Sperm are the often-forgotten component of fertility; there is a focus on oocyte (egg) quality, maternal age, and follicle count, but eggs are only half of the puzzle. It is not only important to have sperm present, but they need to have the correct DNA structure and capacity to successfully transfer the genetic material into the egg. The sperm must also be able to attach and penetrate the outer shell of the egg (zona pelucida). That is a lot to do for such a little cell!
BIOLOGY OF SPERM PRODUCTION
Sperm production generally happens during the entire lifespan following puberty. Sperm begin as stem cells in the testes then go through many different stages of maturation: spermatogonial stem cell → primary spermatocyte → secondary spermatocyte → spermatid → spermatozoa (fully mature sperm cell). It takes between 75-90 days to go from a stem cell to a mature sperm cell. Once produced, they pass from the testes into the epididymis where they are stored until ejaculation. It is in the epididymis where they gain motility, sperm in the testes are generally immotile. Once ejaculation occurs, muscle contractions push the sperm through the rest of the reproductive tract where secretions from different glands (prostate, seminal vesicles, bulbourethral/Cowper’s gland) come together to form the semen.
Sperm production is regulated in a similar way to the menstrual cycle, using Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH). However, the presence of Testosterone is a critical component for sperm maturation and circulates in the blood as well as locally in the testes.
FERTILITY ASSESSMENT
How do we assess the sperm and determine a treatment plan for someone seeking fertility care? We use a variety of tests to help us understand the qualities of the sperm; there is the “standard” semen analysis that looks at concentration (count), motility, and morphology (shape) as well as other physical properties of the semen but there are also new advanced tests that can give us even more insight!
All normal values are taken from the World Health Organization Semen Analysis Manual (2010).
STANDARD SEMEN ANALYSIS
Volume – The expected volume of a semen sample is 1.5 mL or greater. If the sample is less, it may indicate that one of the accessory glands is not functioning properly. If a person is unable to produce any volume of semen, it is called aspermia.
pH – A measure of the acidity-alkalinity of the sample; semen is usually basic as the vaginal environment is more acidic. The expected value is around 8.0 and if it is much higher or lower, it may indicate that one of the accessory glands is not functioning properly.
Viscosity – Immediately after a sample is produced, the proteins in the semen will gel and become slightly solid. Over time (within 1 hour), the sample will liquefy and become more water-like. If the sample does not liquefy properly, the proteins keep it in a gel or viscous (thick) state. If a sample is very viscous, it may be more difficult for sperm to swim out.
Colour – A normal semen sample is white-grey and opaque. It may have a more yellow tint depending on diet or some medications. If a sample is brown, it indicates that there is blood and may indicate infection or damage to the reproductive tract.
Concentration – This measure is how many sperm are present in the sample (in millions per mL). The normal value is 15 million/mL or greater (normozoospermia). If a patient has less that that, it is called oligozoospermia. If it is very low (< 1M/mL) it is called cryptozoospermia. If there are no detectable sperm in the sample, it is called azoospermia. The concentration of sperm is a significant factor in determining a treatment plan. Patients with normozoospermia or mild oligospermia may try timed intercourse (TIC) or intrauterine insemination (IUI), patients with lower concentrations will be recommended to do IVF with intra-cytoplasmic sperm injection (ICSI). A patient with no sperm may be referred to a urologist for further investigation and possible surgical sperm retrieval or advised to use donor sperm.
Motility – The number and type of motion of the sperm is very important. If the number of moving sperm is > 40%, this is considered normal. Sperm should also be progressive, meaning they swim quickly in approximately a straight line. Sperm that are sluggish or swimming in circles are not considered to be normal. Motility is also a significant factor for treatment as successful TIC or IUI requires a good overall motility and progression. Patients with samples below normal parameters may be referred to IVF with ICSI.
Viability – This test is performed when motility is very low (<15%). The sperm is mixed with a dye to determine if sperm are viable (alive). Sperm that does not allow the dye to penetrate are alive, sperm that are dead will have a leaky outer membrane and the dye will get in and they change colour.
Morphology – The shape of the sperm can help indicate the quality of the DNA and proteins inside. Sperm cells are judged using a “Strict” criterion and the normal value is >4% normal shaped cells. Defects in the cells are most commonly found in the head (e.g. large or small, misshapen) but abnormalities are also present in the midpiece/neck (e.g. bent, thin, thick) and the tail (e.g. short, coiled, multiple tails). Poor morphology has a decreased association with TIC and IUI, a patient may be referred directly to IVF with ICSI.
Culture & Sensitivity – If a sample has more than 1 million/mL of “round cells,” which usually consist of white blood cells from the immune system, then we send a portion to an external lab for bacterial culture. A sample may come back positive for a specific bacterial strain; these infections are quite common and are not considered sexually transmitted. A patient with a positive culture will be put on antibiotics then repeat the analysis to make sure the infection has cleared prior to beginning treatment.
Anti-Sperm Antibody Assay – Antibodies are produced by the immune system to help identify foreign objects, if there is injury or an error making sperm, they may be seen as foreign and are targeted for destruction. This would inhibit the cells from being able to move freely or can damage the proteins or DNA inside. A normal result is < 50% antibody attachment. A patient with a high result may be referred for IUI as the processing will help eliminate the antibodies or possibly IVF with ICSI depending on other sperm parameters.
ADVANCED SPERM DIAGNOSTICS
Survival Assay – This test selects the best sperm from a semen sample (the ones that would be used for IUI or IVF) and incubates them for 24h. This will show if the sperm are capable of surviving long enough to reach the egg if swimming in the fallopian tubes or if they will live long enough to fertilize an egg in culture.
DNA Fragmentation (SCSA) – The integrity of the DNA inside the sperm head is incredibly important, this is the genetic material that will combine with the egg DNA to create the embryo. The Sperm Chromatin Structure Assay (SCSA) is the gold standard for testing for breaks in the DNA chain. High DNA Fragmentation (>30%) is correlated with longer time to pregnancy and miscarriage rate in people doing Timed Intercourse or IUI and fertilization failure in IVF. A high DNA Frag can potentially do IUI or IVF, but a very high result (>50%) would likely be referred for IVF with ICSI.
One of the most common questions we receive is “what can I do to improve my sperm?” Sperm health is linked to overall health: eating well, moderate exercise, getting enough sleep, reducing or eliminating alcohol, cigarettes, and marijuana; avoiding injury to the testes (incl too much heat or pressure), and not using voluntary medications (like Testosterone for working out) that have a known impact on sperm are all ways to help make your little swimmers the best they can be. There are causes of sperm-factor infertility that cannot be helped with lifestyle changes like non-obstructive azoospermia, genetic conditions like Y-microdeletions, necessary medical treatments like chemotherapy, and many more.
Sperm quality is a critical component of fertility and a thorough assessment is needed to develop an effective treatment plan. If you have any concerns about your sperm quality, contact us to schedule a standard semen analysis or advanced semen diagnostics today!
