Innovation in medically assisted reproduction (MAR) is at an all-time high, with new technologies being developed for the laboratory and around the patient experience, and deployed quickly and ...effectively. Nevertheless, substantial improvements in the success of infertility care seem to elude the field. This article presents the view that MAR is missing the key innovation motor of mechanistic knowledge, which historically relates to a lack of public resources of the kind afforded to other diseases. It is posited that unless and until we raise infertility at the level of an urgent unmet medical need in the eyes of government and national funding body, innovation will be limited in scope and impact, and be incremental in nature.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The events regulating human preimplantation development are still largely unknown owing to a scarcity of material, ethical and legal limitations and a lack of reliable techniques to faithfully ...amplify the transcriptome of a single cell. Nonetheless, human embryology is gathering renewed interest due to its close relationship with both stem cell biology and epigenetic reprogramming to pluripotency and their importance in regenerative medicine. Carefully timed genome-wide transcript analyses of single oocytes and embryos uncovered a series of successive waves of embryonic transcriptional initiation that start as early as the 2-cell stage. In addition, we identified the hierarchical activation of genes involved in the regulation of pluripotency. Finally, we developed HumER, a database of human preimplantation gene expression, to serve the scientific community. Importantly, our work links early transcription in the human embryo with the correct execution of the pluripotency program later in development and paves the way for the identification of factors to improve epigenetic reprogramming.
The utility of induced pluripotent stem (iPS) cells for investigating the molecular logic of pluripotency and for eventual clinical application is limited by the low efficiency of current methods for ...reprogramming. Here we show that reprogramming of juvenile human primary keratinocytes by retroviral transduction with OCT4, SOX2, KLF4 and c-MYC is at least 100-fold more efficient and twofold faster compared with reprogramming of human fibroblasts. Keratinocyte-derived iPS (KiPS) cells appear indistinguishable from human embryonic stem cells in colony morphology, growth properties, expression of pluripotency-associated transcription factors and surface markers, global gene expression profiles and differentiation potential in vitro and in vivo. To underscore the efficiency and practicability of this technology, we generated KiPS cells from single adult human hairs. Our findings provide an experimental model for investigating the bases of cellular reprogramming and highlight potential advantages of using keratinocytes to generate patient-specific iPS cells.
Mitochondria are fundamental organelles in eukaryotic cells that provide ATP through oxidative phosphorylation. During this process, reactive oxygen species (ROS) are produced, and an imbalance in ...their concentrations can induce oxidative stress (OS), causing cellular damage. However, mitochondria and ROS play also an important role in cellular homeostasis through a variety of other signaling pathways not related to metabolic rates, highlighting the physiological relevance of mitochondria–ROS interactions. In reproduction, mitochondria follow a peculiar pattern of activation, especially in gametes, where they are relatively inactive during the initial phases of development, and become more active towards the final maturation stages. The reasons for the lower metabolic rates are attributed to the evolutionary advantage of keeping ROS levels low, thus avoiding cellular damage and apoptosis. In this review, we provide an overview on the interplay between mitochondrial metabolism and ROS during gametogenesis and embryogenesis, and how OS can influence these physiological processes. We also present the possible effects of assisted reproduction procedures on the levels of OS, and the latest techniques developed to select gametes and embryos based on their redox state. Finally, we evaluate the treatments developed to manage OS in assisted reproduction to improve the chances of pregnancy.
Purpose
The objective of this meta-analysis is to determine whether there is a higher incidence of preeclampsia (PE) in pregnancies achieved by oocyte donation (OD) compared with pregnancies achieved ...by in vitro fertilization with autologous oocytes (IVF).
Methods
A systematic review was performed to identify relevant studies published from January 1994 until April 2015 with at least an abstract in English using PubMed, ISI Web of Knowledge, and clinicaltrials.gov. The 11 studies included in this systematic review were retrospective and prospective cohort studies of women reporting results on the association between oocyte donation vs. in vitro fertilization (exposure) and preeclampsia (outcome).
Results
Oocyte donation is a risk factor for the development of PE compared to IVF cycles, with a weighted OR of 3.12 under a fixed effects method (FEM: no heterogeneity between the studies). The weighted OR under a random effects model was 2.9 (REM: heterogeneity between the studies). The meta-regression analysis showed that neither multiple pregnancies (estimate = 0.08;
p
= 0.19) nor patient age (estimate = −2.29;
p
= 0.13) significantly explained the variability of the effect of oocyte donation on PE. Q statistic was 12.78 (
p
= 0.237), suggesting absence of heterogeneity between the studies.
