Acupuncture and IVF research

Acupuncture has attracted much attention over the last 20 years in relation to IVF and fertility. The following gives details of the most well-known and recent research.

In our opinion much of the research is difficult to evaluate due to the inherent nature of measuring acupuncture itself.

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Objective: To evaluate the effect of acupuncture on in vitro fertilization (IVF) outcomes.
Design: Systematic review and meta-analysis.
Patient(s): Women undergoing IVF in randomized controlled trials (RCTs) who were evaluated for the effects of acupuncture on IVF outcomes.
Setting: Not applicable.
Intervention(s): The intervention groups used manual, electrical, and laser acupuncture techniques. The control groups consisted of no, sham, and placebo acupuncture.
Main Outcome Measure(s): The major outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR). Heterogeneity of the therapeutic effect was evaluated with a forest plot analysis. Publication bias was assessed by a funnel plot analysis.
Result(s): Twenty-four trials (a total of 5,807 participants) were included in this review. There were no significant publication biases for most of the
comparisons among these studies. The pooled CPR (23 studies) from all of the acupuncture groups was significantly greater than that from all of the
control groups, whereas the LBR (6 studies) was not significantly different between the two groups. The results were different when the type of control was examined in a sensitivity analysis. The CPR and LBR differences between the acupuncture and control groups were more obvious when the studies using the Streitberger control were ignored. Similarly, if the underlying effects of the Streitberger control were excluded, the LBR results tended to be significant when the acupuncture was performed around the time of oocyte aspiration or controlled ovarian hyperstimulation.
Conclusion(s): Acupuncture improves CPR and LBR among women undergoing IVF based on the results of studies that do not include the Streitberger control. The Streitberger control may not be an inactive control. More positive effects from using acupuncture in IVF can be expected if an appropriate control and more reasonable acupuncture programs are used. (Fertil Steril_ 2012;97:599–611. _2012 by American Society for Reproductive Medicine.)

Objective: To evaluate the influence of ‘‘true’’ versus ‘‘sham’’ acupuncture on pregnancy rates (PRs) in women
undergoing IVF.
Design: Randomized controlled trial, double-blinded with independent observer.
Setting: Academic infertility clinic.
Patient(s): One hundred sixty patients <38 years old undergoing IVF with or without intracytoplasmic sperm injection.
Intervention(s): Subjects were randomly allocated to the true or sham group and underwent acupuncture 25 minutes before and after ET. Subjects completed a McGill Pain Questionnaire regarding their clinical symptoms during ET.
Main Outcome Measure(s): Clinical PR and clinical symptoms during ET.

Result(s): While the overall clinical PR was 51.25%, there was no significant difference between the arms of the study (true ¼ 45.3% vs. sham ¼ 52.7%); 33.1% of the patients had ultrasound-documented singleton pregnancy, and 15% of patients had twin gestations, while one patient in the true arm had a triplet gestation. There were significant differences in the subjective, affective, and total pain experience between both arms. The subjects in the true arm described their acupuncture session as being more ‘‘tiring’’ and ‘‘fearful’’ and experienced more ‘‘achiness’’ compared with their sham counterparts.
Conclusion(s): There was no statistically significant difference in the clinical or chemical PRs between both groups. Patients undergoing true acupuncture had differing sensory experiences compared with patients in the sham arm. There were no significant adverse effects observed during the study, suggesting that acupuncture is safe for women undergoing ET. (Fertil Steril_ 2011;95:583–7. _2011 by American Society for Reproductive
Medicine.)

Another meta-analysis also reported at an 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 this meta-analysis

CONCLUSION: Currently available literature does not provide sufficient evidence that adjuvant acupuncture improves IVF clinical pregnancy rate..

