Research and reviews

IVF clinics have improved their success rates steadily over the last decade or two. But in recent years these success rates have reached a plateau. Now that follicle stimulation, fertilization of eggs and embryo culture have been developed as far as current technology will allow, successful implantation of the embryo in the uterine lining is where improvement is needed to push success rates up again.

New developments in this area may be coming from an unexpected quarter. The last six years have seen the publication in reputable medical journals, of the results of a number of clinical trials investigating the effect of acupuncture at the time of embryo transfer. Several of these trials have shown a significant increase in pregnancy rates when acupuncture is used particularly when the expectation of success is not high, ie the pregnancy rate overall is quite low. 

Most scientists and clinicians would agree that this is still a controversial area and that more research needs to be done before acupuncture is generally accepted as an integral part of IVF treatment protocols. There is a compelling body of evidence however, of increased numbers of live births among IVF patients having acupuncture, and based on their own clinical experience, one group of IVF clinics in the United States has asserted that acupuncture could be considered a standard component of care for IVF patients.

We look forward to more definitive research in this exciting area.

Acupuncture and embryo transfer

Fertility and Sterility, the official publication of the American Society for Reproductive Medicine publishes juried original articles of scientific excellence in clinical and laboratory research relevant to reproductive endocrinology and physiology.

The studies below have all appeared in the journal Fertility and Sterility. Ten of them found that acupuncture performed close to the time of embryo transfer improved chances of pregnancy. Three reported no effect, and one found a negative effect (which was put down to the fact that the patients had to drive across town after their embryo transfer to reach the acupuncture clinic). More studies are underway to investigate the mechanism behind the effect of acupuncture on implantation of the embryo.

If any provisional conclusions are to be drawn at this stage, it is that acupuncture appears to confer an advantage to clinical trial groups which have an expected pregnancy rate of around 35% or less. Where chance of pregnancy is 50 - 60% then acupuncture applied at the time of embryo transfer may not offer so much benefit. 

Acupuncture and blood flow to uterus and ovaries

In addition to the acupuncture and embryo transfer studies there have been other clinical trials carried out which reveal information relevant to reproductive outcomes:

Reduction of blood flow impedance in the uterine arteries of infertile women with electro-acupuncture. Stener-Victorin E, et al Hum Reprod 1996; 11:1314-1317. Human Reproduction View Abstract

Many studies have shown that reduced blood flow in the uterine arteries is associated with a decreased pregnancy rate following IVF-embryo transfer. This study reported in Human Reproduction (the official journal of the European Society of Human Reproduction and Embryology) shows that after 8 acupuncture treatments blood flow to the uterus was markedly increased. Research carried out by one group of IVF clinics in California has shown that using this protocol to increase blood flow to the uterus, combined with acupuncture on the day of transfer has resulted in a markedly significant improvement in pregnancy rates. See also: Acupuncture & IVF Poor Responders: A Cure? Acupuncture and IVF: State of the ART of Integrative Research

	Ovarian blood flow responses to electro-acupuncture stimulation at different frequencies and intensities in anaesthetized rats Stener-Victorin E et al Autonomic Neuroscience Volume 108, Issues 1-2, 31 October 2003, Pages 50-5 Autonomic Neuroscience View Abstract
The blood flow to the ovaries has also been shown to be enhanced by acupuncture by the same researchers. This study was done on anaesthetized rats, however we can assume a similar mechanism will operate in women.

A Pilot Study Evaluating the Combination of Acupuncture with Sildenafil on Endometrial Thickness Yu W et.al.Presented at the Pacific Coast Reproductive Society Annual Conference 2007 View Abstract

This small pilot study examined the effect of Viagra and acupuncture on the uterine linings of women who had a history of thin linings (<8mm) in previous IVF cycles (including patients who had previously used Viagra alone). They used the above mentioned protocols which improve blood flow to the ovaries and uterus. The researchers found that after acupuncture treatment the thickness of the lining improved to 10 mm or more in all participating patients.

Acupuncture & IVF Poor Responders: A Cure? Magarelli P, Cridennda D. Fertil Steril, 2004;81(Supplement 3):S20 Fertility and Sterility View Abstract

This clinical trial combined the acupuncture protocol used on the day of embryo transfer with the acupuncture treatment protocol designed to increase blood flow to the uterus. The authors report that “Significant increases in pregnancy outcomes were confirmed by this study which demonstrated that both acupuncture treatment protocols could be used together with a synergistic effect.” They add that “this study is the first to demonstrate that the use of acupuncture in patients with poor prognoses (elevated Peak FSH, longer history of infertility, poor sperm morphology) can achieve similar pregnancy rates to normal prognosis patients.”

