Alternative Medicine and Female Infertility

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Hey-Joo Kang, Pak Chung and Raymond Chang Acupuncture

Acupuncture is a vital therapeutic modality in traditional Chinese Medicine and its use can be traced back for centuries. The theory behind acupuncture is based upon the premise that there are patterns of energy flow, or Qi, through the body, which are essential for health. When a disease state exists, the flow of Qi is interrupted and its correction will assist in the healing process. Acupuncture can correct imbalances of flow at identifiable points close to the skin. The flow of Qi is based upon a meridian system of vital channels. The meridians consist of 20 channels interconnected by about 400 acupoints. These acupoints correspond to specific areas on the surface of the body, which demonstrate higher electrical conductance, thought to be due to the increased density of gap junctions along cell borders. These gap junctions serve as "sinks," or converging points for electromagnetic fields. In addition, a higher metabolic rate, temperature, and calcium ion concentration are also observed at these points.

The role of acupuncture in reproductive endocrinology is based upon a more modern and scientific approach that has begun to emerge in the past two decades. A review on acupuncture and female infertility suggested possible etiologies why acupuncture may improve female fertility. Acupuncture has been shown to induce a rise in p-endorphin levels that persists for up to 24 hours after treatment. Beta-endorphin is derived from its precursor protein, pro-opiomelanocortin (POMC), which is present in abundant amounts in neuronal cells of the arcuate nucleus of the hypothalamus, pituitary, medulla, and in peripheral tissues including intestines and ovaries. POMC cleaves to form adrenocorticotropic hormone and p-lipoprotein. Cleavage of p-lipoprotein results in the formation of neuropeptides including p-endorphin.

Endogenous opioid/neuropeptides are believed to influence the menstrual cycle by their actions on gonadotropin releasing hormone (GnRH) secretion. The close proximity of the hypothalamic GnRH pulse generator and p-endorphin center within the arcuate nucleus allows neuropeptides to influence GnRH secretion and, in turn, play a role in ovulatory function. p-endorphin acts to curtail the release of GnRH and blunt the effects of other neuropeptides that are excitatory to the hypothalamus. The role of these opioid peptides has also been implicated in the initiation of the midcycle luteinizing hormone (LH) surge in normal ovulatory women. In fact, the levels of p-endorphin in ovarian follicular fluid of ovulatory women are higher than levels in circulating plasma. Levels of p-endorphin are highest in the preovula-tory follicle, compared to other times in the menstrual cycle.

Since acupuncture treatment impacts p-endorphin levels, which in turn affects GnRH secretion and the menstrual cycle, it is logical to hypothesize that acupuncture may influence ovulation and fertility. Animal studies have revealed that acupuncture treatment normalized GnRH secretion and affected peripheral gonadotropin levels. In human data, various authors have shown that in normally ovulatory or even anovulatory women, acupuncture also influenced plasma levels of follicle stimulating hormone (FSH), LH and estradiol.

The use of electroacupuncture for ovulation induction in anovulatory women with polycystic ovarian syndrome has been reported. The percentage of ovulatory cycles in all subjects was shown to improve from 15% to 66% up to three months after treatment. Responsive patients had significantly lower body mass index, waist-to-hip circumference ratio, serum testosterone concentration, serum testosterone/sex hormone binding globulin ratio, and serum basal insulin level. Therefore, in these selected patients with polycystic ovarian syndrome, acupuncture could be utilized as an alternative or adjunct to conventional pharmacological ovulation induction.

Besides the central modulation of the hypothalamic-pituitary-ovarian axis, the effect of acupuncture on the autonomic nervous system has been described. Acupuncture induces long lasting cardiovascular effects via actions that are sympatho-inhibitory. Sympathetic nerve activity, as measured by norepinephrine levels, skin temperature, blood pressure and pain tolerance threshold, is noted to decrease after acupuncture.

Endometrial thickness, morphology, and uterine artery blood flow have been implicated as crucial parameters for implantation success of human embryos. Despite conflicting results in the utilization of these parameters to predict outcome of in vitro fertilization cycles, it is generally assumed that adequate endometrial thickness with a normal pattern is required to optimize pregnancy rates. Since endome-trial thickness correlates with the adequacy of uterine artery blood flow via its central sympatho-inhibitory effect, acupuncture may reduce uterine artery impedance and therefore increase blood flow to the uterus. Pulsatility indices have been found to be reduced, hence, blood flow increased, following eight consecutive treatments of electroacupuncture. This effect was believed to be caused by a central inhibition of sympathetic activity.

