Infertility

A number of studies have confirmed the efficacy of acupuncture in treating infertility. A noted German study demonstrated that a test group receiving acupuncture in conjunction with IVF achieved a 42% clinical pregnancy rate, whereas the control group that did not receive acupuncture had a 26% pregnancy rate. This study utilized just a single acupuncture session per patient, shortly before or after the transfer of embryos.

Another study demonstrated a 60% success rate when combining IVF with Chinese herbal medicine and acupuncture. Perhaps more importantly, both of these alternative modalities were found to significantly reduce the risk of miscarriage during the course of pregnancy.

One clinical study employing the use of ultrasound observed a marked shift in the color of womens’ ovaries from one that is cloudy to one of a clear hue after acupuncture treatment. Furthermore, the follicles were found to double in number, the lining of the uterus to thicken, and the number of embryos to increase. This test group experienced less side effects from herbal medicine and more importantly, were more at ease.

Studies involving male patients have demonstrated a profound increase in semen quality and the amount of sperm produced following treatment with acupuncture and herbal medicine. Male patients receiving treatment from our clinic in particular, have reported positive, robust sexual benefits.

In 1999, clinical researchers reported that inserting acupuncture needles into specific body points triggers the production of endorphins. In another study, higher levels of endorphins were found in cerebrospinal fluid after patients underwent acupuncture. Endorphins have been shown to reduce anxiety. The production of encorphines also indirectly support strenthing reproductive organs.

The Benefits of Acupuncture and Chinese Herbal Medicine

• Improve the function of the ovaries to produce better quality eggs — Acupuncture and Chinese medicine help to improve ovarian function, allowing for the development of better quality eggs and strong, healthy embryos.
• Regulate the hormones to produce a larger number of follicles — Based upon clinical experience, Chinese medicine can help the ovaries at least double the number of follicles as well as significantly enhance the embryo’s quality and quantity.
• A number of previous studies have demonstrated that acupuncture does influence the activity of the autonomic nervous system. Proper balance of both branches of the Sympathetic and Parasympathetic nervous system is crucial for optimal functioning of reproductive organs, blood flow circulation, hormone balance, immune system, and regulation of menstrual cycle.
• Acupuncture has been reported to promote the circulation of blood in the pelvic cavity and to improve ovarian function (Chang et al. 2000). Research indicates that increased blood flow to the uterus helps the development of follicles, the implantation of the embryo and increases the thickness of the uterine lining.

*Acupuncture has been shown to regulate hormone levels by moderating the release of beta-endorphin levels in the brain, which improves the release of gonadatrophin releasing hormone by the hypothalamus, follicle stimulating hormone from the pituitary gland, and estrogen and progesterone levels from the ovary.

*Acupuncture has been speculated to moderate cyclooxygenase and prostaglandin levels in the uterus, reducing uterine motility to improve implantation rates.

• Relax the patient and reduce their stress — Many patients using IVF drugs experience side effects and high levels of stress associated with trying to get pregnant. Chinese medicine is extremely helpful in reducing stress and alleviating side effects, which helps the patient relax and be more at ease. Stress hormones such as catecholamines (adrenalin, noradrenalin, and dopamine) and hypothalamic-pituitary-adrenal axis interact with hormones which are responsible for normal ovulatory cycles. Furthermore, some hormones that are released during times of stress can cause the uterus to contract and negatively interact with immune cells, both of which will interfere with proper implantation (Gallinelli et al. 2001; Sher et al. 1998).
• Lessen the side effects of drugs used in IVF — Acupuncture and Chinese medicine can help the ovaries respond better to the stimulating drugs by producing more follicles and good equality eggs.
• Improve semen to create better quality and quantity of embryos — Sperm maturation is a process taking between 70-90 days. It is important for male patients to prepare for IVF during this period. It is beneficial that the male receive acupuncture and Chinese herbal medicine for at least three months prior to starting th IVF procedure. A recent trial published in Fertility and Sterility has shown how effective acupuncture can be in the treatment of infertility, leading to significant increases in the number of normal sperm and significant reductions in structural defects at the same time. Also, Chinese herbal medicine can help male patients improve the quality and quantity of sperm and the semen, too. In doing so, the health of the embryo improves and assists more secure implantation.
• Strengthen the immune system and decrease chances of miscarriage — Approximately half of chemical pregnancies result in miscarriage. Therefore, one of the key treatment strategies is to strengthen the patient’s immune system through Acupuncture and Chinese herbs. Once the embryo has been fertilized and implanted into the uterus, it is extremely important to prevent miscarriage with IVF patients. Female patients that are 40 years old or older, experience a miscarriage rate of nearly 50 % with IVF alone. However, with the help of Chinese medicine, the rate of miscarriage can be significantly reduced and the pregnancy can be supported to reach full term.
• While some patients respond to acupuncture quickly, acupuncture does not work overnight. Most patients require a series of ongoing treatments over one month to a year. The recommended treatment schedule is based upon consideration of a variety of factors in each individual case. In many cases, we recommend that the patient start acupuncture and chinese herbal treatment at least 3 months prior to the commencement of the IVF cycle and the patient continue 2 times a week until the day of the transfer.

Recent Research on Acupuncture & IVF

In an article published by W. Paulus, M. Zhang, I. El-Danasouri, E. Strehler and K. Sterzik titled,” Influence of Acupuncture on the Pregnancy Rate in Patients Who Undergo Assisted Reproduction Therapy,” appearing in the April 2002 issue of Fertility and Sterility, German researchers announced that they had increased the success rate by nearly 50 % in women undergoing in vitro fertilization. The researchers, led by Dr. Wolfgang E. Paulus and colleagues at the Christian-Lauritzen-Institut in Ulm, Germany, said they do not know why acupuncture works and plan to conduct more studies. “Acupuncture seems to be a useful tool for improving pregnancy rate after assisted reproductive techniques.” they wrote. “The analysis shows that the pregnancy rate for the acupuncture group is considerably higher than for the control group ( 42.5% versus 26.3%),” they wrote.

Working with a team at the Department of Chinese Medicine at Tongji Hospital in Wuhan, China, Paulus and colleagues tested 160 women undergoing in vitro fertilization. Half received the standard in vitro fertilization, while half were given acupuncture treatments before and after. “We chose acupuncture points that relax the uterus according to the principles of traditional Chinese medicine,” they wrote. They said acupuncture can affect the autonomic nervous system-involved in the control of muscles and glands-and thus, theoretically, should make the lining of the uterus more receptive to receiving an embryo.

According to the report, about 26% of women who did not receive acupuncture became pregnant, compared with nearly 43% of women who underwent the traditional Chinese therapy before and after embryo transfer. There were no differences in age, number of transferred embryos, or the number of previous cycles between the two groups of patients. In this study, women received acupuncture along the spleen and stomach channels in an attempt to relax the uterus and improve the flow of energy to this region. They also received acupuncture needles in their ears to stabilize the endocrine system.

“The results demonstrate that acupuncture therapy improves pregnancy rate,” concluded Dr. Paulus and colleagues” However, more research is needed to determine whether the higher pregnancy rate among women receiving acupuncture was due to actual physiological or psychological effects,” they added. “If these findings are confirmed, they may help us improve the odds for our IVF patients,” Dr. Sandra Carson, president-elect of the American Society of Reproductive Medicine, said in a prepared statement after the publication of this study in Fertility and Sterility.

Article from Acupuncture Today (October, 2005, Vol 06, Issue 10) Abstract of the Article

In many cultures, Women are unfairly blamed for the inability of a sexually active couple to conceive. In reality, men suffer from infertility issues just as frequently as women. According to statistics from the National Infertility Association (an organization also known as RESOLVE), between 35% and 40% of infertility problems among couples are actually caused by male conditions. Several factors may be responsible for male infertility, including low sperm count, abnormal sperm shape and size, and reduced motility. Lifestyle, genetics, and physiological changes can also raise or lower male fertility levels, and can significantly affect a man’s ability to produce offspring.

Previous research has shown that acupuncture can improve fertility levels in women. Fewer studies on male infertility have been conducted, although evidence suggests that acupuncture can have an effect on sperm production and quality, without causing any changes in behavior or sexual desire. A recent trial published in Fertility and Sterility has shown effectiveness of acupuncture in the treatment of the infertility.

Semen samples were collected from each of the men after a 3-day period of sexual abstinence. Two samples were collected from each patient: One obtained the day before treatment began, the other after the last acupuncture treatment. Samples from the treatment group were then randomized with semen samples from 12 untreated control patients and analyzed. Compared to the control group, motility levels increased significantly in semen samples in the men receiving acupuncture. The number and percentage of healthy sperm also increased dramatically in the acupuncture patients. After 10 sessions of treatments, the median percentage of healthy sperm increased more than four-fold. In addition, significant changes in sperm structure and quality were seen in the samples from the acupuncture group. Before treatment, only 22.5% of the sperm samples in the acupuncture patients contained normal-shaped acrosomes, a cap-like structure that develops over the anterior portion of a sperm cell’s nucleus. After treatment, the median percentage of normal acrosome shapes showed a “statistically significant improvement” to 38.5%.

Similarly, the percentage of sperm with a normal axoneme pattern increased significantly among men receiving acupuncture. (The Axoneme is a microscopic structure that contains a series of tubules arranged in a distinct pattern, and is believed to aid in sperm motility.) While acupuncture appeared able to improve the overall quality and structural integrity of sperm, it was ineffective against some common sperm pathologies. Apoptosis levels (Programmed cell death) in sperm samples were reduced slightly, but not to a statistically significant degree. Median percentages of necrosis (unprogrammed cell death) and sperm immaturity also decreased slightly in the acupuncture group, but not to a level considered statistically significant. The authors concluded that despite the inability of acupuncture to significantly reduce some sperm abnormalities, the treatment could be used to improve overall sperm quality, leading to the possibility of increased fertility.

“In conjunction with ART or even for reaching natural fertility potential, acupuncture treatment is a simple, noninvasive method that can improve sperm quality,” the authors concluded. Further research is needed to demonstrate what stages and times in spermatogenesis are affected by acupuncture, and how acupuncture caused the physiologic changes in spermatogenesis.”

CHINESE HERBS AND FERTILITY

by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon. Chinese herbs have a long history of use in aiding fertility. Records indicating herbal treatment of infertility and miscarriage date back to 200 A.D., including mention of formulas that are still used for those purposes today, in the famous medical text Shang Han Lun. The first book devoted solely to gynecology and obstetrics, The Complete Book of Effective Prescriptions for Diseases of Women, was published in 1237 A.D. In modern China, herbs are used to treat infertility in both men and women and the results of large scale clinical trials are reported in Chinese medical journals; these results have been abstracted in English by a research group in Hong Kong since 1986, and translations of whole articles are obtained, by request, from several translators.

THE HERBS USED TO AID FERTILITY

No individual herb is considered especially useful for promoting fertility. Rather, more than 150 different herbs, usually given in complex formulas comprised of 15 or more ingredients according to practicioners, are used in the treatment of infertility with the purpose of correcting a functional or organic problem that caused infertility. The design of the formulas has varied somewhat over the centuries, based on prevailing theories and available resources, and individual practitioners have a preference for particular herbs, thus accounting for some of the variations among formulas that are recommended. However, differences among individuals being treated accounts for the greatest variation in the selection of herbs and formulas to be used. There are some “exotic” materials that are frequently found in fertility formulas, such as deer antler and sea horse, but the prominent materials are derived from roots, barks, leaves, flowers, and fruits. Formulas for men and for women tend to be different, but there is considerable overlap in the ingredients used.

HOW THE HERBS ARE ACQUIRED AND CONSUMED

In China, a number of fertility formulas can be purchased off the shelf in public pharmacies, and for uncomplicated cases, this is often adequate. However most men and women in the Orient are treated for persistent infertility by obtaining prescriptions from a doctor who is expert in Chinese herbs. In the U.S., it is uncommon to find fertility-promoting formulas in stores or other outlets; rather, they are prescribed by acupuncturists, naturopaths, or medical doctors who are familiar with Chinese herbal medicine. Depending on the circumstances, one may be asked to ingest herbs in the form of pills, tablets, granules, or decoctions (teas). Some of the treatment plans involve using a single herb combination regularly, while others suggest using two, or even three, different formulas at different times of the menstrual cycle. All of these means can be effective, so long as the correct formula and correct dosage are used for an adequate period of time.

