Infertility and Womens Health

Identifiable causes of infertility include: ovulatory disorders in 27% of couples; tubal damage in 14% of couples; low sperm count or low sperm quality in 19% of couples. In 30% of couples the cause of infertility remains unexplained (NCCWCH, 2004).

Clare Nasir describes her experiences using acupuncture to complement IVF

Clare Nasir had undergone several IVF treatments before looking to acupuncture as a complementary therapy. The result speaks for itself.

Infertility ART

Currently, about 17% couples in industrialised countries seek medical advice for infertility (Cahill 2002). The definition of infertility is usually the failure to conceive after 1 year of unprotected intercourse (European Society 1996). Infertility can be primary, in women who have never conceived, or secondary, in women who have previously conceived. In the UK, about 10-20% of infertility cases are unexplained (Isaksson 2004). The rest are the result of ovulatory failure (27%), tubal damage (14%), endometriosis (5%), low sperm count or quality (19%), or other causes (5%) (Effective Health Care 1992).

In developed countries, 95% of couples attempting to conceive are successful after 2 years (Brosens 2004). However, the chances of becoming pregnant vary with the cause and duration of infertility, the woman’s age, the woman’s previous pregnancy history, and the availability of different treatment options (Templeton 1998, Collins 1995). For the first 2-3 years of unexplained infertility, cumulative conception rates are 27-46% but decrease with increasing age of the woman and duration of infertility (Collins 1995).

The aims of infertility treatment in conventional medicine are to achieve the delivery of one healthy baby, and to reduce the distress associated with infertility, with minimal adverse effects. Interventions include intrauterine insemination plus controlled ovarian stimulation, in vitro fertilisation, intracytoplasmic sperm injection, gonadotrophin releasing hormone agonists, clomifene and tamoxifen, laparoscopic ovarian drilling, tubal flushing and laparoscopic ablation of endometrial deposits, depending on the cause of the infertility (Al-Inany 2004).

References

Al-Inany H. Female infertility. BMJ Clinical Evidence. Search date April 2004.

Brosens I, Gordts S, Valkenburg M, et al. Investigation of the infertile couple: when is the appropriate time to explore female infertility? Hum Reprod 2004;19:1689 -92.

Cahill DJ, Wardle PG. Management of infertility. BMJ 2002;325:28-32.

Collins JA, Burrows EA, Willan AR. The prognosis for live birth among untreated infertile couples. Fertil Steril 1995;64:22-8.

Effective Health Care. The management of subfertility. Effective Health Care Bull 1992;3:13.

European Society for Human Reproduction and Embryology. Guidelines to the prevalence, diagnosis, treatment and management of infertility, 1996. Hum Reprod 1996;11:1775-807.

Isaksson R, Tiitinen A. Present concept of unexplained infertility. Gynecol Endocrinol 2004;18:278-90.

Templeton A, Morris JK. IVF – factors affecting outcome. In:Templeton A, Cooke ID, O’Brien PMS, eds. 35th RCOG study group evidence-based fertility treatment. London: RCOG Press, 1998:265-73.

How acupuncture can help

Most clinical trials to date suggest that acupuncture may be useful in the embryo transfer stage of in vitro fertilisation, and results in an increased pregnancy rate and a greater number of live births (Cheong 2008, Manheimer 2008, Kong 2009, Chen 2009, Smith 2006, Westergaard 2006), though there have been exceptions (Domar 2009) (see Table overleaf). In one recent large trial the pregnancy rate in the acupuncture group was lower than that of the control (So 2009), thus affecting the results of subsequent reviews (Cheong 2010). This trial used an inappropriately active control treatment, a sort of acupressure, thus casting doubt on the validity of the findings.

Acupuncture may help in the treatment of infertility by:

  • regulating fertility hormones – stress and other factors can disrupt the function of the hypothalamic pituitary-ovarian axis (HPOA). Acupuncture promotes the release of beta-endorphin in the brain, which regulates gonadatrophin releasing hormone from the hypothalamus, follicle stimulating hormone from the pituitary gland, and oestrogen and progesterone levels from the ovary (Anderson 2007).
  • increasing blood flow to the reproductive organs (Ho 2009, Anderson 2007), which can improve the thickness of the endometrial lining, so increasing the chances of embryo implantation.
  • increasing egg production (Jin 2009) and improving oocyte quality (Chen 2009), which could increase the chance of fertilisation.
  • enhancing luteal function (Huang 2009)
  • regulating follicle stimulation hormone-receptor expression (Jin 2009).
  • normalising cortisol and prolactin levels on IVF medication days (Magarelli 2008); reducing stress (Anderson 2007)
  • promoting embryo implantation (Liu 2008).

