3rd Annual Reproductive Genetic Diagnostics
Date: November 30 - December 1, 2017
Venue: Hyatt Regency Cambridge, Cambridge, MA USA

Final Agenda Now Available

Couples undergoing infertility treatments are more aware than ever of preimplantation genetic screening and diagnosis, yet patients and practitioners alike are still struggling with understanding the technologies being used, their capabilities and limitations, and their clinical, legal, and ethical implications. Cambridge Healthtech Institute's Third Annual Reproductive Genetic Diagnostics conference aims to highlight a number of technologies and their differences, as well as how effective they are at uncovering a variety of genetic abnormalities. Considerations for mosaic embryos, biopsy techniques, and genetic counseling will also be discussed. Special attention will be paid to expanded carrier screening, its role in the direct-to-consumer market, and the potential for other molecular tests for infertility and implantation failure. Future directions for the role of gene editing and non-invasive embryo diagnostics will also be discussed.

Final Agenda

Thursday, November 30

7:30 am Registration


8:55 Chairperson's Remarks

Mark Umbarger, Ph.D., Director, Research and Development, Good Start Genetics

9:00 KEYNOTE PRESENTATION: Single Cell Whole Genome Amplification Technologies and the Future of Chromosome Screening

Sunney_XieXiaoliang Sunney Xie, Ph.D., Mallinckrodt Professor, Chemistry and Chemical Biology, Harvard University

Single-cell whole-genome amplification is critical for preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). However, current whole-genome amplification (WGA) methods are limited by low accuracy of copy-number variation (CNV) detection and low amplification fidelity. We have developed a much improved single-cell WGA method, Linear Amplification via Transposon Insertion (LIANTI), which outperforms existing methods, enabling micro-CNV detection with kilobase resolution. This makes it possible to screen embryos with micro deletions in the range of 100k- 10M bases, some of which are known to cause genetic disorders. Balanced Translocations (BT) and Robertsonian Translocations (RT) are among the most common chromosomal diseases that cause infertility and birth defects. Preimplantation genetic diagnosis (PGD) of in vitro fertilized (IVF) embryos enables embryo selection with balanced chromosomal ploidy, but is normally unable to resolve the translocation carrier state. We have developed a method that enables the selection of translocation-free embryos from patients carrying chromosomal translocations. Preimplantation genetic screening (PGS) has been widely used to select in vitro fertilized embryos free of chromosomal abnormalities and to improve the clinical outcome of in vitro fertilization (IVF). A disadvantage of PGS is that it requires biopsy of the preimplantation human embryo, which can limit the clinical applicability of PGS due to the invasiveness and complexity of the process. We have developed a noninvasive chromosome screening (NICS) method based on sequencing the genomic DNA secreted into the culture medium from the human blastocyst. The NICS method offers the potential of much wider chromosome screening applicability in clinical IVF, due to its high accuracy and noninvasiveness.


9:30 Biopsy Techniques: How Do They Affect PGD Results and Where May We Be Going?

Catherine_RacowskyCatherine Racowsky, Professor, Department of Obstetrics, Gynecology & Reproductive Biology, Harvard Medical School; Director, IVF Laboratory, Brigham & Women's Hospital





10:00 Mosaicism: Technical Challenges and Capabilities

Nathan_TreffNathan R. Treff, Ph.D., Chief Science Officer, Genomic Prediction

Contemporary methods of PGS for aneuploidy offer an opportunity to predict mosaicism within a trophectoderm biopsy. However, many challenges remain to be addressed including adequate preclinical validation of sensitivity and specificity for detection of aneuploidy in a mixture of aneuploid and euploid cells, the clinical predictive value of identifying mosaicism in a single biopsy, of specific chromosomes involved, and of the extent of aneuploidy in the mixture. This presentation will discuss these and other limitations and the current capabilities of available technologies for detecting mosaicism with the preimplantation embryo.

