We all are acquainted with various treatment options available in infertility management. From IUI to ICSI and even PGT, we now have a structure catering to different infertility issues. Along with these core procedures, there are certain ‘add-ons’ which supposedly are introduced to enhance the efficiency of these said procedures. These ‘add-on’ techniques are expected to add at least an infinitesimal increase in success rates of IVF. With mushrooming of clinics, more competition and the factor of retaining patients, IVF ‘add-ons’ have assumed greater significance. These procedural accessories can aid especially concerning multiple cycle failures that necessitate their application.

IVF ‘add-ons’ have increased over the years and have branched itself into embryology and clinical domains. Intermixed with glossy terms, they do radiate a promising impact on patients who do expect a new line of hope amidst the existing systems. These add-ons are recommended to bolster your chances in attaining an IVF pregnancy and in certain cases; they may unleash a psychologically positive impact.

As mentioned above, IVF ‘add-ons’ are suggested in both embryological and clinical areas but they also demand a certain indication for their usage. For example, I always stress ICSI should be applied when you have a severe male factor looming in the diagnosis and should not be made mainstream for all the cases. Likewise, ‘Laser hatching’ need not be vouched for all the cases but only when it’s required.

There are few notable examples of IVF ‘add-ons’ which I would briefly elaborate (the embryology ones) and many of them are offered routinely in the majority of the IVF clinics across the world.

Assisted Laser Hatching

Assisted Laser Hatching is an embryology add-on that was introduced to help the embryo hatch from its outer protective covering, the zona pellicuda, and promote implantation after an embryo transfer procedure. ALH can be done in different ways such as zona thinning which is used in case the embryo has an abnormally thicker zona and may be incorporated differently depending upon the type of indication. ALH can be done using various tools but lasers have predominantly been employed and form a routine component of your IVF system today. ALH is also used commonly during a frozen embryo transfer cycle where this system can be utilized especially in case of hardening of the outer covering. ALH may not be an add-on but mainstream when we have to incorporate it for embryo biopsy and PGT!

Artificial Oocyte Activation

Artificial oocyte activation (AOA) is an effective method to prevent total fertilization failure in IVF cycles. AOA performed using a calcium ionophore can induce calcium oscillation in oocytes and initiate the fertilization process. Conventional (IVF) is ineffective concerning severe Male Factor Infertility. In these cases, sperm cannot penetrate the zona pellucida, and intracytoplasmic sperm injection (ICSI) is applied to overcome this problem. ICSI has the potential to achieve fertilization but total fertilization failure occurs in 2% to 3% of ICSI cycles.

Several studies have postulated that fertilization failure after ICSI can be attributed to some defects in oocytes or they remain inactivated despite the proper injection of spermatozoa. This lack of activation can be alleviated by AOA and PF which can be used in cases of male factor infertility. There are few studies focused on PF treatment and AOA but this technique needs more clinical trials and data before it can become a mainstream procedure.

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Embryo Glue

One of the major reasons for failure in IVF-ICSI cycles is the lack of implantation owing to poor coordination and the failure to develop a sticky matrix between the embryo and the endometrial lining. Various modifications have been introduced in the ET medium to improve implantation and pregnancy rates. Protein supplementation has been widely used in ET medium, most common of which is albumin which not only provides viscosity to the culture medium but also acts as a lubricant promoting easy handling and preventing adherence of embryos to the culture dish. Likewise, Hyaluronan (HA) supplementation of culture medium was introduced to improve implantation and pregnancy rate in IVF-ET cycles. HA, a glycosaminoglycan is present in the oviduct and uterine fluid and increases at the time of implantation. EmbryoGlue is a human ET medium, which contains high concentration of HA (0.5 mg/mL) and low concentration of recombinant human albumin (rHA = 2.5 mg/mL). EmbryoGlue is thought to be developed as an ideal medium for blastocyst development and fostering better implantation. EmbryoGlue is said to be advantageous in patients with recurrent implantation failure. However, a large randomized control trial is necessary to evaluate its role in all patients.

Time-Lapse system.

During a cycle, the embryologists remove the embryos from the incubator once per day to assess their development, but this type of monitoring and ascertaining their growth only gives them a snapshot of a dynamic process. The embryos do not tolerate suboptimal conditions whilst checking, which limits the number of observations that can be made. This problem is a significant one for the embryologists, and time-lapse technology may offer a solution. With this technology, the embryos can be monitored without removing them from the incubator. A camera is built inside the incubator which takes pictures of the embryos at regular intervals. With the help of software, a video can be made that captures their development. This type of monitoring allows for the retrieving of much more information on the timing of the cleavages and the dynamics of the morphologic changes. Payne and colleagues were among the first to describe the early events of human embryonic development, and then, Mio and Meada described the kinetics of the events up until the blastocyst stage. Their work was followed by observations made by several other groups that tried to correlate these kinetic and morphologic markers with embryo development, implantation potential, pregnancy rate, and genetic health. Various time-lapse systems are currently used and some examples of them include Embryoscope, EVA system, and the ASTEC time-lapse system. The lapse from my experience is a brilliant innovation but more data needs to be extracted, a better benchmarking system needs to be created for it to be utilized more but it exhibits tremendous potential in embryo selection.

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IVF ‘add-ons’ are good but even they harbor a share of skepticism as some research papers have questioned their effectiveness. Another negative side may be the economic factor which can put an extra burden on the patients who are already feeling the pinch of the exorbitant cost factor in IVF!

IVF ‘add-ons’ are here to stay and as the science becomes more available for infertile couples, the application of these sets of techniques too is expected to rise.

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