General Female Fertility Studies

• A study conducted by the National Institutes of Health and the University of Oxford shows evidence that stress affects fertility. Researchers charted the ovulation cycles of 274 English women aged 18-40 years who were trying to conceive, and who participated in the Oxford Conception Study led by Cecilia Pyper, MB.BS. On the sixth day of her cycle, each woman collected a sample of her saliva, which was subsequently tested for alpha-amylase, an indicator of the body’s response to physical or psychological stress. The women’s saliva samples were also analyzed for cortisol, another hormone produced by the adrenal glands in response to stress. Each woman took part in the study until she became pregnant, or at the end of six menstrual cycles. Stress significantly reduced the probability of conception each day during the fertile window, possibly exerting its effect through the sympathetic medullar pathway. CONCLUSION: The researchers found that, all other factors being equal, women with high alpha-amylase levels were less likely to conceive than were women with low levels, during the fertile window– the six days when conception is most likely to occur. Researchers did not find a correlation between cortisol levels and the chances of conception.

“The study results suggest that finding safe ways to alleviate stress may play a role in helping couples become pregnant,” said Alan E. Guttmacher, M.D., director of the NICHD. “Women trying to get pregnant should identify the stressors in their lives and work to alleviate them through yoga, acupuncture or relaxation therapy”, suggests Dr. William Hurd, division chief of the Reproductive Endocrinology and Infertility Center at University Hospitals Case Medical Center.1

• This is a study which attempts to understand the correlation between women’s stress levels and fecundity and infertility. Data suggest that stress and reproduction are interrelated; however, the directionality of that association is unclear, ie does infertility cause stress or does stress cause infertility? In 2005–2009, reserachers enrolled 501 couples in a prospective cohort study with preconception enrollment at two research sites (Michigan and Texas, USA). Couples were followed for up to 12 months as they tried to conceive and through pregnancy if it occurred. A total of 401 (80%) couples completed the study protocol and 373 (93%) had complete data available for this analysis. Enrolled women collected saliva the morning following enrollment and then the morning following their first observed study menses for the measurement of cortisol and alpha-amylase, which are biomarkers of stress. TTP was measured in cycles. Covariate data were captured on both a baseline questionnaire and daily journals. After adjustment for female age, race, income, and use of alcohol, caffeine and cigarettes while trying to conceive, women in the highest tertile of alpha-amylase exhibited a 29% reduction in fecundity (longer TTP) compared with women in the lowest tertile [fecundability odds ratios (FORs) = 0.71; 95% confidence interval (CI) = (0.51, 1.00); P < 0.05]. This reduction in fecundity translated into a >2-fold increased risk of infertility among these women [relative risk (RR) = 2.07; 95% CI = (1.04, 4.11)]. In contrast, we found no association between salivary cortisol and fecundability. Conclusion: The researchers were unable to determine directionality, but it was clear from the study there exists a strong correlation between stress and infertility.60

• Researchers in this study attempted to evaluate, retrospectively by clinic records, 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. 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. In donor cycles, live birht rates were higher in the acupuncture group (relative risk=1.31, 95% CI 1.02-1.71). Conclusion: The Craig protocol was not found to lower IVF live birht rates. In fact, the Craig protocol was associated with higher live birth rates in donor cycles. These findings should be considered cautiously because more adequately powered, randomized research is needed.61

• This study aimed to assess the effect of Traditional Chinese Herbal Medicine (CHM) in the management of female infertility and on pregnancy rates compared with Western Medical (WM) treatment. The study suggests that management of female infertility with Chinese Herbal Medicine can improve pregnancy rates 2-fold within a 4 month period compared with Western Medical fertility drug therapy or IVF. Assessment of the quality of the menstrual cycle, integral to TCM diagnosis, appears to be fundamental to successful treatment of female infertility.37

• This was a study on the effect of acupuncture treatments on the psychosocial outcomes of women experiencing infertility. Thirty-two women aged 20-45 years received six sessions of acupuncture over 8 weeks. Women were observed for the outcomes on infertility self-efficacy, anxiety and infertility-related stress. At the end of the intervention, those women in the acupuncture group reported significant changes on two domains on the Fertility Problem Inventory. Conclusion: Acupuncture may be a useful intervention to assist with the reduction of infertility-related stress.40