Female infertility

Infertility is the inability of a couple to get pregnant despite having regular unprotected sex. A couple is regarded as infertile if, after regular sexual intercourse, they have not conceived in two years. It is estimated that one in seven UK couples has difficulty conceiving (HFEA, 2006).

Identifiable causes of infertility include: ovulatory disorders in 27% of couples; tubal damage in 14% of couples; low sperm count or low sperm quality in 19% of couples. In 30% of couples the cause of infertility remains unexplained (NCCWCH, 2004). Female fertility declines with age, but the effect of age on male fertility is less clear (NICE, 2004). The difficulties couples encounter when facing fertility problems can lead to stress, which may further decrease chances of conception (Eugster & Vingerhoets, 1999). Acupuncture is a popular treatment choice for infertility (Smith 2010).

References

Eugster A, Vingerhoets AJ. Psychological aspects of in vitro fertilization: a review. Soc Sci Med. 1999 Mar;48(5):575-89.

Human Fertilisation and Embryology Authority (HFEA) Facts and figures for researchers and the media. (2006) www.hfea.gov.uk

National Collaborating Centre for Women’s and Children’s Health Fertility (NCCWCH) Fertility: assessment and treatment for people with fertility problems (full NICE guideline). Royal College of Obstetricians and Gynaecologists. www.rcog.org.uk

National Institute for Health and Clinical Excellence (NICE) Fertility: assessment and treatment for people with fertility problems (NICE guideline). Clinical guideline 11. (2004) www.nice.org.uk

Smith JF, Eisenberg ML, Millstein SG, Nachtigall RD et al. The use of complementary and alternative fertility treatment in couples seeking fertility care: data from a prospective cohort in the United States. Fertil Steril. 2010;93(7):2169-74.

How acupuncture can help

Randomised trials in China have demonstrated significantly better pregnancy rates for acupuncture than medication (Yang 2005, Chen 2007, Song 2008), but these studies may not be of a high quality. In the West, clinical trials on acupuncture for natural fertility (i.e. not as an adjunct to assisted conception) are almost non-existent, though there is a small amount of positive evidence (Gerhard 1992, Stener-Victorin 2000, 2008, 2010).

Research has established plausible mechanisms to explain how acupuncture may benefit fertility:

  • regulating fertility hormones – stress and other factors can disrupt the function of the hypothalamic pituitary-ovarian axis (HPOA), causing hormonal imbalances that can negatively impact fertility. Acupuncture has been shown to affect hormone levels by promoting the release of beta-endorphin in the brain, which affects the release of gonadotrophin releasing hormone by the hypothalamus, follicle stimulating hormone from the pituitary gland, and oestrogen and progesterone levels from the ovary (Ng 2008, Huang 2008, Lim 2010, Stener-Victorin 2010). Further details of these processes are emerging, for example mRNA expression of hormones, growth factors and other neuropeptides (He 2009)
  • increasing blood flow to the reproductive organs – stress also stimulates the sympathetic nervous system, which causes constriction of ovarian arteries. Acupuncture inhibits this sympathetic activity, improving blood flow to the ovaries (Stener-Victorin 2006, Lim 2010), enhancing the environment in which ovarian follicles develop. It also increases blood flow to the uterus (Stener-Victorin 1996, Huang 2008), improving the thickness of the endometrial lining and increasing the chances of embryo implantation.
  • counteracting the effects of polycystic ovarian syndrome (PCOS) – PCOS is one of the most common causes of female infertility. By reducing sympathetic nerve activity and balancing hormone levels, acupuncture has been shown to reduce the number of ovarian cysts, stimulate ovulation, enhance blastocyst implantation and regulate the menstrual cycle in women with PCOS (Stener-Victorin 2000, 2008, 2009, Zhang 2009). It may also help to control secondary effects such as obesity and anorexia (Lim 2010).

Male infertility

The clinical definition of male infertility is the presence of abnormal semen parameters in the male partner of a couple who have been unable to conceive after 1 year of unprotected intercourse (Dohle 2010).

