The redesigned follitropin alfa pen injector: results of the patient and nurse human factors usability testing.

OBJECTIVES: A redesigned pen injector for administration of follitropin alfa (follitropin α) has been developed for use in fertility treatment cycles. Pre-summative and summative usability testing was undertaken to assess the risk of dosing errors compared with the existing follitropin α pen. The study also assessed proper use of and dose selection with the redesigned pen. METHODS: Infertile women who were trying to conceive and specialist nurses were recruited from four cities in Germany. Usability goals relating to proper use of the pen device were defined from a risk assessment and further categorized as critical and functional operational goals. Individual, non-interventional, standardized, usability tests were performed with patients and nurses by four experienced research professionals using questionnaires that also included ease-of-use ratings. A non-standardized qualitative analysis of nurse-patient training sessions was performed in the presence of a research professional; reasons for confidence, safety, possible misunderstandings and risks when handling the pen were noted. RESULTS: The overall risk of dosing errors with the redesigned pen was not higher than with the existing pen. No unexpected operational risks and no major concerns regarding the risk of misuse or dosing errors were identified. CONCLUSIONS: The study provides useful practical information on the redesigned pen from both patient and nurse perspectives.

The redesigned follitropin α pen injector for infertility treatment.

INTRODUCTION: Treatment for infertility may require multiple drugs and complex dosing schedules. Available injection devices for patients who require regular injections during treatment are reviewed in this article, focusing on pen injectors used to self-administer recombinant human follicle-stimulating hormone (follitropin α). Following the introduction of the first and second follitropin α pen injectors in the last decade, a third pen injector with improved design for the administration of follitropin α has been developed for use in fertility treatment cycles. AREAS COVERED: This paper presents the results of the dose accuracy testing with this pen injector that was performed in accordance with international standards (EN ISO 11608-1:2000). This overview also provides an understanding of the key features of the redesigned pen injector that are of interest to healthcare professionals. EXPERT OPINION: The availability of an improved injection device for the delivery of follitropin α used during infertility treatment cycles of ovulation induction and assisted reproductive technology offers patients and healthcare professionals new treatment administration options. As fertility treatment cycles involve the use of several injectable gonadotropins, a standard device that could be used for all such treatments would simplify both the administration and the teaching of administration considerably.

Midluteal serum progesterone levels and pregnancy following ovulation induction with human follicle-stimulating hormone: results of a combined-data analysis.

OBJECTIVE: This retrospective analysis of combined data (one Phase II and three Phase III clinical trials) of patients with oligo- or anovulatory infertility aimed to evaluate the association between pregnancy and midluteal serum progesterone (P4) level following ovulation induction and hence the indicative value of P4 for ovulation and pregnancy achievement. STUDY DESIGN: All patients (n = 913) were treated with human follicle-stimulating hormone. Cycles (n = 1,554) with one or two serum P4 levels in the luteal phase (days 5-12) following human chorionic gonadotropin administration and complete data on cycle outcome were included. RESULTS: Clinical pregnancy was achieved in 295/1,554 (19.0%) cycles; 87.5% of these led to live births (16.6%/cycle). Including and excluding multiple pregnancy data, 88% and 86% of all live births had P4 values >10 ng/mL, respectively. Overall clinical pregnancy rate plateaued at midluteal P4 levels >25 ng/mL but, when multiple pregnancies were excluded, plateaued at 20-25 ng/mL and then decreased. Mean midluteal P4 levels were twice as high in multiple versus singleton pregnancies. CONCLUSION: A midluteal P4 level >10 ng/mL may represent an appropriate threshold for indication of ovulation resulting in live birth. Multiple pregnancies were associated with higher mean midluteal P4 levels.

A comparison of menotropin, highly-purified menotropin and follitropin alfa in cycles of intracytoplasmic sperm injection.

