Medicines (follitropin alpha lutropin alpha) According to the documentation Major organization : COMMITTEE ON PUBLIC PROCUREMENT OF THE REPUBLIC OF DAGESTAN Address : Russian Federation, 367000, [...]
- Published
- 2020
36. Conclusion Of Non-exclusive Discount Agreements In Accordance With Section 130a (8) Sgb V For The Active Substances Listed In Ii.2.4) With The Option Of Concluding Within The Framework Of The So-calle
- Subjects
Galcanezumab ,Fremanezumab ,Rotigotine ,Raltegravir ,Tiotropium ,Aripiprazole ,Sorafenib ,Golimumab ,Follitropin ,Lanreotide ,Business, international - Abstract
Contract notice: Conclusion of non-exclusive discount agreements in accordance with section 130a (8) sgb v for the active substances listed in ii.2.4) with the option of concluding within the framework [...]
- Published
- 2020
37. Cytokine signal suppressor (SOCS) 1-1478 CA/del gene polymorphism in Turkish patients with polycystic ovary syndrome
- Author
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Cuma Bulent Gul, Canan Ersoy, Ozen Oz Gul, Barbaros Oral, Soner Cander, Ferah Budak, Uludağ Üniversitesi/Tıp Fakültesi/Endokrinoloji ve Metabolizma Anabilim Dalı., Uludağ Üniversitesi/Tıp Fakültesi/İmmünoloji Anabilim Dalı., Gül, Özen Öz, Cander, Soner, Budak, Ferah, Oral, Barbaros, Ersoy, Canan, AAI-1005-2021, F-4657-2014, K-7285-2012, and AAH-8861-2021
- Subjects
Luteinizing hormone ,Turkey ,Ovary polycystic disease ,medicine.medical_treatment ,Thyrotropin ,Expression ,Signal transduction ,Polymerase Chain Reaction ,Hip circumference ,Body Mass Index ,0302 clinical medicine ,Insulin ,Urea ,Obstetrics & gynecology ,Waist to height ratio ,High density lipoprotein cholesterol ,Progesterone ,Estradiol ,Variants ,Cholesterol ,Blood ,Health ,Body fat ,Creatinine ,Insulin blood level ,Systolic blood pressure ,Waist circumference ,Statistical model ,Restriction fragment length polymorphism ,Human ,Polycystic Ovary Syndrome ,medicine.medical_specialty ,Pulse rate ,Case control study ,Physical examination ,Major clinical study ,Aspartate aminotransferase ,Triacylglycerol ,SOCS1 polymorphism ,Article ,LDL ,Case-control studie ,03 medical and health sciences ,Age ,Genetic ,Diastolic blood pressure ,Genetics ,Humans ,Women ,Creatinine blood level ,Polymorphism ,Resistin ,Non Insulin Dependent Diabetes Mellitus ,Human RETN Protein ,Testosterone blood level ,Polymorphism, Genetic ,Cytokine signalling ,Proteins ,Body weight ,Anthropometry ,medicine.disease ,Prolactin ,Oligomenorrhea ,Prolactin blood level ,Body height ,Glucose ,Logistic Models ,030104 developmental biology ,Endocrinology ,Prasterone sulfate ,Dyslipidemia ,Premenopause ,chemistry ,Case-Control Studies ,Urea blood level ,Gene polymorphism ,0301 basic medicine ,Aspartate aminotransferase blood level ,Low density lipoprotein cholesterol ,Suppressor of cytokine signaling 1 ,Thyrotropin blood level ,chemistry.chemical_compound ,Gene Frequency ,Polymorphism (computer science) ,Anthropometric parameters ,Prevalence ,Testosterone ,Amenorrhea ,Priority journal ,Androstenedione blood level ,medicine.diagnostic_test ,Homozygote ,Smoking ,Obstetrics and Gynecology ,Middle Aged ,Polycystic ovary ,Triacylglycerol blood level ,Estradiol blood level ,Cholesterol blood level ,Cytokine ,Body mass ,Alanine aminotransferase blood level ,Female ,Blood biochemistry ,Luteinizing hormone blood level ,Adult ,Heterozygote ,Waist hip ratio ,030209 endocrinology & metabolism ,Suppressor of Cytokine Signaling 1 Protein ,Insulin resistance ,Internal medicine ,SOCS1 protein ,medicine ,Obesity ,Triglycerides ,Follitropin blood level ,Genetic polymorphism ,Triglyceride ,business.industry ,Androstenedione ,Cholesterol, LDL ,Follitropin ,Hemoglobin A1c ,DNA polymorphism ,Alanine aminotransferase ,Turk (people) ,Progesterone blood level ,Insulin Resistance ,business ,C peptide ,Uric acid ,Controlled study ,Uric acid blood level - Abstract