The World Health Organization defines male factor infertility as the presence of one or more abnormalities in the semen analysis, or the presence of inadequate sexual or ejaculatory function (Rowe 2004). In 50% of involuntarily childless couples, a male infertility associated factor is found together with abnormal semen parameters (Dohle 2010).

Male fertility requires normal sperm production and sperm transport, and adequate sexual performance, functions that require normal levels of testosterone. Male infertility can be due to a number of factors, including abnormal spermatogenesis; reproductive tract anomalies or obstruction; inadequate sexual and ejaculatory functions; and impaired sperm motility (Patki 2004; Isidori 2005; Dohle 2010). In 30-40% of men, no cause for infertility is found (Dohle 2010). However, in such men, semen analysis reveals a decreased number of spermatozoa (oligozoospermia), decreased sperm motility (asthenozoospermia) and many abnormal forms of sperm (teratozoospermia) (Dohle 2010). Factors that alter spermatogenesis include endocrine disturbances such as low testosterone levels, exposure to medicines or environmental toxins, varicocele, increased scrotal heat, systemic diseases, smoking and alcohol, and testicular torsion and trauma (Cherry 2001; Kunzle 2003; Shefi 2006; Arap 2007). Erectile and ejaculatory dysfunction may be associated with psychological factors, hypogonadism, spinal cord disease, and metabolic and vascular conditions such as diabetes (Dohle 2010). Sperm motility can be reduced in immotile cilia syndrome or in the presence of antisperm antibodies (Arap 2007).

Treatment for male infertility should be targeted to the aetiological factors whenever possible, and includes hormonal treatment, hormonal modulators, corticosteroids, antioxidants, and surgery. Assisted reproductive techniques are often the fastest and most effective method to achieve pregnancy regardless of the aetiology (Isidori 2005; Dohle

References

Arap MA et al. Late hormonal levels, semen parameters and presence of antisperm antibodies in patients treated for testicular torsion. J Androl 2007; 28: 528-32.

Cherry N et al. Occupational exposure to solvents and male infertility. Occup Environ Med 2001; 58: 635-40.

Dohle GR et al. Guidelines on male infertility. European Association of Urology; 2010.

Isidori A et al. Treatment of male infertility. Contraception 2005; 72: 314-8.

Kunzle R et al. Semen quality of male smokers and nonsmokers in infertile couples. Fertil Steril 2003; 79: 287-91.

Patki P et al. Effects of spinal cord injury on semen parameters. J Spinal Cord Med 2008; 31: 27-32.

Rowe PJ et al. WHO manual for the standardized investigation and diagnosis of the infertile male. Cambridge, UK: Cambridge University Press; 2004.

Shefi S, Turek PJ. Definition and current evaluation of subfertile men. Int Braz J Urol 2006; 32:385-97.

How acupuncture can help

Some clinical trials suggest that acupuncture improves sperm motility (Dieterle 2009), increases sperm count (Siterman 2009, Siterman 2001), improves sperm quality (Pei 2005; Gurfinkel 2003) and has a beneficial effect on psychogenic erectile dysfunction (Engelhardt 2003) (see Table overleaf). The research results are promising but still at a preliminary stage in terms of numbers and quality of studies.

Acupuncture may help in the treatment of male infertility (Stener-Victorin 2010), by:

  • lowering scrotal temperature (Siterman 2009);
  • enhancing local microcirculation, by increasing the diameter and blood flow velocity of peripheral arterioles (Komori 2009);
  • reducing inflammation, by promoting release of vascular and immunomodulatory factors (Zijlstra 2003)
  • by improving sperm maturation in the epididymis, increasing testosterone levels, and reducing liquid peroxidation of sperm (Crimmel 2001)

Endometriosis

Endometriosis is a chronic condition characterised by growth of endometrial tissue in sites other than the uterus, most commonly in the pelvic cavity, but also in other parts of the body (RCOG 2006).

This ectopic tissue responds to the hormonal changes of the menstrual cycle, with subsequent bleeding, inflammation, and pain. If the ovaries are affected, endometriotic ovarian cysts may develop (Bulun 009). Although the condition may be asymptomatic, common symptoms include dysmenorrhoea, dyspareunia, non-cyclical pelvic and abdominal pain, and subfertility (RCOG 2006). When endometriosis remains untreated, the disease progresses in around a third of women, but seems either to resolve or does not progress in the rest (DTB 1999). The prevalence is estimated to vary from 2-22% of women and, in women with dysmenorrhoea, the incidence of endometriosis is 40-60% (Johnson 2007).

