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      Patient Preference and Adherence (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the growing importance of patient preference and adherence throughout the therapeutic process. Sign up for email alerts here.

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      Analysis of Nurse and Patient Preferences for Pre-Filled Pen Devices for Self-Injection of Highly Purified Human Menopausal Gonadotropin (HP-hMG, MENOPUR ®)

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          Abstract

          Purpose

          This study aimed to identify the most important attributes for a gonadotropin pen as perceived by assisted reproductive technology (ART) patients and fertility nurses, and to examine how well a prototype HP-hMG (MENOPUR ®) pen reflects these preferences.

          Patients and Methods

          This market research study incorporated a two-part survey with respondents (N=221) from Poland, Spain and the UK. Respondents included patients (n=141) who consulted a fertility specialist in the previous 2 years, and fertility nurses (n=80) who assisted in at least 75 ART cycles/year. Patients were divided into two subgroups depending on their experience with ART (experienced and naïve). Key attributes for an injection pen, as perceived by patients and nurses, were assessed via an online survey and ranked by their relative importance using Anchored Maximum Difference Scaling. After performing a dummy injection, respondents compared the attributes of an unbranded prototype pen against the key attributes identified.

          Results

          Across all survey respondents, the ability to correct the dialed dose was considered to be the most important product attribute of a gonadotropin pen. Confidence in the patient’s ability to inject correctly at home was also identified as a key attribute, considered by both nurses and naïve patients as extremely high. When considering the prototype pen device, almost all study respondents reported a positive experience (99%) with 72% rating it as “very good”. The prototype pen was perceived to possess the key attributes considered important for a gonadotropin pen by patients and nurses, including correcting the dose, the ability to self-inject safely and correctly, ease of preparation and use, and an injection which appeared to be as painless as possible.

          Conclusion

          The prototype pen was found to perform well across all key attributes, especially those considered most important in gonadotropin pens, suggesting that it is a user-friendly option for patients undergoing ART.

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          Most cited references26

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          A randomized assessor-blind trial comparing highly purified hMG and recombinant FSH in a GnRH antagonist cycle with compulsory single-blastocyst transfer.

          To compare the efficacy and safety of highly purified menotropin (hphMG) and recombinant FSH (rFSH) for controlled ovarian stimulation in a GnRH antagonist cycle with compulsory single-blastocyst transfer. Randomized, open-label, assessor-blind, parallel groups, multicenter, noninferiority trial. Twenty-five infertility centers in seven countries. Seven hundred forty-nine women. Controlled ovarian stimulation with hphMG or rFSH in a GnRH antagonist cycle with compulsory single-blastocyst transfer on day 5 in one fresh or subsequent frozen blastocyst replacement in natural cycles initiated within 1 year of each patient's start of treatment. Ongoing pregnancy (primary end point) and live birth rates, as well as pharmacodynamic parameters. The ongoing pregnancy rate after a fresh cycle was 30% with hphMG versus 27% with rFSH for the per-protocol (PP) population and 29% versus 27% for the intention-to-treat (ITT) population. Noninferiority of hphMG compared to rFSH was established. Considering frozen cycles initiated within 1 year, the cumulative live birth rate for a single stimulation cycle was 40% and 38% for women treated with hphMG and rFSH, respectively (both PP and ITT). Significant differences in pharmacodynamic end points were found between the two gonadotropin preparations. Highly purified hMG is at least as effective as rFSH in GnRH antagonist cycles with compulsory single-blastocyst transfer. NCT00884221. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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            The Development of Gonadotropins for Clinical Use in the Treatment of Infertility

