Antisperm antibodies

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Antisperm antibodies (ASA) are antibodies produced against sperm antigens.

Contents

Types

Antisperm antibodies are immunoglobulins of  IgG, IgA, and/or IgM, which are directed against sperm antigens. ASA can be detected in ejaculate, cervical mucus, follicular fluid, and blood serum of both males and females. [1] While IgG and IgA might be present in blood serum and/or genital tract fluids, IgM is only present in blood serum. IgG occurring in genital tract fluids is either produced locally or transuded from blood serum, whereas IgA (secretory type) is always produced locally. [2]

Causes

Traditionally, the breakdown of the blood-testis barrier had been established as the cause of ASA production. This mechanism had been advocated in testicular trauma and surgery, orchitis (mumps), varicocele, bacterial infections (epididymitis, prostatitis), testicular cancer, and unprotected anal intercourse. However, the association between aforementioned conditions and ASA production is controversial. [2] Only chronic obstruction, most typically represented by vasectomy followed by vasectomy reversal, is the only one condition leading constantly to high and permanent ASA titers. [3] Apart from breaching of blood-testis barrier, epididymal distension, raised intraluminal pressure, and sperm granuloma formation leading spermatozoal phagocytosis seem to be contributing factors. [4]

As of 2017, it is unclear how or why women generally do not develop ASA, and why some women do develop them; the clearest correlations are that women whose male partners have ASA in their semen are more likely to have ASA, and women with ASA tend to react only to their partner's sperm and not to other men's sperm. [5] :161 [6] The hypotheses for how women form ASA, as of 2017, includes cross-reactivity with microbial antigens, antibodies raised against ASA in their partner's semen, and a cytokine-driven immune response to ASA in their partner's semen. [5] :165–169 In women, spermatozoa in the genital tract after intercourse are not a factor in the production of antisperm antibodies. But this is possible with a trauma to the vaginal mucosa during the intercourse or the deposition of sperm in the gastrointestinal tract by oral or anal intercourse. [7] [8]

Influence on reproductive processes

In both men and women, ASA production are directed against surface antigens on sperm, which can interfere with sperm motility and transport through the female reproductive tract, inhibiting capacitation and acrosome reaction, impaired fertilization, influence on the implantation process, and impaired growth and development of the embryo. [1] [9]

Diagnosis

Different tests have been developed to identify ASA in various biological substrates. However, only Mixed Antiglobulin Reaction (MAR) test and Immunobead Test (IBT) are currently being recommended by the WHO for the assessment of human sperm antibodies. [10]

MAR test in its original version is based on the classical Coombs test; sperm is mixed with human red blood cells coated with human IgG. A rabbit or goat monospecific anti-human IgG antibody is added. Agglutination (slow “shaky” movements) can be observed if sperm are coated with ASA. Instead of human red blood cells, commercial version of MAR test uses latex particles coated with human IgG ASA. Since the test is performed with fresh semen and the incubation requires only 10 minutes, it renders MAR test a quick and simple screening tool for ASA in human ejaculate. However, samples with very low sperm count (i.e. severe oligoastheno-, or even azoospermia) cannot be evaluated using this method. Also presence of debris or high viscosity of semen can preclude its use.[ citation needed ]

IBT is based on polyacrylamide spheres coated with rabbit anti-human immunoglobulins antibody. These particles are used either to identify ASA bound to sperm (direct IBT), or ASA present in various biological fluids – seminal plasma, cervical mucus, uterine, oviduct or follicular fluid (indirect IBT); the latter one requires addition of donor ASA-free sperm.

ASA might be present also in the cervical mucus of the female. These antibodies might be proved by the postcoital test (PCT). Although the test has been declared obsolete by some authors, it has still been widely used by many gynecologists. [11] The test is performed 8–12 hours after an unprotected sexual intercourse at the estimated time of ovulation, when the cervical mucus is least viscous and thus most permeable for the sperm. The result is considered poor in case of less than 10 sperm per high power field are apparent.

Generally, the main drawback of all tests used for the diagnosis of ASA is a heterogeneity of data presented in available studies, caused by lack of method standardisation, various semen preparations, and inconsistent cut-off values. These facts compromise precise comparison between various methods. [2]

Treatment

Since the precise etiology of ASA production is mostly unknown, causative treatment of ASA-mediated infertility is rarely possible.

Immunosuppressive therapy comprising corticosteroids or ciclosporin has been proposed by several authors with promising results, nevertheless large randomized controlled trials failed to show a clear benefit. Owing to sometimes severe adverse effects, many clinicians are reluctant to treat immune infertile patients with above mentioned drugs.

In the clinical practice, assisted reproductive techniques are being considered as a golden standard for the immune-mediated infertility.