The cause of endometriosis is not known, but several factors are thought to be involved in its development. These include retrograde menstruation; embryonic cells giving rise to depositsin distant sites around the body; an abnormal quantity or quality of endometrial cells; failure of immunological mechanisms; angiogenesis; and the production of antibodies against endometrial cells (Gazvani 2002, Rock 1992, Seli 2003, Kyama 2003, Oral 1996).

Pain due to endometriosis can be functional, neuropathic, due to inflammation, or result from a combination of these. It may be evoked by a low intensity, normally innocuous stimulus (allodynia), it may be an exaggerated and prolonged response to a noxious stimulus (hyperalgesia), or it may be spontaneous in the absence of any apparent peripheral stimulus (Lundeberg 2008). In addition, oestrogens and prostaglandins probably play key modulatory roles in endometriosis and the pain it causes (Lundeberg 2008). Consequently, current medical treatments for the condition include drugs such as NSAIDs, combined oral contraceptives, progestogens, androgenic agents and gonadotrophin releasing hormone analogues, as well as surgical excision of endometriotic lesions. However, management of pain in women with endometriosis is often inadequate.

References

Bulun, S.E. (2009) Mechanisms of disease: endometriosis. New England Journal of Medicine 360(3), 268-279.

Gazvani R. Templeton A. Peritoneal environment, cytokines and angiogenesis in the pathophysiology of endometriosis. Reproduction 2002; 123(2): 217-26.

Kyama C et al. Potential involvement of the immune system in the development of endometriosis. Reproductive Biology and Endocrinology 2003 1; 123.

Johnson N, Farquhar C, 2007. Endometriosis. Clinical Evidence. BMJ Publishing Group Ltd. www.clincalevidence.com

Lundeberg T, Lund I. Is there a role for acupuncture in endometriosis pain, or ‘endometrialgia’? Acupunct Med 2008; 26 (2): 94-110.

Managing endometriosis. Drug & Therapeutics Bulletin 1999; 37: 25-32.

Orl E et al. The peritoneal environment in endometriosis. Human Reproduction Update 1996; 2: 385-98.

RCOG, 2006. The investigation and management of endometriosis. Royal College of Obstetricians and Gynaecologists. www.rcog.org.uk

Rock JA, Markham SM. Pathogenesis of endometriosis. Lancet 1992; 340:1264-7.

Seli E et al. Pathogenesis of endometriosis. Obstet Gynecol Clin North Am 2003; 30: 41-61.

How acupuncture can help

In general, acupuncture is believed to stimulate the nervous system and cause the release of neurochemical messenger molecules. The resulting biochemical changes influence the body’s homeostatic mechanisms, thus promoting physical and emotional well-being. Stimulation of certain acupuncture points has been shown to affect areas of the brain that are known to reduce sensitivity to pain and stress (Wu 1999).

There is preliminary evidence to support acupuncture as an effective treatment for endometriosis, with one small sham controlled trial (Wayne 2008) and a few comparative studies against Western medication (Yan 2008, Xia 2006, Sun 2006), though further research is needed to confirm this.

It has been shown that acupuncture treatment may specifically be of benefit in people with endometriosis by:

  • providing pain relief – by stimulating nerves located in muscles and other tissues, acupuncture leads to release of endorphins and other neurohumoral factors, and changes the processing of pain in the brain and spinal cord (Zhao 2008, Han 2004, Zijlstra 2003, Pomeranz 1987).

reducing inflammation – by promoting release of vascular and immunomodulatory factors Kavoussi 2007, Zijlstra 2003).
regulating levels of prostaglandins (Jin 2009)

Polycystic ovarian syndrome (PCOS)

Polycystic ovarian syndrome (PCOS) is the most common female endocrine disorder. Up to one-third of women in the UK have polycystic ovaries (i.e. 10 or more follicles per ovary detected on ultrasound), and around a third of these are thought to have the syndrome.(DTB 2001) PCOS is strongly associated with hyperandrogenism, ovulatory dysfunction and obesity.(Stener-Victorin 2008) The syndrome also increases the risk for metabolic disturbances such as hyperinsulinaemia and insulin resistance, which can lead to type 2 diabetes, hypertension and an increased likelihood of developing cardiovascular risk factors and impaired mental health later in life.(Stener-Victorin 2008)

Despite extensive research, little is known about the aetiology of PCOS, but the syndrome is associated with peripheral and central factors that influence sympathetic nerve activity.(Stener-Victorin 2008) Thus, the sympathetic nervous system may be an important factor in the development and maintenance of PCOS.

