Transcutaneous electrical acupuncture point stimulation improves pregnancy outcomes in patients with recurrent implantation failure undergoing in vitro fertilisation and embryo transfer: a prospective, randomised trial

Zhenhong Shuai et al, Acup Med, 2019, Vol 37 issue 1, 33-39 Acupuncture In Medicine BMJ

Stimulation of acupuncture points on the abdomen and legs with TEAS (transcutaneous electrical acupuncture stimulation) improved implantation and pregnancy outcomes in women who had previous repeated implantation failure, in this randomised trial involving 122 IVF patients.

 

Abstract

Objective:

To evaluate the effect of transcutaneous electrical acupuncture stimulation (TEAS) on pregnancy outcomes in patients with recurrent implantation failure (RIF) undergoing in vitro fertilisation (IVF).

Methods:

A total of 122 women with RIF undergoing fresh embryo transfer cycle IVF were randomly allocated to a TEAS or mock TEAS (MTEAS) group. Gonadotrophin therapy using a long protocol was provided in both groups. TEAS consisted of 30 min of stimulation (9–25 mA, 2 Hz) at SP6, CV3, CV4 and Zigong from day 5 of the ovarian stimulation cycle once every other day until the day of embryo transfer. The patients in the control group received MTEAS. Implantation, clinical pregnancy and live birth rates were compared.

Results:

In the TEAS group, the implantation rate, clinical pregnancy rate and live birth rate (24.3%, 32.8% and 27.9%, respectively) were significantly higher than in the MTEAS group (12.1%, 16.4% and 13.1%, respectively).

Conclusions:

TEAS significantly improves the clinical outcomes of subsequent IVF cycles among women who have experienced RIF.


Effectiveness of Acupuncture on Pregnancy Success Rates for Women Undergoing in Vitro Fertilization: A Randomized Controlled Trial

Cayir Y et al,  JAMS, 11(4):224-225 · August 2018, Journal of Acupuncture and Meridian Studies

A randomly selected and controlled trial (RCT) found that acupuncture improved pregnancy rates in women who had acupuncture before and on the day of embryo transfer compared to a similar group of women who did not have acupuncture. This trial did not use sham acupuncture as a control, but rather used “usual care” as a control. This finding is at odds with larger trials using sham acupuncture as a control.

This trial also reported a reduced anxiety level in the women who had acupuncture.

This study aimed to investigate the effect of acupuncture on pregnancy success rates applied before and after embryo transfer (ET) in idiopathic IVF patients. Our study was conducted between December-2017 and May-2018 on women aged 23–45 years, who received IVF treatment due to idiopathic infertility. A total of 72 infertile women were randomized to acupuncture (AG; n = 36) and control group (CG; n = 36). Three sessions of acupuncture were applied to AG, first one week before ET, second 30 minutes before ET, and third 30 minutes after ET. CG received no acupuncture. Beta-HCG levels were assessed for conception 12 days after ET. Additionally, STAI-1 state anxiety scale was administered before and after ET to measure anxiety levels in both groups.

The mean age o was 30.9 ± 3.7 years. Positive Beta HCG was detected in 63.9% (n = 23) of the AG and 33.3% (n = 12) of CG (p = 0.009). There was no difference between the groups concerning pre-ET anxiety scores (p > 0.05). STAI-1 score was 57.3 ± 9.8 before ET whereas it was 36.1 ± 6.3 after applying acupuncture in AG (p < 0.001).

It was observed that three sessions of acupuncture before and after ET significantly increased the pregnancy rates in women with idiopathic infertility. It was also found that acupuncture significantly reduced pre-ET stress levels. Acupuncture has advantage of not having any side effects and less cost compared to other treatments providing additional benefits by reducing stress levels, a factor negatively affecting fertility.


Effect of acupuncture vs sham acupuncture on live births among women undergoing in vitro fertilization: a randomized clinical trial

Caroline Smith et al, JAMA, 2018 DOI: 10.1001/jama.2018.5336

Journal of the American Medical Association.

In a large RCT, 848 women at 16 different IVF centres in Australia and New Zealand were given acupuncture (with real or sham needles)  by 80 different acupuncturists. A standardised protocol was delivered on Day 6 of the drug stimulation phase and another before and after the embryo transfer. The data indicated that at this dose of acupuncture, and using these protocol points, there was no significant difference in live births between those who received the real or the sham needles.

The authors admit that ” the lack of frequent treatments was a limitation of our trial” since in real clinical practice acupuncture treatment is individualised with variation in dosing, including more frequent treatment prior to and during the IVF cycle.

They also noted that while a very short course of acupuncture may statistically be no better than sham at improving live birth and pregnancy outcomes, a psycho-social benefit from acupuncture was reported by women undergoing IVF.

