Single-arm, observational study of the ease of use of a redesigned pen device to deliver recombinant human follicle-stimulating hormone (follitropin alfa) for assisted reproductive technology treatment.

PURPOSE: Evaluation of patients' ease of use of the redesigned, disposable, ready-to-use follitropin alfa pen during controlled ovarian stimulation for assisted reproductive technology. METHODS: This single-center, observational, open-label, single-arm study recruited infertile normo-ovulatory women (aged 18-45 years). Nurses trained patients to self-administer recombinant human follicle-stimulating hormone daily using the follitropin alfa pen (300 IU, 450 IU, and 900 IU). Before treatment, patients completed Questionnaire A. Following self-administered treatment, on stimulation days 5-6 and 7-8 (within a day of receiving recombinant human chorionic gonadotropin), patients completed Questionnaire B. Nurses completed an ease-of-learning/teaching questionnaire. The primary endpoint was proportion of patients rating the pen as "easy/very easy" to use (Questionnaire B) on the final visit before recombinant human chorionic gonadotropin. Secondary endpoints included: proportion of patients rating the follitropin alfa pen as easy to learn, use, prepare, deliver, and dispose of (Questionnaires A and B). Proportions (95% confidence intervals [CIs]) were provided for primary and secondary endpoints. Adverse events were reported descriptively. RESULTS: Eighty-six patients received recombinant human follicle-stimulating hormone. Of the 72 patients who had completed the overall assessment questions, 66 (91.7%; 95% CI =82.7%-96.9%) found the pen "easy" to use. Also, 70/86 (81.4%) patients "strongly agreed/agreed" that, overall, it was easy to learn how to use the pen; 72/86 (83.7%) "strongly agreed/agreed" that easily understandable, verbal information was provided; and 70/86 (81.4%) were confident about using the pen correctly. In total, 24/26 nurses (92.3%; 95% CI =74.9%-99.1%) rated the pen as easy to use. Clinical pregnancy rate/patient/cycle/embryo transfer was 37%. Twenty-six ovarian hyperstimulation syndrome events were reported (none severe; 16 patients [19%]); of these, 13 occurred at embryo transfer. CONCLUSION: In this observational study, patients had a high acceptance of the redesigned follitropin alfa pen, with most finding it very easy/easy to use. Assisted reproductive technology nurses found the pen very easy/easy to teach.

A reduction in public funding for fertility treatment--an econometric analysis of access to treatment and savings to government.

BACKGROUND: Almost all assisted reproductive technology (ART) and intrauterine insemination (IUI) treatments performed in Australia are subsidized through the Australian Government's universal insurance scheme, Medicare. In 2010 restrictions on the amount Medicare paid in benefits for these treatments were introduced, increasing patient out-of-pocket payments for fresh and frozen embryo ART cycles and IUI. The aim of this study was to evaluate the impact of the policy on access to treatment, savings in Medicare benefits and the number of ART conceived children not born. METHODS: Pooled quarterly cross-sectional Medicare data from 2007 and 2011 where used to construct a series of Ordinary Least Squares (OLS) regression models to evaluate the impact of the policy on access to treatment by women of different ages. Government savings in the 12 months after the policy was calculated as the difference between the predicted and observed Medicare benefits paid. RESULTS: After controlling for underlying time trends and unobserved factors the policy change reduced the number of fresh embryo cycles by almost 8600 cycles over 12 months (a 16% reduction in cycles, p < 0.001). The policy effect was greatest on women aged 40 years and older (38% reduction in cycles, p < 0.001). Younger women engaged in relatively more anticipatory behaviour by bringing forward their fresh cycles to 2009. Frozen embryo cycles, which are approximately one quarter of the cost of a fresh cycle, were only marginally impacted by the policy. Utilisation of IUI cycles were not impacted by the policy. After adjusting for anticipatory behaviour, $76 million in Medicare benefits was saved in the 12 months after the policy change (0.47% of annual Medicare benefits). Between 1200 and 1500 ART conceived children were not born in 2010 as a consequence of the policy. CONCLUSIONS: The introduction of the policy resulted in a significant reduction in fresh ART cycles in the first 15 months after its introduction. Further evaluation on the long-term impact of the policy with regard access to treatment and on clinical practice, particularly the number of embryos transferred, is crucial to ensuring equitable access to fertility treatment and the health and welfare of ART children.