Many women with PCOS require prolonged treatment. Polycystic ovarian syndrome (PCOS) is characterised by the clinical signs of oligo-amenorrhoea (infrequent or very light menstruation), infertility (failure to conceive), acne, male patterned baldness and hirsutism (excessive hair growth). The current conventional medical treatments for women with PCOS are prescription medications, surgery, and lifestyle changes aimed at controlling symptoms.

References

Stener-Victorin E et al. Acupuncture in polycystic ovary syndrome: Current experimental and clinical evidence. Journal of Neuroendocrinology 2008; 20: 290-8.

Tackling polycystic ovary syndrome. DTB 2001; 39: 1-3

How acupuncture can help

This Factsheet focuses on the evidence for acupuncture in the treatment of PCOS. There are also Factsheets on Anxiety, Depression, Female Fertility, Infertility ART, Obesity, Stress and Type 2 Diabetes, which may have relevant information related to symptoms and conditions associated with PCOS.

Two systematic reviews by the same author (Lim 2010, 2011) of acupuncture for PCOS have drawn conflicting conclusions. One found no truly randomised controlled trials of acupuncture for PCOS and, while it found non-randomised studies that suggested acupuncture was associated with a low adverse events rate and no increased risk of multiple pregnancies, the reviewers concluded that properly designed RCTs are needed before a conclusive statement can be drawn to support the use of acupuncture in the management of PCOS.(Lim 2011) The other review concluded that acupuncture is a safe and effective treatment for PCOS, and may have a role: increasing blood flow to the ovaries, reducing ovarian volume and the number of ovarian cysts, controlling hyperglycaemia by increasing insulin sensitivity and decreasing blood glucose and insulin levels, reducing cortisol levels and assisting in weight loss and anorexia.(Lim 2010) Several randomised controlled trials have been published since the systematic reviews. One trial found that acupuncture can improve the clinical pregnancy rate in patients with PCOS undergoing IVF-ET.(Cui 2011) Another found that abdominal acupuncture treatment can improve the endocrine and metabolic function of patients with obesity-type PCOS.(Lai 2010) A third found low-frequency electroacupuncture and physical exercise improved hyperandrogenism and menstrual frequency more effectively than no intervention in women with PCOS, and that it was superior to physical exercise.(Jedel 2011) Another recent study did not find a difference between ‘real’ and sham acupuncture protocols for women with PCOS.(Pastore 2011), but this may be due to sham acupuncture being an active treatment rather than a placebo (Lundeberg 2009).

In general, acupuncture is believed to stimulate the nervous system and cause the release of neurochemical messenger molecules. The resulting biochemical changes influence the body’s homeostatic mechanisms, thus promoting physical and emotional well-being.

Research has shown that acupuncture treatment may specifically help with symptoms of PCOS by:

  • impacting on beta-endorphin production, which may affect gonadotropin-releasing hormone (GnRH) secretion (Lim 2010; Stener-Victorin 2009; Feng 2009; Manneras 2009);
  • a regulatory effect on follicle stimulation hormone (FSH), luteinising hormone ( LH) and androgens (Lim 2010; Feng 2009);
  • modulating the activity of the sympathetic nervous system and improving blood flow to the ovaries (Stener-Victorin 2006, 2009);
  • regulating steroid hormone/peptide receptors (Feng 2012);
  • downregulating the expressions of serum levels of testosterone and oestradiol (Zang 2009);
  • controlling hyperglycaemia by increasing insulin sensitivity and decreasing blood glucose and insulin levels (Lim 2010);
  • acting on areas of the brain known to reduce sensitivity to pain and stress, as well as promoting relaxation and deactivating the ‘analytical’ brain, which is responsible for anxiety and worry (Hui 2010; Hui 2009);
  • increasing the release of adenosine, which has antinociceptive properties (Goldman 2010), and;
  • reducing inflammation, by promoting release of vascular and immunomodulatory factors (Kavoussi 2007).