Albeit intrauterine insemination (IUI) might circumvent ASA present in the cervical mucus, in a study comprising 119 IUI, no live pregnancy was reported, suggesting involvement of other mechanisms of ASA. [12] Since ASA are usually bound to sperm surface antigens with high affinity, ordinary wash-up used before ICSI is not effective. [2] Thus, some authors recommend treatment of sperm with chymotrypsin/galactose to cleave ASA molecules. [13] However, this method has not been adopted by clinicians as some concerns exist regarding a possible negative impact of this digestive enzyme on sperm surface receptors involved in fertilization. [14]

In vitro fertilization (IVF) reaches lower pregnancy rates in ASA-positive individuals – basically, the higher ASA titers, the more negative outcome. This inverse association is more pronounced in ASA-positive males. [15] It has been reported ASA binding to the sperm head have more negative impact on fertilization than those binding to the sperm midpiece or tail.

If intracytoplasmic sperm injection (ICSI) is added to IVF, similar outcome has been observed in both ASA-positive and ASA-negative couples. Nevertheless, one study showed significantly higher spontaneous pregnancy loss in the ASA-positives. [16]

Prevalence

ASA can arise whenever sperm encounter the immune system. [6] ASA occur in women and men, including women or men who receive anal sex from men or who perform oral sex on men. [17] :210 [7]

ASA have been considered as infertility cause in around 10–30% of infertile couples, and in males, about 12–13% (20,4% in meta-analysis) [9] of all diagnosed infertility is related to an immunological reason. The incidence can well be higher as the contribution to idiopathic infertility (31% of all cases) still remains elusive. However, these antibodies are also present in approximately 1–2.5 % of fertile men and in 4% of fertile women; the presence of ASA in the fertile population suggests that not all ASA cause infertility. [18] :27 Only those antibodies directed against antigens involved in the fertilization process impair fertility. [2]

While around 75% of vasectomized men who have the process reversed by vasovasostomy have high levels of ASA in their blood, [19] :v these circulating antibodies do not affect fertility in men; only ASA in the male reproductive tract appears to do so. [20] :134

About 40-45% of sex workers test positive for antisperm antibodies, compared to just 5% in the control group. [21] Research has shown that these numbers increase for those who do not use contraceptive methods. [7]

Research

As of 2017 research was ongoing in several areas related to ASA.

There is a general effort to identify concrete sperm surface antigens which serve as a target for ASA. As sperm undergoes biological changes including capacitation, acrosome reaction, zona binding, and sperm-egg fusion, the set of sperm surface antigens is highly dynamic in time. Additionally, some of the sperm surface antigens might be incorporated into the plasma membrane of the embryo resulting in postfertilization negative impact of ASA.

Research has been conducted, but not clinically tested, to use sperm antigens or recombinant ASAs as contraceptive vaccines for humans, [22] as well as captive and wild animals. [23]

The mechanisms through which both women and men develop ASA is also poorly understood and a subject of research. [5] :161 [20] :133

Related Research Articles

<span class="mw-page-title-main">Spermatozoon</span> Motile sperm cell

A spermatozoon is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote.

<span class="mw-page-title-main">Intracytoplasmic sperm injection</span> In vitro fertilization procedure

Intracytoplasmic sperm injection is an in vitro fertilization (IVF) procedure in which a single sperm cell is injected directly into the cytoplasm of an egg. This technique is used in order to prepare the gametes for the obtention of embryos that may be transferred to a maternal uterus. With this method, the acrosome reaction is skipped.

Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species. It is the normal state of a human child or other young offspring, because they have not undergone puberty, which is the body's start of reproductive capacity.

<span class="mw-page-title-main">Artificial insemination</span> Pregnancy through in vivo fertilization

Artificial insemination is the deliberate introduction of sperm into a female's cervix or uterine cavity for the purpose of achieving a pregnancy through in vivo fertilization by means other than sexual intercourse. It is a fertility treatment for humans, and is a common practice in animal breeding, including dairy cattle and pigs.

Insemination is the introduction of sperm into a female’s reproductive system for the purpose of impregnating, also called fertilizing, the female for sexual reproduction. The sperm is introduced into the uterus of a mammal or the oviduct of an oviparous (egg-laying) animal. In mammals, insemination normally occurs during sexual intercourse or copulation, but insemination can take place in other ways, such as by artificial insemination.

<span class="mw-page-title-main">Acrosin</span>

Acrosin is a digestive enzyme that acts as a protease. In humans, acrosin is encoded by the ACR gene. Acrosin is released from the acrosome of spermatozoa as a consequence of the acrosome reaction. It aids in the penetration of the Zona Pellucida.

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<span class="mw-page-title-main">Female infertility</span> Diminished or absent ability of a female to achieve conception

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<span class="mw-page-title-main">Ashok Agarwal</span> Medical Scientist

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<span class="mw-page-title-main">Male infertility crisis</span> Observed decline in male fertility and sperm quality

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References

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