The problem with "add-ons" to IVF

Posted on May 11, 2017

Everybody, of course, knows what “add-ons” are, but use of this term in infertility is new and, suddenly, it appears everywhere to be the topic of the moment. Reflecting British lingual sensitivities, Focus on Reproduction, the monthly magazine of the European Society for Human Reproduction and Embryology (ESHRE) in its May 2017 issue used the term “adjuvants” instead of “add-ons.”

The month of March was, likely, the break-through moment for this subject, first when Human Reproduction, the official journal of ESHRE, published an excellent opinion piece by Professor Joyce Harper, PhD, from the University College and Hammersmith Hospital in London, UK, and a group of other well-known investigators from the U.K., Belgium, Australia, Ireland, Sweden and France (Harper et al., Adjuncts in the IVF laboratory: where is the evidence for ‘add-on” interventions? Hum Reprod 2017;32:485-491).

In this manuscript, the authors defined “add-ons” as adjunct treatments and/or tests to routine fertility treatments, usually at additional expense offered to patients with claims of improving chances of live births. Examples discussed in their manuscript were use of “embryo glue” and other adherence compounds, sperm DNA fragmentation, time-lapse imaging, preimplantation genetic screening (PGS), mitochondrial DNA load measurements and routine use of assisted hatching. In reviewing their clinical use, the authors concluded that there presently really is no valid evidence in the literature for safety and/or efficacy of any of these treatments and/or tests and, therefore, for their routine use in association with in vitro fertilization (IVF).

For steady readers of these pages, this may not be news because we, here at CHR, have made this point for years, including in detailed reviews of the utility of time lapse imaging and PGS. However, the fact that Human Reproduction finally published a manuscript, making this point loud and clear, represents progress because that could never happen under the current editors of Fertility & Sterility, the official organ of the American Society for Reproductive Medicine (ASRM), who over years now have demonstrated pronounced biases in favor of accepting manuscripts that favor “add-ons,” while discriminating against articles critical of those practices.

Interestingly, the subject of “add-ons” has been attracting much more attention in the U.K. than the U.S. Yet, “add-ons,” like PGS, are still much more popular in the U.S. than the U.K. or in the rest of Europe.

It all started in November of 2016, when the British Broadcasting Corporation (BBC) in a Panorama Documentary on the subject concluded that many “add-ons,” advertised on fertility clinic websites in the U.K. were not backed up by solid evidence. On a side note, CHR’s Medical Director and Chief Scientist, Norbert Gleicher, MD, was extensively interviewed by BBC producers before that broadcast.

In March of this year, again in the U.K., The Progress Educational Trust organized at the Royal College of Obstetricians and Gynecologists a public debate under the heading, “Fertility Treatment Add-Ons: Do They Add Up?”, in which leading clinical and laboratory experts, the Human Fertilisation and Embryology Authority (HEFA), and the British Fertility Society (BFS) participated. As one would expect, opinions differed, with, as in the U.S., the strongest support for “add-ons” usually coming from parties with considerable financial interests in those procedures/tests, like PGS laboratory owners (and their agents) and corporate IVF interests, as represented by the Founder and President of CARE Fertility, Simon Fishel, PhD, the U.K.'s largest corporate provider of IVF services. Fishel, one of the original scientific pioneers in IVF, has been a strong promoter of time lapse imaging and PGS for years.

Sally Cheshire, the chair of the HEFA, noted that her organization did not regulate drugs or procedures associated with IVF. She, however, announced a new website that will include reliable information on “add-ons” for the public. Others were more outspoken, and Antony Blackburn Starza in a commentary on this public meeting on the website BioNews (, accessed 4/9/17) noted that, “any consent solution without (vigorous further) debate may, therefore, be at risk of operating as a mere procedural justification for what might, at times, remain unethical practice.”

What, indeed, makes these “add-ons” a truly moral issue is that, subconsciously or consciously, their utilization is, often, no longer guided by honest attempts to improve IVF outcomes but by financial necessity, as revenues generated through “add-ons” are becoming an economic lifeline for IVF centers. With third-party reimbursements for IVF over the last decade actually declining in the U.S., many IVF centers derive 30-40% of their IVF cycle revenue now from “add-ons” like PGS since those, usually, are not covered by third party insurers and, therefore, represent significant additional cycle revenue for IVF centers. How far some IVF centers are taking this is best demonstrated by some centers now simply refusing to perform IVF cycles, unless patients consent to the addition of PGS to their cycles.

Similarly, diagnostic laboratories that perform “add-on” tests to IVF are, of course, highly motivated to promote use of their laboratory services. This is nothing new, and was seen decades ago, when specialty laboratories aggressively promoted certain families of blood tests, like immunological testing in association with IVF, and more recently in the aggressive promotion of genetic screening tests. The growth of the laboratory industry surrounding PGS has, however, reached unprecedented proportions, best evidenced by the sale in 2016 of the leading U.S.- and U.K.-based PGS laboratories to Cooper Surgical for hundreds of millions of U.S. dollars.

Why “add-ons,” however, have become a real ethical and practical clinical problem was recently best demonstrated when CHR investigators looked at IVF practices all around the world and noticed (previously unreported) that almost everywhere, including in the U.S., 2014 live birth rates after IVF were lower than in 2004. Up to 2004, in contrast, live birth rates had steadily increased almost everywhere.

Since CHR investigators who did this work submitted a manuscript for publication, we currently are not at liberty to disclose further details of their study. Only so much: In various regions of the world, the declines in live birth rates observed were closely associated with distinct new practice patterns, often including above listed “add-ons” to IVF. In other words, though associations are not always equal to causations, because these observations were made repeatedly in different regions of the world, the likelihood that introduction of certain “add-ons” to routine IVF in those 10 years contributed to observed declines in live birth rates from IVF worldwide is rather convincing.

Unvalidated “add-ons” to IVF, therefore, not only add to already unaffordable high IVF costs for many, and fail, as promised by their proponents, to improve IVF outcomes; but, in addition, often actually reduce live birth chances from IVF for patients.

As our European colleagues apparently are starting, it appears time to recognize the problem in the U.S., and stop this nonsense before it gets worse!

This is a part of the May 2017 CHR VOICE.

Norbert Gleicher, MD, FACOG, FACS

Norbert Gleicher, MD, FACOG, FACS

Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned specialist in reproductive endocrinology, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.

We have helped women bring over 17,800 babies into the world.

Discover your treatment options

Related Articles

  • Breaking News in ScienceLetter to President Biden and Secretary Designate of HHS, Xavier Becerra In a published letter (Santoro et al Reprod Sciences 2021; https:/, a
  • More On COVID-19DOES THE BRITISH STRAIN B.1.1.7 INCREASE MORTALITY OVER D614G? A just published study by British investigators claims that not only infectivity of the
  • Mild Ovarian StimulationTwo prominent voices in the fertility field known as longstanding supporters of mild ovarian stimulation were at it once again (Nargund and Fauser, Reprod Biomed Online 2020;41:569-571) when
  • Brief Case Studies in Clinical InfertilityIs there a place for DHEA and CoQ10 in women undergoing “planned” egg-freezing? At CHR, women undergoing egg-freeing cycles undergo a very

Whats New on CHR

Contact Us

You can also call 212-994-4400 to get in touch with us.

Want to donate your eggs? Fill out the donor application first!

Country *