Study question Are there correlations among human blastocyst ploidy status, standard morphology evaluation and time-lapse kinetics? Summary answer Correlations were observed, in that euploid human blastocysts showed a higher percentage with top quality inner cell mass (ICM) and trophectoderm (TE), higher expansion grades and shorter time to start of blastulation, expansion and hatching, compared to aneuploid ones. What is known already Embryo quality has always been considered an important predictor of successful implantation and pregnancy. Nevertheless, knowledge of the relative impact of each morphological parameter at the blastocyst stage needs to be increased. Recently, with the introduction of time-lapse technology, morphokinetic parameters can also be evaluated. However, a large number of studies has reported conflicting outcomes. Study design, size, duration This was a consecutive case series study. The morphology of 1730 blastocysts obtained in 530 PGS cycles performed from September 2012 to April 2014 that underwent TE biopsy and array comparative genomic hybridization was analyzed retrospectively. A total of 928 blastocysts were cultured in a time-lapse incubator allowing morphokinetic parameters to be analyzed. Partcipants/materials, setting, method Mean female age was 36.8 ± 4.24 years. Four hunderd fifty-four couples were enrolled in the study: 384, 64 and 6 of them performed single, double or triple PGS cycles, respectively. In standard morphology evaluation, the expansion grade, and quality of the ICM and TE were analyzed. The morphokinetic parameters observed were second polar body extrusion, appearance of two pronuclei, pronuclear fading, onset of two- to eight-cell divisions, time between the two- and three-cell (cc2) and three- and four-cell (s2) stages, morulae formation time, starting blastulation, full blastocyst stage, expansion and hatching timing. Main results and the role of chance Of the 1730 biopsied blastocysts, 603 were euploid and 1127 aneuploid. We observed that 47.2% of euploid and 32.8% of aneuploid blastocysts showed top quality ICM (P Limitations, reasons for caution The main limitation of morphology assessment is that it is a static system and can be operator-dependent. In this study, eight embryologists performed morphology assessments. The main limitation of the time-lapse technology is that it is impossible to rotate the embryos making it very difficult to observe them in case of blastomere overlapping or increased cytoplasmic fragmentation. Wider implications of the findings Although there seems to be a relationship between the ploidy status and blastocyst morphology/development dynamics, the evaluation of morphological and morphokinetic parameters cannot currently be improved upon, and therefore replace, PGS. Our results on ongoing pregnancy and miscarriage rates suggest that embryo evaluation by PGS or time-lapse imaging may not improve IVF outcome. However, time-lapse monitoring could be used in conjunction with PGS to choose, within a cohort, the blastocysts to analyze or, when more than one euploid blastocyst is available, to select which one should be transferred. Study funding/competing interests No specific funding was obtained for this study. None of the authors have any competing interests to declare.

Correlation between aneuploidy, standard morphology evaluation and morphokinetic development in 1730 biopsied blastocysts: a consecutive case series study

The accumulation of oxygen in the earth's atmosphere enabled metabolic pathways based on high-energy electron transfers that were capable of sustaining complex multicellular organisms to evolve. This advance came at a price, however, for the high reactivity of oxygen posed a major challenge as biological molecules became susceptible to oxidative damage, resulting in potential loss of function. Many extant physiological systems are therefore adapted, and homeostatically regulated, to supply sufficient oxygen to meet energy demands whilst also protecting cells, and mitochondria in particular, from excessive concentrations that could lead to oxidative damage. The invasive form of implantation displayed by the human conceptus presents particular challenges in this respect. During the first trimester, the conceptus develops in a low oxygen environment that favours organogenesis in the embryo, and cell proliferation and angiogenesis in the placenta. Later in pregnancy, higher oxygen concentrations are required to support the rapid growth of the fetus. This transition, which appears unique to the human placenta, must be negotiated safely for a successful pregnancy. Normally, onset of the maternal placental circulation is a progressive periphery-centre phenomenon, and is associated with extensive villous regression to form the chorion laeve. In cases of miscarriage, onset of the circulation is both precocious and disorganized, and excessive placental oxidative stress and villous regression undoubtedly contribute to loss of the pregnancy. Comparison of experimental and in vivo data indicates that fluctuations in placental oxygen concentration are a more powerful stimulus for the generation of oxidative stress than chronic hypoxia alone. Placental oxidative and endoplasmic reticulum stress appear to play key roles in the pathophysiology of complications of pregnancy, such as intrauterine growth restriction and preeclampsia, through their adverse impacts on placental function and growth. Establishing an inviolable maternal blood supply for the second and third trimesters is therefore one of the most crucial aspects of human placentation.