• This study aimed to evaluate whether acupuncture improves the rates of pregnancy and live birth when used as an adjuvant treatment to embryo transfer in women undergoing in vitro fertilisation. Eligible studies where randomised controlled trials that compared needle acupuncture administered within one day of embryo transfer with sham acupuncture or no adjuvant treatment, with reported outcomes of at least one of clinical pregnancy, ongoing pregnancy, or live birth were compared. Seven trials with 1366 women undergoing in vitro fertilisation were included in the meta-analyses. Complementing the embryo transfer process with acupuncture was associated with significant and clinically relevant improvements in clinical pregnancy (odds ratio 1.65, 95% confidence interval 1.27 to 2.14; number needed to treat (NNT) 10 (7 to 17); seven trials), ongoing pregnancy (1.87, 1.40 to 2.49; NNT 9 (6 to 15); five trials), and live birth (1.91, 1.39 to 2.64; NNT 9 (6 to 17); four trials). Current preliminary evidence suggests that acupuncture given with embryo transfer improves rates of pregnancy and live birth among women undergoing in vitro fertilisation by up to 65%.3SeeFULL TEXT.

• Swedish researchers looked at the role that acupuncture can play in the treatment of infertility and in particular its effect on uterine blood flow.4The pool of women used as test subjects had infertility problems and were diagnosed with decreased blood flow into the uterus which affects endometrial receptivity. When there is a decreased flow of blood into the uterus, treatment options are few and conception is difficult. Using specific points which correspond to the innervation of the uterus, researchers measured the amount of blood flow in women undergoing in vitro fertilization (IVF) treatment. The results showed that there was a significant increase in the blood flow into the uterus with the acupuncture treatment. Researchers attributed the effect of acupuncture to its influence on increased uterine arterial blood flow into the uterus which in turn would increase the chance for oocyte implantation.

• Researchers in Germany looked at the traditional methods of acupuncture to determine its efficacy with the use of traditional points based on Traditional Chinese Medicine combined with assisted reproductive techniques with embryo transfer (in vitro fertilization or IVF).5The acupoints chosen were used to relax the uterus. The main purpose of the study was to evaluate whether acupuncture accompanying embryo transfer increases clinical pregnancy rates.

A total of 160 patients participated in the study, 80 patients receiving acupuncture and assisted reproductive techniques and 80 patients undergoing assisted reproductive techniques without acupuncture. Treatment consisted of an acupuncture treatment before and after IVF. The results showed that the pregnancy rate for the acupuncture group was considerably higher than the control (42.5% acupuncture group versus 26.3% control group). Acupuncture is a useful tool for improving the pregnancy rate after ART.

• The purpose of this study was to provide an overview of the use of acupuncture as an adjunct therapy for in vitro fertilization (IVF), including an evidence-based evaluation of its efficacy and safety and an examination of possible mechanisms of action. Evidence from clinical trials and case series suggests that acupuncture may improve the success rate of IVF and the quality of life of patients undergoing IVF and that it is a safe adjunct therapy. The reviewed literature suggests 4 possible mechanisms by which acupuncture could improve the outcome of IVF: modulating neuroendocrinological factors; increasing blood flow to the uterus and ovaries; modulating cytokines; and reducing stress, anxiety, and depression.6

• Some centres across North America now use assisted reproductive techniques combined with acupuncture. A fertility centre in Colorado Springs, Colorado utilizes both techniques.7The protocol used combines both techniques reported on in the Swedish and German research papers. Initially, the patient undergoes two treatments a week for four weeks of treatment before the IVF transfer which prepares the uterus’ endometrium for implantation by increasing arterial blood flow using acupoints based on the Swedish study. Pre- and post-embryo transfer, the patient is given acupuncture to relax the uterus as outlined in the German study.

There, results show that 16% more women get pregnant and 23% are having births. This combined technique of acupuncture with IVF is superior to IVF alone.