THE SUCCESS RATE FOR CHINESE HERB TREATMENTS

Although the outcome for any given individual cannot be predicted, the clinical studies conducted in China indicate that about 70% of all cases of infertility (male and female) treated by Chinese herbs resulted in pregnancy or restored fertility. Depending on the particular study and the types of infertility treated, success rates ranged from about 50% up to more than 90%. Included in these statistics are cases of infertility involving obstruction of the fallopian tubes, amenorrhea, absent ovulation, endometriosis, uterine fibroids, low sperm count, nonliquification of semen, and other causes. In China, due to the greater experience with using herbs, the ability to directly integrate traditional and modern methods of therapy, and the willingness of individuals to consume relatively large doses of herbs, the success rates are probably somewhat higher than can be achieved in the U.S. at the present time. Nonetheless, U.S. practitioners have had many experiences of success in treating infertility.

DURATION OF TREATMENT TO ATTAIN FERTILITY

In the Chinese clinical studies, daily or periodic use of herbs usually resulted in restored fertility within three to six months. Many Chinese doctors feel that if pregnancy is not achieved within about eight to twelve months, then it is unlikely that the treatment will be successful with continued attempts. In Japan, where doctors give lower dosages of herbs and are restricted to using a smaller range of herbs, treatment time is usually longer: from six to fifteen months. In the U.S., nearly the full range of Chinese herb materials are accessible, but the dosage to be used is usually lower than in China; as a result, it is estimated that pregnancy can be achieved within six to twelve months. It must be remembered, however, that approximately one-third of infertility cases may fail to respond to all reasonable attempts. One advantage of the Chinese herbal approach is that even if pregnancy does not occur, benefits to health can be attained because the herbs address imbalances that affect other aspects of health besides infertility.

SAFETY OF THE HERBS

Chinese herbs are used in the U.S. as traditional foods and not as drugs. As such, there has been no formal testing of either the safety or efficacy of any of the individual herbs or formulas. The Chinese have had long experience using these herbs; from all informal reports and clinical studies, the Chinese claim that the herbs are not only safe to use, but that healthy children are usually born without any problems during delivery. However, it is important to recognize that the use of Chinese herbs is relatively new in the U.S. and that Americans today may have more stringent safety standards than the Chinese have had in the past. Therefore, one should pay attention to perceived adverse responses to the herbs. The Chinese herbs that are used in the U.S. are not overtly toxic, but there are a few possible adverse reactions which are rare and can usually be avoided by slight adjustment in formulation or method of administration. These reactions may include dizziness or headache, dry mouth, nausea, flatulence, or change in bowel conditions. If such reactions are not resolved naturally within about three days or if they are severe, the prescribing physician can make an appropriate adjustment. In any case, by discontinuing use of the herbs, any of these reactions will disappear promptly. Allergic reactions to herbs are rare, but if a person suffers from “environmental allergy syndrome,” then the herbs can also cause the same reactions as other materials encountered in the normal environment.

MECHANISM OF ACTION

The mechanism of action of the herbs is not known precisely, and undoubtedly varies according to the type of infertility problem being treated and the herb formula that is used. The traditional Chinese views are that infertility tends to arise from one or more of three prominent causes:
A “deficiency” syndrome prevents the hormonal system from properly influencing the sexual and reproductive functions. This is said to be a weakness of the “kidney and liver” which may influence various body functions producing symptoms such as frequent urination, weakness and aching of the back and legs, impotence, irregular menstruation, and difficulties with regulation of body temperature.
A “stagnancy” syndrome prevents the sexual and reproductive organs from functioning despite normal hormone levels and normal ability to respond to hormones. This is said to involve a stagnancy of “qi and blood,” which has the impact of restricting circulation to the tissues involved. Qi stagnation is often noted by tense muscles, restrained anger, and digestive disorders; Other symptoms that might arise include abdominal pain or bloating, chronic inflammation, and formation of lumps (including cysts and tumors). Blood stagnation often occurs following childbirth, surgery, injury, or severe infection and is typically noted when there is severe pain (such as dysmenorrhea), or hard swellings and obstructions; abnormal cell growth, including dysplasia and cancer, are thought to involve blood stagnation.
A “heat” syndrome, which causes the affected organs to function abnormally. Heat syndromes may be associated with an infection or inflammatory process. This type of syndrome can produce abnormal semen quality leading to male infertility, while gynecologic infections can maintain female infertility by blocking the passages, altering the mucous membrane conditions, or influencing the local temperature.
In each case, the purpose of the Chinese herbs is to rectify the underlying imbalance to restore normal functions. Western medicine can diagnose tubal blockage (which usually corresponds to blood stagnancy in Chinese medicine) and infection (which corresponds to heat syndromes of Chinese medicine) and in many cases can successfully treat these causes of infertility. However, Western medicine often fails to diagnose deficiency syndromes and most of the stagnancy syndromes. Therefore, the majority of Chinese herb formulas to be applied in the U.S. are those that counteract the deficiency (called tonics) and those that resolve the stagnancy (called regulators).

COMBINING CHINESE HERBS AND WESTERN THERAPIES

In China, the combined use of modern drugs or other Western medical techniques along with Chinese herbs is not uncommon; some doctors are trained in both methods, and Western and traditional doctors often work together in Chinese clinics and hospitals. When the modern methods are applied, the herb therapies do not usually need to be altered compared to cases where the herbs are used alone. Most of the cases of infertility successfully treated in China do not rely on techniques such as in vitro fertilization, which are quite expensive and have only a modest rate of success in the U.S. where the modern fertilization methods are most highly developed.

INFERTILITY PROBLEMS NOT OVERCOME BY USING CHINESE HERBS

It is not advisable to suggest that something simply cannot be accomplished in the field of health care (because there are almost always exceptions), but there are some areas where chances of success are considered quite low. Some women suffer from amenorrhea that is associated with a very low body fat content. This is apparently exacerbated by strenuous exercise (e.g., distance running). Changes in diet and exercise may be necessary with Chinese herbs or other therapeutic methods can be effective. In a few cases, a woman’s immune system will attack her husband’s sperm and thus make fertilization virtually impossible; this can not be overcome with Chinese herbs. People who are under very high levels of stress or who have multiple health problems may need to have these things addressed-partly with use of Chinese herbs-before a reasonably high chance of success can be expected in the specific treatment of infertility.

USE OF HERBS WHEN PREGNANCY OCCURS

The herbs for inducing fertility are usually discontinued once pregnancy is suspected or confirmed. In most cases, it is not necessary to use herbs during pregnancy. Women with a history of miscarriage or who are deemed at high risk for miscarriage (somewhat more common among women who have experienced prolonged infertility) may wish to take herbs that are traditionally used in such cases by Chinese women. Certain herbs can be used during pregnancy to enhance the health of the mother and to counteract symptoms of morning sickness. In addition, it is reported that labor can be made easier by proper application of herbs and acupuncture. Books on the subject of herbal health care for pregnancy and nursing can be traced back to such important works as A Precious Medical Book on Obstetrics for Home Use, published in 1184 A.D.

THREATENED MISCARRIAGE

Threatened miscarriage, if due to an imbalance in the mother’s system (but not if due to genetic problems with the fetus), can often be overcome with application of herbs and possible adjunct therapy with moxa or acupuncture. The method to be used and the procedures to follow should be discussed early in the pregnancy so that appropriate steps can be taken should bleeding, fetal agitation, or early contractions occur. It is important to note that most cases of early miscarriage (sometimes called spontaneous abortion) are not related to an imbalance in the mother’s system but are rather a natural and fairly common event, possibly due to a development problem of the embryo. Later in the pregnancy, weaknesses in the mother’s system or excessive fetal movement, become a more prominent factor. There is a particular herb formula which forms the basis of most treatments aimed at avoiding miscarriage-but the formula is intended to be used mainly as a daily preventive therapy rather than an emergency treatment. Extensive testing in the Orient indicates that the formula is safe to use and it appears highly effective. There are several modified versions of the formula are used to address specific concerns and are probably of equal safety and efficacy during the latter part of pregnancy.

Article from FERTILITY AND STERILITY® VOL. 78, NO. 6, DECEMBER 2002

Copyright ©2002 American Society for Reproductive Medicine
Published by Elsevier Science Inc., Printed on acid-free paper in U.S.A.
Role of acupuncture in the treatment of female infertility
Articles

Raymond Chang, M.D.[a,b] Pak H. Chung, M.D.[b] and Zev Rosenwaks, M.D.[c]

Objective: To review existing scientific rationale and clinical data in the utilization of acupuncture in the treatment of female infertility.

Design: A MEDLINE computer search was performed to identify relevant articles.

Result(s): Although the understanding of acupuncture is based on ancient medical theory, studies have suggested that certain effects of acupuncture are mediated through endogenous opioid peptides in the central nervous system, particularly ß-endorphin. Because these neuropeptides influence gonadotropin secretion through their action on GnRH, it is logical to hypothesize that acupuncture may impact on the menstrual cycle through these neuropeptides. Although studies of adequate design, sample size, and appropriate control on the use of acupuncture on ovulation induction are lacking, there is only one prospective randomized controlled study examining the efficacy of acupuncture in patients undergoing IVF. Besides its central effect, the sympathoinhibitory effects of acupuncture may impact on uterine blood flow.

Conclusion(s): Although the definitive role of acupuncture in the treatment of female infertility is yet to be established, its potential impact centrally on the hypothalamic-pituitary-ovarian axis and peripherally on the uterus needs to be systemically examined. Prospective randomized controlled studies are needed to evaluate the efficacy of acupuncture in the female fertility treatment. (Fertil Steril® 2002;78:1149-53. ©2002 by American Society for Reproductive Medicine.)

Acupuncture as a therapeutic intervention has been extensively studied and is increasingly practiced in the United States. A recent survey of acupuncture released by an NIH Consensus Development panel (1) indicated that although there are inherent problems of design, sample size, and appropriate controls in the acupuncture literature, promising data exist for the use of acupuncture in treating nausea and vomiting (2), postoperative pain (3-5), addiction (6-9), and general pain syndromes (10-12). As a medical technique, acupuncture has also been reported as an adjunct in the treatment of various gynecologic problems (13-15).

Although conventional treatment options for female infertility have been well established, there have been few systematic reviews of complementary or alternative approaches to the treatment of infertility. In light of an increasing trend in the use of complementary and alternative medicine (16) and common inquiry and utilization of such approaches by patients suffering from infertility, we intend to review the existing scientific rationale and clinical data based on which acupuncture may exert an influence on the outcome of female fertility.

In examining the potential usefulness of acupuncture in enhancing female fertility, it is appropriate first to give some theoretical background for acupuncture. Although the theory of acupuncture stems from underlying traditional Chinese medicine premises that would define etiologies for infertility in terms of energy disturbance of imbalances, or organ deficiencies and excesses, we intend to review the existing literature by examining modern medical aspects of the central and peripheral modes of action of acupuncture as they impact on the hypothalamic-pituitary-ovarian axis and the pelvic organs, respectively. Moreover, the effect of acupuncture on anxiety and stress and ensuing potential indirect effects on female fertility will also be discussed.

Background
Acupuncture is the manipulation of thin metallic needles inserted into anatomically defined locations on the body to affect bodily function. The US Food and Drug Administration has recently removed acupuncture needles from the category of experimental medical devices and now regulates them just like it does other devices, such as surgical scalpels and hypodermic needles, under good manufacturing practices and single-use standard of sterility (1).

The general theory of acupuncture is based on the premise that there are patterns of energy flow (Qi) through the body, which are essential for health. Disruption of this flow is believed to be responsible for disease. Acupuncture can correct imbalances of flow at identifiable points close to the skin.

