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The transition from a transcriptionally active state (GV) to a transcriptionally inactive state (mature MII oocytes) is required for the acquisition of oocyte developmental competence. We hypothesize that the expression of specific genes at the in vivo matured (MII) stage could be modulated by posttranscriptional mechanisms, particularly regulation of alternative splicing (AS). In this study, we examined the transcriptional activity of GV oocytes after ovarian stimulation followed by oocyte pick-up and the landscape of alternatively spliced isoforms in human MII oocytes. Individual oocytes were processed and analyzed for transcriptional activity (GV), gene expression (GV and MII), and AS signatures (GV and MII) on HTA 2.0 microarrays. Samples were grouped according to maturation stage, and then subgrouped according to women's age and antral follicular count (AFC); array results were validated by quantitative polymerase chain reaction. Differentially expressed genes between GV and MII oocytes clustered mainly in biological processes related to mitochondrial metabolism. Interestingly, 16 genes that were related to the regulation of transcription and mitochondrial translation showed differences in alternatively spliced isoform profiles despite not being differentially expressed between groups. Altogether, our results contribute to our understanding of the role of AS in oocyte developmental competence acquisition.

Made available in DSpace on 2020-12-10T20:08:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-06-01 As highlighted by European statistics, the employment of donor oocytes is a growing option for women who cannot make use of their own gametes. As the potential recipients are continuously increasing in number, a donor programme which satisfies this demand is mandatory. Improvements in cryopreservation techniques, like oocyte and embryo vitrification, have led to the overcoming of the sequence of stimulation-retrieval-transfer both from a spatial and a temporal point of view, with the development of cryobanks of oocytes permitting crossborder donation. However, while some studies report comparable success when using vitrified and fresh oocytes we still need to investigate whether the use of fresh oocytes give higher live birth rate than cryop reserved ones, when the same number of oocytes are given. The performance of embryo cryopreservation, conversely, seems to be more reliable. A novel approach based on the shipment of frozen sperm from the recipient's country to the oocyte donor's one, where fresh oocytes are inseminated and the resulting embryos frozen and transported back to the referring IVF centre to perform a frozen embryo transfer may be a good strategy. We believe that the use of frozen embryos from fresh oocytes could be associated with a higher cumulative live birth rate per cycle, while favouring personalised oocyte recipient care with a flexible number of oocytes assigned and limiting the burden of travelling abroad. Clin EUGIN, Via Nobili 188-F, I-41126 Modena, Italy Univ Modena & Reggio Emilia, Dept Med & Surg Sci Mother Child & Adult, Largo Pozzo 71, I-41123 Modena, Italy Ist Clin Zucchi, Biogenesi Reprod Med Ctr, Via Zucchi 24, I-20052 Monza, Italy Sao Paulo State Univ, Dept Physiol, Inst Biosci, Rua Prof Antonio Celso Wagner Zanin 250, BR-18618689 Botucatu, SP, Brazil Clin EUGIN, Carrer Balmes 236, Barcelona 08006, Spain Sao Paulo State Univ, Dept Physiol, Inst Biosci, Rua Prof Antonio Celso Wagner Zanin 250, BR-18618689 Botucatu, SP, Brazil

