Little Evidence to Show Benefits of Add-on Fertility Treatments

Peter Kovacs, MD, PhD


March 21, 2017

Adjuncts in the IVF Laboratory: Where Is the Evidence for 'Add-On' Interventions?

Harper J, Jackson E, Sermon K, et al
Hum Reprod. 2017;32:485-491


Over 4.4 million in vitro fertilization (IVF) treatments were performed worldwide from 2008 to 2010, and over 1.1 million children were born as result, according to the latest International Committee for Monitoring Assisted Reproductive Technologies report.[1] In those cycles, the overall pregnancy rate was low, around 25%, with delivery rates just below 20% per retrieval.[1]

Not surprisingly, there has been a constant search for "add-on" treatments to improve outcomes.[2,3] These interventions are often introduced without adequate supportive data as both patients and providers feel that they have no time to wait for the results of properly designed trials. This opinion paper evaluated the evidence behind some of these technologies.


Here is what the authors concluded about each treatment:

Embryo glue is a culture medium enriched with hyaluronan that is given to improve embryo adherence. The published evidence is of moderate quality and suggests a small increase in pregnancy as well as multiple pregnancy rates. Due to this latter finding, careful use is recommended.

Sperm DNA fragmentation testing is controversial, and potential benefits are based on low-quality evidence. Some suggest lower fertilization and implantation rates and higher miscarriage rates with elevated fragmentation indices. Antioxidant therapy to decrease DNA fragmentation is controversial.

Time-lapse monitoring of embryos is beneficial for teaching, quality control, and scheduling laboratory work. Undisturbed culture condition is an added benefit, and there are now universally acceptable algorithms proposed for embryo selection. Prospective validation is still required.

Preimplantation genetic screening (PGS) to detect aneuploid embryos was shown to improve outcomes in young, high-responder patients, though trial methodologic issues were raised. Cost-effectiveness has not been proven, and benefit in more challenging patients has not been documented yet.

Mitochondrial DNA for assessing embryo selection is currently under evaluation in randomized controlled trials, but a screening test is already on the market.

Assisted hatching remains controversial. While there may be certain subgroups where benefit can be gained, in general its use is not recommended as it wasn't shown to improve pregnancy rates.


The desire to have a child is very strong and often pushes patients to accept less proven methods. Without insurance coverage, many can only try IVF once and are willing to do anything to improve their chances. In addition, there is considerable competition among the clinics to attract more patients with extra services.[4]

Interventions are often introduced without proper evaluation with the potential to lower rather than improve outcome. This was the case with PGS-fluorescence in situ hybridization where it took years and multiple randomized controlled trials to show that day-3 biopsy with limited genetic testing was not beneficial.[5] Several aspects of this practice have since been changed, but the available published evidence still only shows benefit in young high responders. Yet many clinics offer it to all couples undergoing IVF.

Immune treatment, endometrial receptivity testing, hematologic therapies, and laboratory interventions have all been shown to have benefits by some studies and no benefit by others.[3] The meta-analysis of evidence usually is based on poor-quality studies, low numbers of cases, and can be at best called controversial, yet all of these interventions are used routinely.

It's important that patients receive appropriate counseling about the known risks, potential benefits, and the potential (unknown) effect on their offspring before they agree to these add-on treatments.



Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: