TCM Style Acupuncture Performed Before and After Embryo Transfer Improves Pregnancy Rates: A Retrospective Study

Acupuncture done before and after embryo transfer increases pregnancy rates up to 57%.
Acupuncture done before and after embryo transfer increases pregnancy rates up to 57%.

Below you will find a research study written by our acupuncturist, Sarah Prater (under her maiden name, Fredrickson) for the journal American Acupuncturist. This was published in the Winter 2014 edition.

By Sarah .J. Fredrickson, MSOM, Dipl OM (NCCAOM), LAc; David B. Youran, Dipl Ac (NCCAOM), LAc; Glen K. Adaniya, PhD; Bradford L. Bopp, MD; Robert M. Colver, MD; Laura M. Reuter, MD

Abstract

Background
Conflicting evidence exists on whether acupuncture is beneficial for patients undergoing in vitro fertilization (IVF) cycles. This retrospective cohort study was undertaken to determine whether a unique protocol of a combined Chinese and Japanese style on-site acupuncture, performed both before and after embryo transfer, affects clinical outcomes.

Design and Setting
Forty-nine patients received a previously untested acupuncture protocol on-site before and after embryo transfer at Midwest Fertility Specialists, Indianapolis, Indiana, in 2007. The acupuncture treatment was performed 45 minutes before and 15 minutes after embryo transfer. The control group consisted of 212 patients who did not receive acupuncture and who underwent IVF cycles in the same time period. All cycles were fresh, non-donor successful embryo transfers. The clinical pregnancy rate (CPR) was defined as the presence of fetal cardiac activity. Data were analyzed using the unpaired t-test and Fisher’s exact test, with significance defined as P < 0.05.

Results and Conclusion

It was found that patients with a positive hCG were slightly higher in the acupuncture group than in the control group (57.1% vs.45.8%, p = 0.16). The acupuncture group also had a higher CPR (55.1% vs. 34.4%, p = 0.01). The miscarriage rate was lower for the acupuncture group compared to the control group (3.6% vs. 22.7%, p= 0.02). These results support the use of acupuncture in conjunction with IVF.

Keywords: TCM, acupuncture, infertility, IVF, embryo transfer
Introduction

Infertility affects roughly 1.5 million women in the United States..1 Many of these women will seek out various fertility treatments, and, of these, in-vitro fertilization is becoming more and more common, with 154,412 IVF “cycles” performed in 2011 versus 112,988 in 2003.2 IVF involves the retrieval and subsequent fertilization of a woman’s eggs,  produced by stimulating the ovaries with medications. The resulting embryos are grown in a laboratory setting and then transferred back into the uterus; this whole process takes approximately two weeks.3 Because of the significant cost, time commitment, and emotional impacts required for each cycle, there is great incentive to improve pregnancy and live birth rates. These rates have improved greatly from 14% of all IVF cycles resulting in a live birth in 1989 to 35% in 2008.4 Despite these profound advances, clinics are still searching for ways to improve this live birth rate.

The use of acupuncture has been regarded as a possible treatment to benefit IVF success rates. It has had obstetric and gynecological usage in China for many centuries. Following the 2002 Paulus study that reported increased pregnancy rates in patients receiving acupuncture before and after embryo transfer,5 many groups examined the impact of varied styles of acupuncture on pregnancy rates before and after embryo transfer. Modern research on this topic has shown mixed results. Some researchers found that groups that had sham or placebo acupuncture had higher pregnancy rates than the true acupuncture groups, although the difference between the two groups was not statistically significant.6,7,8

Complications in varied treatment styles and the effective sham and placebo treatments in acupuncture infertility discussed literature studies are visible in recent searches. This research questions the necessity of using sham or placebo acupuncture when examining the role acupuncture can play in pregnancy rates following IVF. This is due to the objective nature of a pregnancy test and the possibility of an acupuncture-induced stress reduction as the mechanism by which pregnancy rates are increased and thus considered as a therapeutic effect.9 Other research and meta-analysis shows inconclusive results that, during an IVF cycle, acupuncture can improve pregnancy rates. At this time there is not enough evidence to recommend it clinically for all patients.12,13,14