According to the proposed international acupuncture nomenclature by The World Health Organization in 1991 (17), the meridian system consists of 20 meridians interconnecting about 400 acupoints. These acupoints correspond to specific areas on the surface of the body, which demonstrate higher electrical conductance because of the presence of higher density of gap junctions along cell borders. They act as converging points (or sinks) for electromagnetic fields. A higher metabolic rate, temperature, and calcium ion concentration, are also observed at these points. In principle, positive (anode) pulse stimulation of a point inhibits the organ function, whereas negative (cathode) pulse stimulation enhances that function (18). This forms the basis of electroacupuncture, which applies small electrical needles inserted in specific acupoints.

Effects of acupuncture on the hypothalamic-pituitary-ovarian axis and menstrual cycle
Although traditional Chinese medicine understanding of acupuncture is based on ancient medical theory, a modern and scientific neuroendocrine perspective has begun to evolve in the past two decades. Mayer et al. (19) first reported that acupuncture analgesia was induced through endorphin production and antagonized by the narcotic antagonist naloxone. Other studies similarly suggested that certain effects of acupuncture are mediated through the nervous system, within which ß-endorphin and other neuropeptides have been implicated (20-22).

Acupuncture was shown by Petti et al. (20) to cause a significant increase in ß-endorphin levels during treatment, which lasted for up to 24 hours. ß-endorphin is derived from its precursor protein pro-opiomelanocortin, 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 (23-25). Pro-opiomelanocortin cleaves to form adrenocorticotropic hormone and ß-lipoprotein. Further cleavage of ß-lipoprotein yields neuropeptides including ß-endorphin. Aleem et al. (26, 27) demonstrated the presence of immunoreactive ß-endorphin in follicular fluids of both normal and polycystic ovaries.

The influence on gonadotropin secretion and the menstrual cycle by endogenous opioid peptides is believed to be mediated by their action on GnRH secretion (28). The hypothalamic ß-endorphin center and the GnRH pulse generator, in fact, are both situated within the arcuate nucleus. Quigley et al. (29) first reported an increased opioid inhibition of LH secretion in hyperprolactinemic patients with pituitary microadenomas. Ching (30) and Orstead and Spics (31), respectively, showed that opioid peptides suppress GnRH release in rats and rabbits.

The role of these neuropeptides, including ß-endorphin, in the regulation of GnRH secretion in humans has recently been reviewed by Kalra et al. (32) and Pau and Spies (33). Rossmanith et al. (34) demonstrated the role of opioid peptides in the initiation of the mid-cycle LH surge in normal cycling women. Meanwhile, measurement of ß-endorphin in ovarian follicular fluid of healthy ovulatory women revealed much higher levels than that in circulating plasma (35). The highest level of ß-endorphin was noted to be in the preovulatory follicle.

Because acupuncture treatment impacts on ß-endorphin levels, which in turn affect 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 (36, 37). Various investigators have shown that in normally ovulatory or anovulatory women, acupuncture also influenced plasma levels of FSH, LH, E2, and P (38-40). Acupuncture as a surrogate for hCG in ovulation induction was successfully used by Cai (41). Chen and Yu (42) showed that electroacupuncture normalized they hypothalamic-pituitary-ovarian axis, and in another study Chen (43) reported that 6 of 13 anovulatory cycles responded to acupuncture treatment.

A series published from the University of Heidelberg in Germany (44) used auricular acupuncture on 45 infertile women suffering from ovulatory dysfunction such as oligomenorrhea and luteal phase defect. The control group received medical treatment including bromocriptine, dexamethasone, levothyroxine, clomiphene citrate (CC), and gonadotropin. Although the investigators concluded that resumption of ovulatory cycles occurred significantly more often in the acupuncture group compared to the control group, pregnancy rates were not different between the two groups. However, interpretation of study data was very difficult due to the heterogeneity of the patient population and treatment modalities. Moreover, seven pregnancies in the acupuncture group were actually achieved with hormone treatment 6 months after acupuncture was stopped.

Another study by Stenver-Victorin et al. (45) evaluated the use of electroacupuncture for ovulation induction on 24 oligo/amenorrheic women with polycycstic ovarian syndrome (PCOS). The percentage of ovulatory cycles in all subjects was shown to improve from 15% (in a total of 3 months before treatment) to 66% up to 3 months after treatment. Responsive patients were noted to have significantly lower body mass index (BMI), waist-to-hip circumference ratio, serum T concentration, serum T/sex hormone-binding globulin ratio, and serum basal insulin level. They suggested that, in these selected patients with PCOS, acupuncture could be considered as an alternative or adjunct to pharmacological ovulation induction.

A recent prospective randomized controlled study by Paulus et al. (46) compared pregnancy rates in a total of 160 patients undergoing IVG. Acupuncture was performed in 80 patients 25 minutes before and after ET. After controlling confounding variables, clinical pregnancy rate for the acupuncture group (42.5%) was significantly higher than the control group (26.3%).

Peripheral effects of acupuncture
In addition to the central modulation of the hypothalamic-pituitary-ovarian axis, the effects of acupuncture on the autonomic nervous system have been well documented (47). In the early 1980s, Yao et al. (48) reported long-lasting cardiovascular depression induced by acupuncture stimulation of the sciatic nerve in unanesthetized hypertensive rats. In the human, acupuncture was also shown to be sympathoinhibitory. After acupuncture, sympathetic nerve activity as measured by norepinephrine level, skin temperature, blood pressure, and pain tolerance threshold was shown to be decreased (49).

Endometrial thickness, morphology, and uterine artery blood flow have been implicated as important parameters for success of implantation of human embryos (50-57). Despite conflicting results in the utilization of these parameters during various stages of treatment to predict outcome in IVF, it is generally believed that adequate endometrial thickness is required to optimize pregnancy rate. Because endometrial thickness is a function of uterine artery blood flow, Sher and Fisch (58) reported a novel method of using vaginal sildenafil in an attempt to improve uterine artery blood flow and endometrial development in patients undergoing IVF.

With its central sympathoinhibitory effect, acupuncture may contribute to reduce uterine artery impedance and therefore, increase blood flow to the uterus. In fact, Sterner-Victorin et al. (59) demonstrated this when they performed acupuncture in 10 infertile women who were down-regulated by GnRH analog to avoid the effect of endogenous hormone on the uterine artery blood flow.

Pulsatility index in the uterine artery and skin temperature (on the forehead and lumbosacral area) were evaluated in three time periods-before, right after, and 2 weeks after acupuncture treatment (twice a week for 4 weeks). Pulsatility index and skin temperatures were found to be significantly decreased and increased, respectively, both right after and 14 days after acupuncture treatment. This effect was hypothesized to be caused by central inhibition of sympathetic activity.

Acupuncture and stress reduction
It has been well documented that infertility causes stress (60-65), and stress reduction may, in turn, improve fertility (66). However, the relationship between stress and infertility is that of a vicious cycle. Social stigmatization, decreased self-esteem, unmet reproductive potential of sexual relationship, physical and mental burden of treatment, and the lack of control on treatment outcome are just some of the factors that can lead to psychological stress in any couple pursuing infertility treatment. In turn, stress may lead to the release of stress hormones and influence mechanisms responsible for a normal ovulatory menstrual cycle through its impact on the hypothalamic-pituitary-ovarian axis.

The use of acupuncture for reducing anxiety and stress possibly through its sympathoinhibitory property and impact on ß-endorphin levels has been reviewed (67, 68), and the efficacy of acupuncture in depression has also been studied (69). Because the pharmacological side effects of anxiolytic and antidepressant drugs on infertility treatment outcome are largely unknown, acupuncture may provide an excellent alternative for stress reduction in women undergoing infertility treatment.

Discussion
The practice of acupuncture to treat identifiable patho-physiological conditions has been a subject of intense research. The underlying physiologic mechanisms of acupuncture such as the release of opioids and other peptides in the central peripheral nervous system, and its inhibition of the sympathetic nervous system have been increasingly established. Promising results from credible trials have emerged for the use of acupuncture in treating various pain syndromes, substance abuse, and chemotherapy-induced nausea and vomiting.

Although the definitive role of acupuncture in the treatment of female infertility is yet to be established, its neuroendocrine effect on the hypothalamic-pituitary-ovarian axis and the preliminary clinical data reviewed here justifies further clinical trials to systematically examine the efficacy of acupuncture in treating various conditions related to female infertility such as ovulatory dysfunction associated with PCOS. The peripheral impact of acupuncture in improving uterine artery blood flow and hence endometrial thickness also provides encouraging data regarding its potential positive effect on implantation.

Whether these potential beneficial effects of acupuncture on the reproductive system can be translated into improving infertility treatment outcomes will eventually mandate randomized controlled studies of adequate design. Because acupuncture is nontoxic and relatively affordable, its indications as an adjunct in assisted reproduction or as an alternative for women who are intolerant, ineligible, or contraindicated for conventional hormone induction of ovulation deserves serious research and exploration.

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46. Paulus WE, Zhang M, Strehler E, El-Danasouri I, Sterzik K. Influence of acupuncture on the pregnancy rate inn patients who undergo assisted reproduction therapy. Fert Steril 2002;77:721-4.
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Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy – Articles

Wolfgang E. Paulus, M.D.,[a] Mingmin Zhang, M.D.,[b] Erwin Strehler, M.D.,[a]Imam El-Danasouri, Ph.D.,[a] and Karl Sterzik, M.D.[a]

FERTILITY AND STERILITY® VOL. 77, NO. 4, APRIL 2002, Copyright ©2002, American Society for Reproductive Medicine, Published by Elsevier Science Inc.

Objective: To evaluate the effect of acupuncture on the pregnancy rate in assisted reproduction therapy (ART) by comparing a group of patients receiving acupuncture treatment shortly before and after embryo transfer with a control group receiving no acupuncture.

Design: Prospective randomized study.

Setting: Fertility center.

Patient(s): After giving informed consent, 160 patients who were undergoing ART and who had good quality embryos were divided into the following two groups through random selection: embryo transfer with acupuncture (n = 80) and embryo transfer without acupuncture (n = 80).

Intervention(s): Acupuncture was performed in 80 patients 25 minutes before and after embryo transfer. In the control group, embryos were transferred without any supportive therapy.

Main Outcome Measure(s): Clinical pregnancy was defined as the presence of a fetal sac during an ultrasound examination 6 weeks after embryo transfer.

Result(s): Clinical pregnancies were documented in 34 of 80 patients (42.5%) in the acupuncture group, whereas pregnancy rate was only 26.3% (21 out of 80 patients) in the control group.

Conclusion(s): Acupuncture seems to be a useful tool for improving pregnancy rate after ART. (Fertil Steril® 2002;77:721- 4. ©2002 by American Society for Reproductive Medicine.)

Key Words: Acupuncture, assisted reproduction, embryo transfer, pregnancy rate

Acupuncture is an important element of traditional Chinese medicine (TCM), which can be traced back for at least 4,000 years. Acupuncture has been shown to alleviate nausea and vomiting, dental pain, addiction, headache, menstrual cramps, tennis elbow, fibromyalgia, myofascial pain, osteoarthritis, carpal tunnel syndrome, and asthma. Both physiologic and psychological benefits of acupuncture have been scientifically demonstrated in recent years.

However, so far there have been only a few serious trials concerning the use of acupuncture in reproductive medicine. Publications focus primarily on acupuncture therapy for male infertility (1, 2). acupuncture may reduce blood flow impedance in the uterine arteries of infertile women (3). A positive impact of acupuncture on endocrinologic parameters and ovulation in women with polycystic ovary syndrome has been demonstrated (4). In addition, auricular acupuncture was successfully used in the treatment of female infertility (5). In the present study, we chose acupuncture points that relax the uterus according to the principles of TCM. Because acupuncture influences the autonomic nervous system, such treatment should optimize endometrial receptivity (6). Our main objective was to evaluate whether acupuncture accompanying embryo transfer increases clinical pregnancy rate.

