Acupuncture for the Treatment of Infertility
By Judith Balk, MD, MPH, FACOG Assistant Research Professor, University of Pittsburgh, Pittsburgh, PA. Dr. Balk reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study.
A common condition seen in medical practice, infertility is described in Western medicine as the inability of couples of reproductive age to establish a pregnancy by having sexual intercourse within a certain period of time, usually one year.1 In the United States, as many as 15% of all couples are infertile, with higher rates seen in older couples. Although nearly half of all infertile couples have some component of male infertility, only 30% of cases are a result of male infertility alone. Female infertility may be a result of anovulation, pelvic factors such as adhesions and tubal occlusion, or cervical factors.
In Western medicine, treatment is aimed at correcting the etiological factor after ruling out other causes of infertility. It usually is the female partner who presents initially for an infertility problem, often in the context of an annual well-woman examination. In this situation, the primary care provider may initiate certain diagnostic and treatment options. Given the expense and invasive nature of many conventional treatment options for infertility, complementary and alternative therapies such as acupuncture have begun to receive more attention from physicians and patients. Although there remains a paucity of clinical research in this area, the relative safety of acupuncture makes it a reasonable option as part of an initial intervention or in conjunction with conventional therapies.
Etiology in Traditional Chinese Medicine
According to traditional Chinese medicine (TCM), the etiology of infertility also may be multifactorial, and may include constitutional weakness, overwork, excessive physical work, excessive sexual activity at an early age, invasion of cold, and diet.2 TCM treatment attempts to correct the underlying problem through use of herbal preparations and acupuncture. Prescriptions date back hundreds of years, and as early as 259 AD, acupuncture formulae were given for infertility. Prescriptions varied based on the presence or absence of clinical factors such as abdominal pain, white vaginal discharge, and stasis of blood.2
Mechanism of Action
The mechanisms of action by which acupuncture may treat infertility have not been elucidated. One possible mechanism is via hormonal regulation, with acupuncture regulating a dysfunctional hypothalamic-pituitary axis. Another mechanism might be improvement in uterine blood flow, which increases the receptivity of the endometrium to a fertilized egg.
Human StudiesTreatment
Infertile patients may seek assisted reproductive techniques such as in vitro fertilization (IVF). Successful IVF depends on adequate endometrial receptivity. Acupuncture has been demonstrated to improve uterine blood flow impedance, which is a measurement of blood flow to the uterus. It has been considered valuable in assessing endometrial receptivity.3 Ten subjects with a high pulsatility index (PI), a measurement made using Doppler transvaginal ultrasound, were treated with twice weekly acupuncture for the month prior to embryo transfer. A high PI is evidence of decreased uterine artery blood flow. PI decreased both at the time of the embryo transfer and again at follow-up approximately two weeks later. The authors suggest that the effects arise from a central inhibition of the sympathetic activity.
Acupuncture also has been studied as analgesia during infertility treatment. A randomized controlled trial compared acupuncture to alfentanil as anesthesia for oocyte aspiration during IVF.4 One hundred fifty women participated in this study. The acupuncture group experienced discomfort for a longer period of time during oocyte aspiration, but no differences between the groups were noted by visual analog scale, adequacy of anesthesia during aspiration, abdominal pain suffered, or degree of nausea. Surprisingly, the acupuncture group had a statistically significantly higher implantation rate, pregnancy rate, and take home baby rate per embryo transfer. Compared with the alfentanil group, the electroacupuncture group's implantation rate was 27.2% vs. 16.3%; pregnancy rate was 45.9% vs. 28.3%; and take home baby rate was 41% vs. 19.4% per embryo transfer. The same authors are conducting a larger study to corroborate these findings.
A large fibroid may cause infertility. One case report presented a patient with a 13 x 8 x 10 cm fibroid uterus who had secondary infertility, unresponsive to repeated cycles of IVF (the exact number of IVF cycles was not reported).5 This patient underwent acupuncture treatment and her uterus decreased to 7 x 8 x 8 cm, after which she had successful IVF and delivered healthy twins.
The studies cited above all used body points, but auricular (or ear) acupuncture also has been used to treat female infertility.6 Forty-five infertile women with either oligomenorrhea or luteal insufficiency were treated with auricular acupuncture. Results of treatment were then compared with matched subjects who were treated with hormones. Pregnancy rate was similar for both groups, whereas side effects were observed only in the hormone group. However, the groups were not equal even though they were matched on several criteria. The authors conclude that auricular acupuncture seems to offer a valuable alternative therapy for female infertility from hormone disorders. However, lack of randomization and differences between the groups limit the ability to make this conclusion.
