Oocyte donation by gamete intra-Fallopian transfer to amenorrhoeic and cycling patients given replacement steroids

Thirteen procedures of oocyte donation by the gamete intra-Fallopiantransfer (GIFT) technique are described. The patients includedsix women with premature ovarian failure, four normally cyclingwomen with unexplained infertility who responded poorly to super-ovulationinduction in preparation for GIFT, and lastly one woman carrierof a 16/21 balanced translocation. Two patients had oocytesdonated on two occasions. Oocyte donors were recruited eitheramong the patients' relatives (n = 4), or among GIFT or IVFpatients (n = 8), who altruistically donated their extra oocytes.Donors were superovulated and oocytes collected laparoscopicallyor vaginally under ultrasound guidance. Donors did not sufferany complications. Recipients were given exogenous oestrogens,and exogenous progesterone was added from the day of donation.Seven clinical pregnancies were obtained (53.8% per attempt);one set of triplets aborted at 14 weeks. Donation took placeon replacement day 12–18 and pregnancies were obtainedin patients receiving oocytes throughout this temporal window.The increasing availability of embryo-freezing facilities willprobably reduce the number of ova available for donation. Therefore,the patients' families may become a precious source of donatedeggs, especially for those patients having large families, withstrong family ties.     

When poor solubility becomes an issue: From early stage to proof of concept

Drug absorption, sufficient and reproducible bioavailability and/or pharmacokinetic profile in humans are recognized today as one of the major challenges in oral delivery of new drug substances. The issue arose especially when drug discovery and medicinal chemistry moved from wet chemistry to combinatorial chemistry and high throughput screening in the mid-1990s. Taking into account the drug product development times of 8–12 years, the apparent R&D productivity gap as determined by the number of products in late stage clinical development today, is the result of the drug discovery and formulation development in the late 1990s, which were the early and enthusiastic times of the combinatorial chemistry and high throughput screening. In parallel to implementation of these new technologies, tremendous knowledge has been accumulated on biological factors like transporters, metabolizing enzymes and efflux systems as well as on the physicochemical characteristics of the drug substances like crystal structures and salt formation impacting oral bioavailability. Research tools and technologies have been, are and will be developed to assess the impact of these factors on drug absorption for the new chemical entities.

The conference focused specifically on the impact of compounds with poor solubility on analytical evaluation, prediction of oral absorption, substance selection, material and formulation strategies and development. The existing tools and technologies, their potential utilization throughout the drug development process and the directions for further research to overcome existing gaps and influence these drug characteristics were discussed in detail.     

卵巢低反应患者大剂量超排卵的助孕结局

在辅助生殖助孕中通常采用控制性卵巢刺激(controlled ovarian hyperstimulation, COS),以获得适当数量的卵子用于体外受精,既希望获得理想的辅助生殖助孕成功率,又能降低卵巢过度刺激并发症.COS中约有9%~24%[1,2]的卵巢低反应发生率.卵巢低反应者获得有效卵子数少、可移植胚胎数少或无胚胎移植、取消治疗周期率高,累计成功率更低等,导致较差的治疗结局,是辅助生殖助孕中面临的棘手问题.针对卵巢低反应者,大多数辅助生殖中心仍会采用增加促性腺激素(Gn)的起始和(或)总用量以期获得提高助孕结局的目的.而大剂量Gn是否为改善低反应患者助孕结局的有效策略却仍存在争议.     

卵巢低反应者体外受精-胚胎移植的临床结局分析

目的评估首次体外受精-胚胎移植时表现为卵巢低反应的患者接受再次体外受精-胚胎移植治疗的实际意义和调整临床处理过程的价值。方法回顾性分析2004年1月至12月间在北京大学第三医院生殖中心进行体外受精-胚胎移植的206个卵巢低反应病例,共288个周期的临床资料。结果206例卵巢低反应病例首次IVF-ET时临床妊娠率为22%。其中82例接受了再次IVF-ET,临床妊娠率为40.6%,高于首次IVF-ET,经统计学检验差异有显著性(P<0.05),再次IVF-ET的E2峰值,取卵数以及移植胚胎数均高于首次IVF-ET,经统计学检验差异有显著性(P<0.05)。结论首次IVF-ET卵巢低反应的患者经过调整促排卵方案,接受再次IVF-ET时临床妊娠率有所提高。     

Growth hormone co-treatment for ovulation induction may enhance conception in the co-treatment and succeeding cycles, in clonidine negative but not clonidine positive patients

