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Electroacupuncture In Infertile Patients Receiving In-Vitro
Fertilization And Embryo Transfer: A Pilot Study
Judith Balk, MD
Brinda Kalro, MD
James M. Roberts, MD
ABSTRACT
Background Acupuncture may be helpful in treating infertility. However, patients undergoing assisted reproductive techniques may not be willing to undergo additional procedures due to time constraints.
Objectives To determine the feasibility and acceptability of acupuncture in patients undergoing in-vitro fertilization with embryo transfer
(IVF-ET). Secondary aims were to assess pregnancy rates and changes in uterine artery pulsatility index during the IVF cycle.
Design, Setting, and Patients Prospective unblinded intervention trial of 10 infertile women (mean age, 36 years) undergoing IVF-ET at a reproductive endocrinology and infertility office in a university hospital in Pittsburgh.
Intervention Each woman had a baseline Doppler study of the uterine artery. She then had twice-weekly acupuncture (points BL 23, 28, 57, and SP 6) for 4 weeks, up until oocyte retrieval. Repeat Doppler ultrasound was performed the day before oocyte retrieval and then 2 weeks later.
Main Outcome Measures Compliance with study ultrasounds and acupuncture sessions, pregnancy rates, and change in uterine artery Doppler pulsatility index.
Results Compliance with both acupuncture (mean, 98%) and study ultrasounds (mean, 87%) was high. The pregnancy rate was 33% vs 34% in women not receiving acupuncture. Uterine artery pulsatility index was normal in all women at baseline (1.7) and did not change during the study (1.6 after acupuncture and 2.1 at 2-week follow-up).
Conclusions Acupuncture as an adjunctive treatment to assisted reproductive techniques is both feasible and acceptable to patients. Larger studies will need to be performed to determine the efficacy of acupuncture in enhancing the success of IVF-ET.
KEY WORDS
Acupuncture, Electroacupuncture, Infertility, Assisted Reproductive Techniques, In-vitro Fertilization
INTRODUCTION
Infertility is a problem of public health significance. Approximately 2.3% of women of reproductive age (1.26 million) seek advice or treatment for infertility in the United States each year.1 In-vitro fertilization with embryo transfer (IVF-ET), often known as IVF, is a commonly performed treatment in which the oocytes are removed from the ovaries, fertilized in the laboratory, and then transferred back to the patient's uterus. With assisted reproductive techniques such as IVF, many women are able to achieve pregnancy. However, overall success rates of IVF remain less than 30%.2 The causes of failure are multifactorial and include oocyte and embryo quality, uterine receptivity, and ovarian reserve.
Acupuncture appears to be helpful in improving the success rate of assisted reproductive techniques3; preliminary evidence suggests a role for acupuncture in infertility. We conducted a feasibility study to assess whether acupuncture would be acceptable in our infertility population. Improving the success rates of IVF-ET is an area of substantial study in which complementary approaches such as acupuncture may be used.
A major goal of IVF treatment is to maximize the success rate of each cycle, which may require the use of ancillary measures such as medication, stress reduction, and complementary approaches including acupuncture. However, one question that arises is whether women are willing and able to undergo additional treatments such as acupuncture, especially if the research base is inconclusive. Because women undergoing IVF-ET have many stressors,4,5 we wondered whether such women would be willing to undergo potential added stressors by participating in a research study that demanded 8 acupuncture sessions and 3 additional ultrasounds within 6 weeks. This question was important to determine the feasibility of future acupuncture research in the IVF-ET population.
Uterine receptivity is an important determinant of whether implantation is successful,6-8 with decreased uterine perfusion being a cause of infertility.9 Multiple studies have evaluated the role of pulsatility index (PI) of the uterine and ovarian arteries, and the role that an abnormal PI (proposed as >2.5) may play in the failure of IVF.10,11
These studies found differences in the PI of subfertile vs fertile women, with subfertile women having decreased uterine perfusion and elevated uterine artery PI.
The PI is not always assessed by infertility practices because, for one reason, there is no reliable method to improve the uterine artery blood flow. In one study, investigators demonstrated improved uterine blood flow and pregnancy rates after oral administration of hormone therapy.9
Another strategy that has been used to improve the PI is electroacupuncture.12 In a small prospective Swedish study, 10 infertile women with a uterine artery PI >3.0 were treated with electroacupuncture. The PIs significantly decreased at the end of the acupuncture treatment and at 2-week follow-up.12
Our investigation built on the Swedish study12 by assessing the feasibility of performing electroacupuncture in a group of US women undergoing IVF-ET. The presumption was that because acupuncture may not be widely accepted, an adequate clinical study sample size may be difficult to recruit. In addition, many women may not be willing to make the time commitment required of such a study. To accomplish a larger trial of acupuncture in infertility patients, a feasibility and acceptability study was needed. The purpose of our pilot research project was to collect data on the feasibility of a twice-weekly acupuncture regimen in women undergoing IVF-ET.
METHODS
We conducted an unblinded intervention study in women undergoing IVF-ET. Additional ultrasounds were required to determine uterine artery PI.
