‘Add-ons’ are additional treatment options that a patient may choose to add to their IVF cycle to increase their chances of success. IVF clinics have been offering treatment ‘add-ons’ to patients undertaking IVF cycles for years. The efficacy of ‘add-ons’ though has been widely debated in recent years. The HFEA now uses a handy “traffic light rating” system to warn patients about the levels of evidence supporting the use of these additional treatments.
By: Dr. Ed Coats
The fertility industry is growing rapidly and ‘add-ons’ are often adopted by clinics before rigorous research has truly determined their worth. This is a difficult area for patients and clinics alike. Patients are often willing to try the latest techniques if that may help them reach their goal and achieve a pregnancy. Clinics need to remain in touch and up-to-date offering the latest technology in the fast moving world of assisted conception. This is where the water can get a little murky, as not every ‘add-on’ has clear cut evidence for its use and can be costly.
Here is a quick guide to some of the IVF treatment ‘add-ons’ and the evidence for their use.
An ‘endo-scratch’, involves an internal examination like a smear test. A clinician scratches the womb lining (endometrium) around day 18-23 of the cycle preceding your actual treatment cycle. It takes just a few minutes to do but can be uncomfortable and may cause some bleeding. It was thought that an endo-scratch increased the womb’s potential for an embryo to implant. Unfortunately after years of debate a large research trial that studied more than 1300 women has shown the endo-scratch did not increase live birth rates.
Calcium Oocyte Activation
Fertilisation occurs when a sperm and egg fuse. Certain factors from the sperm cause the egg to activate and further divide and develop. This oocyte activation technique involves bathing eggs in a calcium rich solution prior to ICSI, with the aim of activating the egg to achieve better fertilisation rates. The laboratory technique has been deemed to be safe but it should not be used without evidence of a deficiency of ‘Proteinlipase C zeta’ (PLCzeta) in the sperm.
Embryo glue involves using a specific culture media that contains hyaluronic acid. The theory is that the addition of hyaluronic acid to the embryo culture medium prior to embryo transfer may improve the chances of an embryo implanting successfully. There have been many trials looking at this ‘add-on’ to standard IVF treatment and the evidence has been described as being weak.
Elective Freeze All
The concept of electively freezing embryos during an IVF cycle has gained momentum in recent years. Traditionally embryos were frozen when there were excess embryos or if patients were unable to have a fresh embryo transfer. As vitrification (freezing) techniques have improved it has been proposed that elective freezing of embryos rather then immediately transferring them, may improve success rates. Whilst elective freezing helps avoid Ovarian Hyperstimulation and the negative impact this may have on the womb lining (endometrium) there is still a risk with the vitrification technique of damaging embryos. The most powerful research studies in this area currently suggest that live birth rates do not appear to significantly increase with the elective freezing strategies. However, we await the results of several large randomised controlled trials and the “E-freeze” trial which may give us an answer.
Assisted hatching is a laboratory technique used to artificially disrupt the thick membrane (zona pellucida) surrounding the egg. Once an embryo reaches 5-days old it will usually begin to hatch out of this natural protective membrane. Assisted hatching is performed in the laboratory with a laser to artificially rupture the embryo’s outer shell to make it easier for the embryo to break out and implant in the uterus. There is always a small risk that embryos are damaged with this technique. The research so far suggests that there is only a small increase in the number of embryos reaching 6 weeks in their development but there was not an improvement in the actual number of live born babies. Caution is advised until there is better evidence here.
Preimplantation Genetic Testing
Pre-implantation genetic testing (PGT-A) is an technique that is gaining greater energy in UK fertility clinics. Whilst embryos can look very normal under high magnification this is not always the case. PGT involves sampling a few cells usually from a day-5 embryo (blastocyst). This biopsy of just a few cells allows the genetic make-up of the embryo to be assessed. The risks of a biopsy damaging the embryo are small but must be considered. The most common use of this technique is to confirm in a group of embryos which ones are genetically normal (euploid) and have the correct number of chromosomes, and which ones are not (aneuploid) and contain an abnormal number of chromosomes. This technique sounded very promising when it first arrived, offering the patient the opportunity to just replace chromosomally normal embryos but the research has not yet shown this to be the case. In particular patient groups this technique may have a role but its general use for all IVF cycles is not advised.
Time lapse imaging of embryos in culture is used to give more detail about the growth of embryos in the incubator. The stable incubator environment monitors the changing embryo using time lapse photography. During the embryo development in culture time specific morphological changes (morphokinetics) are monitored to determine the best embryo to replace. There has been huge amounts of research in this area of embryology and studies indicate this is a safe technique. However, a recent review looking at several large studies has suggested that this technique doesn’t affect pregnancy or live birth rates. Caution is advised but the outcome of the TILT Trial will guide us further as to the efficacy of this.
Sperm DNA-fragmentation Testing
This technique involves testing a man’s sperm sample to assess the proportion of damaged sperm in the ejaculate. A higher DNA fragmentation percentage can be used to guide patients as to the fragility of the sperm. The chances of natural pregnancy are thought to be reduced when the fragmentation levels are found to be high, and the theory is that treatment of eggs with Intracytoplasmic Injection (ICSI) increases chances of success in these cases. The evidence from studies has not really found this to be conclusive. Men with a high sperm DNA fragility index might also have a surgical recovery of the sperm direct from the testes to reduce the potential damage and exposure of sperm with ejaculation. but even this does not conclusively improve success rates. Caution is advised with this test currently.
There are other less mainstream “add-ons” to IVF treatments to consider here but this overview focuses on some of the more commonly prescribed ones. It just demonstrates that there is still much to learn about these treatments. Ultimately the patients and clinics must decide together how they proceed, but with the lights on amber in most cases proceed with caution until the lights turn green.
By: Dr. Ed Coats