Nevertheless, experts in acupuncture and infertility continue to support more studies on the use of acupuncture before and after embryo transfer to improve pregnancy rates.10 Possible mechanisms of action might be the increased blood flow to the uterus, stimulation of the release of endogenous opioids, and the mediation of neurotransmitter release affecting gonadatropin-releasing hormone and its effect on the menstrual cycle10 or the regulation of cortisol and prolactin during the medication phase of the IVF treatment.11

The purpose of this review of individual cases was to examine the influence of acupuncture before and after embryo transfer on pregnancy rates in patients undergoing IVF. The objective was to determine if acupuncture treatment given before and after embryo transfer (ET) would improve pregnancy rates.

Methods

A retrospective review of charts was done at an Indianapolis fertility clinic on 261 patients who received IVF in 2007. Charts were chosen based on the successful completion of a fresh, non-donor embryo transfer in 2007 with or without acupuncture. No exclusions were made in the acupuncture group, but some statistical outliers within the control group were eliminated to ensure the groups were statistically similar in oocytes per patient, embryo cell count, and embryo fragmentation score. No exclusions were made specifically regarding diagnosis, age, or other factors.

Forty-nine patients received acupuncture by a single board certified licensed acupuncturist on-site before and after embryo transfer. The treatments were given in the same location as the ET to reduce traveling induced stress, which seems to improve results in other studies.12 The 212 patients who did not receive acupuncture served as the control group for this analysis. The charts in both the acupuncture and no acupuncture groups were reviewed retrospectively for beta pregnancy and clinical pregnancy by D.Y and G.A.

Controlled ovarian hyperstimulation was achieved by use of a standard gonadotropin releasing hormone agonist and recombinant follicle stimulating hormone (rFSH) protocol with the dosage varying for each patient. Antral follicle count and E2 levels were not collected for this study. Following human chorionic gonadotropin administration and oocyte retrieval after 36 hours; oocytes were inseminated 2 to 4 hours later by either standard insemination or by intracytoplasmic sperm injection (ICSI). Embryos were scored using standard morphological criteria on the morning of the Day 3 embryo transfer (ET). Embryos were assigned a fragmentation score of 4 if there was no fragmentation, a 3 if less than 10% of the embryo exhibited fragmentation, a 2 if between 10% and 50% of the embryo was fragmented, and a 1 if the embryo had greater than 50% fragmentation.

Acupuncture points were selected according to a combination of traditional Chinese and Japanese acupuncture for the treatment of infertility and through consensus of 4 experts in the field. The points were chosen to harmonize the Kidney and Spleen qi according to Japanese and Chinese theories. Acupuncture treatment was performed 45 minutes before embryo transfer and 15 minutes after embryo transfer. Acupuncture points used before the embryo transfer were Qihai CV-6, Guanyuan CV-4, Sanyinjiao SP-6, Taixi KI-3, Zhongfeng LR-4, Zusanli ST-36 and Yanglingquan GB-34. Acupuncture points used after the embryo transfer were Yinlingquan SP-9, Taichong LR-3, Taixi KI-3, Zusanli ST-36, and Yanglingquan GB-34. All points were needled bilaterally without the elicitation of the de qi sensation and the needle depth varied form 0.25 cun to 0.50 cun.. Needles were retained for 35 minutes. Seirin 0.20 x 30 mm acupuncture needles were used.
The beta pregnancy rate was the percentage of patients who had an initial hCG level, drawn 12 days after the embryo transfer, of 10 mIU/ml or greater. The clinical pregnancy rate (CPR) was defined as the percentage of patients with fetal cardiac activity. The miscarriage rate was the percentage of patients that had a positive hCG level but that failed to develop a fetal heart rate. Data was analyzed using the unpaired t-test and Fisher’s exact test, with significance defined as P < 0.05. The results are expressed as mean standard deviation or percentages as appropriate.