BACKGROUND: Over the last several decades, as a result of an evolution in manufacturing processes, a marked development has been made in the field of gonadotropins for ovarian stimulation. Initially, therapeutic gonadotropins were produced from a simple process of urine extraction and purification; now they are produced via a complex system involving recombinant technology, which yields gonadotropins with high levels of purity, quality, and consistency. METHODS: A retrospective analysis of 865 consecutive intracytoplasmic sperm injection (ICSI) cycles of controlled ovarian hyperstimulation (COH) compared the clinical efficacy of three gonadotropins (menotropin [hMG; n = 299], highly-purified hMG [HP-hMG; n = 330] and follitropin alfa [r-hFSH; n = 236]) for ovarian stimulation after pituitary down-regulation. The endpoints were live birth rates and total doses of gonadotropin per cycle and per pregnancy. RESULTS: Laboratory and clinical protocols remained unchanged over time, except for the type of gonadotropin used, which was introduced sequentially (hMG, then HP-hMG, and finally r-hFSH). Live birth rates were not significantly different for hMG (24.4%), HP-hMG (32.4%) and r-hFSH (30.1%; p = 0.09) groups. Total dose of gonadotropin per cycle was significantly higher in the hMG (2685 +/- 720 IU) and HP-hMG (2903 +/- 867 IU) groups compared with the r-hFSH-group (2268 +/- 747 IU; p < 0.001). Total dose of gonadotropin required to achieve clinical pregnancy was 15.7% and 11.0% higher for the hMG and HP-hMG groups, respectively, compared with the r-hFSH group, and for live births, the differences observed were 45.3% and 19.8%, respectively. CONCLUSION: Although similar live birth rates were achieved, markedly lower doses of r-hFSH were required compared with hMG or HP-hMG.

Patient experience with follitropin alfa prefilled pen versus previously used injectable gonadotropins for ovulation induction in oligoanovulatory women.

OBJECTIVE: To evaluate patient satisfaction with the follitropin alfa prefilled pen (Gonal-f RFF Pen), compared with previously used injectable gonadotropins (vial/ampoules and syringe), in women undergoing ovulation induction (OI). RESEARCH DESIGN AND METHODS: Women aged 18-40 years undergoing OI for oligoanovulatory infertility were enrolled from nine US fertility centers in this prospective, open-label clinical trial. Participants received recombinant follitropin alfa using a prefilled pen. Patient satisfaction was determined using a pre-treatment questionnaire to assess gonadotropin treatments undertaken within 6 months of study initiation and an in-treatment questionnaire to assess satisfaction with the prefilled pen. MAIN OUTCOME MEASURES: The primary endpoint was the proportion of patients who preferred the prefilled pen compared to previous injectable gonadotropin therapies. Efficacy and safety were also assessed. RESULTS: Seventy-three subjects were screened for the study; 62 enrolled, were treated with the follitropin alfa pre-filled pen, and 61 completed the in-treatment questionnaire. Sixty-one of 61 patients who stated a preference preferred the prefilled pen to previous injectable gonadotropin therapies (61/61; 100%; 95% confidence interval: [94.1-100.0%]). One patient did not state a preference. Of these 61 patients, 54 (89%) found that the prefilled pen instructions were easy to understand compared to 17 of 59 (29%) who thought instructions for the conventional syringes were easy to understand. When preparing their dose, significantly fewer patients contacted their healthcare provider two or more times during the treatment cycle when receiving treatment with the prefilled pen (2/61, 3%) than during the first treatment cycle with prior gonadotropin treatment, 11/59 (19%, p = 0.007). The pen interfered slightly or not at all with patients' normal daily activities in 61 of 61 patients (100%) versus 50 of 59 patients (85%) who had this opinion regarding injections during their prior treatment cycles (p = 0.003). All 61 patients who stated a method of injection preference found the prefilled pen less stressful to use than syringes and would recommend the pen to another woman considering gonadotropin treatment. A total of 10/62 (16%) subjects reported 18 treatment-emergent adverse events (AEs). Two cases of ovarian hyperstimulation syndrome occurred post-treatment and one serious AE occurred (post-treatment ectopic pregnancy). Injection site reactions were generally mild to moderate, with mild itching (6 patients, 9.7%) and moderate redness in one patient. Fifteen patients reported mild redness (24.2%). Mild bruising (21.0%), mild pain (33.9%), and mild burning (32.3%) were also reported by patients. Seven patients (11.3%) had moderate pain. CONCLUSIONS: In this open-label, non-comparative study, patients undergoing OI preferred administering gonadotropins using the follitropin alfa prefilled pen compared to their prior use of vials/ampoules and a syringe. Patients using the prefilled pen found it less stressful, easier to use and more convenient than a conventional syringe and would recommend the pen to another woman considering gonadotropin treatment.