Biosimilar recombinant follitropin alfa preparations versus the reference product (Gonal-F®) in couples undergoing assisted reproductive technology treatment : a systematic review and meta-analysis

Acknowledgments Authors would like to thank Dr. Rui Wang (Department of Obstetrics and Gynecology, University of Monash) who contributed to the statistical analysis. Medical writing assistance was provided by Evelina Matekonyte, inScience Communications, Springer Healthcare Ltd., London, UK, and funded by Merck KGaA, Darmstadt, Germany. Funding This study was funded by Merck KGaA, Darmstadt, Germany. Merck KGaA (Darmstadt, Germany) designed and approved the study, took part in data collection and data analysis, and contributed to the data interpretation and final draft of the manuscript. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.Peer reviewedPublisher PD

Morphological selection of embryos and time-lapse technology

AimsThis thesis includes three studies designed to investigate embryo selection in the IVF laboratory. Firstly, the agreement between embryologists when selecting a Day 5 embryo for transfer was evaluated. Following this, the use of time-lapse technology to improve embryo selection was assessed, and finally, the agreement between published time-lapse algorithms when selecting an embryo for transfer was investigated. MethodsIn the first study, ten embryologists morphologically graded and selected a single embryo for transfer using images of day 5 embryos. Inter- and intra-observer agreement was measured using the kappa coefficient. In the second study, time-lapse was used to record morphokinetic parameters of day 5 embryos and their ability to identify a top-quality blastocyst was assessed using logistic regression analyses. Finally, the agreement between published time-lapse algorithms when selecting a single day 5 embryo with the highest implantation potential was evaluated in the third study, as well as the agreement between these algorithms and experienced embryologists. ResultsThe agreement among embryologists in the first study when selecting a day 5 embryo for transfer was generally good. Assessment of agreement with regards to morphological grading was only fair to moderate. When time-lapse was investigated in the second study, eight parameters were found to predict top quality blastocyst formation. However, the resulting composite models had, at best, poor-to-moderate discriminatory capacity to predict blastocyst quality. In the third study, a highly variable agreement was found between published algorithms when selecting an embryo with the highest implantation potential. Moreover, the agreement between these algorithms and embryologists was poor to moderate. ConclusionsThe less than optimal agreement found between embryologists in the first study could negatively impact on pregnancy rates. However, development of a time-lapse model in the second study showed limited ability to increase consistency during embryo selection. Furthermore, the variable agreement between algorithms in the third study raises concerns as to whether they are selecting the embryo with the highest implantation potential in a different clinical setting. This research not only emphasises the need to optimise embryo selection strategies but also highlights that proper external validation of any new technology is required before implementation