To date, there have been few well-designed studies on the potential impact of acupuncture on infertility treatment outcome. One of the most frequently quoted studies is a prospective study by Paulus et al, who evaluated the effect of acupuncture on pregnancy rate in 160 women undergoing in vitro fertilization. Acupuncture was performed in half of the patients 25 minutes before and after embryo transfer while the control group did not receive any acupuncture treatment. Clinical pregnancies were found to be higher in the acupuncture group than the control group (42.5% vs. 26.3%, respectively). The exact mechanism accounting for this result is not known.

Other than its potential central role in affecting hypothalamic pituitary ovarian function and peripheral role in improving uterine blood flow and implantation function, acupuncture has been definitively shown to reduce stress and anxiety through its sympatho-inhibitory property. Undoubtedly, infertility is stress inducing and anxiety provoking. The use of acupuncture to reduce stress is a very viable option when couples undergo the stringent process of evaluation and treatment of infertility. Compared to the conventional administration of antidepressants and anxiolytic drugs, side effects of which are largely unknown on the outcome of infertility treatment, acupuncture presents a relatively benign and simple alternative.

Herbal Treatments

Tonic herbs are generally nontoxic—the safest of all herbs—and usually can be taken on a long-term basis. They can be administered either individually or in compound remedies in which several herbs work together synergistically to strengthen and tone your body. Tonics can be taken as capsules, tinctures, decoctions, infusion or tea. Tonic herbs are commonly thought to enhance female fertility. They are often used in traditional Chinese medicine and by holistic and alternative medical practitioners to boost or balance hormone production in women. It should be cautioned that the mechanism of action and efficacy of many of these herbs have not been substantiated by conventional Western standards.

Chaste berry (vitex agnus-castus)—This European herb is one of the more well-established Western herbs relating to female hormone regulation. It is thought that the sites of action of chaste berry are the hypothalamus and pituitary gland, and that chaste berry increases LH secretion and regulates the release of FSH. Serum progesterone level has been observed to increase with its consumption. The use of chaste berry has been implicated in women with short luteal phase or documented luteal phase defect. Whether this reversal of luteal phase defect is due to improved folliculogenesis or ovulatory event is largely unknown. Chaste berry also inhibits prolactin release and may have a role in the setting of hyperprolactinemia-related menstrual irregularities and infertility. It is also thought to soothe premenstrual tension. To be able to derive the potential benefits of chaste berry, it may have to be taken for three to four months.

Other commonly used herbs which have been anecdotally shown to be benefited for female fertility include Black Cohosh, or Cimicifuga racemosa, Red Clover, or Trifolium pretense, and Dong Quai, or Angelica sinensis.

The use of herbs during infertility treatment, however, has to be carefully considered. Most of the commonly used herbs for fertility enhancement contain a fair amount of plant estrogens or phytoestrogens. Therefore, the decision on medication dosage adjustment during treatment, such as in vitro fertilization, which normally hinges upon estrogen levels, may be impacted by the ingestion of these herbs.

Vitamins and Dietary Supplements

Many vitamins have been implicated in promoting human reproduction. Ascorbic acid (vitamin C) has long been associated with fertility through three of its principal functions, namely promotion of collagen synthesis, hormone production, and protection of cells via production of free radicals. There is evidence that both ovary and testis accumulate ascorbic acid, and both gonads show cycles of tissue remodeling and of steroid secretion that is ascorbate-dependent. One study on in vitro fertilization suggests that the supply of ascorbic acid to the ovary might be a rate-determining factor in the ability of the preovulatory follicle to respond to gonadotropin stimulation. Ascorbic acid may also prevent gametes from damage by free radicals during fertilization. Further research is required to study the exact mechanism of action of ascorbic acid in gonadal physiology and fertility.

Vitamin B12 (cobalamine) deficiency has been reported as an etiology in infertility. Pernicious anemia, though rarely encountered in women of childbearing age in developing countries, has been associated with oligo- to anovulation. Once treated, conception was noted to quickly occur through resumption of ovulation.