OBJECTIVE: To determine the effect of luteal-phase acupuncture on the outcome of IVF / intracytoplasmic sperm injection (ICSI).
DESIGN: Randomized, prospective, controlled clinical study.
SETTING: University IVF center.
PATIENT(S): Two hundred twenty-five infertile patients undergoing IVF/ICSI.
INTERVENTION(S): In group I, 116 patients received luteal-phase acupuncture according to the principles of traditional Chinese medicine. In group II, 109 patients received placebo acupuncture.
MAIN OUTCOME MEASURE(S): Clinical and ongoing pregnancy rates.
RESULT(S): In group I, the clinical pregnancy rate and ongoing pregnancy rate (33.6% and 28.4%, respectively) were significantly higher than in group II (15.6% and 13.8%).
CONCLUSION(S): Luteal-phase acupuncture has a positive effect on the outcome of IVF/ICSI.

A randomized controlled trial that compared real acupuncture with sham acupuncture before and after embryo transfer in 370 patients undergoing IVF treatment. The sham treatment used pressure at the same locations as used for real acupuncture, in effect a comparison of acupuncture and acupressure, not a placebo. The clinical pregnancy rate was significantly higher in the sham acupuncture group than the real acupuncture group (55.1 versus 43.8%, respectively, p=0.038). No significant differences were found in rates of ongoing pregnancy and live birth between the two groups. Reduction of endometrial and sub-endometrial vascularity, serum cortisol concentrations and anxiety levels were observed in both groups. The researchers concluded that placebo acupuncture was associated with a significantly higher overall pregnancy rate than real acupuncture, but that placebo acupuncture may not be inert.

This report describes outcomes for all patients who attended  the The London Bridge Fertility, Gynaecology and Genetics Centre in London over a 2 year period and who had acupuncture .  In the acupuncture group positive pregnancy rates/ET were 44.6% comparing favourably with the non-acupuncture historic control group. When they analysed outcomes in different age groups they discovered that acupuncture intervention was particularly effective in woman in the 35 – 39 and the over 40 group.

OBJECTIVE: To develop a protocol that could be used in future studies to evaluate whether acupuncture improves pregnancy and delivery rates in patients undergoing IVF. DESIGN: Randomized, sham treatment controlled pilot study.
MATERIALS AND METHODS: Patients planning to undergo IVF who meet inclusion/exclusion criteria (age 40 years old at start of stimulation, highest basal FSH 10mIU/mL, 3 prior failed IVF attempts, acupuncture naive) were randomly assigned to an acupuncture treatment group or a sham treatment group.
Treatment sessions occurred before the start of gonadotropin stimulation, the day before the oocyte retrieval, the day before the embryo transfer and the day after the embryo transfer. 24
Acupuncture was performed using manual manipulation at 6 to 10 points depending on the timing of the acupuncture treatment. Sham treated patients had needles placed in non-meridian points at a shallow depth. Patients were also given a questionnaire regarding their impressions of acupuncture treatment and were asked to guess their group assignment.
Data was analyzed using chi-squared for dichotomous outcome variables (e.g. clinical pregnancy rate, number of take home babies) and t-tests for continuous outcomes (e.g. age).
RESULTS: Twenty-two IVF cycles (19 patients) were randomized with thirteen patients completing the study (14 cycles). Five cycles were not completed due to poor response to ovarian stimulation (4 in the sham group, one in the real group). Other reasons for incomplete cycles (all in the sham group) included a persistent ovarian cyst, no viable embryos for transfer and personal reasons. The overall cycle cancellation rate was 32% compared to a 22% cycle cancellation rate for non-study patients of a similar age treated at this center during a similar time period (p.05).
In the 13 patients analyzed, the mean age was 35 years old (SD4.03). There was no statistical difference between true and sham acupuncture groups with respect to age (Sham: Mean35, SD4.6, Real: Mean34, SD4.6). Additionally, there was no significant difference between groups in highest basal FSH, number of oocytes retrieved, or number of embryos transferred. There was a significantly higher chemical pregnancy rate (80% versus 11.0%) in patients receiving true acupuncture compared to sham acupuncture (p.05). The clinical pregnancy rates and the take home baby rates showed a strong trend towards a higher rate with acupuncture treatment though the difference was not statistically significant (60% real treatment vs. 11% sham treatment, p.05.).
Regarding the questionnaire, only one patient correctly guessed their group assignment (real acupuncture). All patients rated their experience as very positive or positive.
CONCLUSION: It is feasible to conduct a randomized, blinded, sham control trial to study the impact of acupuncture on IVF success rates. Such a protocol is well accepted by patients. Preliminary data shows a statistically significant improvement in the biochemical pregnancy rate with acupuncture treatment. Additionally, acupuncture was associated with a strong trend towards higher clinical pregnancy rates and take home baby rates, though more patients will need to be studied to reach any final conclusions.