Conclusions
Pregnancies achieved by oocyte donation confer a threefold increase in the likelihood of developing PE than those achieved by in vitro fertilization with own oocytes. Physicians should be aware of this risk in order to both counsel patients and monitor pregnancies accordingly.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Women of reproductive age have insufficient fertility knowledge and awareness. Reproductive lifespan and assisted reproduction are the primary areas in which awareness is lacking. Relatively ...simple interventions can be used to increase knowledge among university students; however, no intervention has been tested to date in a population with more varied education levels. The aim of this study was to evaluate which intervention most improved fertility knowledge in women attending a fertility centre for oocyte donation. A randomized controlled trial was conducted with three intervention groups: tailored, untailored and control. A questionnaire was administered on the day of the first consultation, and again at the oocyte retrieval. Two hundred and one women were enrolled and completed the pre-test, 109 started the cycle and 90 completed the post-test. The effect of the intervention was measured as the difference between the groups in their score from the pre-test to the post test. Only the tailored group showed a significant increase (+2.5; 95% CI 1.8, 3.3; P = 0.001). Information relating to a woman's most fertile age and limits for childbearing were the most useful. Tailored oral education, therefore, increases fertility knowledge in young women, particularly in relation to their fertility lifespan.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Purpose: The decision to have a child might be postponed by the lack of partner, and elective egg freezing (EEF) can afford single women more time to find a suitable companion to reach the desired ...family structure. Alternatively, some women decide to have a child on their own thorough in vitro fertilization (IVF) or intrauterine insemination (IUI) with donor sperm. This study investigates the motivations and personal characteristics of single women undergoing IVF/IUI or EEF.
Materials and methods: This is a cross-sectional study including 281 heterosexual single women who underwent either IVF/IUI with donor sperm for solo motherhood (208) or EEF (73) in 2015 at a large fertility center. An anonymous electronic survey was sent after starting the treatment.
Results: The most common reason for not having fulfilled the motherhood desire was lack of partner (72.4% IVF/IUI and 65.9% EEF). We found that women undergoing IVF/IUI report a longer motherhood desire, >10 years (71.3% vs. 54.3%), live closer to their families (75.5% vs. 56.5%), and perceive a stronger family support than women undergoing EEF (85.4% vs. 68.8%). Finally, 100% of EEF obviously knew about the possibility of IVF/IUI with donor sperm, while 59.9% of IVF/IUI knew about EEF.
Conclusion: Our results underscore the relevance of family ties in the decision to undergo IVF/IUI as single women. Moreover, these women might not be fully informed about social freezing as an option to postpone motherhood. Health professionals should be aware of these differences when counseling single women on fertility choices.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Adequately selecting the initial follicle-stimulating hormone (FSH) dose during controlled ovarian stimulation (COS) is key for success in assisted reproduction. The objective of COS is to obtain an ...optimal number of oocytes to increase the chances of achieving a pregnancy, while avoiding complications for the patient. Current clinical protocols do achieve good results for the majority of patients, but further refinements in individualized FSH dosing may reduce the risk of poor ovarian response while also limiting the risk of ovarian hyperstimulation syndrome (OHSS) risk. Models to select the first FSH dose in COS have been presented in literature with promising results. However, most have only been developed and tested in normo-ovulatory women under the age of 40 years.
This is a randomized, controlled, multicenter, single blinded, clinical trial. This study will be performed in 236 first cycle in vitro fertilization (IVF) and/or ICSI (intracytoplasmic sperm injection) patients, randomized 1:1 in two arms. In the intervention arm, the dose of FSH will be assigned by a machine learning (ML) model called IDoser, while in the control arm, the dose will be determined by the clinician following standard practice. Stratified block randomization will be carried out depending on the patient being classified as expected low responder, high responder, or normo-responder. Patients will complete their participation in the trial once the first embryo transfer result is known. The primary outcome of the study is the number of metaphase II (MII) oocytes retrieved at ovarian pick up (OPU) and the hypothesis of non-inferiority of the intervention arm compared to the control. Secondary outcomes include the number of cycle cancelations (due to low response or no retrieval of mature oocytes), risk of ovarian hyperstimulation syndrome (OHSS), and clinical pregnancy and live birth rates per first transfer.
To our knowledge, this is the first randomized trial to test clinical performance of an all-patient inclusive model to select the first dose of FSH for COS. Prospective trials for machine learning (ML) models in healthcare are scarce but necessary for clinical application.
ClinicalTrials.gov, NCT05948293 . Registered on 14 July 2023.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Induced pluripotent stem (iPS) cells have generated keen interest due to their potential use in regenerative medicine. They have been obtained from various cell types of both mice and humans by ...exogenous delivery of different combinations of Oct4, Sox2, Klf4, c-Myc, Nanog, and Lin28. The delivery of these transcription factors has mostly entailed the use of integrating viral vectors (retroviruses or lentiviruses), carrying the risk of both insertional mutagenesis and oncogenesis due to misexpression of these exogenous factors. Therefore, obtaining iPS cells that do not carry integrated transgene sequences is an important prerequisite for their eventual therapeutic use. Here we report the generation of iPS cell lines from mouse embryonic fibroblasts with no evidence of integration of the reprogramming vector in their genome, achieved by nucleofection of a polycistronic construct coexpressing Oct4, Sox2, Klf4, and c-Myc.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
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