Standardization of grading embryo morphology

Background Identification of a non-invasive technique to assess embryo implantation potential in assisted reproduction would greatly increase success rates and lead more efficiently to single embryo transfer. Early studies suggested metabonomic analysis of spent culture media could improve embryo selection. The goal of this study is to assess if embryo implantation can be predicted based on proton nuclear magnetic resonance ( 1 H NMR) profiles of spent embryo culture media from patients undergoing transfer of multiple embryos on cycleday 3.Method We conducted a retrospective study in an academic assisted reproduction technology (ART) program and analyzed the data in a university research center. Two hundred twenty-eight spent culture media samples originating from 108 patients were individually analyzed. Specifically, five distinct sets (1 to 5) of different types of spent media samples (volume~14 μL) from embryos that resulted in clinical pregnancy (positive heart rate at 6 weeks gestation) (n 1 029; n 2 0 19; n 3 09; n 4 012; n 5 033; n total 0102) and from embryos that did not implant (n 1 028; n 2 029; n 3 018; n 4 015; n 5 036; n total 0126) were collected on day 3 of embryo growth. The Reprod Genet (2012) 29:1435-1442 DOI 10.1007 media samples were profiled using 1 H NMR spectroscopy, and the NMR profiles of sets 1 to 5 were subject to standard uni-and multi-variate data analyses in order to evaluate potential correlation of profiles with implantation success. Results For set 1 of the media samples, a borderline class separation of NMR profiles was obtained by use of principal component analysis (PCA) and logistic regression. This tentative class separation could not be repeated and validated in any of the other media sets 2 to 5. Conclusions Despite the rigorous technical approach, 1 H NMR based profiling of spent culture media cannot predict success of implantation for day 3 human embryos.

Section: Patient Selection Treatment and Media Sample Collectionmentioning

confidence: 99%

1H NMR based profiling of spent culture media cannot predict success of implantation for day 3 human embryos

Rinaudo

Shen

Hua

et al. 2012

“…Currently, assessment of embryo morphology remains the choice of method. The correlation between developmental potential and morphological parameters, such as the degree of fragmentation, presence and number of nuclei and size, number and symmetry of blastomeres per embryo at distinct inspection points is well-established [12,31,33,36,39,43]. Present morphological evaluation, however, requires inspection outside the controlled environment of the incubator, which exposes the embryos to undesirable changes in critical parameters: temperature, humidity and pH when evaluated [42].…”

Section: Introductionmentioning

confidence: 99%

A randomized clinical trial comparing embryo culture in a conventional incubator with a time-lapse incubator

Kirkegaard

Hindkjær

Grøndahl

et al. 2012

129

Purpose Time-lapse monitoring allows for a flexible embryo evaluation and potentially provides new dynamic markers of embryo competence. Before introducing timelapse monitoring in a clinical setting, the safety of the instrument must be properly documented. Accordingly, the aim of this study was to evaluate the safety of a commercially available time-lapse incubator. Methods In a two center, randomized, controlled, clinical trial 676 oocytes from 59 patients in their 2nd or third treatment cycle, age <38 years and ≥8 oocytes retrieved were cultured in the time-lapse incubator or in a conventional incubator. The primary outcome was proportion of 4-cell embryos on day 2. Secondary outcomes were proportion of 7-8 cell embryos on day 3 and proportion of blastocysts on day 5. Implantation pregnancy rates were registered based on presence of fetal heart activity visualized by ultrasound 8 weeks after embryo transfer. Results No significant difference was found between the time-lapse incubator (TLI) and conventional incubator (COI) in proportion of 4-cell embryos on day 2 irrespective of whether data was analyzed according to ITT (RR TLI/COI : 0.81 (0.65; 1.02)) or PP (RR TLI/COI : 0.80 (0.63; 1.01)). Nor were any significant differences detected in the secondary endpoints; i.e. proportion of 7-8-cell embryos on day three ITT (RR TLI/COI : 0.96 (0.73; 1.26)); PP (RR TLI/COI : 0.95 (0.72; 1.26)) and proportion of blastocysts on day five ITT (RR TLI/COI : 1.09 (0.84; 1.41)); PP (RR TLI/COI : 1.09 (0.83: 1.41)). We found no differences in clinical pregnancy rate or implantation rate. Conclusion Culture in the time-lapse incubator supports embryonic development equally to a conventional incubator.

“…Embryos that passed a standard morphologic assessment were transferred [1,2]. Only when the oocyte was fertilized (assessed as two pronuclear embryos after IVF), the embryo(s) was selected to be imaged.…”

Section: Overall Study Designmentioning

confidence: 99%

“…presence and number of nuclei, and size per embryo at a few static time points [1,2]. However, the development of embryos is a dynamic process, and embryonic morphology may change markedly over a few hours; subtle changes, then, may decide the fate of the embryos without being detected [3,4].…”

Section: Introductionmentioning

confidence: 99%

Abnormally cleaving embryos are able to produce live births: a time-lapse study

Fan

Han

et al. 2016

Purpose This study investigated the prevalence of abnormally cleaved embryos and determined which types of abnormally cleaved embryos (1-3c, 2-4c, 3-5c, 4-6c), might be suitable for transfer based on live birth data. Methods One hundred seventy-one women (whose transferred embryos were confirmed to be either fully implanted or fully unimplanted) provided 1256 embryos, which were analyzed. Results Of these embryos, 320 embryos were transferred, of these transferred embryos, 291 embryos were normal and 29 embryos were abnormal, which five embryos were not analyzed because each one was presented one abnormal cleavage type. These 24 embryos were divided into four groups. Inclusion criteria were as follows: women under 37 years of age undergoing first fresh in vitro fertilization (IVF) treatment with a basal antral follicle count of 5-15, body mass index (BMI) of 18-25 kg/m 2 , number of retrieved oocytes between 5 and 20, and tubal factors as the cause of infertility. Timelapse imaging analysis software was used to compare temporal parameters of normal cleavage and abnormal cleavage groups (there were four abnormal groups, based on the prevalence of abnormal cleavage embryos). Cleavage times were analyzed before the abnormal cleavage occurred, and time intervals were analyzed after the abnormal cleavage based upon the types of abnormal cleavage. In addition, the time intervals of t4-t3 and t8-t5 were also analyzed; corresponding time parameters were measured in the normal group as well. Implantation rate, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate were also measured in the normally cleaved and abnormally cleaved embryos. The prevalence of abnormal cleavage was 15.92 % (200/1256). T8-t5 was the most important parameter in the prediction of potential development (production of a live-born baby) of abnormally cleaving embryos. Conclusions Abnormally cleaving embryos were able to produced live births with T8-t5 the best parameter to predict the developmental potential of abnormally cleaving embryos.