Doi:10.1016/j.fertnstert.2005.12.015

Influence of acupuncture stimulation on pregnancy
rates for women undergoing embryo transfer
Caroline Smith, Ph.D.,a Meaghan Coyle, B.Hlth.Sc. (Acup.),b and Robert J. Norman, M.D.c,d a School of Health Science, The University of South Australia; b Department of Obstetrics and Gynecology, The University ofAdelaide; c Research Centre for Reproductive Health, The Queen Elizabeth Hospital, University of Adelaide; and d Repromed,Adelaide, South Australia, Australia Objective: To evaluate the effects of acupuncture on clinical pregnancy rates for women undergoing ET.
Design: Single-blind, randomized controlled trial using a noninvasive sham acupuncture control.
Setting: Repromed, The Reproductive Medicine Unit of The University of Adelaide.
Patient(s): Women undergoing IVF.
Intervention(s): Women were randomly allocated to acupuncture or noninvasive sham acupuncture with the
placebo needle. All women received three sessions, the first undertaken on day 9 of stimulating injections, the
second before ET, and the third immediately after ET.
Main Outcome Measure(s): The primary outcome was pregnancy. Secondary outcomes were implantation,
ongoing pregnancy rate at 18 weeks, adverse events, and health status.
Result(s): Two hundred twenty-eight subjects were randomized. The pregnancy rate was 31% in the acupuncture
group and 23% in the control group. For those subjects receiving acupuncture, the odds of achieving a pregnancy
were 1.5 higher than for the control group, but the difference did not reach statistical significance. The ongoing
pregnancy rate at 18 weeks was higher in the treatment group (28% vs. 18%), but the difference was not
statistically significant.
Conclusion(s): There was no significant difference in the pregnancy rate between groups; however, a smaller
treatment effect can not be excluded. Our results suggest that acupuncture was safe for women undergoing ET.
(Fertil Steril௡ 2006;85:1352– 8. 2006 by American Society for Reproductive Medicine.)
Key Words: Acupuncture, clinical trial, embryo transfer, pregnancy rate
Some couples might choose to try complementary and alter- controlled. Successful IVF and ET require optimal endome- native medicines before they commence infertility treatment trial receptivity at the time of implantation. Blood flow or might choose to use it as an adjunct while undergoing impedance in the uterine arteries as measured by transvagi- infertility treatment. Acupuncture has long been used for nal ultrasonography expressed as a resistance index, the gynecological and obstetric problems, such as amenorrhea, pulsatility index, is considered to be a useful method for menorrhagia, morning sickness, and problems during labour assessing uterine receptivity. In one small, uncontrolled and delivery and is one complementary and alternative study of electro-acupuncture, lower pulsatility index values medicine considered by some women to assist with infertil- ity treatment. Classic acupuncture refers to the insertion offine needles into specific points of the body. This treatment There have been two randomized controlled trials of acu- has a history dating back 2,500 years and treats illness by puncture administered to women undergoing IVF In restoring a balance in the flow of Qi (energy) in the human the trial undertaken by Paulus et al. 160 healthy women body. Acupuncture today involves modes of stimulation, undergoing IVF or intracytoplasmic sperm injection (ICSI) such as acupressure, transcutaneous electrical nerve stimu- in Germany were randomized to receive acupuncture or no lation, moxibustion, ear acupuncture, and the use of lasers.
acupuncture. Acupuncture was administered 25 minutes be-fore and after ET. Needles were inserted, and the Deqi There have been few randomized controlled trials of acu- needling sensation was obtained. Needles were retained for puncture in the area of reproductive medicine. Two studies 25 minutes before and after the transfer, and acupuncture of acupuncture for male infertility concluded that points were used to move Chi and Blood and calm Chi.
acupuncture might be a useful treatment for men with poor Treatment used a fixed combination of body and auricular sperm density; however, these studies were small and un- acupuncture points. A higher pregnancy rate was found inthe acupuncture group compared with the control group Received September 15, 2005; revised and accepted December 10, (42.5% vs. 26.3%, PϽ.03). However, bias might have arisen from inadequate blinding, and insufficient details were re- Supported by research funds from Repromed and the University of South ported on the sample and effect size.