Eighty-four subjects, premenopausal female patients (n=42, mean (SD) age: 26.4 (4.2) years) diagnosed with polycystic ovary syndrome (PCOS) and age-matched healthy volunteers (n=42, mean (SD) age: 27.6(3.4) years), were included in this study. Data on physical examination, anthropometric measurements and blood biochemistry analysis were recorded for each subject along with analysis for SOCS1-1478 CA/del polymorphism by polymerase chain reaction-restriction fragment length polymorphism. The relation of SOCS1-1478 CA/del polymorphism to PCOS status and insulin resistance was analysed via logistic regression analysis. Mean (SD) levels for BMI (28.5(6.5) vs.22.5 (4.9) kg/m(2), p
- Published
- 2017
38. A multicenter, randomized, phase III study comparing the efficacy and safety of follitropin alpha biosimilar and the original follitropin alpha
- Author
-
Nadezhda Belousova, Ekaterina Morozova, Irina Zorina, Raisa Shalinа, Nina Marilova, S.A. Yakovenko, Yulia Scherbatyuk, Yulia Fetisova, Maria Ovchinnikova, Tatyana Teterina, Galina Kasyanova, M. A. Polzikov, Lali Sichinava, Zarema Barakhoeva, V.P. Apryshko, Lyudmila Vovk, Marina Tischenko, Alexandra Kolotovkina, and Anna Miskun
- Subjects
Adult ,endocrine system ,medicine.medical_specialty ,Pregnancy Rate ,Population ,Ovarian hyperstimulation syndrome ,Follitropin ,Controlled ovarian hyperstimulation ,Reproductive technology ,Hormone antagonist ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Ovulation Induction ,law ,Pregnancy ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,030212 general & internal medicine ,education ,Biosimilar Pharmaceuticals ,education.field_of_study ,030219 obstetrics & reproductive medicine ,business.industry ,Obstetrics and Gynecology ,medicine.disease ,Recombinant Proteins ,Reproductive Medicine ,Female ,Follicle Stimulating Hormone, Human ,business - Abstract
Objective The aim of the present study was to investigate the therapeutic equivalence between the follitropin alpha biosimilar and the reference medication in women undergoing assisted reproductive technologies (ART). Study design This multicenter, randomized (1:1), embryologist-blinded, parallel-group, comparative phase III study involved 110 women aged 20–35 years old with tubal and/or male factors of infertility. All of the subjects underwent controlled ovarian hyperstimulation (COH) using a gonadotropin-releasing hormone antagonist (GnRH-ant) protocol. Over the 5-day fixed-dose regimen, the women received 150 IU/day of follitropin alpha biosimilar (n = 55) or original follitropin alpha (n = 55), followed by dose adaptation. The primary endpoint for assessing the therapeutic equivalence was the number of retrieved oocytes using a pre-determined clinical equivalence margin of ± 3.4 oocytes. Results Similar numbers of oocytes were retrieved in both groups: 12.16 ± 7.28 in the follitropin alpha biosimilar group and 11.62 ± 6.29 in the original follitropin alpha group, with mean difference of 0.546 ± 1.297 oocytes (95% confidence interval [CI]: -2.026, 3.116), p = 0.002 (intention-to-treat [ITT] population). Additionally, no statistically significant differences were found for secondary endpoints: the onset of biochemical (34.7% and 36.7%, p = 0.883), clinical pregnancy (26.5% and 32.7%, p = 0.507), delivery (26.5% and 24.5%, p = 0.817) and take-home baby rate (28.6% and 26.5%, p = 0.816) for the follitropin biosimilar and original follitropin groups (per-protocol [PP] population). Ovarian hyperstimulation syndrome was observed in subjects with a positive pregnancy test in 0% and 3.64% of cases and after triggering ovulation in 7.27% and 3.64% for the follitropin biosimilar and original follitropin groups, respectively. Conclusions This study demonstrated similar therapeutic equivalence and safety profiles between the follitropin alpha biosimilar and the reference follitropin in women who underwent COH in GnRH-ant cycles. Trial registration number 1. Name of the registry: ClinicalTrials.gov . Trial registration number: NCT03088137. Date of registration: 02.03.2017, retrospectively registered. Trial conducted between 08.02.2017 and 17.08.2018, the date of enrollment of the first participant – 08.02.2017. 2. Name of the registry: Russian Ministry of Health, grls.rosminzdrav.ru . Trial registration number: RCT 754. Date of registration: 26.10.2016, prospectively registered.
