Antisperm Antibodies
In normal circumstances, sperm are made in what is called an “immunologically privileged” area, in which they are relatively shielded from the body’s immune system. When these barriers of protection are breached, then the immune system can form antibodies against its own sperm. Some of these antisperm antibodies (ASAs) just float around in the bloodstream, while others can attach to the sperm itself. Usually ASAs are not clinically significant, and most men with them have no fertility problems. However, in a minority of men, these antibodies can cause problems with conceiving a child. In men who test positive for ASAs, there is currently no way to predict whether the antibodies are going to definitely cause fertility problems, other than their impact on standard semen parameters (see below).
Common causes of ASA formation include:
1) Significant trauma to the scrotal region
2) Genital duct infections or inflammation
3) Surgery in the scrotal or genital duct region (including vasectomy)
4) Genital tract obstruction
5) Idiopathic (no causative event known)
Diagnosis of AntiSperm Antibodies
The presence of antisperm antibodies (ASA) are usually suspected when a semen analysis shows a very low motility and/or low grade of motility along with agglutination. Agglutination is when the sperm are stuck together in larger bunches (called “clumping”). Good fertility-specific labs will comment on the presence of the sperm agglutination in a semen sample. Further testing for anti-sperm antibodies can then be done. There are two types of testing for ASA that can be performed: “Indirect” and “Direct” testing.
Indirect ASA Testing
In indirect testing, a blood test looks for the presence of circulating antibodies in the bloodstream. It’s important to note that antibodies circulating in the bloodstream have not been found to have a significant impact on male fertility. I mention this type of testing here because it can be useful for men who have the combination of azoospermia, normal FSH, normal testicular volume, and no reason to have an obstruction (such as previous hernia repair, vasectomy, etc.). In these men, it is often unclear whether there is a sperm blockage problem or, alternatively, maturation arrest (see “Azoospermia” section for more information on maturation arrest).
About 70 percent of men whose azoospermia is caused by an obstruction will be positive for anti-sperm antibodies on indirect ASA testing of the blood, whereas men with nonobstructive azoospermia should not have any anti-sperm antibodies. (However, men with congenital blockages or sperm transport problems will likely not have elevated levels of direct ASA, as opposed to men with an acquired blockage, who usually will.) This information may help to guide treatment options, although without a testicular biopsy it cannot be definitely determined whether the problem is one of production or one of blockage.
Direct ASA Testing
Direct (immunobead) testing, by contrast, looks for antibodies directly attached to the sperm themselves and determines what percentage of sperm have antibodies attached to them. If 20 percent or more of the sperm have antibodies attached to them, that is generally considered significant. The type of antibody present may also be tested for, with immunoglobulin A (IgA) thought to have a more significant impact on fertility than immunoglobulin G (IgG).
AntiSperm Antibodies and Fertility
Anti-sperm antibodies can impact fertility in one of two ways:
1) Sperm motility
ASAs can decrease motility by causing sperm to clump together. Clumped sperm do not swim well, and so they can have trouble traveling up the fallopian tubes to reach an egg.
2) Egg-Sperm Interactions
The second possibility is that antibodies can attach to the head of the sperm, interfering with the normal sperm-egg interactions that are necessary for egg fertilization.
Anti-Sperm Antibodies and Vasectomy Reversals
Most men (70 to 80 percent or more in some studies) who have been tested using the Indirect ASA test following a vasectomy have been found to have anti-sperm antibodies in their bloodstream. It is a common misconception that these anti-sperm antibodies significantly decrease fertility in men who have their vasectomy reversed. In reality, studies have shown that ASA’s present after vasectomy reversals was not associated with differences in the fertility potential of men. [Nam CS. Urol 2024]. In my practice, I occasionally see a man who has sperm agglutination and decreased motility following a successful reversal but this is quite uncommon, occurring in <3-5% of men. In addition, it often goes away on later semen analysis testing consistent with the theory which suggests that vasectomy reversals (by removing the obstruction) may decrease or even eliminate the presence of ASAs. See the section "Fertility Following Vasectomy" for more information regarding vasectomy reversals.