Objective  To determine the efficacy of acupuncture compared with a sham acupuncture control performed during IVF on live births.

Design, Setting, and Participants  A single-blind, parallel-group randomized clinical trial including 848 women undergoing a fresh IVF cycle was conducted at 16 IVF centers in Australia and New Zealand between June 29, 2011, and October 23, 2015, with 10 months of pregnancy follow-up until August 2016.

Interventions  Women received either acupuncture (n = 424) or a sham acupuncture control (n = 424). The first treatment was administered between days 6 to 8 of follicle stimulation, and 2 treatments were administered prior to and following embryo transfer. The sham control used a noninvasive needle placed away from the true acupuncture points.

Main Outcomes and Measures  The primary outcome was live birth, defined as the delivery of 1 or more living infants at greater than 20 weeks’ gestation or birth weight of at least 400 g.

Results  Among 848 randomized women, 24 withdrew consent, 824 were included in the study (mean [SD] age, 35.4 [4.3] years); 371 [45.0%] had undergone more than 2 previous IVF cycles), 607 proceeded to an embryo transfer, and 809 (98.2%) had data available on live birth outcomes. Live births occurred among 74 of 405 women (18.3%) receiving acupuncture compared with 72 of 404 women (17.8%) receiving sham control (risk difference, 0.5% [95% CI, −4.9% to 5.8%]; relative risk, 1.02 [95% CI, 0.76 to 1.38]).

Conclusions and Relevance  Among women undergoing IVF, administration of acupuncture vs sham acupuncture at the time of ovarian stimulation and embryo transfer resulted in no significant difference in live birth rates. These findings do not support the use of acupuncture to improve the rate of live births among women undergoing IVF.


Electroacupuncture for reproductive hormone levels in patients with diminished ovarian reserve: a prospective observational study

Yang Wang et al, 2016, BMJ Acup Med, Vol 34, Issue 5

BMJ Acupuncture in Medicine

This prospective observational study (Level IV) from Beijing examined the effect of electro-acupuncture on women who were diagnosed with poor ovarian reserve, indicated by their baseline FSH level being elevated on Day 2 or 3 of their menstrual cycle, ie between and 11 and 40 mIU/ml.

After 12 weeks of treatment mean FSH levels dropped by nearly a half, a highly significant result. While no firm conclusions can be drawn at this stage, this result indicates that further research is warranted on larger numbers of patients to determine if electro-acupuncture is useful tool for women with low ovarian reserve.

Abstract

Background Effective methods for the treatment of reproductive dysfunction are limited. Previous studies have reported that acupuncture can modulate female hormone levels, improve menstrual disorders, alleviate depression and improve pregnancy rates. However, studies of acupuncture for diminished ovarian reserve (DOR) are lacking.

Objective To carry out a prospective observational study aimed at assessing the effect of EA on the reproductive hormone levels of patients with DOR seeking fertility support and consider its safety.

Methods Eligible patients with DOR received EA for 12 weeks: five times a week for 4 weeks followed by three times a week for 8 weeks. The primary outcome was the change in mean follicle-stimulating hormone (FSH) level at week 12. Mean luteinising hormone (LH) and serum oestradiol (E2) levels, FSH/LH ratios and symptom scale scores were simultaneously observed.

Results Twenty-one patients with DOR were included in the final analysis. Mean FSH levels fell from 19.33±9.47 mIU/mL at baseline to 10.58±6.34 mIU/mL at week 12 and 11.25±6.68 mIU/mL at week 24. Change in mean FSH from baseline was −8.75±11.13 mIU/mL at week 12 (p=0.002) and −8.08±9.56 mIU/mL at week 24 (p=0.001). Mean E2 and LH levels, FSH/LH ratios and irritability scores were improved at weeks 12 and/or 24. Approximately 30% patients reported subjective increases in menstrual volume after treatment.

Conclusions EA may modulate reproductive hormone levels and the effects seem to persist for at least 12 weeks after treatment with no significant side effects. EA may improve the ovarian reserve of patients with DOR, though further research is needed.


Effects of traditional Korean medicine on anti-Mullerian hormone inpatients with diminished ovarian reserve: A retrospective study

Junyoung Jo et al, Comp  Ther  Med  24 (2016) 118–122

Complementary Therapies in Medicine, Elsevier

This Pilot study examined the effect of taking traditional herbal formulas in 22 women who had very low ovarian reserve (measured as AMH <1.1ng/ml). They found that 2 months of taking the herbal formulas increased the AMH significantly (double)  in women below 38 years of age, but not over this age. This study now needs to be repeated with a larger number of women to confirm this result.

Abstract

Objective: The purpose of the present study is to retrospectively evaluate the effect of traditional Korean medicine (TKM) on ovarian reserve by measuring serum anti-Müllerian hormone (AMH) levels in patients with diminished ovarian reserve (DOR).