10:30 Coffee Break in the Exhibit Hall with Poster Viewing

11:10 Determination of the Karyotypic Concordance between Trophectoderm and Inner Cell Mass

Andrea_VictorAndrea Victor, MS, Embryologist/Head of PGS Laboratory, Embryology and Human Molecular Genetics, Zouves Fertility Center

PGS on blastocysts is based on the premise that a TE biopsy is representative of the ICM. Previous studies testing the karyotypic concordance between TE and ICM have used small sample size and/or currently dated technologies. Here, we present data on a NGS-based analysis of concordance between TE and ICM in a large group of embryos, showing that a small but relevant percentage of blastocysts are discordant.

11:40 Low Level Mosaicism: Incidence and Implications on Clinical Pregnancies

Dawn_KelkDawn Kelk, Ph.D., Director, IVF Laboratory, Yale University School of Medicine

As methods for PGS testing have evolved, so has awareness of embryonic mosaicism. The clinical significance of mosaicism is not well understood, but mosaic embryos have resulted in healthy live births. Some mosaic embryos, however, may be diagnosed as aneuploid and potentially be discarded despite an unclear potential for healthy live birth. This talk will discuss our study which examined the rate of low-level mosaicism in blastocysts that were classified as euploid and the relative pregnancy rates compared with blastocysts in which no mosaicism was detected.

12:10 pm Sponsored Presentation (Opportunity Available)

12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:10 Dessert Break in the Exhibit Hall with Poster Viewing

1:50 Chairperson's Remarks

Tim Jenkins, Ph.D., Assistant Professor, Surgery (Division of Urology), University of Utah

1:55 Embryonic Mosaicism: Clinical Interpretation and Genetic Counseling

Andria G. Besser, MS, CGC, Genetic Counselor, NYU Fertility Center, NYU Langone Medical Center

Discussion of the clinical implications of a diagnosis of embryonic mosaicism, with particular emphasis on counseling patients about this type of result, both prior to and after preimplantation genetic screening, as well as during the prenatal period.

2:25 Panel Discussion: When Do We Transfer a Mosaic Embryo?


Joe_Leigh_SimpsonJoe Leigh Simpson, M.D., Senior Vice President , Research and Global Programs, March of Dimes Foundation

Catherine_RacowskyCatherine Racowsky, Professor, Department of Obstetrics, Gynecology & Reproductive Biology, Harvard Medical School; Director, IVF Laboratory, Brigham & Women's Hospital

Alan_PenziasAlan S. Penzias, M.D., Boston IVF; Director, Fellowship Program in Reproductive Endocrinology and Infertility, Associate Professor of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School

Panelists will discuss a number of factors and scenarios for considering transferring a mosaic embryo for an IVF cycle.

  • When and why would we consider making such a transfer?
  • What considerations come in to play?
  • How do maternal age, financial considerations, technology, or other considerations factor in?

3:25 Refreshment Break


3:45 How Advances in Expanded Carrier Screening and Exomes Impact Preimplantation Genetic Diagnosis Testing

Rebekah_ZimmermanRebekah S. Zimmerman, Ph.D., FACMG, Associate Professor, Co-Division Head of Reproductive Genetics, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai

Advances in technology have led to carrier screening panels to include testing for hundreds of disorders. More couples are being found to be at risk of one or more recessive disorders in the absence of family history, and additionally this testing has evolved from targeted genotyping to full gene sequencing with possible reporting of variants of unknown significance (VOUSs). Similarly, increased utilization of diagnostic exome sequencing has produced more rare disease diagnoses as well as reporting of more VOUSs. PGD laboratories are now seeing a significant uptake in the referral of patients who previously would have turned to a more invasive prenatal diagnostic testing. The impact that these advances have had on PGD referrals and related controversies will be discussed.

4:15 Mitochondrial and Nuclear Genome Editing in Zygotes

Keiichiro Suzuki, Ph.D., Professor, Graduate School of Engineering Science, Osaka University; formerly Senior Research Associate, Gene Expression Laboratory, Salk Institute for Biological Sciences

With the current advance of genome editing technologies, it is getting easy to change genomic information in zygote. I will speak about our developed genome editing technologies for mitochondrial and nuclear genomic DNA.