An overview of research in the published Cochrane databases

Acupuncture performed on the day of ET shows a beneficial effect on the live birth rate; however, with the present evidence this could be attributed to placebo effect and the small number of women included in the trials. Acupuncture should not be offered during the luteal phase in routine clinical practice until further evidence is available from sufficiently powered RCTs.
The data from this meta-analysis suggests that acupuncture does increase the live birth rate with in vitro fertilization (IVF) treatment when performed around the time of embryo transfer. However, this could be attributed to placebo effect and the small number of trials included in the review. Larger studies are necessary to confirm the results.

OBJECTIVE: Conflicting evidence exists on whether acupuncture is beneficial for patients undergoing In Vitro Fertilization (IVF) cycles. Therefore, this study was undertaken to determine whether on-site acupuncture, per- formed both before and after embryo transfer, affects clinical outcomes.
DESIGN: Retrospective data analysis.
MATERIALS AND METHODS: The Acupuncture Group consisted of 49 patients who received acupuncture on-site before and after embryo transfer in 2007. The treatment did not follow the Paulus protocol. The Control Group were 212 patients with no acupuncture undergoing IVF cycles in the same time period. The data was subdivided by SART age classifications to determine if acupuncture differentially benefitted certain age groups. Clinical Pregnancy Rate (CPR) was defined as the presence of fetal cardiac activity. Loss Rate was the percentage of pregnancies that did not proceed from a positive hCG to a clinical pregnancy. Data were analyzed using the unpaired t-test and Fisher’s exact test, with significance defined as P < 0.05.
RESULTS: Patients with a positive hCG were significantly higher in the Acupuncture Group for women less than 35 years old (63.3% vs.43.2%, p 1⁄4 0.048). The Acupuncture Group also had a higher CPR in the under 35 category (60.0% vs. 34.6%, p 1⁄4 0.01). There were no differences in the other age groups. Combining all the age groups, the cycle parameters between the two Groups were equivalent, while the CPR was higher and the Loss Rate lower for the Acupuncture group (Table 1).
TABLE 1. Cycle Data for All Age Groups
Acupuncture No Acupuncture P Value
N 49 212
Age 32.6 +4.2 32.0 + 3.8 0.33
No. Oocytes 13.7 + 6.6 13.2 +6.9 0.65 22
Cell Number 6.8 + 2.0 7.0 + 2.1 0.36
Fragmentation Score 2.5 + 0.6 2.5 + 0.6 1.00
No. Embryos Frozen 2.5 + 3.2 2.7 + 3.5 0.85
No. Embryos Transferred 2.3 + 0.6 2.2 + 0.6 0.29
Positive hCG (%) 57.1 (28/49) 45.8 (97/212) 0.16
Clinical Pregnancy (%) 55.1 (27/49) 34.4 (75/212) 0.01
Loss Rate (%) 3.6 (1/28) 22.7 (22/97) 0.02
CONCLUSIONS: Although other studies regarding acupuncture have been inconclusive, perhaps these positive results are related to two important factors. The treatments were performed on-site, eliminating the stress of traveling to another site before and after the embryo transfer. Also, the acupuncture treatment protocol did not follow the traditional Paulus protocol, thereby suggesting there is still more research to be done on how best to treat infertility issues with acupuncture