Study design: We performed a retrospective chart review of patients with DOR who had received TKMfor at least 2 months and had undergone serum AMH tests before and after TKM treatment. A total of 22 patients with DOR were included in the study.

Results: There were no significant differences in AMH levels before and after TKM in all patients (n = 22,p = 0.237). However, when the study population was divided into two age groups (<38 (n = 12) and ≥38years (n = 10)) to determine whether there was a age-related difference in the effect of TKM with DOR, a significant increase in AMH levels before and after TKM was observed in the age <38 (p < 0.05).

Conclusions: TKM may provide an effective option for patients aged <38 years with DOR, but it should be interpreted cautiously as more rigorous research is needed. Further studies in a larger population are needed to confirm these results and to evaluate the effects of improved ovarian reserve on fertility outcomes following TKM in patients with DOR.


Effect of Zishen Yutai Pill on Embryo Implantation Rate in Patients Undergoing Embryo Transfer

ZHU Wen-jie et al, C JIM (Chin) 2002;22(10) ‘ 729,Chinese Journal of Integrative Medicine

In a RCT involving 140 IVF patients 70 were given Zi Shen Yu Tai pills (a famous traditional remedy) after their embryo transfer and pregnancy rates were compared with 70 women who received usual care. The group receiving the Chinese herb formula had a significantly higher implantation and pregnancy rate.

 Objective: To observe the effect of Zishen Yutai pill ( ZYP) on embryo implantation rate in luteal phase of patients undergoing  embryo transfer.

Methods: One hundred and forty subjects were divided into two groups, they were all administered with human chorionic gonadotropin to improve the luteal function. To Group A, ZYP was given additionally for 6 g, three times a day for 14
consecutive days.

Results: In Group A, mean serum progesterone, embryo implantation rate and clinical pregnancy rate were 15.42 +/- 1. 9ug/L, 24. 12% and 51. 52% respectively, significantly higher than those in Group B, 13.92+1.96t~g/L,16.67% and 34.78% (P~0.001, P~0.05 and P~0.05).

Conclusion: Oral administration of  ZYP in luteal phase could raise the embryo implantation rate effectively.


Acupuncture and Chinese herbal treatment for women undergoing intrauterine insemination

Sela K et al, Eur Jn Int Med, Vol 3, 2, 2011, Pgs e77–e81, European Journal of Integrative Medicine

 Many couples prefer to try less invasive methods before doing IVF. IUI is one such method, that involves insemination of washed sperm to the uterus at precisely the time of ovulation. In this study (controlled but not randomised Level III) women who were being treated with acupuncture and Chinese herbs had a 50% higher pregnancy rate than those who weren’t. The average age of women in the control group was 37, while the average age of the women in the Chinese medicine group was 39. This result should be tested in larger RCTs.

 Abstract

Aim: To assess the effect of traditional Chinese medicine (TCM, acupuncture and medicinal herbs) as a therapeutic adjuvant to ovulation induction with intrauterine insemination (IUI) procedures and evaluate its contribution to pregnancy and “take-home baby” rates.

Materials and methods: A comparative retrospective study was carried out in a university – affiliated municipal hospital. All women undergoing artificial insemination by donor spermatozoa (AID) and concomitantly treated with TCM were invited to participate. The enrolled women underwent weekly TCM in parallel with medical therapy. The treatment lasted between 2 and 36 cycles (equivalent to a time period ranging from one month to one year). The control group was comprised of women who underwent AID without TCM and whose data were retrospectively retrieved from hospital files. Pregnancy was assessed by human chorionic gonadotropin findings in blood 12–14 days after IUI. The birth rate was calculated during follow-up.

Results: A total of 29 women aged 30–45 years were enrolled in the study. The historical control group included 94 women aged 28–46 years. Women who combined TCM with the procedures for undergoing IUI had significantly higher pregnancy (OR = 4.403, 95% CI 1.51–12.835, p = 0.007) and birth rates (OR = 3.905, 95% CI 1.321–11.549, p = 0.014) than the control group.

Conclusions: TCM appears to be beneficial as an adjunctive treatment in IUI procedures. Randomized controlled trials are needed to further assess the role of acupuncture and herbs in this setting.


Acupuncture and in vitro fertilization: a retrospective chart review.

Hullender R et al J Altern Complement Med. 2013 Jul;19(7):637-43.
Jnl Alternative and Complementary Medicine

In this observational study, women receiving embryos from donor eggs, were given acupuncture on the day of transfer, and live birth rates were compared with a similar control group. 87% of the women who received donor egg embryos and had acupuncture had a baby compared with 66% in the donor group that did not have acupuncture. This result needs to be tested in a RCT setting.