To investigate the effect of co-treatment with growth hormone(GH) for ovulation induction with human menopausal gonadotrophins(HMG) on conception, we compared the pregnancy rate and responseto co-treatment with GH versus HMG/human chorionic gonadotrophin(HCG) alone in a prospective, randomized, cross-over protocolof volation induction for either in-vivo or in-vitro fertilization(IVF). The main outcome measures were the amount of gonadotrophinused and conception. Co-treatment with GH was associated witha reduction of 30% in gonadotrophin requirement. In 24 clonidinenegative patients 14 pregnancies were achieved (58.3%) eitherin the GH/HMG/HCG cycle or in the succeeding one. GH co-treatmentdid not generate any pregnancy in eight clonidine positive patients.We conclude that growth hormone may increase the pregnancy ratewhen combined with HMG/HCG for ovulation induction, not onlyin the co-treatment cycle but also in the succeeding one. Thebeneficial, synergistic effect of GH co-treatment was detectedin clonidine negative but not in clonidine positive infertilepatients.     

Endometrial and subendometrial blood flow measured during early luteal phase by three-dimensional power Doppler ultrasound in excessive ovarian responders

BACKGROUND: Impaired implantation in assisted reproduction cycles with high serum estradiol (E(2)) concentrations may be related to suboptimal endometrial perfusion. Endometrial and subendometrial blood flow were compared between excessive responders (serum E(2) on the day of HCG >20 000 pmol/l) and moderate responders (E(2) < or =20 000 pmol/l). METHODS: Three-dimensional (3D) ultrasound examination with power Doppler was performed 2, 4 and 7 days after HCG in 32 patients who did not have embryo transfer in order to measure endometrial thickness, pulsatility index (PI)/resistance index (RI) of uterine vessels, and endometrial volume, vascularization index (VI)/flow index (FI)/vascularization flow index (VFI) of endometrial and subendometrial regions. RESULTS: Excessive responders tended to have lower endometrial and subendometrial VI/VFI on HCG +2 and more absent endometrial/subendometrial blood flow. They had significantly higher endometrial FI and subendometrial VFI than moderate responders on HCG +7. Only in the excessive responder group, uterine PI/RI declined significantly from HCG +2 to HCG +7 and endometrial VI/VFI increased significantly from HCG +4 to HCG +7. CONCLUSION: Changes in uterine Doppler flow indices, and endometrial and subendometrial 3D power Doppler flow indices during the early luteal phase were significantly different between moderate and excessive responders.     

Comparison of agonistic flare-up-protocol and antagonistic multiple dose protocol in ovarian stimulation of poor responders: results of a prospective randomized trial

The management of poor responders in IVF has always been a big problem. The ideal approach has yet to be formulated. In this study we aim to compare two alternative stimulation protocols. A total of 48 poor responder patients described from previous cycles were included and grouped into two: group I consisted of 24 patients in 24 cycles in which leuprolide acetate (40 microg s.c. per day) was initiated on cycle day 2 followed by exogenous gonadotrophins on cycle day 3; group II consisted of 24 patients in 24 cycles in which ovarian stimulation included gonadotrophin-releasing hormone (GnRH) antagonist (cetrorelix, 0.25 mg daily during late follicular phase) administration. While only the oestradiol concentrations on the day of HCG were lower in group II compared with group I, the clinical pregnancy and implantation rates among groups did not show any significance. The impact of these two regimens in ovarian stimulation of poor responders seem to be same and to establish these results further randomized studies with larger sample sizes are required.     

The experiences of peer-facilitators delivering a physical activity intervention for emergency service workers and their families

IntroductionEmergency service workers (e.g. police, fire, ambulance officers) are regularly exposed to occupational stressors and potentially traumatic events, resulting in an increased risk of poor mental and physical health. For example, emergency service workers are twice as likely to experience suicidal thoughts compared to the general population and one in ten will develop posttraumatic stress disorder. Despite this, emergency service workers face barriers to accessing traditional mental healthcare. Physical activity is non-stigmatising and may help improve the mental and physical health of this population; however, novel ways to help people engage are needed. Peers with lived experience may be well-placed to co-deliver physical activity programs alongside health professionals. The aim of this study was to understand the experiences of peer-facilitators co-delivering an online physical activity intervention for emergency service workers and their families.MethodsQualitative interviews were conducted with 6 peer-facilitators. Interviews were audio recorded, transcribed, and analysed using exploratory thematic analysis.ResultsTwo main themes were explored. The first theme related to the value of lived experience that reflected two subthemes, i) credibility and relatedness by virtue of experience; and ii) knowledge and confidence by virtue of experience. The second theme related to the impact of the peer-facilitator role on the peers themselves, whereby peer-facilitators reported an increased sense of purpose and social connection.DiscussionThis qualitative study provides insights into how peer-facilitators can complement health professionals in the delivery of physical activity interventions for emergency service workers. Further research is needed to elucidate training requirements and safety protocols.