microRNA, messengerRNA, and Endometrial Receptivity Testing

You’re likely aware by now of the major medical advancements the use of mRNA has brought to vaccination technology and to infectious disease screening thanks to the COVID-19 pandemic. Less well-known are the contributions the use of microRNA has made to genetic screening and diagnosis of diseases like various types of cancer, diabetes, and Alzheimer’s. Additionally, miRNA biomarkers are now being used to help couples have children through in vitro fertilization (IVF), by more accurately identifying their window of implantation (WOI). 

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 plays as a gene regulator 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 vaccines, like that for COVID-19. 

Endometrial receptivity tests (ERTs) for in vitro fertilization (IVF) 

The global rate of infertility continues to rise with as many as 11% of American couples experiencing infertility in their lifetime. As a result, more people than ever are turning to assisted reproductive technologies like in vitro fertilization (IVF). IVF is more effective when you can time the embryo transfer procedure more precisely. 

To that end, endometrial receptivity testing is used to identify your window of implantation (WOI). This test involves a biopsy to collect tissue from your uterus during your estimated WOI. The sample is then analyzed in a lab to determine its receptivity status at the time it was taken. 

As many as 30% of women who have experienced infertility have a displaced WOI that impacts their ability to get pregnant. ERTs are particularly valuable for women who’ve experienced multiple implantation failures or miscarriages, have few viable embryos, are over the age of 35, or have a thinner endometrium. 

What are the advantages of using miRNA for testing? 

There are several advantages to using miRNA biomarkers for endometrial receptivity testing: 

• MicroRNA is more stable than messengerRNA. 

• MicroRNA tests require less genetic material. 
• MicroRNA tests have a lower failure rate. 

Additionally, the tests Inti Labs has developed, MIRA™ and ora™, use an algorithm that analyzes not just the target miRNA biomarkers, but also factors like the patient’s age, BMI, and any uterine abnormalities. 

Reliability 

As we’ve mentioned, miRNA is an incredibly stable testing material. Due to the fact that miRNA can travel between cells, it is often encased in a protective layer. The result is that tests like MIRA™ can be done with smaller tissue samples and with a much lower failure rate. 

Sensitivity 

One of the challenges with endometrial receptivity testing is ensuring that a large enough tissue sample is collected during the biopsy. This can make the procedure more painful and invasive. MessengerRNA-based tests require 30 to 50mg of tissue, whereas MIRA™ requires only 5 to 10mg of tissue from a biopsy. Not only that, but MIRA™ boasts a turnaround time of two weeks, which is half the time any other test takes. 

While the tissue sample size is smaller, MIRA™’s miRNA-based test analyzes 100 novel miRNA biomarkers that target over 600 endometrial receptivity-related genes. By comparison, an mRNA-based test will analyze 50 to 250 ER-related genes. 

Accuracy 

The bottom line is that miRNA profiles have better success rates at determining disease conditions than mRNA profiles. MIRA™ has a 90% success rate of predicting a patient’s WOI. This is one of the most important factors in successful IVF treatment, especially for women who’ve experienced implantation failure. 

Recent ERT analysis 

A recent study published in Human Reproduction concluded that using mRNA-based ERTs may not accurately predict the WOI. The authors’ analysis illustrates there may be little to no benefit of an mRNA-based ERT at all. It is important to note that this re-analysis doesn’t examine the benefit of ERTs for patients experiencing repeated implantation failure (RIF). That said, this report might be the steppingstone to push for better forms of endometrial receptivity analysis, such as miRNA-based testing. 

MIRA™, ora™, and the future of endometrial receptivity testing 

Clinical data has shown that MIRA™’s algorithm can accurately predict patients’ WOI, allowing for more-perfectly timed embryo transfers. It requires less biopsy material and delivers more accurate results. 

ora™ is the first and only non-invasive endometrial receptivity test, able to accurately identify the WOI of patients using simple blood samples. The non-invasive nature of ora™ drastically improves the patient experience, and blood samples taken and stored during the patient’s first IVF cycle can potentially eliminate the need for future costly mock cycles if their first treatment cycle results in implantation failure.