/pdf/oxygen-the-janus-gas-its-effects-on-human-placental-2g4enf6qbz.pdf

Oxygen, the Janus gas; its effects on human placental development and function

The extensive oxygen gradient between the air we breathe (Po2 ~21 kPa) and its ultimate distribution within mitochondria (as low as ~0.5–1 kPa) is testament to the efforts expended in limiting its ...

Defining Physiological Normoxia for Improved Translation of Cell Physiology to Animal Models and Humans

STUDY QUESTION
Can a generally applicable morphokinetic algorithm suitable for Day 3 transfers of time-lapse monitored embryos originating from different culture conditions and fertilization methods be developed for the purpose of supporting the embryologist's decision on which embryo to transfer back to the patient in assisted reproduction?

/pdf/development-of-a-generally-applicable-morphokinetic-5ba0poypie.pdf

Development of a generally applicable morphokinetic algorithm capable of predicting the implantation potential of embryos transferred on Day 3

Modulation of neuronal stem cell differentiation by hypoxia and reactive oxygen species.

Understanding the biology of reproductive organs is essential for the development of assisted reproductive techniques. There is at present no direct evidence for either the concentration and dynamics of intrauterine oxygen tension at the endometrial surface, nor its importance for the receptiveness of the endometrium. In this study a new method measured mid-cycle (ranging from day 12-18) endometrial surface oxygen tension in 21 patients referred to intrauterine insemination (IUI). Time series was measured online for a period of 5-10 min. The (mean) individual oxygen tension among patients varied from 4 to 27% air saturation. Overall mean oxygen tension among all patients was 11.8% air saturation. Within the same patient, considerable time-related variations were observed. Some patients exhibited rhythmic oscillations with a frequency in the order of 1 min, whereas others did not show any regular patterns. A good description of endometrial surface oxygen concentration and dynamics was thus obtained, but given the relatively small number of participants, an association with pregnancy following insemination could not be established. Further studies using this new method could elucidate the association between individual intrauterine activity, embryo implantation and endometrial surface oxygen tension.

https://www.rbmojournal.com/article/S1472-6483(10)61443-5/pdf

Observations on intrauterine oxygen tension measured by fibre-optic microsensors

The goal of embryo selection models is to select embryos with the highest reproductive potential, whilst minimizing the rejection of viable embryos. Ultimately, any embryo selection model must be tested on clinical outcome. We therefore retrospectively tested a published blastocyst prediction model on a large combined set of transferred embryos with known clinical outcome. The model was somewhat effective in that we found a relative increase of 30% for implantation in the model-selected group of embryos. There was, however, a concomitant large rejection of embryos from our test cohort, which actually resulted in pregnancy. This hypothetical experiment highlights the limitations of predicting blastulation only. Crucially, it illustrates that both sensitivity and specificity are important parameters when developing embryo selection models for prospective clinical use.

https://www.rbmojournal.com/article/S1472-6483(14)00246-6/pdf

Limitations of a time-lapse blastocyst prediction model: a large multicentre outcome analysis

Association between women's age and stage, morphology, and implantation of the competent blastocyst: a multicenter cohort study.

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Observations on intrauterine oxygen tension measured by fibre-optic microsensors

Limitations of a time-lapse blastocyst prediction model: a large multicentre outcome analysis

Association between women's age and stage, morphology, and implantation of the competent blastocyst: a multicenter cohort study.