Recruitment
This study was approved by the Magee-Womens Hospital Institutional Review Board. Written informed consent was obtained from all study subjects by the principal investigator prior to initiation of study procedures. Women were recruited from the reproductive endocrinology/infertility practice at Magee-Womens Hospital, University of Pittsburgh. Specifically, a brief mention of the study was made at several orientation seminars for patients considering IVF. Patients who expressed an interest to the infertility staff were contacted by the principal investigator who then gave the patient more information and scheduled the study procedures. The patient's acupuncture treatments were coordinated with her ongoing infertility care.
Eligibility Criteria
All women undergoing IVF-ET were eligible for this study. Since this was a feasibility study, we chose to enroll all women who were interested in study participation. Given that PI is not assessed routinely at Magee-Womens Hospital, it was not a factor used to determine eligibility (as it was in the Swedish study12).
Women with vascular problems such as hypertension, atherosclerosis, and other vascular disorders such as lupus, which might affect not only the PI but also study compliance, were excluded from this study. Age was not an exclusion factor. Women were excluded if they had contraindications to electroacupuncture, such as a pacemaker, previous needle shock from acupuncture, anticoagulation therapy, or allergy to stainless steel acupuncture needles.
Acupuncture Treatment
The acupuncture regimen for our study was that used in the Swedish study.12 We used the same choice of points and types of electrical stimulation, given that this regimen was reportedly effective in improving uterine artery PI. Acupuncture points that inhibit sympathetic outflow at the segmental level were chosen, based on the innervation of the uterus (T12-L2, S2-S3). The acupuncture points used were BL 23, 28, and 57 and SP 6; BL 23 is the back Shu point for the kidney. Indications include treatment of problems of reproduction, including fertility problems; BL 23 can be stimulated for a sympathetic autonomic effect; BL 28 is used for lower genitourinary tract problems; BL 57 is used for kidney and lumbar pain, as well as rectal prolapse and hemorrhoids; and SP 6 is the intersection point for the 3 Yin channels of the leg and is used for reproductive problems.13
We used single-use, sterile, individually-wrapped acupuncture needles (0.25 gauge x 30 mm needles; Seirin, Tokyo, Japan). Twice weekly for 4 weeks prior to embryo transfer, women were treated with the following acupuncture regimen: needles were inserted to a depth of 10-20 mm, with the aim of activating group III muscle-nerve afferents, until needle sensation or De Qi was felt. Needles were then attached to an electrical stimulator (IC-4107 electroacupuncture unit, Ito Co., Tokyo, Japan) for 30 minutes. The points piqured included BL 23, located at L2 level on the erector spinae muscle; BL 28, located at the level of S2 sacral foramen; BL 57, located on the posterior leg, at the lower limit of the belly of the gastrocnemius muscle, between the 2 heads at the musculotendinous junction; and SP 6, located on the medial side of the leg, posterior to the medial margin of the tibia, approximately 5 cm above the prominence of the medial malleolus.
Point location followed standard acupuncture techniques of measurement with the cun (Chinese inch) and palpation. Points on the back (BL 23 and 28) were stimulated with high-frequency (100 Hz) pulses; the extremity needles (BL 57 and SP 6) were stimulated with
low-frequency (2 Hz) pulses. On the back, positive leads were placed on BL 23, negative leads on BL 28. On the leg, positive leads were placed on SP 6, negative leads on BL 57. Each session lasted 30 minutes; the same protocol was followed at each visit.
Pulsatility Index
The PI is a measure of arterial blood flow resistance, measured by Doppler ultrasound. Participants had formal ultrasounds at Magee Womens Hospital Department of Radiology. One ultrasound physician supervised all the study ultrasounds, which were performed using a
transvaginal probe. The radiologist then calculated the PIs from the Doppler study. As in the Swedish study,12 PIs were assessed for each woman at 3 time points: baseline, at the end of the acupuncture sessions (4 weeks), and again at 2-week follow-up.
RESULTS
Ten women participated in the study. The mean age was 36 years, with mean gravidity and parity of 1.3 and 0.1, respectively. On average, 12 oocytes were retrieved (range, 0-30). The mean number of fertilized oocytes and embryos transferred was 5.7 and 2.6, respectively. Table 1 shows the demographic characteristics of the sample as well as details of the IVF-ET cycles.
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Table 1. Patient Characteristics and In-Vitro Fertilization Outcomes
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Variable
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Mean (SD)
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Range
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Patient age, y
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36 (2.9)
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31-41
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Gravidity
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1.3 (1.3)
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0-3
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Parity
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0.1 (0.31)
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0-1
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Pulsatility index
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1.7 (0.43)
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1.0-2.4
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1.6 (0.51)
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0.85-2.3
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2.1 (0.70)
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1.0-3.0
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Endometrial lining, cm
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0.41 (0.17)
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0.20-0.70
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1.1 (0.24)
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0.50-1.3
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Eggs retrieved, No.
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12.1 (8.2)
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0-30
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Eggs fertilized, No.
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5.7 (5.7)
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0-12
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Embryos transferred, No.
