Abstract
The definition of infertility is often described as the inability of a couple to conceive after one year of regular, unprotected sexual intercourse. Male factor infertility is present in approximately 50 percent of the cases and is the primary cause of the infertility in 30 percent of the cases [1]. Male factor infertility can be due to a variety of causes such as trauma, disease, anatomical or genetic abnormalities and many more. However, idiopathic male infertility comprises 30–40 percent of all cases [1].
3.1 Background
The definition of infertility is often described as the inability of a couple to conceive after one year of regular, unprotected sexual intercourse. Male factor infertility is present in approximately 50 percent of the cases and is the primary cause of the infertility in 30 percent of the cases [1]. Male factor infertility can be due to a variety of causes such as trauma, disease, anatomical or genetic abnormalities and many more. However, idiopathic male infertility comprises 30–40 percent of all cases [1].
Standard semen analysis (SA) is considered a fundamental diagnostic tool in the workup of the male fertility status. This essential test evaluates multiple semen parameters such as concentration, motility, morphology, volume and pH [2]. The results of the SA are then compared with reference ranges dictated by the World Health Organization’s (WHO) Laboratory Manual for the examination and processing of human semen [2, 3]. If the results of a SA find parameters to be below the WHO 95th percentile reference range, the likelihood of pregnancy by intercourse becomes less probable [2, 3].
Although the SA is a cornerstone of the male infertility workup, many limitations inherent to the process exist, which facilitate the introduction of random errors into the test and thus cause significant variability in the results [4]. Observer subjectivity, insufficiencies in technician training and an absence of uniform laboratory protocol standardization are just a few of the ways in which the results of SA may be inaccurate and unreproducible [4]. An important additional limitation of laboratory-based SA is the reluctance of some men to make an office visit due the social stigma and embarrassment of infertility-related issues [5]. In light of this, men tend to be less likely than women to seek the care of a medical provider, while men that do seek medical attention are often better educated with higher paying occupations [6].
Since its inception in 1677 with Antonie van Leeuwenhoek’s construction of a self-made microscope, SA has undergone many technological advancements [7]. The advent and application of more sophisticated microscopy has later been met by the rise of the digital age and the advent of computer-assisted sperm analysis (CASA) [8]. More recently, home SA devices have entered the market, with each device having its own unique operational platform designed to measure different semen parameters. The platforms by which these novel diagnostic tools function range from the use of immunochromatography and microfluidics to the utilization of centrifugal technology and smartphone-based applications [5, 9–12].
The increased use of point-of-care monitoring devices over the past two decades has made a dramatic impact on the way medical care is carried out. Sleep apnea diagnosis [13], fall risk [14] and blood glucose [15] monitoring are examples of ways patients now have increased control and knowledge over their health status in the privacy of their homes. However, the social stigma surrounding male infertility often prevents patients from getting the care they need and thus prolonging a couple’s infertile status and chances of a successful pregnancy [5]. As a result, at-home testing devices has allowed men to check their semen quality in the comfort of their home and afterwards contact a fertility specialist if the results are abnormal [16].
3.2 Home Sperm Testing Devices
Several types of home sperm testing devices are available on the market. We have classified them based on the technology and working principle (Table 3.1).
| Testing devices | Technology/working principle | Semen parameters measured |
|---|---|---|
| Smartphone Based (YO home sperm test) | YO clip mini-microscope, user’s phone light source and camera | MSC, sperm concentration and motility |
| Microscope Based (Micra Sperm Test) | Manual microscope evaluation of semen parameters | Sperm concentration, motility and volume |
| Microfluidic Based | Analysis of motile sperm as they progress through differing chambers via channels or pores | Varies per device |
| Centrifugation Based (Trak®) | CentriFluidicTM technology which initiates centrifugal force on sperm and analyzes the condensed pellet | Sperm concentration |
| Immunodiagnostic Based (SpermCheck®) | Chemical labeling of spermatids and sperm-specific proteins to provide an indirect sperm concentration measurement. SwimCount also utilizes ‘swim up’ method to separate and count progressively motile sperm. | Sperm concentration |
| Immunodiagnostic Based (SwimCountTM) | TPMSC, morphology and DNA fragmentation |
3.2.1 Smartphone-Based Devices
The use of cellphones around the world has steadily expanded, reaching a global subscription in 2015 of 96.8 percent [17]. Smartphones, in particular, have a unique application in medicine because they are portable, have considerable processing power, contain high resolution cameras and can connect to the Internet [5]. Although each smartphone-based at-home sperm testing kit is unique, in general terms, most of these devices contain an attachable microscope, multiple sample loading chambers, and operate based on pre-programed software in “app” format, which is compatible with the majority of smartphone operating systems [10, 16].
3.2.2 Microfluidic-Based Devices
The utilization of microfluidic technology to measure semen parameters is found in a variety of home-based SA devices, such as the smartphone based YO Home Sperm Kit and the centrifugal-based Trak Male Fertility Testing System [10, 11]. Based on the principle of counting motile spermatozoa as they swim from one chamber to another (through a pore or channel), microfluidics can provide measures such as a sample’s sperm concentration, motility and the motile sperm concentration (MSC) [10, 16].