• Researchers attempted to evaluate the effectiveness of acupuncture on the reproductive outcome in patients treated with IVF or intracytoplasmic sperm injection (ICSI). Clinical and ongoing pregnancy rates were significantly higher in the group that received acupuncture as compared with controls (37 of 95 [39%] vs. 21 of 87 [26%] and 34 of 95 [36%] vs. 19 of 87 [22%]). Researchers concluded that acupuncture significantly improves the reproductive outcome of IVF/ICSI, compared with no acupuncture.8

• Acupuncture and Poor IVF Responders; A further study in April 2004 confirmed a significant increase in the number of pregnancies in patients who demonstrated elevated peak FSH and a longer history of infertility. This study had an IVF pregnancy rate of 53% in the acupuncture group compared to 38% in the non-acupuncture control group.9

• Acupuncture Reduces Pain After IVF. In this study, 286 women were randomly assigned to receive either electroacupuncture plus para-cervical block or alfentanil (a powerful analgesic) plus paracervical block during oocyte aspiration (egg retrieval). Both interventions induced adequate analgesia, however the electroacupuncture group reported significantly less abdominal pain, other pain, nausea and stress than the medication group, and required significantly less additional analgesic medication.10

• This study was designed to determine the effect of luteal-phase acupuncture on the outcome of IVF/intracytoplasmic sperm injection (ICSI). The clinical pregnancy rate and ongoing pregnancy rate (33.6% and 28.4%, respectively) were significantly higher in the group that received acupuncture than in the control group (15.6% and 13.8%). The study concluded that luteal-phase acupuncture has a positive effect on the outcome of IVF/ICSI.13

• Over a period of three years, acupuncture was offered to patients entering assisted reproduction therapy. Acupuncture sessions were given at varying, but usually weekly, intervals during the in vitro fertilisation (IVF) cycle, and immediately before and after embryo transfer. Twenty two patients (average age 36.2 years) were treated over a total of 26 IVF cycles and 15 pregnancies were achieved, as determined by presence of foetal heartbeat on ultrasound at four weeks post embryo transfer. There was a success rate of 57.7% in the acupuncture group compared with 45.3% for patients in the IVF unit not treated with acupuncture (P > 0.05). Relaxing effects were noted following acupuncture and it is speculated that this may have contributed to the increase in pregnancy rate for the acupuncture group.14

• The aim of this study was to summarise the evidence from systematic reviews (SRs) and meta-analyses assessing the efficacy of acupuncture in treating common gynaecologic conditions. Six electronic databases, including two major English-language databases (PubMed and the Cochrane Library) and four Korean databases, were systematically searched for SRs and meta-analyses concerned with acupuncture and common gynaecologic diseases. The quality of the included studies was assessed using the Overview Quality Assessment Questionnaire. Of the 55 potentially relevant studies that were found, 16 SRs were included in this report. The study concluded that acupuncture was clearly beneficial in the management of chemotherapy-induced nausea and vomiting. In addition, current evidence suggests that acupuncture administered close to embryo transfer during in vitro fertilisation treatment improves the rates of pregnancy and live birth.17

• The purpose of this study was to determine the impact of hypnosis during embryo transfer on the outcome of in vitro fertilitization. Ninety-eight patients undergoing IVF and embryo transfer (ET) cycles were selected at random. Fifety-two clinical pregnancies were obtained. The implantation rate was 28% among those patients undergoing hypnotherapy veresus an implantation rate of 14.4% for the control group. CONCLUSION: This study suggests that the use of hypnosis during ET may significantly improve the IVF/ET cycle outcome in terms of increased implantation and clinical pregnancy rates. Furthermore, it seems that the patients’ attitude to the treatment was more favorable.39

• The purpose of this study was to determine whether 25OH-D (vitamin D) levels in the follicular fluid (FF) of infertile women undergoing IVF demonstrate a relationship with IVF cycle parameters and outcome, hypothesizing that levels of 25OH-D in body fluids are reflective of vitamin repletion status. Eighty-four infertile women undergoing IVF were studied. Serum and FF levels of 25OH-D were highly correlated (r = 0.94). Multivariable logistic regression analysis confirmed FF 25OH-D levels as an independent predictor to success of an IVF cycle; adjusting for age, body mass index, ethnicity, and number of embryos transferred, each ng/mL increase in FF 25OH-D increased the likelihood for achieving clinical pregnancy by 6%. CONCLUSION: Our findings that women with higher vitamin D level in their serum and FF are significantly more likely to achieve clinica pregnancy following IVF-embryo transfer are novel. A potential for benefit of vitamin D supplementation on treatment success in infertile patients undergoing IVF is suggested and merits further investigation.38