Management of AntiSperm Antibodies
If direct (immunobead) testing shows that ASAs are impacting more than 20 percent of sperm and there is a significant decrease in sperm motility, then there are several potential treatment options. Of note, some clinicians will treat for suspected ASA’s without formal immunobead testing if there is high clinical suspicion (significant clumping of sperm and poor motility).
Sperm Washing
One is to combine sperm washing with intrauterine insemination (IUI). The washing process can sometimes break up the agglutinated sperm and improve sperm motility. Before proceeding with IUI, a test wash can be done at the time of a semen analysis to see if the washing process will significantly improve motility. Small studies have shown a pregnancy rate of up to 15–30 percent when IUI is combined with sperm washing. A small study in 1996 suggested that medical therapy (see below) did not add much extra benefit to the outcomes of IUI in men with ASAs. [Grigoriou O. EurJObstGynReprodBiol 1996]
Medical Therapy
A second approach is via the immune system. Since antibodies against sperm are an immunologic reaction, using corticosteroids to slightly suppress the immune system should have the potential to decrease antibody levels and improve sperm quality. However, studies looking at whether this works have had mixed results. To see if there is any benefit for a particular man, a doctor can prescribe a ten-day course of prednisone (e.g. 10 mg by mouth once per day) prior to a repeat semen analysis. If significant improvements in sperm motility are seen on the new semen analysis, then the man can take prednisone 10 mg daily for days 1 through 10 of the woman’s menstrual cycle (with day 1 defined as the day of first full menstrual flow). A possible alternative is for the man to take prednisone 20 mg daily for days 1 through 10 of the woman’s menstrual cycle, followed by prednisone 5 mg daily for days 11 through 14 of her cycle (the lower dose serves to taper off from the higher initial dose; higher doses of corticosteroids should never be stopped abruptly).
Several studies have shown improvements in semen motility as well as natural pregnancy rates with the use of corticosteroids in men with clinically significant ASAs [Omu AE. EurJObstGynReprodBiol 1996][Hendry WF. Lancet 1979][ Hendry WF. Lancet 1990] but these finding of improvement have not been reproduced in every study. [Haas GG. FertSteril 1987][DeAlmeida M. IntJAndrol 1985]
The steroids can be used for as long as a year, with repeat semen analysis testing every three months to ensure that the man is continuing to respond to the corticosteroids. If longer term steroid regimens are to be used, some physicians recommend taking an anti-ulcer medication such as ranitidine (Zantac), famotidine (Pepcid), or nizatidine (Axid) while on the steroids, to decrease the risk of gastrointestinal side effects.
The use of corticosteroids is not without risks. Fortunately, severe side effects are uncommon, but it is important to be aware of them. Potential side effects include:
1) Aseptic necrosis of the hip and compression fracture of bones (rare, but can necessitate hip replacement or cause permanent
disability)
2) Mood changes
3 )Altered glucose metabolism, possibly indicating diabetes
4) New onset or worsening of peptic ulcer disease
5) Acne
6) Gastrointestinal side effects (diarrhea, bloating, increased gas)
7) Weight gain
8) Facial flushing
9) Impaired wound healing
10) Fluid retention
11) High blood pressure
12) Glaucoma
13) Insomnia
Side effects are generally related to higher dosages and longer durations of treatment. Men with known risk factors, such as elevated blood sugar levels, glaucoma, congestive heart failure, or peptic ulcer disease, should check with their primary care physician before starting these medications.
Combined Sperm Washing and Medical Therapy
If a test wash of the sperm does not improve sperm motility, then sometimes combining corticosteroids with sperm washing can help. A test sperm wash following a seven-to-ten-day course of prednisone 10 mg once a day can be performed to see if this results in improved sperm motility. If significant improvements are seen, then the man can take prednisone 10 mg daily for seven to ten days prior to IUI, or prednisone 20 mg by mouth daily for seven to ten days prior to IUI, followed by prednisone 5 mg by mouth daily for four days (to taper off the higher dosage).
IVF/ICSI
If sperm washes and corticosteroids are not effective, then IVF/ICSI is a very effective treatment. Since a single sperm is directly injected into each egg in the laboratory, the sperm do not need to swim or interact normally with the egg, and therefore the impact of any ASAs is irrelevant. Adding oral corticosteroid therapy for men with ASAs who are going through IVF does not appear to improve treatment outcomes. [Lahteenmaki A. HumReprod 1995].=