Reprint requests: Caroline Smith, Ph.D., The Australian Centre for Natural Quintero evaluated the effectiveness of acupuncture as Health and Wellness, 2 The Parade, Norwood, SA 5006, Australia(E-mail: [email protected]).
an adjunct to IVF. Seventeen women were randomized to Fertility and Sterilityா Vol. 85, No. 5, May 2006 Copyright 2006 American Society for Reproductive Medicine, Published by Elsevier Inc.
receive acupuncture or sham acupuncture in a double-blind, All women received three treatment sessions. The first crossover trial; however, only seven women completed the took place on day 9 of stimulating injections, and the second study. Two women in each group achieved an ongoing and third were immediately before and after ET. The time pregnancy. Of the seven who crossed over to the other from randomization to ET varied (depending on women’s treatment arm, two women in the acupuncture group response to stimulation); however, the mean length of time achieved an ongoing pregnancy, compared with one in the sham acupuncture group. Although the investigators found A structured interview was used to determine the infertil- that acupuncture significantly reduced the amount of gonad- ity diagnosis from a traditional Chinese medicine (TCM) otropin used (PϽ.05), no effect on the pregnancy rate was perspective. This included a tongue examination, palpation of the radial pulse, and a history of symptoms. Diagnosis In two retrospective clinical studies Magarelli et al.
was made with the approach described in Maciocia The explored the effects of acupuncture on IVF outcomes, using patterns identified included kidney yang, kidney yin, blood the protocols reported by Sterner-Victorin et al. and deficiency, blood stagnation, damp, and Qi stagnation Paulus et al. Magarelli et al. reported higher preg- The acupuncture treatment protocol was based on the pro- nancy rates (51% vs. 36%, PϽ.05) and lower miscarriage tocol reported by Paulus et al. Two modifications were rates (8% vs. 20%, PϽ.05) among those subjects receiving made: an initial acupuncture treatment was administered acupuncture compared with subjects in the comparison before ET, and two acupuncture points were excluded (liver group. The second study explored the influence of acupunc- 4 and governing vessel 20). Acupuncture was administered ture stimulation among subjects described as “poor respond- with point selection based on the TCM diagnosis. Points ers to IVF.” Fifty-seven subjects received acupuncture, and were needled bilaterally, and Acuglide (Helio Medical Sup- 94 received no acupuncture. A significant increase in the plies, San Jose, CA) 0.18 mm ϫ 30 mm needles were pregnancy rate was found for subjects receiving acupuncture inserted with a guide tube to tissue level and stimulated (53% vs. 38%, PϽ.01) Methodological limitations, such manually to elicit the Deqi response (needling sensation).
as selection bias, might have influenced the study findings.
The number of needles inserted ranged from 6 to 14 for thefirst treatment and were 13 and 10 in the second and third The research to date suggests that acupuncture might have treatments, respectively. Needles were retained for 25 min- a role in increasing pregnancy rates among women under- utes per treatment. Two acupuncturists administered acu- going IVF. There is clearly a need for a larger, pragmatic, puncture treatments, with the majority being administered by well-designed, randomized controlled trial to determine the the primary acupuncture researcher (M.C.).
effectiveness of acupuncture on pregnancy rates amongwomen undergoing IVF. In this article we report the findings For women in the control group, sham acupuncture points from a randomized controlled trial evaluating the effect of were used. These were located close to but not on the real acupuncture on pregnancy rates for women undergoing ET.
acupuncture points. These included points located on thefoot anterior to the junction of the third and fourth metatar- MATERIALS AND METHODS
sals, 4 cun (anatomical units) below and two fingerbreadthslateral to the knee, 2 cun above kidney 3 between the spleen Women undergoing IVF or ICSI were recruited from Re- and kidney meridians, 3 cun lateral to the midline level with promed, The Reproductive Medicine Unit of The University conception vessel 5 and 7, and 2 cun above the wrist crease of Adelaide. Women with a planned ET were eligible for between the lung and pericardium meridians.
