Much has been written about how personalized medicine – also known as “precision medicine” – may improve treatment for serious health conditions including cancer, heart disease and auto-immune disease. Based on an individual’s genetic makeup (and more) it may be described simply as “delivering the right treatment for the right patient at the right time.”
The field is incredibly complicated and rapidly changing, with an expected lag between research and application to clinical diagnosis and treatment. Precision medicine involves not just looking at genes but also the physiology of a single cell of proteins (proteomics) and other complex workings at the cellular level.
Now, precision medicine is poised to help in the area of infertility. It has potential to help with both the diagnosis and treatment of infertility. Some suggest that in time it may even help with prevention.
Personalized reproductive medicine is still relatively in its infancy compared to other medical conditions. There are some areas where precision medicine is starting to be used and areas that hold promise. One challenge is the lack of large clinical studies and the challenges in conducting research in reproductive medicine. Your fertility clinic should be up-to-date with clinically appropriate advances.
Many individual factors influence fertility treatment decisions including your specific diagnosis, age, health status, and lifestyle. If you have a family history of inherited disease, your situation may also call for pre-treatment screening of your partner and yourself or genetic screening of your embryo. As always, you should discuss these issues with your fertility specialist.
Fertility specialists already use biomarkers to help make treatment decisions. One example is measuring the anti-Müllerian hormone (AMH) found in a woman’s blood serum. This hormone level has potential in predicting ovarian reserve and response to ovarian stimulation which helps determine the most effective dose of fertility drugs for the best response.
Personalizing Endometrial Receptivity
One of the better known uses of precision medicine for infertility is the genetic test that most accurately determines how receptive a woman’s endometrium (inner uterine lining) is for implanting an embryo.
Some women may experience fertility issues from problems with their endometrium receptivity. With fertilization in the woman’s body, the normal reproductive physiology processes determine the time for the embryo to implant. However, with in vitro fertilization (IVF), the embryo must be transferred on the right day to increase the chances of pregnancy.
Different approaches are used to evaluate endometrial receptivity; one is a test that measures “the expression patterns of different genes in an endometrial biopsy.” The endometrium receptivity array (ERA) test is based on next generation screening (NGS) of the 236 genes identified as involved in endometrial receptivity.
The test involves a minimally invasive biopsy performed in the cycle before the IVF cycle on the day the endometrium is supposedly most receptive. Analyzing the gene expression patterns of specific marker genes provides information as to whether the “right genes are expressed at the right time.” Based on these results, the date of embryo transfer can be adjusted if necessary.
The test has shown clinical promise in patients with repeated IVF failures. The results allow personalization of the implantation window and may be helpful for women who have experienced repeated implantation failures.
However, the test is yet to be validated, that is, proven to result in better outcomes than when the test is not used.
Male Infertility and the Potential of Personalized Medicine
Male fertility problems are the cause of an infertility diagnosis among couples approximately half the time. In addition, many causes of male infertility remain unknown. As a result, genomics and proteomics represent examples of methods to investigate the molecular level of male infertility.
Experts suggest there is room for improvement in both early diagnosis/diagnosis of male infertility and drug development. Further, personalized medicine has potential for targeted diagnostic and therapeutic advances.
For example, the diagnostic tool to determine male infertility is largely limited to semen analysis. This is considered a basic test that provides “an overall estimate of infertility. In the diagnosis of infertile men; the typical parameters of the semen analysis are sperm motility, sperm morphology, concentration or count.”
Researchers point out that human seminal plasma (HSP) includes “rich molecules made by the male reproductive glands.” One group of researchers write in the Journal of Reproductive Infertility that “exploring the human seminal plasma proteome…is…an unexplored gold mine of bio-marker for male infertility and male reproduction disorder.”
HSP might be helpful in identifying and treating oxidative stress (OS) which plays an important role in sperm performance. It results from an imbalance between reactive oxygen species (ROS) and anti-oxidants. Using HSP may be “very suitable for anti-oxidant therapy studies,” however, there are no parameters for HSP analysis. An estimated 25%-40% of men with infertility have higher degrees of ROS than fertile men.
Medication to address male infertility appears to be helpful and some researchers believe this may be true of antioxidant therapy. The authors conclude that “research in this field and the researchers and physicians must collaborate more. This can dramatically help develop new therapies for male infertility. Although this is a long way off, early results are promising.”
Another precision test for male infertility is sperm DNA integrity. Generally, men who are infertile tend to have higher levels of sperm DNA damage. Currently, several different types of tests are used to analyze the general health of sperm DNA using a sample, including:
- Sperm chromatin structure assay (SCSA) testing
- Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay
- Single-cell gel electrophoresis (COMET) assay
To date, a number of studies link such damage to problems with sperm function affecting poor embryo development, decreased implantation rates, and miscarriage. Other studies show no association.
For now, existing data don’t show a consistent relationship with abnormal sperm DNA and pregnancy outcomes. Still, infertility specialists are hopeful that improvement in techniques and further research may lead to clinical validation for using the tests. Test predictability may improve with additional research, as new techniques are developed, and current techniques are better understood.
For now, sperm DNA integrity testing is still considered “experimental” and not recommended for those undergoing routine fertility evaluation. The hope is that in the not too distant future the tests can be used to distinguish between fertile and infertile men and help determine which infertility treatments might be most effective.
Just as precision medicine is making a difference in prolonging life with treatment that is much more effective with serious illness, we may now be on path where it will also help in creating life.