OBJECTIVE: The aim of this study was to evaluate the effects of acupuncture on embryo transfer by comparing the rates of clinical pregnancy. 25
DESIGN: Retrospective, interventional and longitudinal study.
MATERIALS AND METHODS: Study with a total of 111 cycles of patients who underwent assisted reproduction techniques: in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) from June/2005 to January/ 2007: 52 cycles with acupuncture and 59 cycles without acupuncture. Acupuncture was performed, in specific points of the body including the ear, immediately before and after the embryo transfer procedure and the needles were retained for 30 minutes per session. The embryo transfer was carried out under ultrasound guidance and luteal phase support was given by trans-vaginal progesterone administration (Utrogestan) and intramuscular progesterone. Outcome measure was clinical pregnancy rate.
RESULTS: The clinical pregnancy rate per cycle was observed in 27 of 52 (51.9%) patients in the acupuncture group and 21 of 59 (35.6%) patients in the control group (P 1⁄40,083). The mean age was 36.1 6.1 years in the control group and 36.4 years in the acupuncture group (P1⁄40.785). The mean number of embryo transferred was 3.3 in the control group and 3.6 in the acupuncture group (P1⁄40.462). The technique of embryo transfer was 5 cycles of IVF and 54 cycles of ICSI in the control group and 5 cycles IVF and 47 cycles of ICSI in the acupuncture group (P 1⁄41.000). Both groups did not show statistics difference in the mean age, number of embryo transferred and the technique procedure.
CONCLUSIONS: Although there was a higher pregnancy rate in the acupuncture group, this difference was not statistically significant, probably because of the small number of patients in both group. Acupuncture seems to be an important coadjutant in the treatment of infertility with IVF or ICSI, and further research is needed to demonstrate its precisely effect.

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 cannot be excluded. Our results suggest that acupuncture was safe for women undergoing ET.

OBJECTIVE: To evaluate the effect of acupuncture on reproductive outcome in patients treated with IVF/intracytoplasmic sperm injection (ICSI). One group of patients received acupuncture on the day of ET, another group on ET day and again 2 days later (i.e., closer to implantation day), and both groups were compared with a control group that did not receive acupuncture.

DESIGN: Prospective, randomized trial.
SETTING: Private fertility center.
PATIENT(S): During the study period all patients receiving IVF or ICSI treatment were offered participation in the study. On the day of oocyte retrieval, patients were randomly allocated (with sealed envelopes) to receive acupuncture on the day of ET (ACU 1 group, n = 95), on that day and again 2 days later (ACU 2 group, n = 91), or no acupuncture (control group, n = 87).
INTERVENTION(S): Acupuncture was performed immediately before and after ET (ACU 1 and 2 groups), with each session lasting 25 minutes; and one 25-minute session was performed 2 days later in the ACU 2 group.
MAIN OUTCOME MEASURE(S): Clinical pregnancy and ongoing pregnancy rates in the three groups.
RESULT(S): Clinical and ongoing pregnancy rates were significantly higher in the ACU 1 group as compared with controls (37 of 95 [39%] vs. 21 of 87 [26%] and 34 of 95 [36%] vs. 19 of 87 [22%]). The clinical and ongoing pregnancy rates in the ACU 2 group (36% and 26%) were higher than in controls, but the difference did not reach statistical difference.
CONCLUSION(S): Acupuncture on the day of ET significantly improves the reproductive outcome of IVF/ICSI, compared with no acupuncture. Repeating acupuncture on ET day +2 provided no additional beneficial effect.

