Male

Immunological

Infertility

田美策 孙钦辉 魏源 魏艳 王思宇

Sir Frank Macferlane Burnet

Clonal Selection Theory

There are various lymphocyte clone,each of them bears a single type of Ag receptor of unique specificity.

Ag receptor—Ag’s specific interactions lead to lymphocytes activation (proliferated ), then produce both Ab and memory cells.--- Clone selection

Those clones whose receptor can recognize self will be destroyed or learn to tolerance to self Ags (forbidden clones) at early stage.—Clone deletion

forbidden clones can be revival and cause antoimmunity

Clonal Selection Theory

For male, spermatogenesis commences( 发生 ) well after the development of neonatal (new born) immune tolerance

And for female, sperm is definitively “non-self”

Mechanisms normally in place to modify the immune response and prevent immune reaction Blood-testis barrier Sperm plasma immunosuppressive

factors ( 精浆免疫抑制因子 )

The barriers may be disrupted, result in the exposure of sperms to the immune system.

And thus the production of antibody

research on sperm as an antigen has been making little progress

So what do we know about sperm as an antigen?

MostlyMembraneproteins

Spermatogenic cells

Sustentacular cells

Deputy gonadal components

( 副性腺成分 )

Mechanism of anti-sperm antibody causing infertility

Direct binding influence

Function impairment of antigen molecules

Direct binding influence1.Occlude the

sperm penetration through the cervical mucus

2.Accelerate the clearance of sperms in the female genital canal (mainly carried out by complements)

Antigen function impairment

Inhibit fertilization

AsAb binds to Ag P36 and P18, manifesting a reduction of penetration through zona pellucida and oval membrane.

Induced spontaneous acrosome( 顶体 ) activation and acrosomal enzyme lost

Failure of fertilization………

Diagnostic techniques

Traditional methods sperm membrane extract( 膜提取

物 ) or motile sperms( 活动精子 ) as antigen to detect AsAb

Being questioned for deficiency and uncertainty

Diagnostic techniques

According to WHO

Diagnostic basis the surface of motile sperm is

attached by immunoglobulin positive result of IBT or MAR

IBT----immunobead test( 免疫珠试验 )

Utilize polyacrylamide beads( 聚丙酰烯胺珠 ) coated with Ig to human IgG, M and A to detect AsAb.

MAR----mixed agglutination reaction( 混合凝集试验 )

Uses anti-human Ig to mediate agglutination between latex( 胶乳 ) beads or SRBC labeled with human Ig and viable sperms ( 活性精子 )

Standard of IBT and MAR

The percentage of viable sperms attached by AsAb among all viable sperms

Detect not only the existence of Ig, but also the position of attachment

Clinical therapy

Different percentage and site of attachment have different clinical significance

It is recommended to choose different methods according to the percentage of sperms attached by AsAb, particularly to their heads.

From the lowest highest

We choose IUI IVF ICSI

Clinical therapy

IUI----intrauterine insemination

Send sperms directly into the uterine cavity

First choice for male immunological infertility

IUI----intrauterine insemination

IVF---- in vitro fertilization Not only overcomes the

difficulty of AsAb-attached sperms penetrating the cervical mucus, but also make sure there are enough sperms contacting with ovum.

IVF---- in vitro fertilization

ICSI----intracytoplasmic sperm injection The most

effective method for severe immunological infertility

But with the highest cost

tens of thousands of dollars!

Other options

Isolation therapy (using condom) Immune inhabitation (large-dose-glucocorticoid

injection)

…….

There are questions remaining to be answered!!!

Acknowledgements

Sperm antigen---------------------- 魏艳 Production of AsAb---------------- 魏源 Mechanism of infertility----------- 田美策 Diagnostic techniques------------ 孙钦辉 Clinical therapy--------------------- 王思宇

Thanks all !