- Published
- 2019
39. A cost-effectiveness analysis comparing the originator follitropin alfa to its biosimilars in patients undergoing a medically assisted reproduction program from a French perspective
- Author
-
Laurence Fresneau, Maurel Frédérique, Michael Grynberg, Nicoleta Petrica, Ségolène Paillet, Harinala Ravonimbola, Claire Murphy, Carole Doré, AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Marginal cost ,medicine.medical_specialty ,Cost effectiveness ,[SDV]Life Sciences [q-bio] ,Ovarian hyperstimulation syndrome ,Follitropin ,INFERTILITY ,03 medical and health sciences ,0302 clinical medicine ,RECOMBINANT FSH ,medicine ,In patient ,health care economics and organizations ,business.industry ,030503 health policy & services ,Health Policy ,WOMEN ,Biosimilar ,Cost-effectiveness analysis ,medicine.disease ,EFFICACY ,GONAL-F(R) ,3. Good health ,Clinical trial ,030220 oncology & carcinogenesis ,Emergency medicine ,ICSI CYCLES ,0305 other medical science ,business - Abstract
International audience; Objective: To assess the cost-effectiveness (CE) of the originator follitropin-alpha (Gonal-F) in patients undergoing a medically assisted reproduction (MAR) program in comparison to its biosimilars Bemfola and Ovaleap in a French context. Methods: A CE model was developed for France with a National Health Service (NHS) perspective. Clinical, safety, and dosage data were derived from pivotal clinical trials that compared Gonal-F to Ovaleap and Bemfola. Costs pertaining to drugs, hospitalizations, specialist visits, and examinations were retrieved from the French Programme de Medicalisation des Systemes d'Information (PMSI) hospital database, literature review, and French clinical experts using 2017 Euro tariffs. In order to test the robustness of results, deterministic one-way sensitivity analyses were carried out on the main variables to assess the impact of treatment cost, probability of birth, ovarian hyperstimulation syndrome (OHSS) rates, and dosage. Results: The average incremental cost per live birth with OHSS and without OHSS was euro259.56 and euro278.39, respectively, for Gonal-F compared to the pooled biosimilars (i.e. Ovaleap and Bemfola). GONAL-F had an incremental efficacy of 0.06 over the pooled biosimilars. The incremental cost-effectiveness ratio for Gonal-F with OHSS ranged from euro3,274.80 to euro4,877.76 compared to the pooled biosimilars, owing to the additional live births reported with Gonal-F. Sensitivity analyses also supported results from the base case analyses, with Gonal-F being cost-effective or the dominant strategy in most cases. Conclusion: Gonal-F seems to be a cost-effective strategy compared to its biosimilars Ovaleap and Bemfola, irrespective of the incidence of OHSS events, but further data are needed to confirm these results.
- Published
- 2019
40. Gonadotropin Hormones and Their Receptors
- Author
-
James A. Dias, Prema Narayan, and Alfredo Ulloa-Aguirre
- Subjects
endocrine system ,medicine.medical_specialty ,urogenital system ,medicine.drug_class ,Follitropin ,Ovary ,Biology ,Human chorionic gonadotropin ,Syncytiotrophoblast ,medicine.anatomical_structure ,Endocrinology ,Internal medicine ,medicine ,Gonadotropin ,Receptor ,Luteinizing hormone ,reproductive and urinary physiology ,hormones, hormone substitutes, and hormone antagonists ,Hormone - Abstract
The gonads (ovary, testis) produce gametes (oocytes and spermatozoa). The pituitary glycoprotein hormones luteinizing hormone (LH, lutropin) and follicle-stimulating hormone (FSH, follitropin) are gonadotropins because their targets are the gonads. Another hormone produced by the syncytiotrophoblast of the human placenta is human chorionic gonadotropin (hCG, choriogonadotropin), and its activity is like LH. This review describes the protein structure, gene structure, and regulation of biosynthesis of both the gonadotropins and their membrane bound receptors. The functions of both hormones and receptors are covered extensively, as well as naturally occurring mutations that have been identified in disease states and therapies derived from their study.
- Published
- 2019
41. Inj Follitropin Alpha Recombinant Dna Follicle Stimulating H
- Subjects
Follicle-stimulating hormone ,DNA ,Follitropin ,Railroads ,Business, international - Abstract
Tenders are invited for Inj follitropin alpha recombinant dna follicle stimulating h...... Tender Type: Limited Eligibility Criteria : - Major organization : CENTRAL RAILWAY Address : 2nd Floor, New Administrative [...]