Vitamin B6 (pyridoxine) and vitamin E have been shown to be vital to human reproduction. Women deficient in these vitamins demonstrate return of normal menstrual function and fertility upon replacement. Vitamin B6 has been used in the treatment of premenstrual symptoms, but whether symptoms are actually due to primary insufficiency is unclear.

There are many dietary supplements which have been associated with improving female fertility: folic acid, magnesium, selenium, iron and zinc. In a study investigating the effects of caffeine on conception, women drinking green tea (as opposed to other caffeinated beverages) were found to approximately double their odds of conception, though the design of the study did not control for several potential variables.

One supplement, L-arginine, an amino acid, was used as an adjunct in poor responders during in vitro fertilization treatment. Believed to be able to improve circulation to the reproductive organs, including the endometrium, L-arginine may play a role in enhancing oocyte development and implantation of the embryo. Battaglia et al studied uterine and follicular Doppler flow in response to L-arginine treatment during in vitro fertilization treatment in poor responders. The L-arginine treatment group showed multiple benefits, including improved Doppler flow rates, a lower cancellation rate and an increased number of oocytes collected and embryos transferred. Out of 17 women supplemented with L-arginine, 3 conceived as compared to 0 of 17 in the nonsupplemented group.

Many studies have attempted to show particular vitamins or dietary supplements may be involved in regulation or improvement of female fertility are small and not necessarily randomized or placebo-controlled. Given the benign nature of these supplements (in appropriate dosages) and lack of adverse effects in general, it seems reasonable to recommend that women interested in fertility evaluate their own nutritional needs and personalize inclusion of these elements in their diet or as daily supplements. More studies are needed to establish their exact role in reproduction.

Mind/Body Techniques

Infertile women most often turn to modern western medicine to increase their chances of conception. However medical treatments may only represent part of the solution. Some believe that adding mind/body techniques may help women cope with the mental and physical stress associated with the evaluation and treatment process. Although it is difficult to quantify the impact of stress on the outcome of infertility treatment, mind/body programs have been positively shown to improve handling of stress, reduce anxiety, change one's attitude and outlook, and banish negative thoughts. These attributes will benefit infertile women in regaining control of their lives and improve a couple's relationship during their struggle to conceive. In one well-known study done in Boston on 284 infertile women, stress level was significantly reduced, and 42% became pregnant within 6 months of completing the mind/body program.

Key Points

Alternative medicine encompasses various approaches to female fertility. Acupuncture has been used for thousands of years in traditional Chinese medicine. Its benefits have long been recognized to improve health, decrease stress, and more recently, potentially improve reproductive capabilities. Herbal treatment has also been an integral part of alternative medicine to treat menstrual and ovulatory

dysfunction, and indirectly infertility. Certain vitamins and dietary supplements are vital in the metabolism and health of reproductive cells and organs. Last but not least, mind/body programs and psychological counseling will serve to relieve stress and anxiety associated with infertility. Western medicine is usually quite targeted at the 'diseased' organ whereas the approach in alternative medicine is toward the entire body. When the overall well being of the individual is cared for, improvement in reproductive function should follow. We have only begun to correlate the beneficial effects of alternative approaches in infertility treatment with western biologic plausibility.

Suggested Reading

1. Chang R, Chung P, Rosenwaks Z. Role of acupuncture in the treatment of female infertility. Fertil Steril 2002; 78:1149-1153.

2. Paulus W, Zhang M, Strehler E et al. Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy. Fertil Steril 2002; 77:721-724.

3. Stener-Victorin E, Waldenstrom U, Andersson SA et al. Reduction of blood flow impedance on the uterine arteries of infertile women with electro-acupuncture. Hum Reprod 1996; 11:1314-7.

4. Hardy M. Herbs of special interest to women. J Am Pharm Assoc 2000; 40(2):234-42.

5. Luck MR, Jeyaseelan I, Scholes RA. Ascorbic acid and fertility. Biol Reprod 1995; 52:262-266.

6. Battaglia C, Salvatori M, Maxia N et al. Adjuvant L-arginine treatment for in vitro fertilization in poor responder patients. Hum Reprod 1999; 14:1690-1697.

7. Westphal LM, Lake Polan M, Sontag Trant A et al. A nutritional supplement for improving fertility in women. J Reprod Med 2004; 49:289-293.

8. Domar AS, Seibel MM, Benson H. The mind/body program for infertility: A new behavioral treatment approach for women with infertility. Fertil Steril 1990; 53:246-9.

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