Materials and Methods

This study was a prospective randomized trial at the Christian-Lauritzen-Institut in Ulm, Germany. It was approved by the ethics committee of the University of Ulm. A total of 160 healthy women undergoing treatment with in vitro fertilization (IVF; n = 101) or intracytoplasmic sperm injection (ICSI; n = 59) were recruited into the study. The age of the patients ranged from 21 to 43 (mean age: 32.5 = 4.0 years). The cause of infertility was the same for both groups (Table 1). Only patients with good embryo quality were included in the study. Using a computerized randomization method, patients were assigned into either the acupuncture group or the control group.

Ovarian stimulation, oocyte retrieval, and in vitro culture were performed as previously described (7). Transvaginal ultrasound-guided needle aspiration of follicular fluid was performed 36 to 38 hours after hCG administration. Immediately after follicle puncture, the oocytes were retrieved, assessed, and fertilized in vitro. Sperm preparation and culture conditions did not differ for either group.

In cases of severe male subfertility, ICSI was preferred, as described in the literature (8). Forty-eight hours after the IVF or ICSI procedure, embryos were evaluated according to their appearance as type 1 or 2 (good), type 3 or 4 (poor), as described in literature (9).

Just before and after embryo transfer, all patients underwent ultrasound scans of the uterus using a 7-MHz transvaginal probe (LOGIQ 400 Pro, GE Medical Systems Ultra-sound Europe, Solingen, Germany). Pulsed Doppler curves of both uterine arteries were measured by one observer. The pulsatility index (PI) for each artery was calculated electronically from a smooth curve fitted to the average waveform over three cardiac cycles.

A maximum of three embryos, in accordance with German law, were transferred into the uterine cavity on day 2 or 3 after oocyte retrieval. For embryo replacement, the patient was placed in a dorsal lithotomy position, with an empty bladder. The cervix was exposed with a bivalved speculum, then washed with culture media prior to embryo transfer. Labotect Embryo Transfer Catheter Set (Labotect GmbH, Go¨ ttingen, Germany) was used for atraumatic replacement owing to the curved guiding cannula with a ball end, allowing the set to be used reliably even with difficult anatomic conditions. The metallic reinforced inner catheter shaft al lowed safe passage through the cervical canal. When the catheter tip lay close to the fundus, the medium containing the embryos was expelled and the catheter withdrawn gently. After this procedure, the patient was placed at bed rest for 25 minutes. All oocyte retrievals and embryo transfers were performed by one examiner using the same method. The examiner was not aware of the patient’s treatment group (control or acupuncture).

At the time of the embryo transfer, blood samples (10 mL) were obtained from the cubital vein. Plasma estrogen was determined by an immunometric method using the IMMULITE 2000 Immunoassay System (DPC Diagnostic Product Corporation, Los Angeles, CA).

Luteal phase support was given by transvaginal progesterone administration (Utrogest®, 200 mg, three times per day; Kade, Berlin, Germany). Progesterone administration was initiated on the day after oocyte retrieval and was continued until the serum ß-hCG measurement 14 to 16 days after transfer and, in cases of pregnancy, until gestation week 8.

Each patient in the experimental group received an acupuncture treatment 25 minutes before and after embryo transfer. Sterile disposable stainless steel needles (0.25 X 25 mm) were inserted in acupuncture point locations. Needle reaction (soreness, numbness, or distention around the point = Deqi sensation) occurred during the initial insertion. The needles were left in position for 25 minutes and then removed. The depth of needle insertion was about 10 to 20 mm, depending on the region of the body undergoing treatment. Before embryo transfer.

In addition, we used small stainless needles (0.2 X 13 mm) for auricular acupuncture. Two needles were inserted in the right ear, the other two needles in the left ear. The four needles remained in the ears for 25 minutes. The side of the auricular acupuncture was changed after embryo transfer. The patients in the control group also remained lying still for 25 minutes after embryo transfer. All treatments were performed by the same well-trained examiner, in the same way.

The primary point of the study was to determine whether acupuncture improves the clinical pregnancy rate after IVF or ICSI treatment. Student’s t-test was used as a corrective against any possible imbalance between the two groups regarding the following variables: age of patient, number of previous cycles, number of transferred embryos, endometrial thickness, plasma estradiol on day of transfer, method of treatment (IVF or ICSI), and blood flow impedance in the uterine arteries (pulsatility index). Chi-square test was used to compare the two groups. All statistical analyses were carried out using the software package Statgraphics (Manugistics, Inc., Rockville, MD).

Results

A total of 160 patients was recruited for the study. Patients who failed to conceive during the first treatment cycle were not reentered into the study. According to the randomization, 80 patients were treated with acupuncture, and 80 patients underwent the usual therapy without acupuncture.

As Table 1 shows, there were no statistically significant differences between the two groups with respect to the following covariants: age of patient, number of previous cycles, number of transferred embryos, endometrial thickness, plasma estradiol on day of transfer, or method of treatment (IVF or ICSI). Clinical indications for ART were the same for patients of both groups. The blood flow impedance in the uterine arteries (pulsatility index) did not differ between the groups before and after embryo transfer.

The analysis shows that the pregnancy rate for the acupuncture group is considerably higher than for the control group (42.5% vs 26.3%; P=.03).

Discussion

The acupuncture points used in this study were chosen according to the principles of TCM (10): Stimulation of Taiying meridians (spleen) and Yangming meridians (stomach, colon) would result in better blood perfusion and more energy in the uterus. Stimulation of the body points as well as stimulation of the ear points would sedate the patient. Ear point would influence the uterus and stabilize the endocrine system.

The anesthesia-like effects of acupuncture have been studied extensively. Acupuncture needles stimulate muscle afferents innervating ergoreceptors, which leads to increased ß-endorphin concentration in the cerebrospinal fluid (11). The hypothalamic ß-endorphinergic system has inhibitory effects on the vasomotor center, thereby reducing sympathetic activity. This central mechanism, which involves the hypothalamic and brainstem systems, controls many major organ systems in the body (12). In addition to central sympathetic inhibition by the endorphin system, acupuncture stimulation of the sensory nerve fibers may inhibit the sympathetic outflow at the spinal level. By changing the concentration of central opioids, acupuncture may also regulate the function of the hypothalamic-pituitary-ovarian axis via the central sympathetic system (13).

Stener-Victorin et al. (3) reduced high uterine artery blood flow impedance by a series of eight acupuncture treatments, twice a week for 4 weeks. They suggest that a decreased tonic activity in the sympathetic vasoconstrictor fibers to the uterus and an involvement of central mechanisms with general inhibition of the sympathetic outflow may be responsible for this effect. In our study, we could not see any differences in the pulsatility index between the acupuncture and control group before or after embryo transfer. This may be due to a different acupuncture protocol and the selected sample of patients with high blood flow impedance of the uterine arteries (PI ≥ 3.0) in the Stener-Victorin et al. study.

As we could not observe any significant differences in covariants between the acupuncture and control groups, the results demonstrate that acupuncture therapy improves pregnancy rate.

Further research is needed to demonstrate precisely how acupuncture causes physiologic changes in the uterus and the reproductive system. To rule out the possibility that acupuncture produces only psychological or psychosomatic effects, we plan to use a placebo needle set as a control in a future study.

References

1. Siterman S, Eltes F, Wolfson V, Lederman H, Bartoov B. Does acupuncture treatment affect sperm density in males with very low sperm count? A pilot study. Andrologia 2000;32:31-9.

2. Bartoov B, Eltes F, Reichart M, Langzam J, Lederman H, Zabludovsky N. Quantitative ultramorphological analysis of human sperm: fifteen years of experience in the diagnosis and management of male factor infertility. Arch Androl 1999;43:13-25.

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

4. Stener-Victorin E, Waldenstrom U, Tagnfors U, Lundeberg T, Lindst-edt G, Janson PO. Effects of electro-acupuncture on anovulation in women with polycystic ovary syndrome. Acta Obstet Gynecol Scand 2000;79:180 -8.

5. Gerhard I, Postneek F. Auricular acupuncture in the treatment of female infertility. Gynecol Endocrinol 1992;6:171-81.

6. Stener-Victorin E, Lundeberg T, Waldenstrom U, Manni L, Aloe L, Gunnarsson S, Janson PO: Effects of electro-acupuncture on nerve growth factor and ovarian morphology in rats with experimentally induced polycystic ovaries. Biol Reprod 2000;63:1497-503.

7. Strehler E, Abt M, El-Danasouri I, De Santo M, Sterzik K. Impact of recombinant follicle-stimulating hormone and human menopausal gonadotropins on in vitro fertilization outcome. Fertil Steril 2001;75: 332-6.

8. Palermo GD, Schlegel PN, Colombero LT, Zaninovic N, Moy F, Rosenwaks Z. Aggressive sperm immobilization prior to intracytoplasmic sperm injection with immature spermatozoa improves fertilization and pregnancy rates. Hum Reprod 1996;11:1023-9.

9. Plachot M, Mandelbaum J: Oocyte maturation, fertilization and embryonic growth in vitro. Br Med Bull 1990;46:675-94.

10. Maciocia G. Obstetrics and gynecology in Chinese medicine. New York: Churchill Livingstone, 1998.

11. Hoffmann P, Terenius L, Thoren P. Cerebrospinal fluid immunoreactive beta-endorphin concentration is increased by voluntary exercise in the spontaneously hypertensive rat. Regul Pept 1990;28:233-9.

12. Andersson SA, Lundeberg T. Acupuncture-from empiricism to science: functional background to acupuncture effects in pain and disease. Med Hypotheses 1995;45:271-81.

13. Chen BY, Yu J. Relationship between blood radioimmunoreactive beta-endorphin and hand skin temperature during the electro-acupuncture induction of ovulation. Acupunct Electrother Res 1991;16:1-5.

14. Kim J, Shin KH, Na CS. Effect of acupuncture treatment on uterine motility and cyclooxygenase-2 expression in pregnant rats. Gynecol Obstet Invest 2000;50:225-30.

Acupuncture in IVF Demonstrates Promising Results in New Study – Articles

Medical experts are finding potential in the use of acupuncture as adjunctive therapy for women undergoing infertility treatment. In a new study testing the feasibility of this alternative approach, doctors compared outcomes between two groups of patients: those who underwent acupuncture combined with IVF, and those who underwent IVF alone.(1)

A Medical Approach with a Long History

Acupuncture is one of the most ancient medical treatments in the world, dating back several millennia, originating in China, but finally becoming popular in more modern times in the United States in the early 1970s. The practice is used not just as an adjunctive infertility treatment, but also a wide variety of medical conditions.

It involves applying a range of procedures that stimulate anatomical points on the body. The technique that has been studied the most scientifically involves penetrating the skin with thin, solid, metallic needles.

Traditional Chinese medicine holds that there are more than 2,000 acupuncture points on the body, and that these connect with more than a dozen main and secondary pathways known as meridians. Chinese medicine practitioners believe these meridians conduct energy, or qi (chee), throughout the body. Essentially, acupuncture helps maintain the balance between qi and the opposing forces of yin and yang, which in turn regulates spiritual, emotional, mental and physical balance.(2)

“Western medicine takes a very different approach,” explained lead study investigator Paul Magarelli, MD, PhD, a practicing reproductive endocrinologist and medical director of the Reproductive Medicine & Fertility Center in Colorado Springs. “We use medications. We override [biological] systems.”

Yet while treatment for infertility, such as in-vitro fertilization (IVF), has taken major strides in the last two decades, odds are that couples won’t achieve a pregnancy 60% of the time by solely using the Western approach, Magarelli explained. “A lot of the time, the patient gets one try at becoming pregnant, mainly because of the cost,” he said.

Considering the Alternative

Thus, patients have begun looking at alternative options, mainly integrative medicine, in hopes of boosting those odds, Magarelli said.

That was one motivation for this study. But Magarelli says he didn’t always believe in the potential of complementary approaches like acupuncture. “I just did not feel that the data existed that supported acupuncture,” he recalled. Over time, studying the medical literature about the topic intrigued him enough to launch a study of his own.

In a previous analysis, Magarelli recruited patients with the poorest prognoses (over age 35, several male factor, elevated FSH level, or those who failed IVF in the past) in his clinic, who were given acupuncture in combination with IVF, and compared them with the same types of patients who received IVF alone. Two years later, he and his colleagues retrospectively evaluated the data.