	A randomized, controlled, double blind, cross-over study evaluating acupuncture as an adjunct to IVF. Quintero R et al, Fertil Steril, 2004;81(Supplement 3):S11-12 Fertility and Sterility View Abstract
This pilot study showed that a significantly lower amount of gonadotropins (IVF drugs) was used when IVF was combined with standard acupuncture, ie the acupuncture appeared to make the ovaries more responsive to the drugs. Increased ovarian responsiveness could be a useful effect for women who produce small numbers of eggs. This trial needs to be repeated with larger numbers of patients.

Changes in serum cortisol and prolactin associated with acupuncture during controlled ovarian hyperstimulation in women undergoing in vitro fertilization–embryo transfer treatment Magarelli, PC, D Cridennda, M Cohen. Fertil Steril 2009 in press Fertility and Sterility View Abstract

A number of women going through IVF were given acupuncture to increase blood flow through the uterine arteries in the immediate weeks before egg collection. The researchers found that the women who had acupuncture showed beneficial changes in serum levels of stress hormones compared to the control group of women who did not have acupuncture. The acupuncture treatments appear to normalize levels of cortisol and prolactin which have been artificially depressed by the IVF drugs. This may have implications for both egg quality and implantation. In addition the pregnancy and live birth rate was significantly higher in the acupuncture group.

Acupuncture and sperm

Quantitative evaluation of spermatozoa ultrastructure after acupuncture treatment for idiopathic male infertility. Pei J et al Fertil Steril. 2005 Jul;84(1):141-7 Fertility and Sterility View Abstract

A group of infertile men who had pathological semen analyses according to WHO criteria, were treated with acupuncture twice a week for 5 weeks. A statistically significant increase after acupuncture in the percentage and number of sperm with no structural defects was demonstrated compared to the control group of patients who received no treatment. They concluded that male infertility patients could benefit from having acupuncture. A general improvement of sperm quality, specifically in the ultrastructural integrity of spermatozoa, was seen after acupuncture.

	Effect of acupuncture on sperm parameters of males suffering from subfertility related to low sperm quality. Siterman S et al Arch Androl. 1997 Sep-Oct;39(2):155-61 Archives of Andrology View Abstract
A group of infertile men with abnormal semen analysis were randomly divided into 2 groups; one group was given 10 acupuncture treatments over 5 weeks, and the other group, no treatment. Significant improvements (p < 0.05) were demonstrated in the acupuncture group compared to the control group, in particular improved motility and morphology.

Does acupuncture treatment affect sperm density in males with very low sperm count? A pilot study. Siterman S et al Andrologia. 2000 Jan;32(1):31-9. Andrologia View Abstract

This pilot study once again showed a positive effect of acupuncture on sperm count - but this time on men with such low sperm counts (or no sperm) that they would usually require a testicular biopsy to extract sperm for use in an IVF cycle. Seven of the 15 men with no sperm at all produced sperm detectable by the light microscope after a course of 10 acupuncture treatments (p < 0.01) ie enough sperm could be produced for ICSI to be performed without recourse to testicular biopsy. The control group with similar semen analysis had no treatment and showed no change after 3 months.

Effects of acupuncture and moxa treatment in patients with semen abnormalities. Gurfinkel E et al Asian J Androl. 2003 Dec;5(4):345-8. Asian Journal of Andrology View Abstract

In a prospective, controlled and blind study, a group of infertile men (married for 3 - 11 years without children) were randomized into two groups, the treatment group receiving 10 acupuncture treatments and the control group receiving sham acupuncture treatments. The patients in the acupuncture group demonstrated a significant increase in the percentage of normal forms compared to the control group.

Influence of acupuncture on idiopathic male infertility in assisted reproductive technology. Zhang M et al J Huazhong Univ Sci Tech Med Sci.2002;22(3):228-30 Journal of Huazhong University ( Abstract in Chinese)

This trial looks at sperm behaviour in an IVF setting. It was a “before and after” study involving 82 infertile men with pathological semen abnormalities and who’s sperm achieved a poor fertilization rate in at least 2 IVF/ICSI cycles. They were given acupuncture twice a week over 8 weeks and the IVF/ICSI cycles were repeated. The fertilization rates after acupuncture (66.2%) were significantly higher than that before treatment (40.2%) (P < 0.01).

A prospective randomized placebo-controlled study of the effect of acupuncture in infertile patients with severe oligoasthenozoospermia Dieterle et al Fertil Steril 2009 Oct; 92 (4): 1340–3 Fertility and Sterility

In this first prospective, randomized, single-blind, placebo-controlled study, 28 infertile patients with severe oligoasthenozoospermia received acupuncture according to the principles of traditional Chinese medicine (TCM) and 29 infertile patients received placebo acupuncture. A significantly higher percentage of motile sperm (World Health Organization categories A–C), but no effect on sperm concentration, was found after acupuncture compared with placebo acupuncture.

