Abstract

A decision model was constructed to compare genetic testing and not testing, for the transfer of all suitable embryos, one at a time, from a cycle with up to ten embryos, until a first live birth was achieved or there were no more embryos available (a full cycle). Two strategies were investigated: (i) a fresh transfer with subsequent serial warmed cryopreserved embryo replacement, and (ii) freeze-all prior to serial embryo replacement. Sensitivity analyses were performed to assess the effect of embryo warming survival and diagnostic accuracy on cumulative rates. Cost-effectiveness was assessed using the incremental cost-effectiveness ratio for a live birth event, and a clinical miscarriage avoided. Reproductive outcome probabilities were obtained from published prospective non-selection studies, and costs from websites and publications.Given 100% embryo warming survival and no false abnormal genetic test results, the live birth rate for a full cycle was the same with and without testing for both transfer strategies. Compared to not testing, it was theoretically possible for testing to be favoured for live birth only for the fresh and frozen transfer strategy, where more than one embryo was available, and dependent on the efficiency of warming survival and the positive predictive value of the test; however, this was unlikely to be cost-effective from a society perspective without a substantial reduction in genetic testing costs. For both transfer strategies, when more than one embryo was available, testing was more likely to achieve a live birth event following the first attempt with fewer attempts required overall. Testing was likely to be effective to avoid a clinical miscarriage but also to be expensive from a society perspective compared to the cost of dilation and curettage.

Highlights

  • Ovarian stimulation and in vitro fertilisation of oocytes with spermatozoa is widely used to treat couples with infertility or genetic disorders in order to assist with the conception of a child

  • In the first instance it was assumed that every embryo was potentially available for transfer (100% warming survival) and that none was excluded incorrectly due to the genetic test (100% per to years predictive value (PPV) for aneuploidy test (AT) or AT + viability test (VT))

  • When more than one embryo is available, the analysis presented here supports the argument that using a freeze-all strategy no embryo selection technique can improve on the serial transfer of every warmed embryo from a stimulation to achieve a live birth, and demonstrates that caution should be exercised when drawing a conclusion about the effectiveness of PGS if a trial does not include the outcome of cryopreserved embryos [16]

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Summary

Introduction

Ovarian stimulation and in vitro fertilisation of oocytes with spermatozoa is widely used to treat couples with infertility or genetic disorders in order to assist with the conception of a child. Genetic testing offers the potential to transfer one embryo at a time in the fewest possible number of transfer procedures to optimise a woman’s chance of achieving a healthy singleton live birth event, substantially reducing the risk of clinical complication associated with multiple pregnancy, and miscarriage due to chromosome aneuploidy. There have been many advances in the technology used for genetic testing and assisted conception, and in particular reliable blastocyst culture and effective cryopreservation enable the sampling of multiple cells from an embryo with sufficient time to perform advanced genetic tests. Advances in cryopreservation techniques mean that it has become possible to carry out serial transfer of all available embryos one at a time without genetic testing; this has the advantage of avoiding false abnormal results from genetic testing and optimising the potential for of a live birth from a stimulated cycle [7].

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