• The aim of this study was to examine the effect of acupuncture on self-efficacy for women receiving acupuncture for fertility support. Pretest and posttest measurement of infertility self-efficacy was conducted in this prospective observational study. Subjects were recruited from three acupuncture practices in South Eastern Australia. Women aged 18 to 45 years presenting for acupuncture treatment for natural conception or as an adjunct to assisted reproductive technology participated in this study. Consecutive new patients were invited to take part if they were planning a minimum of four acupuncture treatments as part of a current episode of care. The study found a significant increase in total infertility self-efficacy scale (ISE) scores from baseline and after four acupuncture treatments (N = 13; t [12] = 3.15, P = .008). Four women showed clinically significant improvement on ISE total scores using the significant change index. CONCLUSIONS: The data suggests that acupuncture improves self-efficacy and psychological coping for women experiencing delays with falling pregnant.19

• This study shows that despite differences between acupuncturists’ point selection and generally a highly variable practice between international acupuncture experts, a high degree of consensus exists amongst expert acupuncturists supporting treatment protocol for women undergoing Assisted Reproductive Technology (ART) treatment.READ MORE

• The aim of this study was to assess modalities of acupuncture treatments in fertility centers and compare them with investigated acupuncture treatments in randomized controlled trials (RCTs) related to ART. One in 5 couples is affected by infertility. To increase the effectiveness of assisted reproductive technology (ART) adjuvant acupuncture treatments are frequently administered. 180 fertility centers in Switzerland, Germany and Austria were invited to participate in an online survey assessing the provision of acupuncture in ART. Acupuncture was offered by 33 (38.4%) of all responding fertility centers (n = 86; responder rate = 47.8%). In 39.4% the selection of acupuncture points is standardized or semi-standardized (24.2%) and in 27.3% based on individual TCM-diagnosis. Body acupuncture using needle stimulation was mentioned most frequently (84.8%). Some clinics reported additional use of auricular acupuncture (24.2%) and moxibustion (21.2%). Treatment providers were mainly physician-acupuncturists (84.8%). Compared to the RCTs, these researchers found strong differences in point selection, mode of stimulation, and professional background of treatment providers. From this study it is clear that the selection of an acupuncturist is crucial to the success of the treatment. 45

• Infertility affects about 15% of couples in Western-societies with most progressing to fertility clinics for treatment. Despite being common, infertility is often experienced as a lonely road for affected couples. In this paper the researchers expand on their previously published findings of women’s experiences with infertility or difficulty of viable pregnancy who had sought Traditional Chinese Medicine (TCM) therapy in Australia, and focus on women’s quality of life, coping strategies, and support needs. Women reported through both questionnaires and interviews compromised quality of life due to the high level of distress, guilt, grief, and frustration caused by infertility. Reserachers noted that in infertility, ongoing emotional and instrumental support is pivotal to the wellbeing and quality of life of the affected. Traditional Chinese Medicine addresses some support needs in infertility not routinely available in the Western model of care. More peer-led and professional-led support groups are greatly needed for women experiencing infertility to help break isolation and raise awareness of integrative approaches to fertility management.49

• Assisted reproductive technologies (ART) are increasingly utilised for resolving difficulties conceiving. These technologies are expensive to both the public purse and the individual consumers. Acupuncture is widely used as an adjunct to ART with indications that it may assist reducing the time to conception and increasing live birth rates. Heterogeneity is high between treatment protocols. The aim of this study was to examine what fertility acupuncturists consider key components of best practice acupuncture during an ART cycle, and to establish an acupuncture protocol by consensus. Conclusion: Despite a lack of homogeneity in the research and clinical literature on ART and acupuncture, a consensus amongst experts on key components of a best practice treatment protocol was possible. Such consensus offers guidance for further research.41

• The purpose of this study was to determine whether changes in serum cortisol (CORT) and PRL are affected by acupuncture (Ac) in Ac-treated IVF patients. Blood samples were obtained from all consenting new infertility patients and serum CORT and serum PRL were obtained prospectively. Patients were grouped as controls (IVF with no Ac) and treated (IVF with Ac) according to acupuncture protocols derived from randomized controlled trials. Conclusion: There appears to be a beneficial regulation of CORT and PRL in the acupuncture group during the medication phase of the IVF treatment with a trend toward more normal fertile cycle dynamics.52

