Accuracy of assessing embryo ploidy of human embryos with PGS in association with IVF

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Gwendoline Marsh
6 years ago
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1 Accuracy of assessing embryo ploidy of human embryos with PGS in association with IVF Norbert Gl eicher, MD M e d i ca l D i re c t o r A n d Chief Scientist, C e n t e r Fo r H u m a n Re p ro d u c t i o n, N ew Yo r k, N Y Pre s i d e nt, Fo u n d ation Fo r Re p ro d uctive M e d i c i n e, N ew Yo r k, N Y Pro fe s s o r ( A d j ), Ro c kefe l l er U n i vers i t y, N ew Yo r k, N Y Pro fe s s o r ( A d j ), Department O f Obstetrics & Gy n e cology, V i e n n a U n i vers i t y S c h o o l Of M e d i c i n e, V i e n n a, A u st r i a AAB College of Reproductive Biology Symposium, Houston, TX, May 15-18, 2017

2 Conflict Statement Dr. Gleicher is listed as co-inventor on a number of pending patent applications claiming diagnostic and therapeutic benefits from determination of CGG repeat numbers and ovarian FMR1 genotypes and sub-genotypes. Dr. Gleicher is co-inventor of awarded U.S. patents, claiming therapeutic benefits for supplementation of DHEA in women with diminished ovarian reserve, a topic discussed in this talk. Other patent applications in regards to DHEA and other fertility-related claims, with no relationship to this talk, are pending. Dr. Gleicher receives royalties from, and owns shares in Fertility Neutraceuticals, LLC, a distributor of a DHEA product. Dr. Gleicher is co-inventor of three pending patent applications claiming potential therapeutic benefit for anti-müllerian hormone (AMH) in infertile women. Dr. Gleicher owns shares in OvaNova Laboratories, LLC.

3 Outline The PGS hypothesis Assumptions underlying PGS Mathematical evidence that PGS cannot work Experimental evidence that PGS cannot work Clinical evidence that PGS does not work

4 Outline The PGS hypothesis Assumptions underlying PGS Mathematical evidence that PGS cannot work Experimental evidence that PGS cannot work Clinical evidence that PGS does not work

5 The PGS Hypothesis Aneuploidy is a major cause of IVF failure and miscarriages after IVF Elimination of aneuploid embryo before embryo transfer, therefore, will improve IVF outcomes and reduce miscarriages

6 Outline The PGS hypothesis Assumptions underlying PGS Mathematical evidence that PGS cannot work Experimental evidence that PGS cannot work Clinical evidence that PGS does not work

7 PGS Assumptions A TEB can reliably determine embryo ploidy at blastocyst stage Ploidy at blastocyst stage reflects ultimate fetal ploidy Diagnostic platforms are accurate

8 The Value of PGS

9 Outline The PGS hypothesis Assumptions underlying PGS Mathematical evidence that PGS cannot work Experimental evidence that PGS cannot work Clinical evidence that PGS does not work

10 Can a single TEB reliably reflect the whole TE?

12 P-values for observing no mosaicism, given different hypotheses r and a threshold of 0.05 (dotted line) P-values for observed mosaicism, given different hypotheses r, and varying numbers of abnormal-aneuploidy cells in biopsy

13 Outline The PGS hypothesis Assumptions underlying PGS Mathematical evidence that PGS cannot work Experimental evidence that PGS cannot work Clinical evidence that PGS does not work

14 A single TEB, therefore, cannot reliably represent the complete TE Does the TE reflect the inner cell mass (ICM)? Not very well! Orvieto et al 2016 Gynecol Endocrinol Bolton et al 2016 NATURE Communications Can the embryo self-correct after blastocyst stage? Yes! Bolton et al 2016 NATURE Communications

16 Reversine Treatment Induces Aneuploidy in Mouse Embryos

17 Effects of Pre-Implantation Chromosome Mosaicism on Embryo Development and Survival

18 Outline The PGS hypothesis Assumptions underlying PGS Mathematical evidence that PGS cannot work Experimental evidence that PGS cannot work Clinical evidence that PGS does not work

23 Greco and et al, N Engl J Med 2015;373:

24 To believe that a single TEB can offer information on whether an embryo can be transferred or should be discarded is, therefore, obviously mistaken!

25 2016 PGDIS Guidelines

26 2016 PGDIS Guidelines

29 Hypothesis

30 Is there anybody in the room who believes we should continue with PGS?

Vidali, MD* Qi (Vicky) Wang, PhD Andrea Weghofer, PhD, MS, MBA, MD* Yan-Guang Wu, PhD* Yao Yu, PhD* Affiliates University of Rochester School of

31 CHR Staff (* Visiting Scientists) David F Albertini, PhD David H Barad, MS, MD Ali Brivanlou, PhD, MD* Sarah Darmon, PhD, MS Dieter Egli, PhD* Norbert Gleicher, MD Vitaly A Kushnir, MD Emanuela Lazzaroni-Tealdi, MS Nicolas Santiquet, PhD Kenneth Seier, MS* Aya Shohat-Tal, PhD* Andrea Vidali, MD* Qi (Vicky) Wang, PhD Andrea Weghofer, PhD, MS, MBA, MD* Yan-Guang Wu, PhD* Yao Yu, PhD* Affiliates University of Rochester School of Medicine and Dentistry: Aritro Sen, PhD Rockefeller University: Ali Brivanlou, PhD, MD Gist Croft, PhD Salk Institute for Biological Studies: Pradeep Reddy, PhD

Nothing more controversial than PGS

Nothing more controversial than PGS Norbert Gleicher, MD M e d i c a l D i r e c t o r a n d C h i e f S c i e n t i s t, C e n t e r F o r H u m a n R e p ro d u c t i o n, N e w Yo r k, N Y P r e s i