Dysmenorrhoea

Dysmenorrhoea is painful cramps originating in the uterus just prior to or during menstruation. It can be primary (i.e. without any organic pathology) or secondary (i.e. associated with a pathological condition, such as endometriosis or ovarian cysts). The pain usually lasts between 8 and 72 hours.(Fraser 1992)

Adolescent girls are more likely than older women to have primary dysmenorrhoea because the condition can get better with age. Secondary dysmenorrhoea tends to be less common in adolescents, as onset of causative conditions may not have occurred yet. Estimates suggest that around 25-50% of adult women and about 75% of adolescents experience pain with menstruation, and some 5-20% report severe pain that prevents them from carrying on with their usual activities.(Zondervan 1998; Harlow 2004) The longer the mean duration of menstruation the more severe the dysmenorrhoea. Also, younger age at menarche and cigarette smoking have been associated with dysmenorrhoea.(Harlow 1996; Sundell 1990)

Conventional treatment is aimed at relieving pain and includes NSAIDs, the oral contraceptive pill, depo-medroxyprogesterone acetate, levonorgestrel-releasing intrauterine device, danazol and leuprolide acetate.

References

Fraser I. Prostaglandins, prostaglandin inhibitors and their roles in gynaecological disorders. Bailliere’s Clinical Obstet Gynaecol 1992;6:829-57.

Harlow SD, Campbell OM. Epidemiology of menstrual disorders in developing countries: a systematic review. BJOG 2004;111:6-16.

Harlow SD, Park M. A longitudinal study of risk factors for the occurrence, duration and severity of menstrual cramps in a cohort of college women. Br J Obstet Gynaecol 1996;103:1134-42.

Sundell G et al. Factors influencing the prevalence and severity of dysmenorrhoea in young women. Br J Obstet Gynaecol 1990;97:588-94.

Zondervan KT et al. The prevalence of chronic pelvic pain in the United Kingdom: a systematic review. Br J Obstet Gynaecol 1998;105:93-9.

How acupuncture can help

Recent systematic reviews of randomised controlled trials (RCTs) found that both acupuncture (Cho 2010a) and acupressure (Cho 2010b) are effective for primary dysmenorrhoea, providing significantly more pain relief than pharmacological treatments. Comparisons of acupuncture with sham acupuncture produced variable results and no significant difference overall (Cho 2010a). This is consistent with the viewpoint that sham controls are active interventions, not placebos, providing unreliable results with a tendency to underestimate acupuncture’s effects (Lundeburg 2009; Sherman 2009). Two earlier systematic reviews (Yang 2008; Proctor 2002) found a lack of high quality trials on acupuncture for dysmenorrhoea and so could not draw firm conclusions. Since then there have been further RCTs, especially from China (Wong 2010; Chen 2010; Zhu 2010; Wang 2009), hence the stronger conclusions in the 2010 reviews. The most compelling evidence comes from a large, high quality German trial that also found acupuncture to be cost-effective (Witt 2008). Also see our other factsheets on Premenstrual syndrome and Endometriosis. For other gynaecological conditions the research base is scanty (Smith 2010). For example, a systematic review of trials on acupuncture for fibroids found no trials that fit their inclusion criteria (Zhang 2010). (see Table overleaf)

Acupuncture may help reduce symptoms of dysmenorrhoea by:

  • regulating neuroendocrine activities and the related receptor expression of the hypothalamus-pituitary-ovary axis (Liu 2009; Yang 2008)
  • increasing nitric oxide levels, which relaxes smooth muscle and hence may inhibit uterine contractions (Wang 2009)
  • increasing relaxation and reducing tension (Samuels 2008). Acupuncture can alter the brain’s mood chemistry, reducing serotonin levels (Zhou 2008) and increasing endorphins (Han, 2004) and neuropeptide Y levels (Lee 2009), which can help to combat negative affective states
  • stimulating nerves located in muscles and other tissues, which leads to release of endorphins and other neurohumoral factors, and changes the processing of pain in the brain and spinal cord (Pomeranz, 1987; Zijlstra 2003; Cheng 2009);
  • reducing inflammation, by promoting release of vascular and immunomodulatory factors (Zijlstra 2003; Kavoussi 2007)

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