- Published
- 2020
42. Conclusion Of A Non-exclusive Discount Agreement In Accordance With Section 130 A (8) Sgb V For The Active Ingredient Follitropin Beta
- Subjects
Follicle-stimulating hormone -- Laws, regulations and rules ,Antitrust law ,Time ,Follitropin ,Government regulation ,Antitrust issue ,Contract agreement ,Business, international - Abstract
Contract notice: Conclusion of a non-exclusive discount agreement in accordance with section 130 a (8) sgb v for the active ingredient follitropin beta GWQ ServicePlus AG intends to conclude non-exclusive [...]
- Published
- 2020
43. Global Biosimilars Market (2020 to 2025) - New Indications and the Patent Expiry of Biologic Products Present Lucrative Opportunities
- Subjects
Contract manufacturing -- Forecasts and trends ,Chronic diseases -- Forecasts and trends ,Glucagon -- Forecasts and trends ,Somatotropin -- Intellectual property -- Forecasts and trends ,Interferon -- Intellectual property -- Forecasts and trends ,Adalimumab -- Intellectual property -- Forecasts and trends ,Etanercept ,Monoclonal antibodies ,Erythropoietin ,Infliximab ,Hormones ,Follitropin ,Biological response modifiers ,Insulin ,Granulocyte colony-stimulating factor ,Rituximab ,Follicle-stimulating hormone ,Diseases ,Antibodies ,Respiratory system agents ,Pituitary hormones ,Glycoproteins ,Calcitonin ,Production management ,Market trend/market analysis ,General interest ,News, opinion and commentary - Abstract
DUBLIN: Research and Markets has issued the following press release: The 'Biosimilars Market by Product (Insulin, Interferon, Etanercept, Infliximab, Rituximab, Glucagon, Calcitonin), Manufacturing (In-house, Contract) & Indication (Oncology, Chronic Disease, [...]
- Published
- 2020
44. Outlook on the Worldwide Biosimilars Market to 2025 - Featuring Sandoz, Pfizer, Eli Lilly & Teva Pharmaceutical Among Others - ResearchAndMarkets.com
- Subjects
Contract manufacturing -- Forecasts and trends ,Chronic diseases -- Forecasts and trends ,Somatotropin -- Forecasts and trends ,Biological response modifiers -- Forecasts and trends ,Monoclonal antibodies -- Forecasts and trends ,Interferon -- Forecasts and trends ,Etanercept ,Glucagon ,Erythropoietin ,Enoxaparin ,Infliximab ,Hormones ,Follitropin ,Insulin ,Granulocyte colony-stimulating factor ,Rituximab ,Follicle-stimulating hormone ,Diseases ,Antibodies ,Glycoproteins ,Calcitonin ,Production management ,Market trend/market analysis ,Business ,Business, international - Abstract
DUBLIN -- The 'Biosimilars Market by Product (Insulin, Interferon, Etanercept, Infliximab, Rituximab, Glucagon, Calcitonin), Manufacturing (In-house, Contract) & Indication (Oncology, Chronic Disease, Blood Disorder, Autoimmune Disease), Region - Global Forecast [...]
- Published
- 2020
45. The global biosimilars market size is projected to reach USD 35.7 billion by 2025 from USD 11.8 billion in 2020, at a CAGR of 24.7%
- Subjects
Somatotropin -- Reports -- Forecasts and trends ,Monoclonal antibodies -- Reports -- Forecasts and trends ,Etanercept ,Glucagon ,Erythropoietin ,Hormones ,Follitropin ,Biological response modifiers ,Insulin ,Granulocyte colony-stimulating factor ,Follicle-stimulating hormone ,Antibodies ,Backup software ,Glycoproteins ,Interferon ,Production management ,Market trend/market analysis ,Banking, finance and accounting industries - Abstract
(GlobeNewswire) - Reportlinker.com announces the release of the report 'Biosimilars Market by Product, Manufacturing & Indication, Region Global Forecast to 2025' - https://www.reportlinker.com/p04604343/?utm_source=GNW The monoclonal antibody segment is anticipated to [...]