Results

The number of oocytes, cell number, fragmentation score, number of embryos frozen and number of embryos transferred in both groups was equivalent. Positive hCG was slightly higher in the acupuncture group versus the control group (57.1% vs. 45.8%). The clinical pregnancy rate for the patients receiving acupuncture was significantly higher than the control group (55.1% vs. 34.4%). In addition, the loss rate was significantly lower in the acupuncture group (3.6% vs. 22.7%). ( Insert Table 1/ and Graph)

All fresh, non-donor IVF cycles that ended in successful embryo transfer were included in the study. No exclusions were made in the acupuncture group, but some statistical outliers within the control group were eliminated to ensure the groups were statistically similar in oocytes per patient, embryo cell count, and embryo fragmentation score. No exclusions were made specifically regarding diagnosis, age, or other factors.
There were no adverse events related to the acupuncture treatment reported.
Discussion

Although other studies regarding acupuncture and IVF are inconclusive, perhaps the positive results in this study relate to several important factors .12,13,14 Acupuncture attempts to stimulate the body’s own reproductive potential, which may help to explain the positive results of this study. In addition, the treatments were performed on-site, eliminating the stress of traveling to another site before and after the embryo transfer.

Because the patients in this study received acupuncture immediately before and after ET, this could also explain the positive results. Studies showing treatment immediately before and after treatment at the same site had higher pregnancy rates in the acupuncture group compared with studies that did not specify time of acupuncture.12,13 The higher clinical pregnancy rate and lower miscarriage rate in the acupuncture group may be due to increased blood flow to the uterus.10

The unique combination of the Chinese and Japanese styles of the acupuncture treatment protocol in this study suggests there is still more research needed on the best protocols to treat infertility issues with acupuncture. This study was limited by its chart review nature and would benefit from having been a randomized controlled trial. The small number of patients in the acupuncture group as compared to the control group reflects that.

Also, considering that patients themselves elected to join either the acupuncture or control group, it is possible that the acupuncture patients had a healthier lifestyle, or some other confounding factor, which could have impacted results. There was no way to account for these factors during the chart analysis as charts were chosen only based upon the patients’ completion of a fresh, non-donor IVF cycle in 2007. Additionally, there was no way to determine if anyone in the control group received acupuncture from another practitioner on the day of ET, which may have affected the results. Due to these limitations, this analysis suggests there is still more research to be done on how best to treat infertility issues with acupuncture.

Conclusion

The results of this study point to the possibility that acupuncture is safe and may increase both clinical pregnancy rates and beta pregnancy rates in women undergoing IVF ET. In addition, this study showed a decrease in the loss rate among women in the acupuncture group. In comparison with the inconclusive results found in the literature, this study had a few key differences, including acupuncture performed on-site, acupuncture being performed immediately before and after ET, and the usage of a unique Chinese- and Japanese-derived type protocol.

A blinded, randomized study containing a larger number of  patients is necessary to determine if these results are clinically useful. Additionally, more research should be done to identify the key factor (or factors) within the methods of this study that led to the positive results.

References

1. Centers for Disease Control and Prevention [Internet]. Atlanta: CDC; c2013 [cited 2013 June] FastStats. Available from: http://www.cdc.gov/nchs/fastats/fertile.htm

2. Society for Assisted Reproductive Technology [Internet]. Birmingham (AL): SART; c1996-2013 [cited 2013 June] Available from: https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?ClinicPKID=0

3. Society for Assisted Reproductive Technology [Internet]. Birmingham (AL): SART; c1996-2013 [cited 2013 June] Available from: http://www.sart.org/detail.aspx?id=1903

4. Society for Assisted Reproductive Technology [Internet]. Birmingham (AL): SART; c1996-2013 [cited 2013 June] Available from: http://www.sart.org/SART_Success_Rates/

http://www.sart.org/SART_Success_Rates/

5. Paulus WE, Zhang M, Strehler E, El-Danasouri I, Sterzik K. Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy. Fertility &  Sterility. 2002 Apr; 77(4): 721-4.