“Those patients who were treated with the acupuncture [and] who were poor prognosis had equivalent pregnancies to those [considered] good prognosis patients,” Magarelli explained, an outcome he found “amazing”.

This led to the latest study involving “good prognosis” patients. Specifically, the researchers wanted to determine the efficacy of traditional acupuncture combined with auricular (or ear) acupuncture. These approaches are used to either improve uterine bloodflow or help relax the uterus prior to embryo transfer in IVF.

One hundred fourteen patients undergoing in-vitro fertilization after controlled ovarian hyperstimulation were included in the study. Only those women described as having a good response to ovarian hyperstimulation and whose partners’ sperm morphology (quality) was also good were analyzed for the research.

Each patient underwent ovarian hyperstimulation using a standard protocol, including the use of gonadotropins and a gonadotropin releasing-hormone (GnRH) agonist or antagonist. Each woman who then responded well to ovulation induction underwent either electro stimulation acupuncture or traditional combined with auricular acupuncture in conjunction with IVF. For this study, 53 underwent acupuncture combined with IVF, and 61 underwent IVF alone.

The investigators then analyzed successful pregnancies in the group of women, as well as the miscarriage rate.

Acupuncture Patients Had Improved Outcomes

Of those in the acupuncture group, 51 percent achieved a successful pregnancy, the research team noted. That compares to 36 percent of those who underwent IVF alone. Comparatively, the miscarriage rate was 8% and 20% in the acupuncture versus non-acupuncture group, respectively.

There were no ectopic (Tubal) pregnancies in the group of women who underwent acupuncture, but 9% of those in the group without acupuncture had a Tubal pregnancy. The investigators also reported 23% more births per pregnancy among those who had acupuncture as part of their infertility treatment.

“In previously published data, acupuncture was reserved for poorer prognosis patients, and enhanced outcomes were observed,” wrote Magarelli and his colleagues. “In this study, we demonstrated that good prognosis patients would also benefit from inclusion of published acupuncture protocols.”

They say this is the first published study to include birth-related IVF outcome in patients also treated with acupuncture.

Why does acupuncture theoretically work for infertility? Medical experts hypothesize that the ancient approach positively impacts opioid production in the central nervous system, which in turn, positively influences gonadotropin secretion.(3) These naturally-produced opioids, like endorphins, are similar to the actions of opiate drugs. Gonadotropins are the hormones that help promote normal reproductive function in the body. They include follicle-stimulating hormone (FSH), which helps promote follicle maturity prior to the release of an egg in women, and sperm production in men.(4) Experts also suggest acupuncture has a positive effect on uterine bloodflow.

For the Future

The study will likely be expanded early next year, Magarelli study. In the next phase, data will be collected on all patients, regardless of prognosis. “I would suspect that … we’re going to see that, across the board, we can improve anywhere between 5 percent and 15 percent the number of babies successfully created through the process of IVF and acupuncture,” he said.

“What blows me away, personally, is how I have absolutely seen things that I didn’t think were possible by placing a needle somewhere.”

Magarelli PC, Cridennda DK, Cohen M. Acupuncture and good prognosis IVF patients: Synergy. 60th Annual Meeting of the American Society for Reproductive Medicine. 2004 Oct 16-20. Philadelphia, PA.
National Center for Complementary and Alternative Medicine (NCCAM). National Institutes of Health (NIH).
Chang R, Chung PH, Rosenwaks Z. Role of acupuncture in the treatment of female infertility. Fertil Steril 2002 Dec;78(6):1149-53.-+
Department of Obstetrics and Gynecology. Geneva University Hospital. Sexual Hormones. Available at: http://www.gfmer.ch/Endo/Lectures_08/sexual_hormones.htm. Accessed November 2, 2004.

Traditional Chinese Medicine (TCM) an Ancient Medicine Enhances the Results of IVF High-Tech Fertility Treatments Articles

Traditional Chinese Medicine has been used for thousands of years to help couples become pregnant. With the technology of Modern Medicine couples that have been struggling to become parents now have a good chance of fulfilling their dreams.

In Vitro Fertilization (IVF) has become a popular choice for many couples. Now, high tech joins with the ancient wisdom of acupuncture. Many studies have shown that Acupuncture can enhance the pregnancy rates of women going through IVF. Two studies, which have gotten the most attention on the use of Acupuncture combined with IVF, are

1) Influence of Acupuncture on the Pregnancy rate on patients who undergo assisted reproduction therapy. Paulus et al. Fertility & Sterility Vol 77:No.4, April 2002

2) Reduction In blood flow impedance in the uterine arteries of infertile women with electro-acupuncture. Stener-Victorin et al. European Society for Human Reproduction and Embryology.

The Stener-Victorin study used a series of acupuncture treatments using electro acupuncture. The protocol requires at least eight acupuncture treatments before retrieval of the eggs. This specifically increases the blood flow to the uterus which in tern helps the fertility medications reach the ovaries. This provides a better stimulation to the ovaries. The other benefit is that the uterine wall lining develops a nice thick environment and makes a better place for the embryo to imbed. Without this plush lining the embryo has no place to imbed.

These studies demonstrated a 10 to 15% improvement in pregnancy rates in those patients who augmented their traditional IVF treatments with acupuncture. It took Western Reproductive Techniques over 8 years for a 10% improvement in IVF statistics and 4 more years to improve it by another 10%. These studies would suggest providing patients with acupuncture treatments is a very positive practice.

Acupuncture Treatments and Pre and Post embryo transfer acupuncture protocols were used in these studies. The study (which has been submitted for presentation and publication) studied reproductive outcomes in over 160 patients receiving IVF, or IVF & ICSI (50% pregnancy rates per cycle in the acupuncture patients). It is reported that the “good prognosis” patients (those patients who have a good chance of success) could be made to have better outcomes (16% more pregnancy) by using acupuncture during their IVF cycle. The most remarkable discovery was that the acupuncture group had a significantly higher live birth rate. Since the goal here is to have a baby not just to achieve pregnancy, this is a remarkable finding. Another remarkable finding was that no ectopic pregnancies were reported in the acupuncture group versus 9% in the non- acupuncture group. More research needs to be done to support this finding.

There are secondary benefits from acupuncture that patients report:

The patient reports that their stress and anxiety levels are lessened
Greater attunement to their own bodies and the changes they experience
Most of the women lovingly call their acupuncture treatments “needle naps”
The patients also get a sense that they have some control and can contribute to their IVF cycle.
Acupuncture is the placement of fine needles into specific acupoints along the pathways of energy in the body. This works by sending messages to the brain almost like programming a computer. The basis of all TCM is energy or “Qi”. Energy flows in patterns of electricity through our bodies, cells and tissues. This Qi is conducted through protein molecules giving us energy and life. This energy is carried through our bodies via pathways of energy called meridians. These meridians make up a web or network of channels, which sets up communication between every organ in your body. Oriental doctors have mapped these channels out over the course of thousands of years of experimentation and observation. The insertion of fine needles into the acupoints along the meridians produces measurable effects on different parts of the body. This in how acupuncture can affect abdominal organs, such as the kidneys, liver and uterus by placing needles in arms and legs.

Some of the acupuncture points used in the studies mentioned above make absolute sense to a TCM practitioner. These acupoints achieve balance by holding the Qi up, moving the blood (a natural heparin affect) regulates the uterus by building a nice plush uterine wall lining.

Relationship Between Blood Radioimmunoreactive Beta-Endorphin and Hand Skin Temp During The Electro-Acu Induction of Ovulation-Articles

Chen Bo Ying M.D. Lecturer of Neurobiology
Institute of Acupuncture Research,
and
Yu Jin, MD., Prof of Gynecology
Obstetricus and Gynecology Hospital
Shanghai Medical University
Shanghai, People’s Republic of China

(Received October 24, 1990; Accepted with revisions,
December 8, 1990)
ACUPUNCTURE & ELECTRO-THERAPEUTICS RES.,
Vol. 16, pp. 1-5,1991

Abstract:
Thirteen cycles of anovulation menstruation in 11 cases were treated with Electro-Acupuncture (EA) ovulation induction. In 6 of these cycles which showed ovulation, the hand skin temperature (HST) of these patients was increased after EA treatment. In the other 7 cycles ovulation was not induced. There were no regular changes in HST of 5 normal subjects. The level of radioimmunoreactive beta-endorphin (rß-E) fluctuated, and returned to the preacupunctural level in 30 min. after withdrawal of needles in normal subjects. After acupuncture treatment, the level of blood rß-E in cycles with ovulation declined or maintained the range of normal subjects. But the level of blood rß-E and increase of HST after acupuncture(r=-0.677, P <0.01). acupuncture treatment is able to regulate the function of the hypothalamic pituitary-ovarian axis. Since a good response is usually accompanied with the increase of HST, monitoring HST may provide a rough but simple method for prediciting the curative effect of acupuncture treatment. The role of rß-E in the mechanism of acupuncture treatment ovulation induction was discussed.

KEY WORDS: Electro-Acupuncture (EA), Hand Skin Temperature (HST), radioimmunoreactive beta-endorphin (rß-E), ovulation, radioimmunoassay (RIA)

INTRODUCTION

In our previous work, it has been demonstrated that acupuncture treatment is an effectual method of ovulation induction (1). The present work studied the relationship between the curative effect of acupuncture treatment and the changes of the HST and the level of blood beta-endorphin.

MATERIALS AND METHODS

Selection and Treatment of Cases

Eleven cases of chronically anovulatory patients including 9 cases of polycystic ovarian disease (PCO), 1 case of hypogonadotropic amenorrhea and case of oligomenorrhea were treated with acupuncture treatments in 13 menstruation cycles. They were 22 to 35 years of age and their courses of disease were 3 to 12 years. The basic body temperature (BBT) of these patients was monophase for at least 3 months. Each patient accepted the vaginal dropping cell examination twice or more a week. The results showed that the eosinocyte index (EI) of 10 cases was less than 30% and the EI of 1 case was more than 70%.

On the 10th day of each menstruation cycle, the patients were treated with acupuncture. Before and after the acupuncture treatment, HST was measured by a semiconduct thermometer and blood samples were collected from the forearm vien of patients for ß-E RIA. Five healthy woman voluteers with normal menstruation cycle were selected as controls. They were 31 to 35 years old and the menstruation cycle was 28 days. BBT showed change of biphase. All of them were healthy in premenorrhea and did not take any drug one month before acupuncture treatment.

Plasma ß-Enorphin Radioimmunoassay

The blood samples were added to 100ug/ml bacitracin for inhibiting blood aminopeptidase and centrifuged at 3,000g for 15 min. The plasma was stored at -40°C.

The sensitive radioimmunoassay was performed as a routine in our lab (2,3), to determine the concentration of ß-E in the samples of plasma. Each estimative tube was added 0.1ml 1:8000 rabbit ß-E antiserum, 0.1ml¹²⁵I-ß-E . That is 0.03ml sheep antiserum to rabbit gamma-globulin diluted 20-fold with RIA buffer was added to each tube, than shaken and incubated at 0-4°C for 24 hours, and centrifuged at 3,000g for 15 min. The supernatant was poured out and the precipitate was counted for radioactivity in Model FH 408 gamma counter. ß-E contents were quantitated according to the standard curve which was performed at the same time with the sample tubes. The least detected quantity of RIA was 10pg/tube.

RESULTS

Clinical Observation

It was adopted standards of ovulation that BBT showed biphase and EI became cyclic variation. Six of 13 menstruation cycles treated with acupuncture treatment showed ovulation, while the other 7 cycles failed to do so. No acupuncture effect was found in normal control subjects.

In the 13 anovulatary cycles, increased HST occurred in 6 cycles, of which 5 cycles showed ovulation after acupuncture treatment. 7 cycles manifested decreased HST and only one of them produced ovulation (Table 1). No regular change was seen in HST in normal subjects.

Table l. Effect of acupuncture Induction of Ovulation in 13 Cycles

Changes of HST Ovulation No Ovulation Total

Increased 5* 1 6
Decreased 1 6 7

• P<0.05 as estimated by X² test

Change of Plasrna rß-E

In normal menstruation cycles the level of plasma rß-E before and after acupuncture fluctuated and returned to the preacupural level after 30 minutes.

