What is miRNA? Understanding the Science Behind ORA™
Fertility science has come a long way. There are many products on the market today that support and bolster your chances of getting pregnant during an IVF cycle. If you are over the age of 34, only have a small number of viable embryos to work with, or have experienced miscarriages or implantation failure, your fertility specialist is likely to recommend undergoing endometrial receptivity testing and analysis.
However, not all endometrial receptivity tests (ERT) are made equal. Most ERTs use messenger RNA biomarkers to identify endometrial receptivity status, which involves a tissue biopsy to collect a sample of your uterine lining. ORA™, on the other hand, uses microRNA biomarkers, which are more stable and allow for analysis using only a simple blood sample.
What is miRNA?
MicroRNA, or miRNA, is a type of genetic biomarker that is responsible for managing which types and what quantities of proteins our cells make. MicroRNA interacts with mRNA to control gene expression, which is why it’s found in most cell types. Gene expression refers to whether a particular gene is making too much, too little, or the normal amount of protein at a given time.
Over 2600 distinct miRNA have been found in the human genome, with novel miRNA being discovered all the time. MicroRNA is an ideal candidate to use as biomarkers in diagnostic tests and prognostic tools. The role miRNA play as gene regulators means they’re found in all bodily fluids, tissues, and most cell types. MicroRNA is also much more stable and tolerant than mRNA, which means it carries a lower margin of error when used in testing.
What is mRNA?
Messenger RNA (mRNA) is a type of single-stranded RNA involved in protein synthesis. Its role is to carry protein information from the DNA in a cell’s nucleus to the protein-making machinery located in the cell’s cytoplasm (watery interior). Breakthroughs in the use of mRNA have led to the development of novel vaccine, like that for COVID-19.
What exactly can miRNA tell us?
The scientific consensus is that miRNA is involved with regulating around 60% of human RNA from a given cell. Since miRNA moves between cells, it is typically transported as part of a protein complex. This helps to protect the miRNA, and keep it stable. These circulating miRNAs can resist decay for up to four days at room temperature, and have also survived extreme temperature fluctuations and a wide range of pH values. This means that diagnostic tests relying on miRNA biomarkers can use smaller samples with a lower failure rate than with mRNA-based analysis.
The small size, stability, abundance, and specificity of miRNA will make them one of the most utilized biomarkers for developing new, faster, and more sensitive methods of disease detection and therapeutic intervention going forward.
Some examples of how miRNA is used
In recent years, scientists have been studying the practical applications of miRNA in medicine and microbiology. They are particularly excited about the potential miRNA offers as biomarkers for diagnosing infections and non-infectious diseases, and for assessing conditions that impact gut and reproductive health.
Research has identified novel miRNAs in blood and tissue that can indicate the presence of many types of cancer, including breast, colorectal, lung, liver, and prostate cancer. By identifying and cataloguing miRNAs that are related to cancer, this is improving early detection, which leads to better prognoses and more effective treatments.
The potential of miRNA-based diagnosis is also being studied with diabetes and Alzheimer’s, non-infectious diseases in which disrupted miRNA conditions have been observed.
They’ve additionally been observed in infectious diseases like HIV, malaria, and the Ebola virus. MicroRNA also play an important role during early-stage detection of infectious diseases, as it provides reliable results before antibodies and viral RNA are detectable.
How Inti Labs and ORA™ use miRNA
As infertility rates continue to rise, more people are turning to science to help with having kids. Among women dealing with infertility, around 30% of them have displaced windows of implantation (WOI). The best way to precisely identify a displaced WOI is by taking an ERT. So, if you haven’t identified your WOI, it is possible that your endometrium will be out of sync with your embryo at the time of your transfer – this is a leading cause of implantation failure.
Multiple studies have shown that miRNA regulates the status of the endometrial lining. This means that we can test for miRNA biomarkers to determine what stage of receptivity your endometrium has reached at the time of your biopsy procedure.
There are roughly 300 miRNA biomarkers identified that interact with more than 1000 genes related to endometrial receptivity. These are the specific biomarkers that make up the panel analyzed by ORA™.
What is endometrial receptivity testing?
Endometrial receptivity testing is a type of genetic testing designed to find out the receptivity status of the endometrium. Endometrial receptivity is crucial to successful embryo implantation, which is why doctors frequently recommend endometrial receptivity tests. When creating your personalized IVF protocol, your fertility specialist relies on your test results to determine the exact timeline of your treatment cycle.
By analyzing a blood sample, ORA™ can identify the precise timing of your unique window of implantation. This can be especially important for women who have already experienced implantation failure, or only have a small number of viable embryos to work with.
How is endometrial receptivity analysis done?
When preparing for IVF treatment, you may undergo a mock cycle to get an understanding of your menstrual cycle and what kind of medications you will need in your treatment cycle. As part of this process, your fertility specialist will perform a biopsy procedure during the two- to three-day period that is estimated to be your window of implantation (WOI). If you aren’t undergoing a mock cycle, your fertility specialist can perform the biopsy at the same time your uterine exam.
This biopsy will collect a tissue sample from your endometrium, which will then be analyzed in a lab. There are three possible results of this analysis: pre-receptive, receptive, and post-receptive. Receptive means your WOI occurs when expected. Pre- and post-receptive results mean your WOI is displaced, and your doctor can schedule your embryo transfer accordingly.
Why is using miRNA better than using mRNA?
Unlike mRNA, miRNA is a very stable genetic material found in all bodily fluids, tissues, and most cell types. For these reasons, receptivity testing with miRNA biomarkers can be done with smaller samples, and with a much lower margin of error.
What this means for patients, is that ORA™ can be done with with just a simple blood sample, and will return conclusive results over 99% of the time, virtually eliminating the need for re-testing.
Should I ask my fertility specialist about ORA™?
A displaced WOI can happen to anyone, regardless of age. There are some circumstances where you may wish to undergo receptivity testing preemptively. If any of the following situations apply to you, ORA™ may be able to help:
- A history of implantation failure or miscarriage
- Few remaining high-quality embryos
- A thinner endometrium
- Age 35 or older*
*While all ages have the possibility of having a displaced window of implantation, recent data has shown that this is an increased possibility for patients 35 or older.
ORA™ has been shown to increase the IVF pregnancy rate by as much as 70%, which means undergoing fewer cycles before you successfully achieve pregnancy.