Two abstracts retrospectively assessed the efficacy of acupuncture in their IVF population.7,8 The first abstract is difficult to evaluate because the tables referenced in the text are not present.7 In this retrospective study, data were extracted from medical records between January 2001 and November 2003. The investigators included 147 women, 53 who received acupuncture and 94 who did not. Demographic factors, diagnoses, IVF protocols, and type of gonadotropin protocols used were not different between groups. However, length of time infertile and peak follicle stimulating hormone (FSH) did demonstrate significance, but since the tables are missing, it is not clear which direction the differences follow. The investigators modified the acupuncture by dropping 15 patients, thus elevating the PI significantly. After this modification, pregnancy rates were significantly different between groups: 53% for the acupuncture group and 38% for the non-acupuncture group. The authors concluded that this was the first study to demonstrate that the use of acupuncture in patients with poor prognoses (elevated FSH, longer history of infertility, and poor sperm morphology) can achieve pregnancy rates similar to normal prognosis patients. They also concluded that acupuncture was useful in patients with a normal PI as well as an abnormal, elevated PI. Again, the abstract nature and the missing tables limit the usefulness of this study.
An American Society for Reproductive Medicine meeting included a presentation of results from a retrospective case-control study, evaluating 114 infertile patients undergoing controlled ovarian hyperstimulation with gonadotropins and GnRH agonist and antagonist for IVF-embryo transfer (ET) in a private practice IVF clinic.8 Only IVF patients with normal day 3 FSH, normal uterine artery PI, sperm morphologies that met Kruger Strict Criteria, and good response to ovarian hyperstimulation were analyzed. Of the 114 patients, 53 received acupuncture and 61 did not. The acupuncture protocol used the reduction of uterine PI protocol as reported by Stener-Victorin3 and the pre-/post-embryo transfer protocol as reported by Paulus et al.9 Cycles were grouped according to patients who received no acupuncture and patients who received either one or both acupuncture treatments. The groups were similar with respect to prognostic and demographic factors. Pregnancy rates (PR) and miscarriage rates (SAB) were statistically improved in those who received acupuncture compared to those who did not (51% vs. 36% PR and 8% vs. 20% SAB rate). Similarly, birth rates per cycle were significantly higher in the acupuncture group, and ectopic rates were statistically lower in the acupuncture group. The investigators concluded that acupuncture is helpful even in the good prognosis group by improving live birth rates, decreasing miscarriages, and decreasing ectopic pregnancies. The authors did not attempt to separate the amount of acupuncture patients received or to determine whether one protocol was more helpful than the other.
The Paulus protocol utilized acupuncture at the time of embryo transfer.9 In this prospective, randomized trial at a fertility center, 160 patients undergoing IVF-ET with good quality embryos received either embryo transfer with acupuncture (n = 80) or embryo transfer without acupuncture (n = 80). The groups were similar at baseline with respect to prognostic factors. The acupuncture protocol utilized both body points and auricular points. The main outcome was clinical pregnancy, defined as the presence of a fetal sac by ultrasound six weeks after embryo transfer. Clinical pregnancies were documented in 42.5% of patients in the acupuncture group and 26.3% in the control group. This difference was statistically significant (P = 0.03). Since this study involved a relatively large number of subjects randomized to treatment groups, many confounders should be equally distributed between groups. Based on the group comparisons, it appears that randomization was successful. This trial has fairly rigorous methodology.
Another abstract presented results of the effects of acupuncture as an adjunct to IVF.10 The trial methodology is described as a randomized, controlled, double-blind, crossover study, but evaluating the study is difficult because only an abstract is published. How the study is double-blind is unknown, since the acupuncturist administering the treatments likely was not blinded to the treatment group. Sham acupuncture, using a needle-like device, was used as a control. Neither the acupuncture protocol nor detail on the control procedure is described. Women who had a history of failed IVF cycles and normal FSH, uterine cavity, and semen analysis were included. Seventeen subjects were enrolled and seven subjects completed both arms of the study. The numbers are difficult to evaluate, but the investigators note that a significantly lower amount of gonadotropins was used in the acupuncture group. A 70% pregnancy rate was achieved with acupuncture and IVF, compared to 25% in the sham group. However, the important result is not the pregnancy rate, which includes chemical pregnancies and miscarriages, but the live birth rate or the ongoing pregnancy rate. In this study, there were three ongoing pregnancies in the sham group and four in the acupuncture group. Lack of detail precludes an adequate analysis of this study.