In the 13 anovulatory cycles the level of plasma rß-E on the 10th day of the cycles was higher but not statistically significant from that of normal subjects.

After acupuncture treatment the plasma rß-E contents of 6 cycles with ovulation either declined or maintained within the range of normal. And the plasma level of 7 cycles that failed to show ovulation after acupuncture treatments were significantly higher than those of normal subjects and 6 ovulatory cases as estimated by t test (P<0.05), (Table 2).

Table 2. Changes of blood ß-E level before and after acupuncture treatment* (pg/ml)

Group of cases No. of cycles Before EA After EA

Ovulation 6 65.59 ± 24.15 38.86 ± 10.11
No ovulation 7 65.59 ± 24.15 80.09 ± 22.16**
Normal 5 38.84 ± 10.13 41.52 ± 6.40

*The values in this table are Mean ± SE **P<0.05

Cycles which showed increase of HST after acupuncture treatment were associated with a declination of plasma rß-E Ievel but in cycles where HST decreased, the plasma rß-E level elevated after acupuncture treatment. There was a negative correlation between changes of plasma rß-E and HST as measured by rank correlation (r=0.677, P<0.01).

Discussion

According to our clinical practice of using acupuncture to cure barreness, the curative effect was related to the changes of patients’ HST. In general, provided that the body temperature was normal and the environmental temperature was constant round 25°C, the HST may reflect the state of sympathetic system of a patient.

From present results, it seems that the successful rate of acupuncture ovulation induction was higher in patients with the depression of sympathetic activity. In normal subject whether HST increased or declined, no influence in ovulation was found. These results suggest that the relationship of ovulation and HST in normal women is different from that in anovulatory patients. Yen and his colleagues (4) first reported that enogenous opioid peptides can inhibit pituitary pulse secreting LH. Fumiko, Akio and Michael reported in succession that morphine, ß-E and dynorphin can also depress LH pulse secretion (5,6,7). These substances may exert their action via regulating the secretion of LH-RH in hypothalmus. Acupuncture can affect the central opioid peptide level (2,8,9) thus it may regulate the function of hypothalamic-pituitary-ovarian axis via brain endogenous opiod peptides, such as ß-E and dynorphin etc.

In this study 11 cycles were PCO and the blood LH level in these cycles was marked higher than that of normal subjects. Acupuncture may promote the release of ß-E in the brain and reduce LH-RH secretion from hypothalamus. Therefore, the blood LH content released from the pituitary was decreased. This might be one of the mechanisms of Acupuncture ovulation induction.

The injection of ß-E into rat cerebellomedullary cisterm resulted in the increase of blood epinephrine (E), norepinephrine (NE) and dopamine (DA) levels, and there was a positive correlation in the dose of ß-E and the levels of blood E, NE, and DA (10). The result suggests that control ß-E may influence the activity of the sympathetic system. Our study showed that the sympathetic activity in normal subjects was not affected and the level of blood ß-E was relatively stable. Thus acupuncture was not able to influence the normal ovulatory cycles. In anovulatory patients, especially in PCO cases, acupuncture can depress sympathetic activity resulting in the increase of HST and the lowering the level of blood ß-E.

These results suggest that in anovulatory cases the hyperactive sympathetic system can be depressed by acupuncture and the function of the hypothalamus-pituitary-ovarian axis can be regulated by acupuncture via central sympathetic system. This might be another possible mechanism of acupuncture ovulation induction.

Our study also suggest that measuring HST my provide a rough but simple method for predicting the effect of acupuncture ovulation induction.

ACKNOWLEDGEMENT

This report has been directed by Prof. He Lian Fang.

REFERENCES

1. Yu Jin, Zheng Hua-Mei, Chen Bo-Yeng, Relationship of hand temperature and blood ß-endorphinelike immunoreactive substance with electroacupuncture induction of ovulation, Acupuncture Research vol. 11 (2), pp. 86-90, 1986.
2. Chen Bo-Ying, Pan Xiao-Ping, Jiang Cheng-Chuan, Chen Shang-Qun, Correlation of pain threshold and level of ß-endoprphin like immuno-reactive substance in human CST during electroacupuncture analgesia, Acta Physiologica Sinica vol. 36 (2), pp. 193-197, 1984.
3. He Xiao-Ping, Chen Bo-Ying, Zhu Jin-Ming, Cao Xiao-Ding, Change of Leu-enkephalin and ß-endorphin-like immunoreactivity in the Hippocampus after electroconvulsive shock and electroacupuncture, Acupuncture & Electro-Therapeutics Res., Int. J., vol. 14 (1), pp.131-139, 1989.
4. Quigley, M.E., Sheeham, K.L., Casper, R.F. and Yen, S.S.C., Evidence for an increased opioid inhibition of luteinizing hormone secretion in hyperprolactinemic patients with pituitary microadenoma, J. Clin. Endocrinol, Metabol, vol.50 (3), pp. 427-436, 1980.
5. Fumiki Kinoshita, Yoshikatsu Nakai, Hideki Katakami, Hiroo Imura, Suppressive effect of dynorphin (1-13) on luteinizing hormone release in conscious rat, Life Sci. vol. 30 (22), pp. 1915-1919, 1982.
6. Akio Adabori, Charles A. Barraclough, Effect of morphine on luteinizing hormone secretion and catecholmine turnover in the hypothalamus of estrogen-treated rats, Brain Res. vol. 362 (2) pp. 221-226, 1986.
7. K. Michael Orstead, Harold G. Spics, Inhibition of hypothalamic gonadotropin releasing hormone release by endogenous opioid peptides in the female rabbit, Neuroendocrinology, vol. 46 (1), pp. 14-23, 1987.
8. Richard S.S., Cheng, S, Pomeranz, B., Electroacupuncture analgesia could be mediated by least two pain relieving endorphin and non-endorphin systems, Life Sci., vol. 25 (22), pp. 1951-1968, 1979.
9. Chen Bo-ying, Wang De-Ling, Pan Xiao-Ping, Changes of opiate likesubstances (OLS) level in perfusate of periaqueductal gray (PAG) after electroacupuncture and brain stimulation, Acta Physiologica Sinica vol. 34 (4), pp.385-391, 1982.
10. Glen R. Van Loon, Nathan M. Appel, Doris Ho, ß-endorphin-induced stimulation of central sympathetic outflow: ß-endorphin increases plasma concentration of epinephrine, norepinephrine, and dopamine in rats, Endocrinology, vol. 109 (1), pp. 46-53, 1981.

Effects of acupuncture and moxa treatment in patients with semen abnormalities

Edson Gurfinkel, Agnaldo P. Cedenho, Ysao Yamamura, Miguel Srougi
Human Reproduction Division, Discipline of Urology, São Paulo Federal University, Paulista School of Medicine, São Paulo, Brazil
Asian J Androl 2003 Dec; 5: 345-348

Abstract
Aim: To evaluate the effect of Chinese Traditional Medicine, acupuncture and moxa treatment, on the semen quality in patients with semen abnormalities. Methods: In a prospective, controlled and blind study, nineteen patients, aged 24 years ~ 42 years and married for 3 years ~ 11 years without children with semen abnormalities in concentration, morphology and/or progressive motility without apparent cause, were randomized into two groups and submitted to acupuncture and moxa treatment at the therapeutic (Study Group) and the indifferent points (Control Group), respectively, for 10 weeks. Semen analyses were performed before and after the treatment course. Results: The patients of the Study Group presented a significant increase in the percentage of normal-form sperm compared to the Control Group (calculated U=16.0, critical U=17.0). Conclusion: The Chinese Traditional Medicine acupuncture and moxa techniques significantly increase the percentage of normal-form sperm in infertile patients with oligoastenoteratozoospermia without apparent cause.

1 Introduction

It is known that men are responsible for 47 % of the infertility problems [1, 2]. Despite the scientific medical advances, 40 % of the infertile patients who present abnormal semen analysis remain with no definite etiologic diagnosis, making the clinical treatment limited and frustrating [3]. On the other hand, some authors have successfully treated patients with varicocele or prostatitis and semen abnormalities using techniques of the Chinese Traditional Medicine [4-7]. We have proposed this prospective, controlled and blind study on infertile patients presented semen abnormalities in concentration, morphology and/or progressive motility to evaluate if acupuncture and moxa treatments could improve the semen parameters.

Patients sought infertility treatment in the Human Reproductive Division of the Department of Gynecology and Discipline of Urology of the São Paulo Federal University Paulista School of Medicine between January 1999 and September 2000. Nineteen patients without children were included with semen abnormalities in concentration, morphology and/or progressive motility detected in 2 semen analyses at the Human Reproduction Laboratory of São Paulo Federal University. They were otherwise healthy. The patients were randomized into two groups: the Study Group [n=9, aged 24 years ~ 43 years (mean 33.4 years) and married for 5 years ~ 11 years (median 7.6 years)] and the Control Group [n=10, aged 26 years ~ 42 years (mean 31.6 years) and married for 3 years ~ 8 years (median 6.1 years)]. The clinical investigation was approved by the Institutional Review Board.

Exclusion criteria
Patients with sperm concentration<5×106/mL, leukocytospermia, previous reproductive organ surgery or usage of drugs acting on the genito-urinary tract within 1 year were excluded.

Treatment

Patients of the Study Group were treated with classic acupuncture and moxa (warming acupuncture points) at the therapeutic points (Tables 1 & 2). Stainless steel disposable needles (0.25 mm×30 mm, Lautz Company, Brazil) were used. Needle depth and direction at each point were in accordance with the acupuncture treatment fundamentals [9], obtaining needling sensation (Teqi) at each point. Moxa was applied up to the appearance of local erythema. For this, the artemisia wool (Chinese National Medicines and Health Products Imp. Exp. Corp. Human Branch, Beijing, China) were used. Each session of treatment consisted of 25 minutes of acupuncture and 20 minutes of moxibustion, twice a week. The whole treatment course lasted 10 weeks. After the treatment course, an additional semen analysis was performed by a technician not knowing the details of the patient.

Control Group

The control patients had acupuncture and moxa treatment performed at non-therapeutic indifferent points. Four ventral acupuncture points, two over the anterosuperior iliac spines and two over the acromioclavicular regions and four dorsal moxa points, two over the scapula and two over the posteroinferior spine, bilaterally were selected. The procedure was similar to those of the Study Group. Similarly, a semen analysis was performed at the end of the course

Semen analysis

Semen samples were obtained by masturbation after 3 days ~ 5 days sexual abstinence. After 30 min of liquefation at 37 ℃, semen analyses were performed according to the laboratory manual of World Health Organization⁸, while the sperm morphology was estimated as per Kruger et al [9]. Analyses were performed by two experienced technicians.

Statistical analysis

The Wilcoxon Tests [10] was used to compare the pre- and post-treatment data and the Mann-Whitney test¹⁰ to compare the two groups in relation to the calculated percentage data. Nullity hypothesis rejection level was set in 5 %.

Results

All patients completed the treatment, indicating a good patient tolerance to the procedure. However, statistical analysis was performed with 8 patients in the Study Group. One was excluded on account of incomplete seminal data.

The patients of the Study Group presented a significant increase in the percentage of normal-form sperm compared to the Control Group (Table 3). The comparison of other pre- and post-treatment data (volume, concentration, progressive motility and number of round cells) did not show significant differences between the two groups.