OBJECTIVE: The study was conducted to examine several adjunct treatment regimens administered before and after embryo transfer and determine if one treatment was more efficacious than any of the alternative regimens on in vitro fertilization (IVF) outcome. We compared two different acupuncture stimulation modes, needle and laser acupuncture, with sham laser acupuncture, relaxation, or no intervention treatment on implantation and pregnancy rates in women undergoing IVF. 30

DESIGN: Prospective single blind randomized trial. MATERIALS AND METHODS: Patients (n258) who had been scheduled for embryo transfer (ET), signed informed consent and were randomly assigned to one of 5 study treatment regimens; needle acupuncture (AC; 53), laser acupuncture (LZ AC; n53), sham laser acupuncture (placebo)(LZ sham; n52), relaxation (RX; n50), or no intervention treatment (NT; n50). All treatments were administered 25 minutes before ET and immediately after ET. The patient and acupuncturist were unaware of whether the laser system was active which allowed for a double-blind control group for the laser acupuncture treatment. Comparisons of various parameters between groups were conducted by 2 tests and one-way ANO- As.. Multinomial logistic regression analysis was used to control for the potentially confounding effects of day of embryo transfer (day 3 vs.5) and number of embryos transferred which are known to relate to IVF outcome, to further analyze the impact of adjunct treatment regimens on implantation and pregnancy rates. Probability of P 0.05 was considered to be statistically significant.
RESULTS: No differences in terms of cycle type, day of embryo transfer, or physician performing transfer were found between treatment groups. Neither day of transfer (p0.079) or egg number (P 0.082) were significant independent predictors of implantation or conception when interactions between parameters were considered in all 5 groups. All acupuncture treatments were well tolerated.
CONCLUSION: Conception and implantation rates were highest with traditional needle acupuncture. IVF treatment outcomes did not differ between patients treated with laser or sham laser acupuncture. This study did not have the statistical power to detect treatment differences in pregnancy rates between needle acupuncture and no treatment (i.e., at least 200 subjects are needed to detect differences in CP rates of 54.7 and 44% with 80% power) which may be due to sample size, transfer of embryos of varying quality and variations in stimulation protocols. However, while not statistically significant, needle acupuncture produced a clinically significant effect (greater than 10% increase in clinical pregnancy rate) compared with relaxation or no treatment which warrants further investigation.

OBJECTIVE: The purpose of this study was to replicate previous research on the efficacy of acupuncture in increasing pregnancy rates in IVF and determine if the increase in conceptions was due to a placebo effect.
DESIGN: This was a randomized, controlled, prospective, single blind design.
MATERIALS AND METHODS: 83 women scheduled to undergo embryo transfer from a fresh cycle using their own eggs were recruited to participate in the study. Subjects completed a battery of demographic and psychological questionnaires prior to randomization and were then 31
assigned to either the acupuncture or control condition. Acupuncture subjects received the protocol first described by Paulus et al, 2002, which included 22 needles, for 25 minutes prior to and again 25 minutes following embryo transfer. Control subjects lay quietly for the same amounts of time.
All subjects completed another battery of psychological questionnaires following their second acupuncture/control session which focused on their sense of optimism about the outcome of the cycle. All IVF staff remained blind to subject assignment.
RESULTS: The mean age of the acupuncture patients was 36.5 and for the control subjects was 35.3 (p0.05). The mean number of embryos transferred for the acupuncture patients was 2.58 and for the controls 2.56 (p0.05). The pregnancy rate (defined as a positive HCG level 11 days following ET) was 53.84% in the acupuncture group and 52.94% in the control group (p0.05). There were also no significant differences between the two groups in optimism level post-embryo transfer, although there was a trend for the acupuncture group to express more optimism.
CONCLUSION: The use of acupuncture with IVF patients was not associated with an increase in pregnancy rates or optimism. This study did not replicate previous research. Possible explanations include the fact that this study differed in three ways from the Paulus et al study:
all ET patients were eligible, not just patients with good embryo quality,
all staff were blind to subject assignment, not just the attending physician,
patients completed several psychological questionnaires which might have impacted them in some way.
Since there were no differences in pregnancy rates, it was not possible to determine if acupuncture is associated with a placebo effect

