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Anticipating STAR: A triumph of optimism over scepticism?

by
Alan Thornhill, Ph.D.
| Jun 30, 2016

It’s often said that a day makes a difference in politics. In science, a decade makes a huge difference. It is almost a decade since Mastenbroek and colleagues (1) put an end to what we now think of as a primitive form of Preimplantation Genetic Screening (PGS) with their large randomised clinical trial (RCT) targeting a handful of different chromosomes using FISH on a single cell from a day 3 embryo. Indeed, in their hands they demonstrated that this approach actually reduced a woman's chance of having a baby.

During the intervening decade, advances have been made in many different aspects of the PGS process: blastocyst culture and biopsy, vitrification, and the simultaneous analysis of all twenty-four chromosomes. On its own, each advance has contributed to improved IVF outcomes allowing patients to better plan their families in terms of facilitating single embryo transfer, reducing miscarriage, improving implantation rates and reducing the time to pregnancy (2-6). In combination, they are very powerful and today form the basis of many successful IVF programmes around the world.

While success stories from an ever-increasing number of IVF centres adopting PGS are compelling, they do not convince everyone. Since 2007, there has been a desire from many clinicians to see more clinical evidence of the benefits of PGS- and rightly so. What is surprising during the past decade is that despite the publication of a growing number of RCTs, observational studies, meta-analysis and national data set analyses investigating the utility of PGS, all of which have shown benefits (3-8), scepticism remains.

In an era where patient information and informed consent is paramount, it is concerning that most guidelines relating to PGS from professional bodies are out of date and do not reflect the advances made and positive results obtained with PGS (9-11). For this reason, I am excited about the STAR trial (12), which has completed enrolment and the results of which are eagerly anticipated. STAR is a large multicentre, international, blinded RCT which aims to compare the outcomes at 20 weeks following transfer of a single vitrified blastocyst screened using the VeriSeq™ PGS assay versus an unscreened vitrified blastocyst.

Will this trial, if successful, be enough to move the sceptics? I hope that patients undergoing IVF are given all the information they need to make an informed decision.

Click here to download and listen to the June 14 webinar from Mr. Stuart Lavery of Hammersmith and Queen Charlotte’s & Chelsea Hospitals, London, on how IVF units are investigating the utility of PGS to ensure the most viable embryo is transferred. Mr. Lavery will share his PGS experience in routine practice and his participation in the STAR study.

References:

  1. Mastenbroek S, Twisk M, van Echten-Arends J, Sikkema-Raddatz B, Korevaar JC, Verhoeve HR, Vogel NE, Arts EG, de Vries JW, Bossuyt PM, Buys CH, Heineman MJ, Repping S, van der Veen F.Glujovsky D1, Blake D, Farquhar C, Bardach A. In vitro fertilization with preimplantation genetic screening. N Engl J Med. 2007 Jul 5;357(1):9-17.
  2. Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database Syst Rev. 2012 Jul 11;(7):CD002118.
  3. Forman EJ, Hong KH, Ferry KM, et al. In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial. Fertil Steril. 2013;100(1):100-107.e101
  4. Yang Z, Liu J, Collins GS, et al. Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study. Mol Cytogenet. 2012;5(1):24.
  5. Scott RT, Upham KM, Forman EF, et al. Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases IVF IRs and delivery rates: a randomized controlled trial. Fertil. Steril. 2013; 100(3):697-703.
  6. Forman EJ, Tao X, Ferry KM, Taylor D, Treff NR, Scott Jr R.T. Single embryo transfer with comprehensive chromosome screening results in improved ongoing pregnancy rates and decreased miscarriage rates. Human Reprod. 2012;27(4):1217-22.
  7. Lee E, Illingworth P, Wilton L, Chambers GM. The clinical effectiveness of preimplantation genetic diagnosis for aneuploidy in all 24 chromosomes (PGD-A): systematic review. Hum Reprod. 2015;30(2):473-483.
  8. Chang J, Boulet SL, Jeng G, Flowers L, Kissin DM. (2016) Outcomes of in vitro fertilization with preimplantation genetic diagnosis: an analysis of the United States Assisted Reproductive Technology Surveillance Data, 2011-2012. Fertil Steril. 105(2):394-400.
  9. Twisk M, Mastenbroek S, van Wely M, Heineman MJ, Van der Veen F, Repping S. Preimplantation genetic screening for abnormal number of chromosomes (aneuploidies) in in vitro fertilisation or intracytoplasmic sperm injection. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005291. Review.
  10. Anderson RA, Pickering S. The current status of preimplantation genetic screening: British Fertility Society Policy and Practice Guidelines. Hum Fertil (Camb). 2008 Jun;11(2):71-5.
  11. Harper J, Coonen E, De Rycke M, Fiorentino F, Geraedts J, Goossens V, Harton G, Moutou C, Pehlivan Budak T, Renwick P, Sengupta S, Traeger-Synodinos J, Vesela K. What next for preimplantation genetic screening (PGS)? A position statement from the ESHRE PGD Consortium Steering Committee. Hum Reprod. 2010 Apr;25(4):821-3.
  12. Single Embryo TrAnsfeR of Euploid Embryo (STAR) ClinicalTrials.gov Identifier: NCT02268786

 

 

 

 

 

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