STUDY QUESTION: Which are the main research interests among patients of assisted reproductive technologies (ART)?SUMMARY ANSWER: Patients identified as research priorities that deserve further investigation: success rates and risks of ART, side-effects of treatments, resources to cope with infertility, effectiveness of alternative therapies, lifestyle habits to protect fertility, oocyte quality and ovarian reserve, and causes of genetic or hereditary infertility.WHAT IS KNOWN ALREADY: The involvement of patients and caregivers in setting research agendas in medicine has gathered significant momentum in the last decade. Patients’ involvement in setting research priorities offers several benefits: improved patient knowledge and awareness of their condition; greater understanding of the medical professionals of the impact of the condition on patients’ quality of life; reduced costs associated with redundant research activities. This is may be also applicable to research in infertility and ART, where patients’ interests have never been explored before.STUDY DESIGN, SIZE, DURATION: This is a cross-sectional study that consists of an anonymous online survey, which was sent up to three times to 2112 patients from 11 fertility centers in 5 countries between January-December 2018. The study design was based on the James Lind Alliance priority setting partnership model, which comprises the identification of patients groups, the exploration of the research agenda, the analysis of collected data and identification of priorities.PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 2112 patients were contacted, and 945 surveys were answered (RR: 44.7%). Patients were asked to identify research questions relevant to them in the areas of infertility causes and prevention, fertility treatments (medication and ART), and the emotional aspects of infertility. Answers were categorized in topics and ranked by frequency. A long list of the top-30 research topics was extracted from the aggregate results, from which, a short list of the top-10 research topics was created. At the end, 10 research questions related to each of the 10 research topics were constructed, based on the answers given by patients.MAIN RESULTS AND THE ROLE OF CHANCE: Female (845, 89.4%) and male (100, 10.6%) patients were included. The mean age of patients was 37.8 (SD 1.74). Most of the patients did not have children at the time of the survey (523, 59%), while 51 (5.7%) were pregnant. Sixty (6.3%) patients did not start treatment, 579 (61.3%) were performing a treatment with their own gametes and 304 (32.2%) were treated through gamete donation. Patients were mainly interested in the effectiveness of ART -especially per clinical profile-, side effects of drugs, protection of fertility and prevention of infertility –especially through diet and exercise-, and psychological aspects of the infertility journey. The top-10 research questions (and weight) obtained were: 1) What are the side-effects of ART treatments? (41.6%); 2) What are the most effective methods to cope with infertility from the psychological point of view? (37.2%); 3) What effects could diet have on fertility? (25.9%); 4) What are ART success rates per clinical profile? (25.9%); 5) Are there habits and lifestyle factors that could prevent infertility? (20.0%); 6) What are the long-term risks associated to ART? (18.5%); 7) Are alternative therapies such as acupuncture, yoga, and meditation effective to treat/prevent infertility? (18.5%); 8) What is the impact of exercise on fertility? (15.4%); 9) How does oocytes quantity and quality affect fertility? (9.5%); 10) What are the genetic patterns or hereditary conditions causing/related to infertility? (9.5%).LIMITATIONS, REASONS FOR CAUTION: Although all respondents had attended a fertility center, not all of them were diagnosed as infertile (i.e. single women) and had started treatment at the time of response, while a few were pregnant; their priorities for research might have been influenced by their infertility journey. Also, all participants attended private fertility centers: areas of interest may be different in public settings.WIDER IMPLICATIONS FOR THE FINDINGS: Researchers and clinicians should keep in mind that, in addition to improvement of treatments’ success rates and side-effects, patients greatly value research on causes, prevention and emotional aspects of infertility. As their views might differ from those of medical professionals, patients’ voices should be incorporated in setting infertility research priorities.

OBJECTIVES: Different perinatal and neonatal adverse outcomes have been reported to be increased in frozen embryo transfer pregnancies compared with fresh embryo transfer with patient's own oocytes. Concerning preeclampsia, it has also been reported to be increased after frozen embryo transfer. The objective of this study is to asses if there is an increased risk of preeclampsia and gestational hypertension in pregnancies achieved with oocyte donation after frozen embryo transfer compared to fresh embryo transfer. STUDY DESIGN: Retrospective cohort study of 433 patients who underwent a cycle with donated oocytes either after fresh (n?=?353) or frozen embryo transfer (n?=?80) between March 2013 and April 2016 at a large fertility clinic. Participants are pregnant patients who reached the 20th week of gestation. The risk of preterm preeclampsia (presenting before 37 weeks of gestation), term preeclampsia (presenting at or after 37 weeks of gestation) and gestational hypertension are presented as unadjusted and adjusted odds ratio (OR). RESULTS: Frozen embryo transfer have similar risk for developing preterm preeclampsia compared to fresh embryo transfer, with an OR of 1.95 (CI 95% 0.72, 5.26, p?=?0.18), as well as term preeclampsia (OR 0.3, 95%CI 0.04, 2.35, p?=?0.25), and gestational hypertension (OR 1.45, 95% CI 0.75, 2.81, P?=?0.27). CONCLUSIONS: Despite a high prevalence of preeclampsia in pregnancies achieved by oocyte donation, the freezing-thawing process does not confer more risk than the fresh embryo transfers in preterm preeclampsia, term preeclampsia or gestational hypertension.

INTRODUCTION: Pregnancies after gamete donation are at higher risk of developing pre-eclampsia (PE) than those achieved by IVF with patient's own gametes. We aim to assess whether pregnancies achieved with both oocyte and sperm donation (double donation, DD) are at an increased risk of developing PE and gestational hypertension (GH) compared to those achieved by oocyte donation alone (OD). MATERIALS AND METHODS: Retrospective cohort study of 433 patients who reached the 20th week of gestation with either DD (n?=?81) or OD (n?=?352) between March 2013 and April 2016 at a fertility clinic. The risk of preterm PE, term PE, and gestational hypertension (GH) are presented as unadjusted and adjusted odds ratio (OR). RESULTS: DD have a higher risk of preterm PE than OD, with an OR of 3.02 (95%CI 1.11-8.24; p?=?0.031). We found no difference in the risk of term PE (OR 0.26, 95%CI 0.03-1.98; p?=?0.19) or of GH (OR 1.23, 95% CI 0.63-2.43; p?=?0.55). DISCUSSION: Pregnancies with DD are at higher risk of developing preterm PE than OD alone. Patients, and physicians treating them, should be made aware of the elevated risk of PE in these gestations, in order to start prophylactic measures during the first weeks of pregnancy.