Discussion

This study showed that the treatment of patients with oligo-, asteno-, terato- and oligoastenoteratozoospermia without apparent cause using acupuncture and moxa techniques can positively influence semen quality, once it improves semen morphology. This result was in accordance with Gerhard et al [5]. The possible mechanism by which acupuncture and moxa improve the sperm morphology may include their possible action through the nervous system. Acupuncture points are areas histologically differentiated, capable of generating an action potential which is conducted by the neural fibers A delta and/or C [11-13]. This stimulus at the posterior column medulla level can create a somatovisceral reflex arc or climb to superior centers, such as the reticular formation, thalamus and cerebral cortex [14, 15]. The response can be probable testicle and epididymis vasodilation. This fact is important when we correlate semen quality and the abnormal presence of reactive oxygen species (ROS). Previous studies have demonstrated that there were lower levels of seminal antioxidant agents in infertile patients, especially in those with compromised sperm motility, than in fertile men [16, 17, 18]. Besides, Gerhard et al [5], Siterman et al [6] and Siterman et al [7] indicated that in the treatment of infertile men with acupuncture, the best results were obtained in those with genital tract inflammation and varicocele, two sources of ROS [19, 20]. Thus, the lipidic peroxidation process in sperm plasma membrane and the high toxicity of the generated fatty acid peroxides proposed as being responsible for the functional and morphological alterations [21], would benefit from the vasodilatation caused by acupuncture and moxa treatments. This vasodilatation would supply antioxidant supplementation as vitamins C and E and glutathione to prevent plasma membrane damage by ROS, thus allowing the gamete recovery [16, 22]. Despite the small number of patients in this study, acupuncture and moxa treatments seem to favorably modify normal-form sperm counting.

In conclusion, the Chinese Traditional Medicine acupuncture and moxa techniques significantly increase the percentage of normal-form sperm in patients with oligoastenoteratozoospermia without apparent cause.

References

[1] María IH, Aguilar RC, Ayala AR. Estudio del hombre estéril. Ginecol Obstet Mex 1997; 65: 368-72.
[2] Oldereid NB, Rui H, Purvis K. Male partners in infertile couples. Personal attitudes and contact with the Norwegian Health Service. Scand J Soc Med 1990; 18: 207-11.
[3] de Kretser DM. Male infertility. Lancet 1997; 349: 787-90.
[4] Fischl F, Riegler R, Bieglmayer CH, Nasr F, Neumark J. Die beeinflubbarkeit der samenqualität durch akupunktur bei subfertilen männern. Geburtsh u Frauenheik 1984; 44: 510-2.
[5] Gerhard I, Jung I, Postneek F. Effects of acupuncture on semen parameters/ hormone profile in infertile men. Mol Androl 1992; 4: 9-25.
[6] Siterman, S, Eltes F, Wolfson V, Zabludovsky N, Bartoov B. Effect of acupuncture on sperm parameters of males suffering from subfertility related to low sperm quality. Arch Androl 1997; 39: 155-61.
[7] Siterman S, Eltes F, Wolfson V, Lederman H, Bartoov B. Does acupuncture treatment affect sperm density in males with very low sperm count? A pilot study. Andrologia 2000; 32: 31-9.
[8] World Health Organization. WHO Laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 4th ed. Cambridge: Cambridge University Press; 1999. p 7-14.
[9] Kruger TF, Ackerman SB, Simmons KF, Swanson RJ, Brugo SS, Acosta AA. A quick, reliable staining technique for human sperm morphology. Arch Androl 1987; 18: 275-7.
[10] Siege S, Castellan Jr NJ. Nonparametric statistics. New York: Mc Graw Hill; 1988.
[11] Dornette WH. The anatomy of acupuncture. Bull N Y Acad Med 1975; 51: 895-902.
[12] Lu GW, Xie JQ, Yang J, Wang YN, Wang QL. Afferent nerve fiber composition at point zusanli in relation to acupunture analgesia. A functional morphologic investigation. Chin Med J (Engl) 1981; 94: 255-63.
[13] Zonglian H. A study on the histologic structure of acupuncture points and types of fibers conveying needling sensation. Chin Med J (Engl) 1979; 92: 223-32.
[14] Haber LH, Moore BD, Willis WD. Electrophysiological response properties of spinoreticular neurons in the monkey. J Comp Neurol 1982; 297: 75-84.
[15] Ammons WS. Characteristics of spinoreticular and spinothalamic neurons with renal input. J Neurophysiol 1987; 58: 480-95.
[16] Lewis SE, Sterling ES, Young IS, Thompson W. Comparison of individual antioxidants of sperm and seminal plasma in fertile and infertile men. Fert Steril 1997; 67: 142-7.
[17] Bhardwaj A, Verma A, Majumdar S, Khanduja KL. Status of vitamin E and reduced glutathione in semen of oligozoospermic and azoospermic patients. Asian J Androl 2000; 2: 225-8.
[18] Fujii J, Iuchi Y, Matsuki S, Ishii T. Cooperative function of antioxidant and redox systems against oxidative stress in male reproductive tissues. Asian J Androl 2003; 5: 231-42.
[19] Aitken RJ, Buckingham DW, Brindle J, Gomez E, Baker HWG, Irvine DS. Analysis of sperm movement in relation to the oxidative stress created by leukocytes in washed sperm preparations and seminal plasma. Hum Reprod 1995; 10: 2061-71.
[20] Lenzi A, Picardo M, Gandini L, Lombardo F, Terminali O, Passi S, et al. Glutathione treatment of dyspermia: effect on the lipoperoxidation process. Hum Reprod 1994; 9: 2044-50.
[21] Rao B, Soufir JC, Martin M, David G. Lipid peroxidation in human spermatozoa as related to midpiece abnormalities and motility. Gam Res 1989; 24: 127-34.
[22] Sharma RK, Agarwal A. Role of reactive oxygen species in male infertility. Urology 1996; 48: 835-50.

Direct effects of Chinese herbal medicine “hachuekkito” on sperm movement

Yamanaka M; Kitamura M; Kishikawa H; Tsuboniwa N; Koga M; Nishimura K; Tsujimura A; Takahara S; Matsumiya K; Okuyama A Department of Urology, Osaka University Medical School

Nippon Hinyokika Gakkai Zasshi, 89(7):641-6 1998 Jul (ISSN: 0021-5287)

BACKGROUND AND PURPOSE: Chinese herbal medicine, “Hochuekkitto” is widely used for male infertility in Japan. There have been many reports concerning its clinical usefulness but very few reports of in vitro experiments studying the mechanism of its effects. In addition to stimulating germ cells, we analyzed its direct effects on sperm using computer assisted semen analyzer (CASA). MATERIALS AND METHODS: Motile sperm were prepared using swim up technique from semen collected from ten healthy volunteers. Sperm movements (motility, velocity, linearity) were analyzed by CASA after adding either serum containing anti-sperm antibody (ASA) or normal serum with or without Hochuekkito.

RESULTS: Two hours after adding serum with ASA, the decrease of sperm motility was significantly reduced from 25.1% (92.8%–>67.7%) to 12.5% (92.9%–>80.6%) by adding Hochuekkito. No significant difference in velocity and linearity was observed between two groups. By adding normal serum, any of three parameters differed significantly with or without Hochuekkito. CONCLUSION: Protective effects of Hochuekkito on sperm was suggested. Although normal sperm with ASA was used in this report, since the sperm of infertile patients are said to be more fragile, this results imply that direct protective effect is one of the mechanism of Hochuekkito for male infertility

Substitution of Acupuncture for HCG in Ovulation Induction Articles

Cai Xuefen
Obstetrical & Gynecological Hospital,
Zhejiang Medical University, Zhejiang Province 310006

Journal of Traditional Chinese Medicine 17 (2):119-121,1997
By using human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG), fairly good clinical therapeutic efficacy has been obtained in the treatment of infertility. However, difficulties are brought about due to the ovarian hyperstimulation syndrome (OHSS) easily induced by these two drugs. Therefore, we attempted to use acupuncture instead of HCG in the induction of ovulation from 1989 to 1992, and satisfactory therapeutic effect was achieved as reported in the following.

General Data

Ten patients were hospitalized with confirmed diagnosis of infertility and totally observed for 11 menstrual cycles (one patient had recurrence of OHSS for 2 times). Their ages ranged from 27 to 30 years with an average of 29 years. After treatment by HMG, all patients manifested OHSS in varying degrees. In accordance with the criteria for grading of OHSS issued by WHO, among these 11 menstrual cycles 4 cycles were mild (ovarian slight enlargement less than 5 cm with symptoms of slight malaise of lower abdomen); 7 were moderate (marked enlargement of ovary with nausea, vomiting and abdominal distension); no severe case occurred (extreme enlargement of ovary with hydrothorax, ascites, pycnemia and electrolyte disturbance). In order to prevent the exacerbation of OHSS caused by combined use of HMG and HCG, acupuncture was used after HMG treatment to replace HCG for the ovulation induction in 11 menstrual cycles of these patients.

Therapeutic Method

1.5-3 cun long filiform needles (no. 28-30) were used. Several infertility acu pointswere selected according to the signs and symptoms as adjuvant points. The manipulation techniques included twirling, rotating, lifting and thrusting. Reinforcing method was used in Shenshu point and the remaining points were punctured by reducing manipulation. The needling sensation should be transmitted toward both sides of lower abdomen. When arrival of Qi, retained the needles for 15 min. and manipulated the needles intermittently during the retaining period to enhance the stimulation. Moxibustion with moxa stick was used for some of these acupoints.

Observation of Therapeutic Effect

Criteria for assessment of therapeutic effect: Therapeutic effect was appraised mainly by comparison of ultrasonic B examination after needling with that before treatment and referred to the score of cervix uteri and basal body temperature to sit judgment on ovulation. Ovulation occurred within 24 h after 1st needling was considered as marked effect; ovulation within 72 h after 2-3 times of needling was effective; no ovulation occurred after 72 h after more than 3 times of needling was scored as ineffective.

Results of Treatment

Of the 11 menstrual cycles, marked effect was shown in 5 cycles, effective in 5 cycles and failed in 1 cycle. Among the 10 markedly effective and effective cycles, ovulation was induced in 2 cases after needling and diagnosed pregnancy by blood HCG assay and ultrasonography. In 9 of the 10 cycles treated with acupuncture for ovulation induction without using HCG and other drugs, the symptoms of OHSS were significantly remitted or even disappeared. Only in one cycle, HCG (with dosage less than for ovulation) was used after needling to maintain the function of corpus luteum and resulted in exacerbation of OHSS and finally remitted by drug treatment.

Typical Case

Fang, 27-year-old, suffered from polycystic ovary syndrome. She was unpregnant after married 2 years and the menstruation was only 1-2 times a year. The basal body temperature was monophase. No effect was observed using clomiphene and then treated with HMG. From the day 5, for bleeding due to withdrawal of progesterone, intramuscular injection of HMG was given at a dose of 150 U once a day for 8 days. The score of cervix uteri was 12 mark. The ultrasonogram showed that the size of right ovary was 9.6 cm x 7.8 cm x 4.6 cm and the left side was 9.2 cm x 7.2 cm x 4.7 cm. Both sides of ovary had 10-20 follicles with maximum size 1.8 cm. In order to avoid severe OHSS, acupuncture was used instead of HCG for ovulation induction after stopping HMG treatment. On the next day after the first needling, the basal body temperature elevated from 36.3°C to 36.8°C and the score of cervix uteri fell from 12 mark to 9 mark, and ultrasonic B examination suggested that part of the follicles were ovulated. After the l9th day of ovulation, the blood concentration of HCG started rising and after 40 days the blood level of HCG reached to 35.6 ng/ml. The ultrasonogram showed that the diameter of embryonic sac was 1.5 cm and early pregnancy was diagnosed.

Discussion

It was reported in literature that using HMG-HCG in the induction of ovulation, the ovulatory rate was about 70%-90%, but the incidence of OHSS might be 10%-15.4% and even life-threatening in the severe case. At present, there were no satisfactory measures for the prevention and remission of OHSS. In most reports, it is considered that when OHSS inclines to occur, stopping injection of HCG is the effective way to avoid severe OHSS. However, stopping HCG would not only discontinue the ovulation of HCH, but also gave up the already developed follicles. Our clinical practice demonstrated that acupuncture is effective in ovulation induction and also the remission of OHSS induced by HMG. Furthermore, we also noted that in most OHSS patients enlarged ovaries and numerous developed follicles were revealed. As a result of excessive follicles developed, dysplasia of ova and insufficiency of corpus luteum often occurred, thus leading to uneasy pregnancy after ovulation. So it is reasonable to infer that using some Chinese drugs benefiting the function of corpus luteum or using certain amount of progesterone as supplementary treatment after acupuncture, the pregnancy rate could be raised.