inclusion; women previously randomized to the trial wereexcluded. Eligible women were identified by a research The Streitberger (Asiamed, Pullach, Germany) placebo nurse and were provided with information about the study.
needle (0.30 mm ϫ 30 mm) was used Because the tip The trial also received media coverage, resulting in some of the needle is blunted, skin penetration did not occur.
women self-referring to the study. Recruitment took place Needles were manually “stimulated” by lifting and thrusting between May 2003 and January 2005 and was approved by the handle of the needle and by running a fingernail along the the Women’s and Children’s Hospital’s research and ethics handle. The acupuncturist held the placebo needle in place with one hand while “stimulating” the needle with the otherhand. Each point was stimulated bilaterally for approxi- Information on demographics, fertility history, and health mately 3 minutes. Treatment duration was approximately 25 status was collected from subjects. Subjects were randomly minutes. This noninvasive sham procedure was selected allocated to a study group by selection of the next sealed because it closely resembles a style of TCM acupuncture envelope in the sequence for each stratification by number of IVF cycles (first, second, third, fourth, fifth or more) andmaternal age (Ͻ35 years, 35–37 years, 38 to 39 years, and The primary outcome was pregnancy, defined as the num- Ն40 years). Randomization was in balanced, variable blocks ber of couples achieving a clinical pregnancy (demonstration of random size (2, 4, 6) prepared by a researcher not involved of fetal heart activity on ultrasound scan). Secondary out- in the trial. Women were allocated to receive treatment with comes were implantation (defined as demonstration of a acupuncture or with noninvasive sham acupuncture.
gestational sac on ultrasound scan and calculated as a per- centage of the total embryos transferred), ongoing pregnancy with the most common reasons for infertility attributed to rate at 18 weeks, adverse events, and health status according male infertility and tubal factors. The SF36 scores were to the MOS 36 Short Form Health Survey (SF36) lower for women in the study cohort on the social function,vitality, mental health, and emotional role function domains Assessment of health status at the time of trial entry and compared with the South Australian population; however, after ET was made with the SF36. The SF36 is a multi-item higher scores were seen on the physical function and phys- scale measuring eight key health concepts: physical func- ical role function domains compared with the South Austra- tioning, role limitation due to physical health problems, lian population No differences existed between the two bodily pain, general health, vitality, social functioning, role groups, suggesting that the randomization produced compa- limitation due to emotional problems, and mental health well-being. The possible score range is 0 –100, with 100being the best possible score. The posttreatment question-naire included an evaluation of any adverse effects and an Pregnancy Outcome
assessment of which group subjects thought they were allo- presents the primary and secondary outcomes. Grad- ing was performed on all embryos with the score developedby Cummins et al. 1986 No difference in the grading of The power analysis was based on data presented by Paulus embryos was found between groups. The pregnancy rate, et al. which reported a pregnancy rate of 42.5% in the defined as fetal heart rate on ultrasound scan, was 31% in the treatment group and 26% in the control group. For women acupuncture group and 23% in the control group. For those undergoing IVF at Repromed, the pregnancy rate was 30% subjects receiving acupuncture, the odds of achieving a this was used for the control group pregnancy pregnancy was 1.5 higher than the control group but again rate. A trial of 114 women per group would detect a differ- did not reach statistical significance. The pregnancy rate was ence between groups, assuming a power of 80%, two-sided also not found to differ between groups among women aged testing at the 5% significance level.
Ͻ35 years (50% vs. 33%, PϽ.11). The ongoing pregnancy Data were analyzed with commercial software (Statistical rate at 18 weeks was higher in the treatment group, but the Package for the Social Sciences 11.5.1; SPSS, Chicago, IL).
difference was not statistically significant (28% vs. 18%).
