Kathleen Lin, MD, a board-certified female fertility specialist, is founding physician at Sound Fertility Care in Seattle.
Dr. Lin’s Philosophy Even though my practice uses the latest science and research in the care we provide, we also manage to remain old-fashioned in the best ways. Sound Fertility Care has committed to a solo physician model in order to establish and foster a direct relationship with my patients. I consider this a vital component to successful fertility treatment.
For many couples, infertility can be a painful and isolating experience. It’s my goal, along with our entire fertility team, to create a positive and supportive place. We strive to educate patients in a respectful way so that they can make the best decisions possible in order to achieve what we all want: a healthy outcome.
I believe medicine should be dispensed in a simple way. We’ve made it so complex that it can take away from what is essential, which is spending time getting to know your patients. To be able to offer various scenarios on how to safely achieve the best outcomes for your family, I first need to see you, listen to your concerns, and walk myself in your shoes. Then we can intertwine the latest research and techniques to your tailored care.
After receiving her bachelor's degree from Yale University, Kathleen Lin, MD, completed her medical degree at Albert Einstein College of Medicine, followed by a residency in obstetrics and gynecology at NewYork-Presbyterian Hospital and Weill Cornell Medical Center. She completed her fellowship training in reproductive endocrinology and infertility at the University of Pennsylvania, as well as an additional clinical fellowship in male infertility at the Center for Male Reproductive Medicine and Microsurgery at NewYork-Presbyterian Hospital and Weill Cornell Medical Center.
Dr. Lin spent four years as an assistant professor of medicine in the department of obstetrics and gynecology at the University of Washington in Seattle, where she worked to establish the division of reproductive endocrinology and infertility. In 2014, she founded the solo practice Sound Fertility Care, which provides patient-focused, advanced, affordable, and comprehensive fertility treatment options.
Lin: This can sound scary to some people. “Oh my gosh, the DNA is broken! Is it going to lead to some terrible outcome?” The good news is, it’s not so scary, and there are ways to address this.
It’s the sperm’s job to deliver DNA to the egg. The DNA of sperm is fragile, and sometimes there can be little breaks in the “backbone” that connects the DNA. The breaks can be single-stranded or double-stranded. Double-stranded breaks are more associated with poor outcomes. Repair of these DNA breaks relies heavily on the quality of the egg.
The DNA breaks can be caused by different factors, such as dilated veins or changes in temperature in the testes, systemic inflammation, medical conditions, and even things like a poor diet or lack of physical activity. Advanced age can also be a factor in sperm DNA fragmentation, as well as toxins like smoking, alcohol, and environmental pollution.
Sperm DNA fragmentation is associated with higher recurrent pregnancy loss, poor embryo progression and embryo quality, and is associated with lower pregnancy rates for in vitro fertilization (IVF).
Lin: Research suggests that the threshold for DNA Fragmentation Index (DFI) is 30 percent, meaning that if the percentage of sperm with DNA breaks is higher than that it can lead to those poor outcomes I mentioned.
The way we determine the DFI is with DNA fragmentation tests. These tests involve staining the sperm to detect the breaks and then counting how many sperm look like they have a lot of DNA breaks.
In the clinical setting, it can be a little harder to do some of the research-based tests because of the special equipment and expertise necessary; but there are good options that can give us the information we need:
Halo (sperm chromatin dispersion assay) is the test we use in our clinic. It’s performed by removing proteins that keep the DNA structurally looped. In a normal sperm that doesn’t have fragmented DNA, a “halo” is formed by loops of DNA at the head of the sperm. If there isn’t dispersion, it indicates fragmented DNA.
There are other tests that use different ways of “tagging” the breaks in sperm DNA:
Comet assay uses a gel can that can identify damaged DNA and see the difference between single-stranded or doubled-stranded breaks.
TUNEL (terminal deoxynucleotidyl transferase-mediated nick end labeling assay) and SCSA (sperm chromatin structure assay) both use dyes or stains that turn different colors depending on whether the sperm DNA is intact or broken.
Acridine orange is a fluorescent dye that labels and detects moderate to high levels of DNA breaks.
Lin: This is an significant consideration: Who should have their sperm tested, and at what point in fertility care will this information be most useful to us? The Society for Translational Medicine has issued guidelines (published in September 2017 in Translational Andrology and Urology) for when it’s appropriate to perform sperm DNA fragmentation testing in male infertility:
Couples Who Have Experienced Recurrent Pregnancy Loss. I think it’s important that we explore both male and female factors. Often times infertility testing and efforts are focused purely on the female.
Men With an Existing Varicocele. Varicocele are these dilated veins in the scrotum. This condition is associated with increased sperm DNA fragmentation.
Prior to a Couple Doing IVF or Even IUI. This test can provide vital information since sperm DNA fragmentation is a potentially modifiable factor.
Lin: A critical (but not always easy!) way we can try to reduce the number of breaks in the sperm DNA is through lifestyle changes that reduce oxidative stress. When we reduce toxins in the body, we can see a decrease in sperm defragmentation. Here are a few things I recommend:
Because sperm production takes about three months to complete, improvements in sperm DNA fragmentation as a result of lifestyle changes or surgery would take about three to six months.
If there is a shorter timeline due to the female’s age or other reasons, there are some faster ways to improve the sperm quality that involves sperm processing in IUI or IVF treatments.
One way is by filtering sperm through a density gradient, which reduces the amount of DNA fragmentation in the pellet of sperm that’s being used for fertilization. In a process called ICSI, which stands for intracytoplasmic sperm injection, the selected sperm is directly injected into the egg. Since you only need one sperm per egg in IVF, you can be really selective in the way you filter the sperm to get to the sperm with the best motility and with lower DNA fragmentation.
We can also select sperm with intact DNA with PICSI (physiological intracytoplasmic sperm injection), which are special dishes that have hyaluronic acid wells. The sperm that are able to bind to the hyaluronic acid molecules have a lower DNA fragmentation. It’s another level of selection to be able to use in the laboratory that requires advanced reproductive technologies.
Remember, when we use laboratory technology, we only need one good sperm for every egg!