3.2.3 Centrifugation-Based Devices
Centrifugation-based devices such as the “Trak Male Fertility Testing System” operate based on the principle of centrifugal force. Trak utilizes the induced movement of sperm cells from an initial loading inlet chamber (containing a pre-loaded density medium), through a progressively narrowing collection channel and into a column where the cells are condensed for evaluation [11].
3.2.4 Manually Operated Microscope Devices
Home SA devices based solely on the manual use of a microscope are currently available to the public. Priced at $85, the FDA-approved Micra Sperm Test includes a microscope, slides and a counting grid for the user to manually determine their own sperm count, motility and volume. However, studies have shown that the correct use of Micra requires an experienced operator as it is highly susceptible to user error by the layperson [10].
3.2.5 Immunodiagnostic-Based Devices
Immunodiagnostic home sperm tests operate based on unique principles designed for each individual device. Generally, these devices provide an indirect measure of sperm concentration via a lateral flow immunochromatographic test, which uses monoclonal antibodies designed for sperm specific antigens [12]. The signal generated when these antibodies bind to or “label” their respective antigens has a direct relation to sperm count and thus facilitates the enzyme-linked immunosorbent assay (ELISA)-based visualization of a semen sample’s concentration [12].
3.3 Performance of Food and Drug Administration-Approved Home Sperm Testing Devices
3.3.1 YO Home Sperm Test
Developed in 2017, the YO Home Sperm Test (Medical Electronics Systems, Ltd., Caesarea Industrial Park, Israel) utilizes the video function built into most smartphones and operates based upon the software programed in its app [16]. The YO Home Sperm Test operates by mixing a liquefaction powder into a semen sample, transferring 20 µL of that sample onto a YO slide via the fixed transfer pipette and inserting it into the YO device [16]. Next, the YO device’s microscope, in conjunction with the phone’s camera and light source, record a 30-second video of the sperm; the built-in software then analyzes the sample (Figure 3.1) [16].
Figure 3.1 Components of the YO Home Sperm Test. (A) Photo of the YO kit contents, including (a) YO testing clip, (b) collection cup, (c) vial of liquefaction powder, (d) fixed volume transfer pipettes, and (e) fixed coverslip slide. (B) Sample loading into the filling chamber (highlighted in pink). (C) The assembled YO clip with inserted testing slide. (D) Screenshot of the captured sample as seen on the phone screen.
The YO Home Sperm Test measures a semen sample’s motile sperm concentration (MSC), a composite value of the sample’s concentration and motility. MSC is a unique measurement that provides greater insight into a patient’s fertility outlook as opposed to simply reporting a patient’s semen parameters [16]. Recent data has shown that, when compared to the laboratory-based automated sperm quality analyzer (SQA-Vision), the YO Home Sperm Test’s MSC results present a moderate to good correlation with SQA-Vision. For example, the Pearson and Concordance correlations for sperm concentration utilizing the YO iPhone 7 was observed to be 0.96 and 0.96, respectively [16]. However, the correlations were 0.97 and 0.92, respectively, when utilizing the YO Galaxy S7.
An advantage of the YO Home Sperm Test includes the software’s compatibility with both PC and Mac products, with the user interface being simple and easy to operate for both operating systems. Additionally, running of multiple tests is made easy by the YO Refill Kit which is readily available for purchase. The ability to measure MSC and generate an easy to interpret “YO Score” of low, moderate or high is based upon a cut-off value of 6 × 106/mL MSC. The advantage is that this integrated parameter consisting of the concentration and the motility provides valuable information regarding the patient’s fertility status [16].
Disadvantages of this device include the price of the YO products, which range from $45.95 to $89.95 (yospermtest.com/shop/). Similarly, the number of semen parameters evaluated by the YO Home Sperm Test is lacking when compared to other such devices. Although there are many benefits inherent to smartphone-based tests, the simple fact that the YO Home Sperm Test requires a smartphone will prevent some underserved patients from being able to use the device.
3.3.2 SpermCheck Fertility
Developed in 1999, SpermCheck Fertility (similar to Fertilmarq) is an immunodiagnostic at-home SA device, which operates based upon the principle of lateral flow immunochromatography [12]. Utilizing monoclonal antibodies, which bind or “label” only spermatids and the sperm specific acrosome-protein SP-10, SpermCheck provides an indirect measure of the sperm concentration in approximately seven minutes [12].
SpermCheck is operated by collecting 100 µL of liquefied semen via a calibrated pipette and thoroughly mixing the sample with a detergent buffer used to solubilize the SP-10 protein. Next, the test cassette is loaded by adding four drops of sample into each of the two sample wells (Denoted “S”) found below the two test strips. Initially, “control lines” denoted “C” will appear to indicate the test is functioning properly (Figure 3.2). After approximately seven minutes, the test lines denoted “T” should appear on both strips (the strip labeled “20M” and the strip labeled “5M”), if the sperm concentration is >20 × 106 sperm/mL [12]. However, if the sperm concentration is <20 × 106 sperm/mL but >5 × 106 sperm/mL, the test line will appear only in the “5M” strip on the left. Similarly, if the concentration is <5 × 106sperm/mL, no test lines will appear (Figure 3.2) [12].