4:45 Two Birds, One Stone: Combining Single-Gene Preimplantation Genetic Diagnosis with Embryonic Aneuploidy Screening to Optimize Clinical Outcomes

Kara_GoldmanKara N. Goldman, M.D., FACOG, Assistant Professor, Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, New York University Langone Medical Center

PGD for monogenic disorders and 24-chromosome aneuploidy screening have each independently changed the landscape of clinical reproductive genetics. PGD and PGS can be performed concurrently using a small sample of biopsied trophectoderm cells, but despite the many advantages of PGS and ease of dual-screening, this has not yet become standard practice. Understanding the clinical advantages of combining PGD with PGS, measured against the potential downsides, is key to determining how the practice of PGD should evolve to improve clinical outcomes. Data will be discussed comparing outcomes of PGD with and without concurrent aneuploidy screening to explore the clinical value of dual-screening.

5:15 Close of Day

Friday, December 1

8:00 am Breakfast Breakout Roundtable Discussions


8:55 Chairperson's Remarks

Kara N. Goldman, M.D., FACOG, Assistant Professor, Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, New York University Langone Medical Center

9:00 Quantifying Mitochondrial DNA to Predict Implantation: Myth or Reality

Manuel_ViottiManuel Viotti, Ph.D., Senior Scientist, Embryology and Human Molecular Genetics, Zouves Fertility Center

The quantity of mitochondrial DNA in an embryo has been proposed as a biomarker of implantation, but recent studies have challenged this concept. Why is there discordance between different reports, and should it be used as a predictive tool in the clinic?

9:30 Immunologic Testing and Treatment Prior to IVF and for Recurrent Pregnancy Loss

Jason_FranasiakJason Franasiak, M.D., FACOG, Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Reproductive Medicine Associates of New Jersey and Thomas Jefferson University

Amongst the factors which affect implantation failure of apparently reproductively competent embryos, the immune system has been perhaps both the most plausible and the most debated. Many investigators have developed and employed a wide range of immune tests and treatments aimed at manipulating the milieu to favor implantation. While the knowledge of the immune system's role in implantation is certain, our understanding of the physiology, let alone the pathophysiology, remains incomplete. It is imperative that we gain more clear evidence of cause and in order to test and implement treatment paradigms. In the meantime, immune testing or empiric treatment with immune modulators must be approached with caution.

10:00 Uncovering Novel Cytogenetic and Molecular Etiologies for Male Infertility

Samantha_SchilitSamantha Schilit, MA, Ph.D. Candidate, Genetics, Harvard Medical School

Identifying genes involved in unexplained infertility not only informs an understanding of the mechanisms regulating fertility, but also provides information to support diagnosis, genetic counseling and eventual therapeutic intervention. In this study, we identified dysregulation of SYCP2 in a man with oligospermia and 46,XY,t(20;22)(q13.3;q11.2). Using patient LCL, budding yeast, and mammalian models, we have dissected the molecular mechanisms underlying both SYCP2 misexpression as well as the resulting male infertility.

10:30 Sponsored Presentation (Opportunity Available)

11:00 Coffee Break


11:20 Chairperson's Remarks

Manuel Viotti, Ph.D., Senior Scientist, Embryology and Human Molecular Genetics, Zouves Fertility Center

11:25 Germline Epigenetics: Potential Diagnostic Utility for Fertility, Embryogenesis, and Offspring Health

Timothy_JenkinsTim Jenkins, Ph.D., Assistant Professor, Surgery (Division of Urology), University of Utah

Sperm epigenetic patterns may offer clues to both spermatogenic abnormalities as well as reproductive potential and offspring health. We explore these important marks and their role in infertility, embryogenesis, and even offspring disease susceptibility. Further, we will discuss the efficacy of using epigenetic data in diagnostic testing.

11:55 Diagnostics for Male Infertility Foreshadowing the Future

Stephen_KrawetzStephen Krawetz, Ph.D., Charlotte B. Failing Professor of Prenatal/Fetal Diagnosis and Therapy, Ob/Gyn and Molecular Medicine & Genetics, Wayne State University School of Medicine

Next generation approaches are being developed to understand the information that Dad delivers upon fertilization. One example is sperm RNA elements that identify those males who are likely to father a child and that provide the opportunity to assess his current state of being and the possible state of the next generation. Interim analysis has also suggested their usefulness as surrogates of exposures.

12:25 pm Close of Reproductive Genetic Diagnostics

* The program is subject to change without notice, due to unforeseen reason.