The initial analysis examined the demographic and baseline Subjects’ health status did not differ between groups.
characteristics of women randomized to the trial. Any dif- Overall, however, the SF36 scores declined over the study ferences in prognostic variables were taken into account in intervention for the physical function, bodily pain, mental subsequent analyses of the major outcome variables. The main analyses undertook an “intention-to-treat” approachand compared differences in the primary study outcome No difference was found between groups for other study measure between the two groups. Comparisons were made endpoints: number of oocytes retrieved (weighted mean dif- between groups with ␹2 tests and by constructing relative ference 0.84, 95% CI Ϫ0.64 to 2.32), fertilization rate (RR risks (RRs); 95% confidence intervals (CIs) were based on 1.08, 95% CI 0.99 to 1.17), number of embryos transferred differences between groups. Levels of significance were (weighted mean difference 0.04, 95% CI Ϫ0.17 to 0.25), and reported at PϽ.05 and PϽ.01.
biochemical pregnancy rate (RR 1.16, 95% CI 0.87 to 1.56).
Side Effects
Of the 469 women assessed for eligibility, 215 declined to Subjects were asked whether they had experienced any side participate, and a small number were identified as being effects after any of their treatments. These were categorized ineligible Of the 228 subjects randomized, an into positive and negative side effects. The most frequently intention-to-treat analysis was performed on the primary reported side effects were relaxation (51% vs. 67%), feeling endpoint, pregnancy outcome. Thirty-six women (15%) calm and peaceful (55% vs. 64%), or feeling energized (10% were unable to comply with the treatment protocol because vs. 12%). Subjects in the control group were more likely to their cycle was cancelled or the ET was not undertaken.
report relaxation as a side effect of acupuncture (PϽ.05).
Seven women with a cancelled cycle were excluded from To examine the effect of blinding, subjects were asked which group they thought they had been allocated to. Twenty- The mean age of women participating in the trial was 36 six subjects (11%) correctly guessed their group allocation years The majority of subjects were receiving their . Of the 16 subjects who correctly guessed that they first fertility cycle, had a body mass index in the overweight were in the treatment group, the reasons given included category, were nonsmokers (90%), were currently drinking feeling positive, calm, relaxed, or better (6 women); gut alcohol (67%), were employed outside the home (85%), and feeling (3); positive thinking (3); point location (e.g., time had finished high school (83%). The majority of women taken to locate the points, accuracy in placement of nee- (69%) had not received acupuncture previously. More than dles) (2); and 1 subject guessed her group allocation. Of 50% of women reported a history of infertility Ͼ2 years, the 10 subjects who correctly guessed that they were in RCT of acupuncture at ET
Assessed for eligibility: 469
Randomized: 228
Cycle cancelled: 9 Pregnant: 8 Egg collection earlier than expected: 6 Egg collection after trial ceased: 2 Interpreter required: 1 Smith. RCT of acupuncture at ET. Fertil Steril 2006. the control group, the reasons included the placement of We examined whether previous experience of acupuncture needles (e.g., focus on feet, placement of needles, and would lead subjects to correctly identify their group allocation.
points used) (6); gut feeling (1); never had acupuncture This analysis was based on 71 subjects (32 in the treatment before (1); to avoid disappointment (1); and 1 subject group and 39 in the control group). After the first treatment 73% of subjects were unsure of their group allocation, and after thethird treatment 68% were unsure of their group allocation.
After the third treatment, a difference was found between Participants with previous acupuncture experience were not subjects’ perception of their group allocation (PϽ.05). Of the more likely to be able to correctly guess their group allocation 24 subjects who correctly guessed that they were in the treat- ment group, the reasons for their decision included feelinggood, relaxed, calm, positive, happier, warm, or better (12); thetreatment itself (e.g., points chosen, time to locate points, sense DISCUSSION
of accuracy in the method or care of treatment administration) The results from this study did not show a significant increase (4); positive thinking (4); and other reasons (4). Of the 10 in the pregnancy rate between acupuncture and sham acupunc- subjects who correctly guessed that they were in the control ture groups; however, a smaller treatment effect can not be group the reasons for their decision included a lack of sensa- excluded. Our results suggest that acupuncture was safe for tions (4); needle placement (3); and other reasons (3).