Abstract

Objectives: In 2007, Craig et al. reported the results of a randomized controlled trial in which a standardized acupuncture protocol performed on the day of embryo transfer (ET) resulted in lower pregnancy rates after in vitro fertilization (IVF). Between 2005 and 2007, the Craig protocol was used by one of the authors (LHR) at an infertility clinic unaffiliated with the Craig et al. trial. The objective was to retrospectively review clinic records to evaluate the effect of the Craig protocol in both donor and nondonor IVF cycles on four outcomes: (1) live births; (2) biochemical pregnancies; (3) adverse outcomes; and (4) live births in nondonor cycles across age groups established by the Society for Assisted Reproductive Technology.

Design: The study design was a retrospective chart review.

Setting: The study was conducted at a private infertility clinic.

Patient(s): Patients underwent fresh, donor (N=70) or nondonor (N=402) IVF-ET.

Intervention(s): The Craig protocol included the following points before ET: GV-20, CV-6, ST-29, SP-8, PC-6, LV-3; Shenmen and Brain on the left ear; and Uterus and Endocrine on the right ear. After transfer the points were LI-4, SP-10, ST-36, SP-6, KI-3; Uterus and Endocrine on the left ear; and Shenmen and Brain on the right ear.

Main Outcome Measure(s): Live births (LB) beyond 24 weeks’ gestation was the main outcome measure.

Result(s): In nondonor IVF cycles, there were no differences in LB across age groups (odds ratio [OR]=1.04, 95% confidence interval [CI] 0.68-1.57), biochemical pregnancies (OR=0.60, 95% CI 0.27-1.33), or adverse outcomes (OR=0.63, 95% CI 0.31-1.26). In donor cycles, LB were higher in the acupuncture group (relative risk=1.31, 95% CI 1.02-1.71).

Conclusions: In this observational study, the Craig protocol was not found to lower IVF LB. In fact, the Craig protocol was associated with higher LB in donor cycles. These findings should be considered cautiously because more adequately powered, randomized research is needed.


Effects of Chinese Medicines for Tonifying the Kidney on DNMT1 Protein Expression in Endometrium of Infertile Women During Implantation Period

Lian Fang et al Jnl Alt Compl Med, 2013, Vol 19, 4, 353–359
The Journal of Alternative and Complementary Medicine

In this Australia it is preferred by many IVF clinics that their patients do not take Chinese herbs during the medication phase of the IVF cycle. However in China it is more accepted and herbs are used during IVF cycles in some clinics. This small RCT showed that taking herbs for three months prior to and during the IVF cycle improved egg quality and pregnancy rate in IVF patients, additionally lower doses of FSH were needed. Larger RCTs are needed to replicate this result before firm conclusions can be reached.

Abstract

Objectives: The purpose of this study was to explore the effects of Erzhi Tiangui Granule (ETG) on DNA methyltransferases (DNMT) 1 protein expression in endometrium of infertile women with Kidney-yin Deficiency syndrome.

Methods: A randomized, double-blinded, placebo-controlled clinical trial was conducted. Sixty-six (66) infertile patients who had Kidney-yin Deficiency syndrome and who were to undergo in vitro fertilization–embryo transfer (IVF-ET) were randomly assigned to either a treatment group or a control group according to a random table. Besides gonadotropin (Gn) therapy in both groups, the treatment group received ETG for 3 menstrual cycles before IVF, and the control group received placebo granules. The ETG and the placebo granules were made with similar color and shape, as well as in the same packaging. The scores of the Kidney-yin Deficiency syndrome were assessed. Other outcome measures included the dosage and duration of Gn, the number of retrieved oocytes, the rate of high-quality oocytes, the rate of high-quality embryos, the fertilization rate, and the clinical pregnancy rate. DNMT1 protein expression in the endometrium was measured in the midluteal phase.

Results: The difference in the syndrome score change before and after treatment between the two groups was statistically significant ( p < 0.05). The dosage and duration of Gn were significantly lower in the treatment group than those in the control group ( p < 0.05). The high-quality oocyte and embryo rates, and clinical pregnancy rate were all higher in the treatment group than those in the control group ( p < 0.05). The fertilization rate was not significant when compared to the placebo group. No difference was found in the number of retrieved oocytes between the two groups. The DNMT1 protein expression in the endometrium was much more abundant in the treatment group than that in the control group ( p < 0.05).

Conclusions: For the infertile patients undergoing IVF, the Chinese recipe for tonifying the Kidney as an adjunct treatment could reduce Gn dosage and treatment duration, alleviate clinical symptoms, and improve the clinical pregnancy rate. The increased level of DNMT1 protein expression after treatment may lead to enhanced endometrial receptivity. This finding may explain the improvement in clinical pregnancy rate.