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2.6 (1.2)
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0-4
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Compliance was calculated as the percentage of visits that the participant attended. The mean compliance with the acupuncture sessions was 98% (1 woman missed 1 visit; all other participants attended all acupuncture sessions). Compliance with the study ultrasounds averaged 87% (SD, 23%; range, 33%-100%). One woman refused her 2nd and 3rd ultrasounds after her cycle was canceled due to poor stimulation. Two other women canceled their 3rd ultrasounds after their pregnancy test results were negative. Seven women completed all study ultrasounds.
Study acceptability was calculated as the number of women participating from those who had heard a brief mention of the study during orientations: 10 women were recruited from a pool of 49 who had attended the orientations. Active recruitment (individual discussions with potential participants) was not attempted due to the small sample size planned. Thus, with no advertising and no personnel devoted to recruitment, and only a brief mention at the orientation, acceptance was 20%.
Pregnancy rate was calculated for the group receiving acupuncture and compared with groups not receiving acupuncture; the study power was inadequate to detect a statistical difference. The pregnancy rate in the group that completed the IVF-ET cycle was 33%, compared with 34% in women not receiving acupuncture.
The PI was assessed before and after acupuncture and at follow-up 2 weeks later. Each uterine artery was assessed and the mean of the PI was calculated. The mean PI was 1.7, 1.6, and 2.1 for baseline, end of acupuncture, and follow-up, respectively. These findings are within normal limits and not statistically different from each other.
DISCUSSION
We found acupuncture both feasible and acceptable in our infertility population. Because this was a pilot study, we elected to study only 10 participants to determine if a larger study is feasible. Many women expressed interest in the study, but not early enough in their IVF cycle to receive acupuncture 4 weeks prior to oocyte retrieval. In a larger study, we will have study personnel devoted to recruitment to enable enrollment in a timely fashion. Given that 10 women were recruited with minimal effort in a 5-month recruitment period, the feasibility of a larger trial is high.
This pilot study was not designed or powered to determine changes in PI or pregnancy rate. As predicted by the normal PI for these women at baseline, PI did not change and small numbers did not reveal an altered pregnancy rate. If larger numbers of women with abnormal PI are recruited, demonstrating a change is likely. Having demonstrated feasibility with this intense intervention, it is now practical to proceed to a full randomized clinical trial.
CONCLUSION
Based on our pilot study, acupuncture as an adjunctive treatment to assisted reproductive techniques is both feasible and acceptable to patients. Compliance with acupuncture treatments and with additional study procedures was high. The additional time commitment to the study procedures did not deter patients from participating in the study, and more patients expressed an interest than could be accommodated in this pilot study. Our findings demonstrated that use of acupuncture in the infertility population may be acceptable.
FUNDING
This study was funded by the Beckwith Institute Innovation Award Fund Program, Pittsburgh, Pennsylvania.
ACKNOWLEDGEMENT
We thank Dolly Gibala, IVF patient coordinator, for her assistance in data collection and with administrative issues.
REFERENCES
- Mishell DR, Stenchever MA, Droegemueller W, Herbst AL. Comprehensive Gynecology. 3rd ed. Philadelphia, Pa: Mosby; 1997:1113-1159.
- Cramer DW, Liberman RF, Powers D, et al. Recent trends in assisted reproductive techniques and associated outcomes. Obstet Gynecol. 2000;95:61-66.
- Paulus WE, Zhang M, Stehler E, El-Danasouri I, Sterzik K. Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy. Fertil Steril. 2002;77:721-724.
- Verhaak CM, Smeenk JMJ, Eugster A, van Minnen A, Kremer JAM, Kraaimaat FW. Stress and marital satisfaction among women before and after their first cycle of in-vitro fertilization and intracytoplasmic sperm injection. Fertil Steril. 2001;76:525-531.
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- Fugino Y, Ito F, Matuoka I, et al. Pulsatility index of uterine artery in pregnant and non-pregnant women. Hum Reprod. 1993;8:1126-1128.
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Doppler assessment of uterine artery impedance in a subfertile population. Fertil Steril. 1994;61:53-58.
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AUTHOR INFORMATION
Dr Judith Balk is an Obstetrician-Gynecologist, and Assistant Research Professor at University of Pittsburgh and Magee-Womens Hospital in Pittsburgh, Pennsylvania.
Judith Balk, MD*
Magee-Womens Hospital
Dept of Obstetrics, Gynecology, and Reproductive Sciences
300 Halket St
Pittsburgh, PA 15213
Phone: 412-641-1440 • E-mail: rsijlb@mail.magee.edu
Dr Brinda Kalro is a Reproductive Endocrinologist at Magee-Womens Hospital, University of Pittsburgh. Dr Kalro conducts in-vitro fertilization and other infertility procedures.
Dr Brinda Kalro
E-mail: bkalro@mail.magee.edu
Dr James Roberts is Vice Chair of the Department of Obstetrics-Gynecology, and Chair of the Magee-Womens Research Institute at Magee-Womens Hospital, University of Pittsburgh.
James Roberts, MD
E-mail: rsijmr@mail.magee.edu
*Correspondence and reprint requests
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