Participant demographic and baseline characteristics.
True acupuncture
Noninvasive sham acupuncture
Characteristic
(n ؍ 110)
(n ؍ 118)
P
Note: Values are mean (SD) or n (%).
Smith. RCT of acupuncture at ET. Fertil Steril 2006. The study might have been underpowered, with the sample size egg collection, transfer of embryos of varying quality (the Paulus calculation based on the effect size of the Paulus study. Our results study transferred good-quality embryos only), and there were also suggest a smaller treatment effect from acupuncture with a post minor variations in treatment protocol.
hoc power effect of 27.4%, requiring a sample size of 484 subjects.
Our study can not be directly compared with the Paulus study Compared with other clinical trials of acupuncture, our our study protocol included a first treatment administered before study included a larger sample size. Other strengths of this RCT of acupuncture at ET
Primary and secondary outcomes by group.
Noninvasive sham
Risk ratio
Pregnancy outcome
acupuncture
acupuncture
P
Grading of embryo 1
Implantation achieved (defined as
demonstration of a gestational sac on
ultrasound)
Pregnancy achieved (all women)
(fetal heart on ultrasound)
Pregnancy at 18 weeks
SF36 mean (SD)
Note: Values are n (%) or mean (SD).
Smith. RCT of acupuncture at ET. Fertil Steril 2006. trial include high compliance and low loss to follow-up; The pregnancy rate for women in the control group of the loss to follow-up was associated with the IVF cycle being study was lower than the overall pregnancy rate at Re- cancelled rather than their being any association with promed. This might have been influenced by the age of acceptability of the research. Both groups were also com- subjects in the study and an overrepresentation of women parable for sociodemographic characteristics and repro- with poor pregnancy outcomes from previous IVF cycles.
Data from Repromed indicate that our study might have been Subjects’ views on study group allocation.
True acupuncture
Noninvasive sham acupuncture
Perceived group allocation
(n ؍ 109)
(n ؍ 118)
P
Smith. RCT of acupuncture at ET. Fertil Steril 2006. underrepresented by younger women (46.5% vs. 38.6%) and trial; Kristyn Willson (The University of Adelaide) and Ms. Kerena Eckert overrepresented by women aged 35–39 years (30.9% vs.
(The University of South Australia) for their statistical support; and CarolHorn, acupuncturist.
35.0%) and Ͼ40 years (22.5% vs. 26.3%), who are lesslikely to have a positive outcome REFERENCES
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9. Coyle ME, Smith CA. A survey comparing TCM diagnosis, health The clinical implications from our research suggest that status and medical diagnosis in women undergoing assisted reproduc- acupuncture does not have any adverse effects at the time of 10. Streitberger K, Kleinhenz J. Introducing a placebo needle into acupunc- egg retrieval and ET. The study suggests there might be a ture research. Lancet 1998;352:364 –5.
smaller treatment effect and that acupuncture might have a 11. Ware JE, Sherbourne CD. The MOS 36 Item Short Form Health Survey promising role as an adjunctive therapy in reproductive (SF-36). I. Conceptual framework and item selection. Med Care 1992; 12. Repromed. 2001 Pregnancy rates. Available at: Further research is needed to evaluate the efficacy of acupuncture at the time of ET. A large trial with appropriate 13. Cummins JM, Breen TM, Harrison KL, Shaw JM, Wilson LM, Hen- power is required, as well as acupuncture research to exam- nessey JF, et al. A formula for scoring human embryo growth rates inin vitro fertilization: its value in predicting pregnancy and in compar- ine the physiological changes in the uterus and the repro- ison with visual estimates of embryo quality. J In Vitro Embryo 14. Repromed. Outcomes for women aged Ͻ38 years for Jan-Jun at Re- Acknowledgments: The authors thank all the women participating in the trial; the staff at Repromed who contributed to the implementation of the RCT of acupuncture at ET

Source: http://fertility-acupuncture.dk/pdf/Smith%20akupunktur.pdf