Heat shock proteins (HSP) were first identified in cells after exposure to elevated temperature. Subsequently HSP have been identified as a critical component of a very complex and highly conserved cellular defence mechanism to preserve cell survival under adverse environmental conditions. HSP are preferentially expressed in response to an array of insults, including hyperthermia, free oxygen radicals, heavy metals, ethanol, amino acid analogues, inflammation and infection. HSP interact with intracellular polypeptides and prevent their denaturation or incorrect assembly. In addition HSP are also involved in several processes essential for cellular function under physiological conditions. HSP production is enhanced during in-vitro embryo culture and they are among the first proteins produced during mammalian embryo growth. The spontaneous expression of HSP as an essential part of embryo development is well documented and the presence or absence of HSP influences various aspects of reproduction in many species. Finally, HSP are immunodominant antigens of numerous microbial pathogens, e.g. Chlamydia trachomatis, which have been recognized as the main cause of tubal infertility. Many couples with fertility problems have had a previous genital tract infection, have become sensitized to microbial HSP, and a prolonged and asymptomatic infection may trigger immunity to microbial HSP epitopes that are also expressed in man. Antibodies to both bacterial and human HSP are present at high titres in sera and hydrosalpinx fluid of many patients undergoing in-vitro fertilization (IVF). In a mouse in-vitro embryo culture model, these antibodies impaired the mouse embryo development at unique developmental stages. Recent studies indicate an association between a previous infection, immunity to HSP and reproductive failure.

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Two-cell mouse embryos (B6D2F1) were cultured in the presence or absence of 100 microg/ml monoclonal antibodies specific for the mammalian 60 kDa (HSP60), 70 kDa (HSP70) and 90 kDa (HSP90) heat shock proteins. Embryo development was evaluated after 3, 5 and 7 days in culture by determining the number of blastocysts, hatched blastocysts and outgrown trophoblasts at the successive time points. At day 3, only 29% (22/75) of the embryos cultured with anti-HSP60 antibody developed to the blastocyst stage (P < 0.0001) as compared to 67% (31/46) of the embryos cultured with anti-HSP70, 72% (43/60) cultured with anti-HSP90, and 79% (49/62) in medium plus mouse IgG1. By day 5, hatched embryos were present in 28% (13/ 46) of the cultures containing anti-HSP70 (P < 0.0001), as opposed to 57% (34/60) containing anti-HSP90 and 73% (45/62) containing IgG1. At day 7, outgrown trophoblasts were observed in 9% (4/46) of cultures containing anti-HSP70 (P < 0.0001), 45% (27/60) containing anti-HSP90 (P < 0.01) and 66% (41/62) cultured in medium plus IgG1. Antibodies to different heat shock proteins exerted a detrimental effect on mouse embryo development at unique development stages. Immune sensitization to heat shock proteins may be a cause of reproductive failure.

Acupuncture has been used to treat infertility extensively, including ovulatory dysfunction, in vitro fertilization and embryo transfer (IVF-ET), and male infertility. This review summarizes the recent studies which investigated the role of acupuncture in infertility. In conclusion, most of the existing studies suggest a positive effect of acupuncture in infertility treatment. Firstly, acupuncture may improve ovulation by modulating the central and peripheral nervous systems, the neuroendocrine and endocrine systems, the ovarian blood flow, and metabolism. Secondly, acupuncture can improve the outcome of IVF-ET, and the mechanisms may be related to the increased uterine blood flow, inhibited uterine motility, and the anesis of depression, anxiety and stress. Its effect on modulating immune function also suggests helpfulness in improving the outcome of IVF-ET. Finally, the studies suggest that acupuncture plays a positive role in male infertility, the mechanism of which is not yet clear. Even though a positive effect of acupuncture in infertility has been found, well-designed multi-center, prospective randomized controlled studies are still needed to provide more reliable and valid scientific evidence. Furthermore, it is urgent and necessary to clarify the mechanism of acupuncture for infertility.

The combined presence of IgA Ab to human 60 kDa HSP, leukocytes and other established infection/inflammation markers in semen might suggest a potential role of the immune response to heat shock proteins (HSP) in cases of silent male genital tract infection, but the results do not indicate a marked relationship of HSP 60 Ab in seminal fluid with standard parameters of semen quality.