Assisted reproductive technology: public funding and the voluntary shift to single embryo transfer in Australia.

OBJECTIVES: To calculate cost savings to the Australian federal and state governments from the reduction in twin and triplet birth rates for infants conceived by assisted reproductive technology (ART) since 2002, and to determine the number of ART treatment programs theoretically funded by means of these savings. DESIGN AND SETTING: Costing model using data from the Australia and New Zealand Assisted Reproduction Database, the National Perinatal Data Collection and Medicare Australia on ART treatment cycles undertaken in Australia between 2002 and 2008. MAIN OUTCOME MEASURES: Annual savings in maternal and infant inpatient birth-admission costs resulting from the reduction in ART multiple birth rate; theoretical number of ART treatment programs funded and infants born by means of these savings. RESULTS: The reduction in the ART multiple birth rate from 18.8% in 2002 to 8.6% in 2008 resulted in estimated savings to government of $47.6 million in birth-admission costs alone. Theoretically, these savings funded 7042 ART treatment programs comprising one fresh plus one frozen embryo transfer cycle, equating to the birth of 2841 babies. Fifty-five per cent of the increased use of ART services since 2002 has been theoretically funded by the reduction in multiple birth infants. CONCLUSIONS: Against a backdrop of supportive public funding of ART in Australia, a voluntary shift to single embryo transfer by fertility clinicians and ART patients has resulted in substantial savings in hospital costs. Much of the growth in ART use has been theoretically cross-subsidised by the move to safer embryo transfer practices.

Gonadotropin control of inhibin secretion and the relationship to follicle type and number in the hpg mouse.

Inhibin is secreted in two distinct heterodimeric forms, A and B, but the mechanism for the differential control of these two forms is unclear. To evaluate the relationship between secretion of inhibin forms and folliculogenesis, the effects of gonadotropins on inhibin concentrations were studied in parallel with stereological enumeration of ovarian follicle types in gonadotropin-deficient hypogonadal (hpg) female mice treated with recombinant human FSH (10 IU/day), hCG (1 IU/day), or both for 20 days. Treatment with FSH alone significantly increased blood concentrations of both inhibin A and inhibin B, whereas hCG alone had no effect on either inhibin. The combination of FSH and hCG further increased the concentration of inhibin A but had no effect on the concentration of inhibin B beyond that of FSH. The number of primordial follicles per ovary was significantly reduced in FSH-treated hpg mice, but was not affected by hCG treatment. Antral follicles were absent in the untreated hpg mice, present following treatment with FSH, and were present in only limited numbers following hCG treatment alone. Preovulatory follicles were observed only in the wild-type and combined FSH and hCG treatment groups. These results demonstrate that secretion of both inhibins is associated with the presence of antral follicles. Inhibin A secretion is increased by the presence of preovulatory follicles, whereas the concentration of inhibin B is not affected. The observed effects of gonadotropins on inhibin A and B secretion may be explained by corresponding gonadotropin effects on follicle development.

Effect of progestin-only pill on pituitary-ovarian axis activity during lactation.

We have monitored effects of progestin-only pill (POP) on ovarian activity during breastfeeding. Twenty-one women, using barrier methods (BM) of contraception and 9 women on POP were enrolled 6 weeks postpartum (PP) and followed-up to 18 weeks PP. There was little change in plasma follicle-stimulating hormone and luteinizing hormone, and no differences between BM and POP. POP did not affect plasma estradiol. There was no difference between BM and POP in plasma inhibin B concentrations. The size of follicles was similar in both groups in all time points. There was an increase in the endometrial thickness from 6 weeks PP to 18 weeks PP in BM (3.7 +/- 0.5 vs. 5.4 +/- 0.6 mm, p < 0.05), but no differences within the POP group or between the treatment groups. POP does not suppress gonadotropins nor affect growth of ovarian follicles during breastfeeding. Thus, the contraceptive effect of POP is likely mediated through local actions at the endometrium and cervix in a manner similar to that in menstruating women.