Acupuncture and well being of IVF patients

	The Impact of Acupuncture on in Vitro Fertilization Outcome. Domar A et al Fertil Steril 2009 Vol 91 Issue 3 pg 723 - 6 Fertility and Sterility View Abstract
One of the trials that investigated the effect of acupuncture on IVF pregnancy rates also collected data on the subjective experience of these women. The authors write “Acupuncture patients reported significantly less anxiety post-transfer and reported feeling more optimistic about their cycle and enjoyed their sessions more than the control subjects”.

	Understanding Women's views towards the use of Acupuncture while undergoing IVF treatment. Smith C and De Lacey S, 2008 In press FSA conference 2008 View Abstract
This qualitative study found that most women who had acupuncture as an adjunct to IVF treatment reported increased well being, reduced anxiety and an increase in capacity to cope with the stresses of IVF and infertility treatments.

Building resilience: A preliminary exploration of women's perceptions of the use of acupuncture as an adjunct to In Vitro Fertilisation De Lacey S, Smith C and Paterson C, BMC Complementary and Alternative Medicine 2009, 9:50 BioMed Central View Abstract

Resilience is an interesting and important concept when applied to couples doing IVF.    Studies of acupuncture involving women dealing with chronic health issues have shown that women experienced relief of presenting symptoms but also increases in energy, increase in relaxation and calmness, reduction in the reliance of prescription drugs (such as analgesics), quicker healing from surgery and increased self awareness and well being. Such effects indicate a reduction of stress that in turn may diminish the number of treatment cycles needed for pregnancy to occur. But further, reducing the number of cycles a woman must undertake to reach her goal of motherhood reduces the overall cost of IVF.

Meta Analyses and Recent Reviews

Effects of acupuncture on rates of pregnancy and live birth among women undergoing in vitro fertilisation: systematic review and meta-analysis. Manheimer E et al. BMJ 2008;336 pg 545-549 British Medical Journal View Abstract

Early in 2008, the prestigious British Medical journal published its own analysis of the acupuncture in a meta analysis of 7 of these trials; ie they chose only those which met strict research criteria. The authors concluded, “The odds ratio of 1.65 suggests that acupuncture increased the odds of clinical pregnancy by 65% compared with the control groups… In absolute terms 10 patients would need to be treated with acupuncture to bring about one additional clinical pregnancy. These are clinically relevant benefits.” And when they analysed the 4 trials that measured live births in addition to pregnancy rates, they found that acupuncture increased the odds by 91% and that the number of patients who would need to be treated to bring about an additional pregnancy dropped to 9. Impressive as these results are they may still be an underestimate, since the authors included women who’s IVF cycles were cancelled before transfer. The accompanying editorial in the BMJ makes the comment that adding acupuncture to IVF improved pregnancy rates more than any other recent improvement or advance in IVF technology.

Acupuncture and Assisted Conception Cheong Y et al, Cochrane Database of Systematic Reviews Nov 2008, Issue 4. Cochrane Review View Abstract

Another group of researchers have analysed updated clinical trial data and have come to the same conclusion as those who published the BMJ meta analysis, namely acupuncture is a useful addition to IVF. It has been published as a Cochrane Review. The Cochrane Collaboration is an international and independent organization dedicated to making up-to-date, accurate information about the effects of healthcare readily available worldwide.

A Systematic Review and Meta -analysis of the effect of Acupuncture on Outcome of in Vitro Fertilisation Treatment El-Toukhy T et al BJOG 2008 115 (10); 1203 -13 British Journal of Obstetrics and Gynaecolgy View Abstract

Another meta analysis also reported at the annual fertility conference indicated that in the trials they chose to include they found no effect of acupuncture on IVF treatment.This meta analysis included a trial which had been excluded from the previous analysis because it employed different methodology and therefore introduced a degree of heterogeneity which reduces the validity of the meta analysis.

Traditional Chinese medicine and infertility. Huang, S T and Chen, A P C, Current Opinion in Obstetrics & Gynecology. 2008, 2(3):211-215. Current Opinion in Obstetrics & Gynecology View Abstract

A recent review of current medical literature carried out by researchers in Taiwan noted that “traditional Chinese medicine could regulate the gonadotropin-releasing hormone to induce ovulation and improve the uterus blood flow and menstrual changes of endometrium. In addition, it also has impacts on patients with infertility resulting from polycystic ovarian syndrome, anxiety, stress and immunological disorders.” Their review concludes “Integrating the principles and knowledge from well characterized approaches and quality control of both traditional Chinese medicine and Western medical approaches should become a trend in existing clinical practice and serve as a better methodology for treating infertility.”

	The Role of Acupuncture in the Management of Subfertility Ng E H et al Fertil Steril. 2008 Jul;90(1):1-13. Fertility and Sterility View Abstract
Another review of the literature from a group in Hong Kong concludes that the positive effect of acupuncture in the treatment of subfertility may be related to the central sympathetic inhibition by the endorphin system, the change in uterine blood flow and motility, and stress reduction.