Gonadotrophins are routinely used for follicular stimulation in ovarian induction (OI) and assisted reproduction techniques (ART). Follicle-stimulating hormone (FSH) and HMG (human menopausal gonadotrophin) are used during OI and ART to stimulate the growth and recruitment of immature follicles in the ovary [1, 2]. FSH is currently available in two preparations: urinary FSH (u-FSH) and recombinant FSH (r-FSH). HMG and u-FSH are extracted from the urine of postmenopausal women, whereas r-FSH, which became available in 1996, is produced using recombinant DNA technology.
Daily injections of recombinant peptides are required for several conditions such as growth hormone for growth deficiencies in children. Injections that are required on a long-term, regular basis must be quick, simple and as pain free as possible to ensure patients comply with treatment . During treatment for OI and ART, gonadotrophins have to be injected daily for an average of 10 days and are often reconstituted from freeze-dried peptides. Traditionally, HMG has been administered as an intramuscular injection. However, the development of the higher purity FSH preparations has enabled subcutaneous injections to be used. Advances in FSH formulations have been accompanied by progress in the devices available for the delivery of the peptides. The subcutaneous administration systems that have evolved for r-FSH generally enable self-administration at home and have led to improvements in patient satisfaction and quality of life [4–10].
It is well established that treatment outcomes can be affected by patient compliance, and that compliance is related to treatment choice and method of administration. For example, therapies that are easier to administer and cause less injection site pain are associated with higher rates of compliance than those that are difficult to administer and cause pain [4, 7, 10, 11]. It has been demonstrated previously that patients, who receive subcutaneous injections for IVF, reported experiencing less pain than those who receive intramuscular injections . Moreover, it has been documented that patients can make errors in the reconstitution of freeze-dried peptides for self-administration at home, and pregnancy rates are higher in patients who prepare and administer injections correctly .
The follitropin-alpha (Gonal-f) filled-by mass (FbM) prefilled pen (Merck Serono SA, Geneva, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany) is a ready-to-use disposable injection delivery device. The pen contains premixed follitropin alfa filled-by-mass, which provides more accurate and consistent dosing than r-FSH filled-by-bioassay . Routine use of follitropin-alpha in ART was well accepted by patients participating in a German observational study; in addition, study patients required less training to use follitropin-alpha pens compared with vials or ampoules . More importantly from a compliance point of view, patients preferred the prefilled pen compared with another loadable device (a reusable pen with loadable cartridges) . Results from two other studies suggest that the follitropin-alpha prefilled pen had higher patient and nurse acceptance than the follitropin-beta pen (supplied in glass cartridges to be used with a pen injector; Puregon; Organon, Roseland, NJ, USA) . Another survey found that more patients preferred the follitropin-alpha prefilled pen to the follitropin-beta cartridge pen or urofollitropin (Ferring Pharmaceuticals, Suffern, NY, USA) administered with a needle-free reconstitution device and conventional syringe. Additionally, patients stated that the ease of use, dosing mechanism and reduced potential for dosing errors were the factors that they found most important .
The current study was designed to evaluate overall patient satisfaction, ease of learning and use, and injection site pain associated with the follitropin-alpha (FbM) prefilled pen. A secondary comparison was made with other systems of gonadotrophin administration. The study—which involved over 650 patients treated at 23 Japanese fertility centres—was the largest study of patient preference to be performed in Japan.