            The first commercially available gonadotropin product was a human chorionic gonadotropin (hCG) extract, followed by animal pituitary gonadotropin extracts. These extracts were effective, leading to the introduction of the two-step protocol, which involved ovarian stimulation using animal gonadotropins followed by ovulation triggering using hCG. However, ovarian response to animal gonadotropins was maintained for only a short period of time due to immune recognition. This prompted the development of human pituitary gonadotropins; however, supply problems, the risk for Creutzfeld–Jakob disease, and the advent of recombinant technology eventually led to the withdrawal of human pituitary gonadotropin from the market. Urinary human menopausal gonadotropin (hMG) preparations were also produced, with subsequent improvements in purification techniques enabling development of products with standardized proportions of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) activity. In 1962 the first reported pregnancy following ovulation stimulation with hMG and ovulation induction with hCG was described, and this product was later established as part of the standard protocol for ART. Improvements in immunopurification techniques enabled the removal of LH from hMG preparations; however, unidentified urinary protein contaminants remained a problem. Subsequently, monoclonal FSH antibodies were used to produce a highly purified FSH preparation containing <0.1 IU of LH activity and <5% unidentified urinary proteins, enabling the formulation of smaller injection volumes that could be administered subcutaneously rather than intramuscularly. Ongoing issues with gonadotropins derived from urine donations, including batch-to-batch variability and a finite donor supply, were overcome by the development of recombinant gonadotropin products. The first recombinant human FSH molecules received marketing approvals in 1995 (follitropin alfa) and 1996 (follitropin beta). These had superior purity and a more homogenous glycosylation pattern compared with urinary or pituitary FSH. Subsequently recombinant versions of LH and hCG have been developed, and biosimilar versions of follitropin alfa have received marketing authorization. More recent developments include a recombinant FSH produced using a human cell line, and a long-acting FSH preparation. These state of the art products are administered subcutaneously via pen injection devices.
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              Clinical outcome following stimulation with highly purified hMG or recombinant FSH in patients undergoing IVF: a randomized assessor-blind controlled trial.

              LH activity may influence treatment response and outcome in IVF cycles. A randomized, assessor-blind, multinational trial compared ongoing pregnancy rates (primary end-point) in 731 women undergoing IVF after stimulation with highly purified menotrophin (HP-hMG) (n = 363) or recombinant FSH (rFSH) (n = 368) following a long GnRH agonist protocol. Patients received identical pre- and post-randomization interventions. One or two embryos were transferred on day 3. More oocytes were retrieved (P < 0.001) after rFSH treatment (11.8) compared with HP-hMG treatment (10.0), but a higher proportion developed into top-quality embryos (P = 0.044) with HP-hMG (11.3%) than with rFSH (9.0%). At the end of stimulation, lower estradiol (E(2)) (P = 0.031) and higher progesterone (P < 0.001) levels were found with rFSH, even after adjusting for follicular response. The distribution of hypo-, iso- and hyper-echogenic endometrium showed a significant (P = 0.023) shift towards the hyperechogenic pattern after rFSH treatment. The ongoing pregnancy rate per cycle was 27% with HP-hMG and 22% with rFSH [odds ratio (95% confidence interval): 1.25 (0.89-1.75)]. Superiority of HP-hMG over rFSH in ongoing pregnancy rate could not be concluded from this study, but non-inferiority was established. Pharmacodynamic differences in follicular development, oocyte/embryo quality, endocrine response and endometrial echogenicity exist between HP-hMG and rFSH preparations, which may be relevant for treatment outcome.
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                Author and article information

                Journal
                Patient Prefer Adherence
                Patient Prefer Adherence
                ppa
                Patient preference and adherence
                Dove
                1177-889X
                17 May 2023
                2023
                : 17
                : 1281-1292
                Affiliations
                [1 ]Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel , Brussels, Belgium
                [2 ]Ferring Pharmaceuticals , Gentilly, France
                [3 ]CARE Fertility Group , Nottingham, UK
                Author notes
                Correspondence: Judith A Smith, CARE Fertility Nottingham , John Webster House, 6 Lawrence Drive, Nottingham Business Park, Nottingham, NG8 6PZ, UK, Tel + 44 0 115 852 8100, Email judith.smith@carefertility.com
                [*]

                These authors contributed equally to this work

                Article
                385247
                10.2147/PPA.S385247
                10200119
                36f92c03-9c40-4b26-ba3a-943db740b081
                © 2023 De Mesmaeker et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 06 August 2022
                : 02 May 2023
                Page count
                Figures: 5, Tables: 2, References: 27, Pages: 12
                Funding
                Funded by: funded by Ferring Pharmaceuticals;
                This study was funded by Ferring Pharmaceuticals.
                Categories
                Original Research

                Medicine
                fertility,ovarian stimulation,patient preference,assisted reproductive technology,gonadotropin-injection pen

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