- Published
- 2020
46. The global biosimilars market size is projected to reach USD 35.7 billion by 2025 from USD 11.8 billion in 2020, at a CAGR of 24.7%
- Subjects
Somatotropin -- Forecasts and trends -- Reports ,Monoclonal antibodies -- Forecasts and trends -- Reports ,Etanercept ,Glucagon ,Erythropoietin ,Hormones ,Follitropin ,Biological response modifiers ,Insulin ,Granulocyte colony-stimulating factor ,Follicle-stimulating hormone ,Antibodies ,Backup software ,Glycoproteins ,Interferon ,Production management ,Market trend/market analysis ,Business, international ,Law - Abstract
(GlobeNewswire) - Reportlinker.com announces the release of the report 'Biosimilars Market by Product, Manufacturing & Indication, Region Global Forecast to 2025' - https://www.reportlinker.com/p04604343/?utm_source=GNW The monoclonal antibody segment is anticipated to [...]
- Published
- 2020
47. Outlook on the Worldwide Biosimilars Market to 2025 - Featuring Sandoz, Pfizer, Eli Lilly & Teva Pharmaceutical Among Others
- Subjects
Chronic diseases -- Forecasts and trends ,Contract manufacturing -- Forecasts and trends ,Biological response modifiers -- Forecasts and trends ,Monoclonal antibodies -- Forecasts and trends ,Etanercept ,Glucagon ,Infliximab ,Follitropin ,Insulin ,Rituximab ,Diseases ,Antibodies ,Interferon ,Calcitonin ,Production management ,Market trend/market analysis ,Business ,Business, international - Abstract
M2 PRESSWIRE-March 30, 2020-: Outlook on the Worldwide Biosimilars Market to 2025 - Featuring Sandoz, Pfizer, Eli Lilly & Teva Pharmaceutical Among Others (C)1994-2020 M2 COMMUNICATIONS RDATE:30032020 The 'Biosimilars Market [...]
- Published
- 2020
48. Biosimilars Market by Product, Manufacturing & Indication and Region - Global Forecast to 2025
- Subjects
Contract manufacturing -- Forecasts and trends -- Reports ,Chronic diseases -- Forecasts and trends -- Reports ,Glucagon -- Forecasts and trends -- Reports ,Somatotropin -- Forecasts and trends -- Reports ,Interferon -- Forecasts and trends -- Reports ,Adalimumab -- Forecasts and trends -- Reports ,Etanercept ,Monoclonal antibodies ,Erythropoietin ,Infliximab ,Hormones ,Follitropin ,Biological response modifiers ,Insulin ,Granulocyte colony-stimulating factor ,Rituximab ,Follicle-stimulating hormone ,Diseases ,Antibodies ,Respiratory system agents ,Pituitary hormones ,Glycoproteins ,Calcitonin ,Production management ,Market trend/market analysis ,Banking, finance and accounting industries ,Business - Abstract
Dublin, March 30, Mar 30, 2020 (GLOBE NEWSWIRE via COMTEX) -- The 'Biosimilars Market by Product (Insulin, Interferon, Etanercept, Infliximab, Rituximab, Glucagon, Calcitonin), Manufacturing (In-house, Contract) & Indication (Oncology, Chronic [...]
- Published
- 2020
49. The global biosimilars market size is projected to reach USD 35.7 billion by 2025 from USD 11.8 billion in 2020, at a CAGR of 24.7%
- Subjects
Somatotropin -- Forecasts and trends -- Reports ,Monoclonal antibodies -- Forecasts and trends -- Reports ,Etanercept ,Glucagon ,Erythropoietin ,Hormones ,Follitropin ,Biological response modifiers ,Insulin ,Granulocyte colony-stimulating factor ,Follicle-stimulating hormone ,Antibodies ,Backup software ,Glycoproteins ,Interferon ,Production management ,Market trend/market analysis ,Banking, finance and accounting industries ,Business - Abstract
New York, March 30, Mar 30, 2020 (GLOBE NEWSWIRE via COMTEX) -- Reportlinker.com announces the release of the report 'Biosimilars Market by Product, Manufacturing & Indication, Region - Global Forecast [...]
- Published
- 2020
50. Biosimilars Market Size, Share, Trends, Growth Analysis By Type And Region, Forecast Report To 2025 | Million Insights
- Subjects
United States. Food and Drug Administration -- Statistics -- Reports ,Follitropin ,Industrial research ,Company growth ,Business ,Business, international - Abstract
M2 PRESSWIRE-March 24, 2020-: Biosimilars Market Size, Share, Trends, Growth Analysis By Type And Region, Forecast Report To 2025 | Million Insights (C)1994-2020 M2 COMMUNICATIONS RDATE:24032020 According to new report [...]
- Published
- 2020
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