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Procedures of In vitro Fertilization

Human in vitro fertilization is a process in which the egg and sperm are fertilized in vitro, meaning outside of the body in a Petri dish. (In vitro means in glass.) The fertilized embryo is then implanted into the female’s uterus. IVF was first successful in the United States in 1981. Since then, it has become a widely accepted method of treatment for infertile couples.

There are various causes of infertility, many of which can successfully be treated with IVF. The indications for in vitro fertilization include:

• Fallopian tube obstruction
• Oligospermia (Low sperm count)
• Abnormal cervical factor
• Immunologic factor-husband or wife
• Infertility after tubal surgery
• Infertility after treatment for endometriosis
• Unexplained infertility

The following is an overview of the steps of IVF.

1. Regulation of hormones

Once pretreatment screening of a couple has taken place, the IVF specialist or team will attempt to regulate and control the hormones prior to beginning IVF. There are many different methods to performing the various steps with in vitro fertilization. Presently, the most common method is for female patients to take oral contraceptive pills for the first month. Recently, there have been some physicians who do not give birth control pills to women over age 40 or if they have high FSH levels. When trying to control ovulation, one common method is for the patient to take leuprolide acetate (Lupron) before or after stopping birth control pills. Another current method is to give ganerelix (Antagon) three days prior to the hCG (Human chorionic gonadotropin) injection to control ovulation.

2. Stimulation of ovulation

There is a choice of basic stimulation protocols available to the patient and physician. There is no single approach to ovulation stimulation that works equally well for all patients. Physicians will be guided by the person’s medical history, and perhaps also by previous responses to those agents, in determining the stimulation protocol best suited for each patient.

Even when the woman has normal ovulation function, ovulation stimulation will be employed in almost all cases in order to induce development of the maximum number of follicles containing mature oocytes. Commonly used drugs, such as menotrophins (Pergonal or Repronex), follitropin beta (Follistim), and follitropin-alpha (Gonal-F), are given to stimulate the ovaries to produce more follicles and regulate the hormones. Pergonal and Repronex contain both the LH (Luteinizing hormone) and FSH (follicle-stimulating hormone), while Follistim and Gonal-F contain only FSH.

3. Monitoring Follicular development

During the stimulation phase, the ovarian response is usually monitored with some combination of ultrasound examinations to track follicular development and blood tests to measure hormone levels (primarily estrogen and LH). As the follicles mature, these tests may be performed daily over a 4-6 day interval.

During the final stages of follicular development and egg maturation, the patient will be given a hCG (human chorionic gonadotropin) injection. This is timed 34-36 hours prior to the egg retrieval, just before ovulation would occur, and helps to change immature eggs into mature or metaphase II eggs.

4. Oocyte retrieval

Various techniques have been used for oocyte aspiration. In the past, laparoscopy was usually employed. This is procedure that makes small incisions, usually two or three, on the abdomen. Currently, the most common method being used is the transvaginal USG approach. Guided by ultrasound scanning, a physician inserts a long, thin needle through the vagina and into the ovary, thereby emptying the follicles. The needle is connected to a suction pump and the fluid from each accessible follicle within the ovary is aspirated.

Not all the eggs retrieved will be mature or normal in appearance. The percentage of eggs achieving fertilization depends on many factors. Some eggs that appear to be mature and normal in appearance will not become fertilized even when exposed to normal sperm. Not all eggs exposed to sperm will go on to division (cleavage). Not all eggs fertilize and even those that do may not all continue to divide beyond the four cell stage. As an example, a typical cycle may produce twelve eggs of which eight become fertilized and seven begin to divide in a satisfactory fashion.

Depending on the female patient’s age, 2-4 will be transferred to the uterus and two or three will be cryopreserved (frozen).

5. Laboratory component

If the follicle is mature, a visible amount of granulosa cells will accompany the aspirated fluid in which the mature ovum is found. This fluid is examined by an embryologist under a microscope in order to identify and isolate the egg complex. The oocyte is identified and graded for its maturity, placed in an incubation medium within a petri dish, and finally transferred into the incubator. Eggs are usually cultured in the incubator for 3-6 hours depending on maturity before being exposed to sperm.

For semen, various forms of preparation can be used, from a simple washing and centrifugation, to a more complicated “swim-up” procedure that separates only motile sperm to be used for insemination. To perform insemination, between 50,000-500,000 motile sperm per milliliter are needed. When sperm quality and or numbers are low, it may be necessary to hold the egg under the microscope and inject a single sperm into the interior of the egg (a procedure known as intracyto-plasmic sperm injection or ICSI).

6. Embryo growth in culture

Once the oocyte has been fertilized with the sperm, it is examined approximately 15-18 hours later for fertilization and switched from the incubation medium to a growth medium that contains twice the amount of protein. Next, the fertilized egg is returned to the incubator and kept there until the time of transfer, usually around 48-72 hours after insemination. The fertilized egg is ordinarily in the four or eight cell stage before transfer of the embryo can take place.

7. Embryo transfer

Approximately 2-6 days after insemination, the dividing embryos selected for replacement in the uterus are loaded into a soft plastic catheter. Using a small volume of medium, the biologist loads the catheter and the physician passed it through the cervix wall into the uterine cavity. Most programs transfer 2-3 embryos in patients under age 35 undergoing their first cycle of treatment, and 3-4 in those ages 35-40 to maximize their chance of success while minimizing multiple pregnancies. Additional healthy embryos may be frozen in liquid nitrogen to be used later if implantation and pregnancy do not occur.

8. Luteal phase monitoring

After ovulation has occurred, supplemental progesterone in the form of vaginal suppositories, injections, or micronized oral tables may be added. Ultrasonography may be employed to measure ovarian size, particularly if hyper stimulation is suspected.

Pregnancy testing is usually performed 12-14 days after egg retrieval. If the results are positive, progesterone levels will be checked and the pregnancy test repeated in order to measure the rate of rise in hCG that occurs in early pregnancy. Using vaginal ultrasonography, a fetal sac typically can be seen 25 days following egg retrieval, and by the 35th day, fetal heart motion can be observed.

Research in Acupuncture, Infertility and IVF, related articles

Acupuncture on the day of embryo transfer significantly improves the reproductive outcome in infertile women: a prospective, randomized trial. Westergaard LG, Mao Q, Krogslund M, Sandrini S, Lenz S, Grinsted J. Fertility Clinic Trianglen, Hellerup, Denmark. Fertil Steril. 2006 May; 85(5):1341-6. Epub 2006 April 5.

Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer. Smith C, Coyle M. Norman RJ. School of Health Science, the University of South Australia, South Australia, Australia. Fertil Steril. 2006 May; 85(5)1352-8. Epub 2006 April 5

Acupuncture prior to and at embryo transfer in an assisted conception unit — a case series. Johnson D. Chobham Acupuncture Clinic, Chobham, Surrey. Acupuncture Med. 2006 Mar; 24(1):23-8

Effect of acupuncture on the outcome of in vitro fertilization and intracytoplasmic sperm injection: a randomized, prospective, controlled clinical study. Dieterie S. Ying G, Hatzmann W, Neuer A. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Witten/Herdecke, Dortmund, Germany. Fertil Steril. 2006 May; 85(5): 1347-51. Epub 2006 Apr 17.

Stress and outcome success in IVF; the role of self-reports and endocrine variables. Smeenk JM, Verhaak CM, Vingerhoerts AJ, Sweep CG, Merkus JM, Willemsen SJ, van Minnen A, Straatman H, Braat DD. Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Center, PO Box 9101, NL-6500 HB Nijmegen, The Netheriands. Hum Reprod. 2005 Apr; 20(4):991-6. Epub 2005 Jan 21.

Electro-acupuncture as a preoperative analgesic method and its effects on Implantation rate and neuropeptide Y concentrations in follicular fluid. Stener-Victorin E, Waldenstrom U, Wikland M, Nilsson L, Hagglund L, Lundeberg T. Department of Obstetrics and Gynaecology, Goteborg University, Gothenburg, Sweden. Hum Reprod. 2003 Jul: 18(7): 1454-60.

Izumi S, Makino T. Department of Obstetrics and Gynecology, Center for Growth and Reproductive Medicine, Tokai University School of Medicine, Issehara, Kanagawa, Japan. Tokai J Exp Clinic Med. 2003 Apr; 28(1):9-15

Alternative treatments in reproductive medicine: much ado about nothing. Acupuncture- a method of treatment in reproductive medicine: lack of evidence of an effect does not equal evidence of the lack of an effect. Stener-Victorin E, Wikland M, Waldenstrom U, Lundeberg T. Department of Obstetrics and Gynaecology, Gutenberg University, SE-413 45 Goteborg, Sweden. Hum Reprod. 2002 Aug; 17(8): 1942-6

Role of acupuncture in the treatment of female infertility Chang R, Chung PH, Rosenwaks Z. The Institute of East-West Medicine, New York, New York, USA, The Department of Internal Medicine, Weill Medical College of Cornell University, New York, New York, USA, The Center for Reproductive Medicine and Infertility, Weill Medical College of Cornell University, New York, New York, USA, Fertil Steril 2002 Dec;78(6):1149-53.

Auricular acupuncture in the treatment of female infertility. Gerhard I, Postneek F. Department for Gynecological Endocrinology and Reproduction, Women’s Hospital, University of Heidelberg, Germany, Gynecol Endocrinol. 1992 Sep; 6(3):171-81

Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy. Paulus WE, Zhang M, Strehler E, EL-Danasouri I. Sterzik K. Department of Reproductive Medicine, Christian-Lauritzen-Institut, Ulm, Germany Fertil Steril 2002 Apr; 77(4): 721-4

Reduction of blood flow impedance in the uterine arteries of infertile women with electro-acupuncture. Stemer-Victorin E, Waldenstrom U, Andersson SA, Wikland M. Department of Obsterics and Gynaecology, Fertility Centre Scandinavia, University of Gothenburg, S-413 45 Gothenburg, Sweden. Hum Reprod. 1996 Jun; 11(6): 1314-7

Acupuncture Treatment For Infertile Women Undergoing Intracytoplasmic Sperm Injection. Emmons S, Patton P.Obstetrics and Gynecology, Oregon Health Sciences University, Portland, OR. Medical Acupuncture: A Journal for Physicians by Physicians, 2000

The Impact of group psychological Interventions on distress in infertile women. Domar AD, Clapp D, Slawsby E, Kessel B, Orav J, Freizinger M. Mind/Body Medical Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, USA. Health Psychol. 2000 Nov; 19(6):568-75

Does recommending timed intercourse really help the infertile couple? Agarwal SK, Haney AF. Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina. Obstet Gynecol. 1994 Aug; 84(2): 307-10.

Stress and other environmental factors affecting fertility in men and women: overview. Negro-Vilar A. Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Environ Health Perspect. 1993 Jul; 101 Suppl 2:59-64.

Psychosocial stress as a cause of infertility. Wasser SK, Sewall G, Soules MR. Endocrine Research Laboratory, Smithsonian Institution, Front Royal, Virginia 22630. Fertil Steril. 1993 Mar; 59(3):685-9

Stress and human reproduction. Schenker JG, Meirow D, SchenkerE. Department of Obstetrics and Gynecology, Hadassah University Hospital, Jerusalem, Israel. Eur J Obstet Gynecol Reprod Biol. 1992 Jun 16;
45(1):1-8

Tim H. Tanaka, PhD., D. Ac., RMT, RNCP, BCIAC obtained acupuncture training and licensing in Japan with 20 years of clinical experience. Dr. Tanaka is the Director of The Pacific Wellness Institute, Toronto, Ontario and Visiting Research Fellow at the Acupuncture Department, Tsukuba College of Technology in Japan. For general Information about acupuncture, visit Acupuncture-Treatment.com.

Hopps CV, Goldstein M. Male infertility: the basics.

Levine D. Boxers or Briefs: myths and facts about men’s infertility.

Pei J, Strehler E. Noss U et al. Quantitative evaluation of spermatozoa ultra structure after acupuncture treatment for idiopathic male infertility. Fertility and Sterility July 2005; 84(1):141-7