6. Moy I, Milad MP, Barnes R, Confino E, Kazer RR, Zhang X. Randomized controlled trial: effects of acupuncture on pregnancy rates in women undergoing in vitro fertilization. Fertility & Sterility. 2011 Feb; 95(2): 583-7.

7. Andersen D, Lossl K, Nyboe Andersen A, Furbringer J, Bach H, Simonsen J, Larsen EC. Acupuncture on the day of embryo transfer: A randomized controlled trial of 635 patients. Reproductive Biomedicine Online. 2010 Sep; 21(3): 366-72.

8. So EW. Ng EH, Wong YY, Lau EY, Yeung WS, Ho PC. A randomized double blind comparison of real and placebo acupuncture in IVF treatment. Human Reproduction. 2009 Feb; 24(2): 341-8.
9. Manheimer E. Selecting a control for in vitro fertilization and acupuncture randomized controlled trials (RCTs): How sham controls may unnecessarily complicate the RCT evidence base. Fertility & Sterility. 2011 Jun 30; 95(8): 2456-61.

10. Stener-Victorin E, Humaidan P. Use of acupuncture in female infertility and a summary of recent acupuncture studies related to embryo transfer. Acupunct Med. 2006 Dec; 24(4):157-63.
11. Magarelli PC, Cridennda DK. Cohen M. Changes in serum cortisol and prolactin associated with acupuncture during controlled ovarian hyperstimulation in women undergoing in vitro fertilization-embryo transfer treatment. Fertility & Sterility. 2009 Dec; 92(6):1870-9.
12. Manheimer E, Zhang G, Udoff L, Haramati A, Langerberg P, Berman BM, Bouter LM. Effects of acupuncture on rates of pregnancy and live birth among women undergoing in vitro fertilization: systemic review and meta-analysis. BMJ. 2008;336:545.

13. El-Toukhy T, Sunkara S, Khairy M, Dyer R, Khalaf Y, Coomarasamy A. A systematic review and meta-analysis of acupuncture in in vitro fertilisation. BJOG: An International Journal of Obstetrics & Gynaecology. 115: 1203–1213. doi: 10.1111/j.1471-0528.2008.01838.x 2008.

14. Cheong Y, Nardo LG, Rutherford T, Ledger W. Acupuncture and herbal medicine in in vitro fertilization: a review of the evidence for clinical practice. Human Fertility. 2010 March; 13(1): 3-12.

Bios

Sarah J. Fredrickson, MSOM, Dipl OM (NCCAOM), LAc, completed a BS in biology at Indiana University in 2005 and completed her Master’s Degree in Acupuncture at Southwest Acupuncture College in Santa Fe, New Mexico, in 2008. She is currently in practice at Indiana Reproductive Acupuncture. Her clinical interests include infertility, prenatal care, and other women’s health issues.

David B. Youran, Dipl AC (NCCAOM), LAc, is the director and founder of Indiana Reproductive Acupuncture. He studied acupuncture and Oriental medicine during a four year apprenticeship program taught by Dr. Thomas Duckworth at the Inochi Institute in St. Louis, Missouri. He is the first acupuncturist in Indiana to specialize solely in treating infertility and pregnancy wellness issues.

Glen Adaniya, PhD, graduated from Northwestern University and earned his MS and PhD in Biomedical Engineering at the University of Illinois in Chicago.

Bradford Bopp, MD, graduated from The Ohio State University, attended medical school at the University of Southern California, completed his residency in obstetrics and gynecology and his fellowship in reproductive endocrinology at Harvard University.

Robert Colver, MD, graduated from Indiana University, obtained his medical degree from the Indiana University School of Medicine, completed his residency in obstetrics and gynecology at St. Vincent Hospital in Indianapolis, and served a fellowship in reproductive endocrinology and infertility at the Medical College of Georgia.

Laura Reuter, MD, graduated from Cornell University, earned her medical degree at the University of Illinois, completed her residency in obstetrics and gynecology at Wayne State University, and completed a fellowship in reproductive endocrinology at the University of Illinois.


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