Perfection of Embryology Practice Over the Last 10 Years is the Main Source of Improvement of IVF treatment outcomes.

Prepared at the American College of Embryology Practice Committee request by Dmitri Dozortsev, Stephan Krotz and Michael Allon. 

 

We compiled publicly available data collected by the US Center for Disease Control to determine the impact of innovations in different categories of patients from 2001 to 2010.  A Linear regression model demonstrated statistically significant improvement for patients across all age categories.

 

Using ANCOVA analysis, no difference was found in the level of improvement between donor egg recipients (DER) and patients less than 35 years of age. At the same time, the improvement in these two groups has been significantly higher than in older patients at p<0.05%.  Virtually every technological innovation is employed for the treatment of all patients, and therefore cannot explain the disproportional benefit to a particular group. The only technique that by its nature cannot be used for all IVF patients equally is extended in vitro culture of embryos to the blastocyst stage for selection of the highest quality embryo.  

 

In the past, the best embryos were identified using morphological criteria after only 2-3 days of in vitro culture. However, the predictive value of early embryo morphology development and delivery of a term infant has proven to be unreliable⁴. Blastocyst culture extends the in vitro development of the embryos to 5 days outside of the body prior to the transfer back into the uterus.⁴ It has been adapted by a majority of IVF clinics worldwide over the last 10 years, and has enabled a considerable improvement in embryo selection. In fact, some clinics use this technique to identify a single best embryo for transfer. In contrast, older patients have fewer embryos on average, limiting the impact of any advances in embryo selection⁵.  Furthermore, very commonly in older patients all available embryos are transferred without any selection.

 

In itself, it is not surprising that extended in vitro culture would have improved IVF outcomes. However, the high likelihood that it is potentially the most significant source of IVF improvement over the last decade is startling.

 

This is another reminder that delaying infertility treatment narrows patient’s options and limits the potential benefit of technological improvements. 

 

Furthermore, it can be predicted that a more recent embryo selection tools, such as embryos screening for chromosomal errors using  Preimplantation Genetics Screening (PGS) and time-lapse video of embryo development will be the main engine for the improvements in IVF success and not only in terms of a chance of pregnancy. In fact, it is the time to redefine IVF success as transfer of single embryo that resulted in a singleton pregnancy and delivery.  

 

However, embryo selection, including selection of a single embryo for a transfer while increasing IVF effectiveness and improving obstetrics outcome does not address the fundamental ethical issues of creating human embryos, majority of which will be destroyed.

 

This can only be addressed with selecting gametes before fertilization and creating the single embryo that will lead to delivery of a healthy baby. This goal, as ambitios as it may sound, may actually be achieved within the next ten years.   

 

 

Table 1. Live birth rate according to the patient’s category. Source: CDC IVF clinics success rates. 

 

Year	Donor Egg         Recipients	n	<35	n	35-37	n	38-40	n	41-42	n
2010	56%	9866	47%	41741	38%	21366	28%	21739	16%	10120
2009	55%	10151	47%	42384	38%	21860	28%	22144	17%	9845
2008	55%	10718	47%	43296	37%	23326	28%	21793	17%	9783
2007	55%	10321	46%	42127	37%	23504	27%	20612	16%	9335
2006	54%	10049	45%	41369	37%	23376	27%	19775	15%	9346
2005	52%	9649	43%	41302	36%	22624	25%	19482	13%	8997
2004	51%	9823	43%	40853	36%	21019	25%	19174	15%	8487
2003	51%	8970	43%	39852	37%	20056	26%	18660	15%	8185
2002	50%	8394	43%	37591	37%	19110	26%	17454	15%	7733
2001	47%	7722	41%	35984	35%	17791	25%	16283	15%	7044

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

References:

 

1. Malizia BA, Hacker MR, Penzias AS. Cumulative live-birth rates after in vitro fertilization.

N Engl J Med. 2009 Jan 15;360(3):236-43.

 

2. Zhao Y, Brezina P, Hsu CC, Garcia J, Brinsden PR, Wallach E. In vitro fertilization: four decades of reflections and promises. Biochim Biophys Acta. 2011 Sep;1810(9):843-52. Epub 2011 May 13.

 

3. The cumulative embryo score: a predictive embryo scoring technique to select the optimal number of embryos to transfer in an in-vitro fertilization and embryo transfer programm. Steer CV, Mills CL, Tan SL, Campbell S, Edwards RG. Hum Reprod. 1992 Jan;7(1):117-9.

 

4. Accuracy of day 3 criteria for selecting the best embryos. Milki AA, Hinckley MD, Gebhardt J, Dasig D, Westphal LM, Behr B. Fertil Steril. 2002 Jun;77(6):1191-5.

 

5. de los Santos MJ, Mercader A, Galán A, Albert C, Romero JL, Pellicer A. Implantation rates after two, three, or five days of embryo culture. Placenta. 2003 Oct;24 Suppl B:S13-9.