Human Female StudiesHormone Levels
Chinese investigators studied 10 anovulatory women and five women with normal menstrual cycles.11 Subjects were treated with electroacupuncture for 30 min/d for three days per month for 13 cycles. Changes in blood hormone concentration were measured. Beta-endorphin, luteinizing hormone (LH), and FSH normalized in those who ovulated but did not change in those who did not ovulate. However, the determination of ovulation was not described, and other important methodological details are missing.
Another Chinese study was equally difficult to interpret.12 Thirty-four subjects with amenorrhea and dysfunctional uterine bleeding received acupuncture three times per week for three months. The terms that the authors use are unclear. Criteria for the efficacy of therapy for inducing ovulation were defined as markedly effective, effective, or ineffective, based on ultrasound, basal body temperature, and presence or absence of menstruation. Thirty-five percent, 48%, and 18% were markedly effective, effective, and ineffective, respectively. An endocrine profile was performed in 20 subjects before and after treatment. FSH, LH, and estradiol normalized compared to pre-acupuncture values. However, the time during the menstrual cycle at which the blood was drawn was not stated; different timing could greatly skew these results.
Safety
Several prospective investigations of the adverse effects associated with acupuncture have supported its relative safety.13-15 The most frequently reported adverse effects were needling pain and hematoma.
Conclusion
A small number of studies have been conducted to investigate the effect of acupuncture on female infertility. Lack of rigorous design, inadequate definitions, and language barriers all make the present data unconvincing. Research of acupuncture in IVF has several barriers. One is the lack of insurance coverage for IVF cycles, where the high out-of-pocket costs might reduce a subject's willingness to receive a sham treatment. Another is the high variability in prognostic factors such as age and ovarian response. One other barrier is the high variety of different agents used in an IVF cycle, and controlling for each of these variables would be logistically impossible. In all acupuncture studies, there are methodological issues to consider, such as whether to give the subjects a standardized treatment or an individualized treatment, and what an appropriate control for acupuncture is. Acupuncture studies in infertility are methodologically very difficult to conduct.
Recommendation
More clinical research is now available to support the use of acupuncture as an adjunct to IVF. However, given the lack of details present in studies published in abstract form only, and the lack of randomization in the Magarelli analyses, only the Paulus protocol can be fully evaluated. It is a rigorous study that clearly demonstrates the effectiveness of acupuncture at the time of embryo transfer. Although the data suggest that acupuncture might be useful in both good prognosis and poor-prognosis IVF patients, prospective randomized studies are necessary to fully evaluate this question.
References
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3. Stener-Victorin E, et al. Reduction of blood flow impedance in the uterine arteries of infertile women with electro-acupuncture. Hum Reprod 1996;11:1314-1317.
4. Stener-Victorin E, et al. A prospective randomized study of electro-acupuncture versus alfentanil as anaesthesia during oocyte aspiration in in-vitro fertilization. Hum Reprod 1999;14:2480-2484.
5. Sternfeld M, et al. The effect of acupuncture on functional and anatomic uterine disturbances: Case report-secondary infertility and myomas. Am J Acupuncture 1993;21:5-7.
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8. Magarelli P, et al. Acupuncture and good prognosis IVF patients: Synergy. ASRM annual meeting; Philadelphia, PA: Oct 16-20, 2004.
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10. Quintero R. A randomized, controlled, double-blind, cross-over study evaluating acupuncture as an adjunct to IVF. Fertil Steril 2004;81:11-12.
11. Chen BY. Acupuncture normalizes dysfunction of hypothalamic-pituitary-ovarian axis. Acupunct Electrother Res 1997;22:97-108.
12. Mo X, et al. Clinical studies on the mechanism for acupuncture stimulation of ovulation. J Tradit Chin Med 1993;13:115-119.
13. MacPherson H, et al. The York acupuncture safety study: Prospective survey of 34,000 treatments by traditional acupuncturists. BMJ 2001;323:486-487.
14. White A, et al. Adverse events following acupuncture: Prospective survey of 32,000 consultations with doctors and physiotherapists. BMJ 2001;323:485-486.
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Balk J. Acupuncture for the treatment of infertility. Altern Ther Women's Health 2005;9(10):73-77.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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