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Pierre Zitoun,1 Jaya Parikh,2 Martine Nijs,3 Wenjie Zhang,4 Rachel Levy-Toledano,5 Boxiong Tang6 1American Hospital of Paris, Neuilly-sur-Seine, France; 2Lister Fertility Clinic, London, UK; 3Nij Geertgen, Elsendorp, the Netherlands; 4WG Group, New York, NY, USA; 5Theramex HQ UK Limited, London, UK; 6Teva Pharmaceuticals, Frazer, PA, USA Purpose: The purpose of this study was to assess product-specific features for a variety of self-administered injection devices and identify key factors that patients and nurses in select European markets find most important when selecting injection devices for self-administration of recombinant human follicle-stimulating hormone and urinary human follicle-stimulating hormone for fertility/reproductive therapy.Patients and methods: Patients (N=402) in France, Italy, Spain, Germany, the UK, the Netherlands, and Belgium, as well as reproductive/fertility nurses (N=40) in Germany, Italy, France, Spain, and the Czech Republic were surveyed. All patients were previously prescribed a follicle-stimulating hormone (FSH) treatment for either in vitro fertilization or ovulation induction. Patient and nurse preferences for attributes across all injection devices in the market were obtained via an online questionnaire and evaluated using the maximum differential scaling (MaxDiff) and conjoint analyses, which captured the relative importance of the selected FSH injection device attributes to determine specific qualities in overall product preference.Results: Both the MaxDiff and conjoint analyses indicated that, for patients and nurses, the ideal FSH injection device would be a highly accurate, multi-use reusable pen injector with a dial-back function that would be easy for both use and education/instruction. Patients and nurses each selected attributes pertinent to their own experiences with the FSH injection device. Categorically, patients valued factors that resulted in minimal impact on daily life, including reduced injection volume to minimize injection-site pain, as well as a reusable device that would be easy to use; nurses placed greater value on a device that would be easy to teach in order to instruct the greatest number of patients while minimizing risk.Conclusion: Patient and nurse preferences were aligned on certain selected attributes of the FSH products. Although this study was an unbranded examination of attributes across all injection devices currently in the market, results demonstrated that the preferred product attributes were all characteristics of the Ovaleap® Pen. Keywords: infertility, prefilled pen device, recombinant human follicle-stimulating hormone, urinary follicle-stimulating hormone, preference

With the successful use of Assisted Reproduction, in particular intracytoplasmic sperm injection (ICSI), to treat infertile couples we have become less discriminating with the quality of spermatozoa we use to treat our patients. Numerous studies have shown the presence of nuclear DNA strand breaks in human ejaculated spermatozoa. The reason why human spermatozoa, in particular from men with abnormal semen parameters, possess these abnormalities in their nuclear DNA is still not clear. Two processes that have been linked to the presence of nuclear DNA strand breaks in spermatozoa are anomalies in apoptosis during spermatogenesis or problems in the packaging of the chromatin during spermiogenesis. Understanding the mechanisms responsible for producing abnormal spermatozoa in the human will improve our knowledge about certain causes of male infertility. More importantly, the impact of such sperm, if selected to perform ICSI, needs to be better understood so that any detrimental paternal effects can be avoided.

In this preliminary prospective randomized study of 420 patients undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI), 17 patients (4%) developed moderate to severe ovarian hyperstimulation syndrome (OHSS). Re-evaluation for OHSS on day 4 and 6 after oocyte retrieval identified one patient with continuous risk for severe OHSS, resulting in cancellation of the transfer (1/17, 5.8%). Prospectively, two of three patients had the zona pellucida of the blastocyst removed by pronase exposure prior to transfer. Significantly more patients became pregnant when a zona-free blastocyst was transferred in comparison to transfer of a single zona-intact embryo (9/11 or 82% versus 1/5 or 20%; P < 0.01). Higher ongoing singleton pregnancy rates were obtained when the zona pellucida was removed prior to the transfer (6/11 and 1/5 respectively). This preliminary prospective randomized study indicates that by prolonging the evaluation time for patients at risk of developing OHSS for up to 6 days after the oocyte retrieval, those patients at risk for developing severe OHSS can be identified. Transferring a single zona-free day 5 embryo (blastocyst) and freezing of the supernumerary embryos offers the patient with moderate OHSS an optimal chance for a singleton pregnancy, while avoiding the serious maternal complications of ovarian hyperstimulation syndrome.

Since the first reports of successful pregnancies in humans after treatment with intracytoplasmic sperm injection (ICSI), intensive investigations have focused on several important aspects of this form of assisted reproductive technology. In addition to the technical development of ICSI and increasing understanding of the biochemical and biophysical processes involved during fertilization after injection of an immobilized sperm, studies have aimed to define the indications for patients for a first-line ICSI treatment. One of the major concerns is of course the safety of the technique in terms of the health and reproductive life of the babies born after ICSI. The rhesus monkey is an excellent model to investigate all aspects of this micromanipulation technique. This article provides an evaluation of ICSI.

The sperm-hyaluronan binding assay (HBA) is a diagnostic kit for assessing sperm maturity, function and fertility. The aim of this prospective cohort pilot study was to evaluate the relationship between HBA and WHO sperm parameters (motility, concentration and detailed morphology) and possible influence of sperm processing on hyaluronic acid binding. A cohort of 68 patients undergoing a first combo in vitro fertilisation/intracytoplasmic sperm injection treatment after failure of three or more intrauterine insemination cycles were included in the study. Outcome measures studied were fertilisation rate, embryo quality, ongoing pregnancy rate and cumulative pregnancy rate. HBA outcome improved after sperm preparation and culture, but was not correlated to detailed sperm morphology, concentration or motility. HBA did not provide additional information for identifying patients with poor or absent fertilisation, although the latter had more immature sperm cells and cells with cytoplasmic retention present in their semen. HBA outcome in the neat sample was significantly correlated with embryo quality, with miscarriage rates and ongoing pregnancy rates in the fresh cycles, but not with the cumulative ongoing pregnancy rate. No threshold value for HBA and outcome in combo IVF/ICSI treatment could be established. The clinical value for HBA in addition to routine semen analysis for this patient population seems limited.

A microfluorimetric assay was designed to monitor beta-glucuronidase (beta-gluc) activity during the early development of mouse embryos and was also applied to measure beta-gluc activity in human sperm cells and single human oocytes. Mouse oocytes and preimplantation embryos at different stages of development, failed fertilized human oocytes, and human sperm cells were collected, and beta-gluc activity was analysed. In the mouse, beta-gluc activity could be measured starting from the morula stage on in a pooled sample of 15 embryos and at blastocyst formation in one single embryo. beta-Gluc activity was low in human sperm cells. The enzyme could be readily demonstrated in 87 per cent of non-fertilized human oocytes. Considerable variation in beta-gluc activity was noticed between individual oocytes.