OBJECTIVE: To evaluate the effect of acupuncture on the pregnancy rate in assisted reproduction therapy (ART) by comparing a group of patients receiving acupuncture treatment shortly before and after embryo transfer with a control group receiving no acupuncture.
DESIGN: Prospective randomized study. 35
SETTING: Fertility center.
PATIENT(S): After giving informed consent, 160 patients who were undergoing ART and who had good quality embryos were divided into the following two groups through random selection: embryo transfer with acupuncture (n = 80) and embryo transfer without acupuncture (n = 80).
INTERVENTION(S): Acupuncture was performed in 80 patients 25 minutes before and after embryo transfer. In the control group, embryos were transferred without any supportive therapy.
MAIN OUTCOME MEASURE(S): Clinical pregnancy was defined as the presence of a fetal sac during an ultrasound examination 6 weeks after embryo transfer.
RESULT(S): Clinical pregnancies were documented in 34 of 80 patients (42.5%) in the acupuncture group, whereas pregnancy rate was only 26.3% (21 out of 80 patients) in the control group.

CONCLUSION(S): Acupuncture seems to be a useful tool for improving pregnancy rate after ART.

Other papers.

Some research papers have also looked not just at clinical results but mechanistic basis and other elements of the acupuncture, ivf and patient relationship such as patient requirements and well being

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‖.

Nobody knows how exactly acupuncture might boost IVF success, Domar said, although she suggests that it has something to do with a woman’s mental state at the time of embryo transfer.
Abstract
Objective: To replicate previous research on the efficacy of acupuncture in increasing pregnancy rates (PR) in patients undergoing IVF and to determine whether such an increase was due to a placebo effect. Design: Prospective, randomized, controlled, single blind trial.
Setting: Private, academically affiliated, infertility clinic.
Patient(s): One hundred fifty patients scheduled to undergo embryo transfer.
Intervention(s): Subjects were randomized to either the acupuncture or control group. Acupuncture patients received the protocol, as first described by Paulus and his colleagues, for 25 minutes before and after embryo transfer. Control subjects lay quietly. All subjects then completed questionnaires on anxiety and optimism. The IVF staff remained blind to subject assignment.
Main Outcome Measure(s): Clinical PRs, anxiety, optimism. 66
Result(s): Before randomization both groups had similar demographic characteristics including age and psycho- logical variables. There were no significant differences in PRs between the two groups. 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.
Conclusion(s): The use of acupuncture in patients undergoing IVF was not associated with an increase in PRs but they were more relaxed and more optimistic.

These investigators aimed to determine if acupuncture affects the levels of perceived stress at the time of embryo transfer, and whether either acupuncture or changes in stress levels play a role in the success rate in IVF. The patients who received acupuncture in this study had both higher rates of pregnancy, and lower levels of stress both before and after embryo transfer. They postulated that reducing stress at the time of embryo transfer could result in less vasoconstriction and improved uterine receptivity.
Abstract
The aim of this paper was to determine the effect of acupuncture on perceived stress levels in women on the day of embryo transfer (ET), and to determine if perceived stress levels at embryo transfer correlated with pregnancy rates. The study was an observational, prospective, cohort study based at the University IVF center.
Patient(s): 57 infertile patients undergoing IVF or IVF/ICSI.
Interventions(s): Patients were undergoing Embryo Transfer with or without acupuncture as part of their standard clinical care.
Main outcome measure(s): Perceive Stress Scale scores, pregnancy rates.
Result(s): women who received this acupuncture regimen achieved pregnancy 64.7%, whereas those without acupuncture achieved pregnancy 42.5%. When stratified by donor recipient status, only non-donor recipients potentially had an improvement with acupuncture (35.5% without acupuncture vs. 55.6% with acupuncture). Those who received this acupuncture regimen had lower stress scores both pre-ET and post-ET compared to those who did not. Those with decreased their perceived stress scores compared to baseline had higher pregnancy rates than those who did not demonstrate this decrease, regardless of acupuncture status.
Conclusions(s): The acupuncture regimen was associated with less stress both before and after embryo transfer, and it possibly improved pregnancy rates. Lower perceived stress at the time of embryo transfer may play a role in an improved pregnancy rate