• Acupuncture has been used to treat infertility extensively, including ovulatory dysfunction, in vitro fertilization and embryo transfer (IVF-ET), and male infertility. Researchers attempted to review recent studies in the field of fertility acupuncture. Conclusion: Most of the existing studies suggest a positive effect of acupuncture in infertility treatment. Firstly, acupuncture may improve ovulation by modulating the central and peripheral nervous systems, the neuroendocrine and endocrine systems, the ovarian blood flow, and metabolism. Secondly, acupuncture can improve the outcome of IVF-ET, and the mechanisms may be related to the increased uterine blood flow, inhibited uterine motility, and the anesis of depression, anxiety and stress. Its effect on modulating immune function also suggests helpfulness in improving the outcome of IVF-ET. Finally, the studies suggest that acupuncture plays a positive role in male infertility, the mechanism of which is not yet clear. Even though a positive effect of acupuncture in infertility has been found, well-designed multi-center, prospective randomized controlled studies are still needed to provide more reliable and valid scientific evidence. Furthermore, it is urgent and necessary to clarify the mechanism of acupuncture for infertility.53

• Infertility patients are increasingly using complementary and alternative medicine (CAM) to supplement or replace conventional fertility treatments. Researchers in Canada had the objective of determining the roles of CAM practitioners in the support and treatment of infertility. Semi-structured interviews were conducted in Ottawa, Canada in 2011 with CAM practitioners who specialized in naturopathy, acupuncture, traditional Chinese medicine, hypnotherapy and integrated medicine. Researchers concluded integrated infertility patient care through both collaboration with CAM practitioners and incorporation of CAM’s holistic, individualized and interdisciplinary approaches would greatly benefit infertility patients.62

• Researchers in this study wished to observe the effect of electro-acupuncture (EA) on the clinic outcomes and the occurrences of ovarian hyper-stimulation syndrome (OHSS) in in vitro fertilization and embryo transplantation. 109 patients who routinely received in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at Reproductive Center were assigned to the control group (56 cases) and the EA group (53 cases). Patients in the control group received controlled ovarian hyper-stimulation (COH) referring to GnRH-a long protocol. On the basis of COH, those in the EA group received EA from the day of Gn injection to the day of embryo transfer. Estradiol (E2), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and angiotensin (AT) II were measured in all patients on the day of hCG injection, the day of ovum pick up (OPU), and the day of embryo transfer (ET), respectively. The oocyte retrieval rate, good quality embryo rate, clinical pregnancy rate, the abortion rate, and the occurrence of OHSS were compared between the two groups. Researchers concluded EA, as an adjunctive therapy, could reduce the occurrence of OHSS in IVF. Besides, it did not decrease good embryo rates and pregnancy rates in IVF-ET, which might be associated with lowering local vascular permeability of ovaries.63

• Patients often ask us at Total Wellness, how far in advance of their IVF cycle they should receive acupuncture treatments? This study appears to be one of the first studies to attempt to answer that question.

In recent years, acupuncture has become more and more popular in the management of subfertility. Researchers in this study evaluated the impact of acupuncture during in vitro fertilization (IVF) treatment on the outcomes of clinical pregnancy in published randomized studies. This study was a systematic review and meta-analysis. This study showed that acupuncture did not significantly improve the IVF clinical pregnancy rate when performed only at the time of embryo transfer (ET), while researchers found pooled (cumulative) benefit of acupuncture for IVF when performed at follicle phase and 25 min before and after ET, as well as 30 min after ET and implantation phase. This finding is significant, as it speaks to both the timing of acupuncture and the cumulative effects of acupuncture.64

• This is one of the first studies that attempts to distinguish the effects of acupuncture alone as compared to acupuncture plus the full complement of traditional Chinese medicine. Patients undergoing IVF received either acupuncture or whole-systems traditional Chinese medicine (WS-TCM) as an adjuvant IVF treatment. WS-TCM is a complex intervention that can include acupuncture, Chinese herbal medicine, dietary, and lifestyle recommendations. In this retrospective cohort study, 1231 IVF patient records were reviewed to assess the effect of adjuvant WS-TCM on IVF outcomes. The primary outcome was live birth. The researchers concluded overall, IVF with adjuvant WS-TCM was associated with greater odds of live birth in donor and non-donor cycles.65

• The objective of this study was to observe the impacts on endometrial and pregnancy outcomes treated with acupuncture and moxibustion in the patients of in vitro fertilization-embryo transfer (IVF-ET) and explore the application value, of acupuncture and moxibustion in IVF-ET treatment. One hundred and fourteen patients of IVF-ET treated with standard long-term program at luteal phase were randomized into an observation group and a control group, 57 cases in each one. In the observation group, at the beginning of ovulatory induction, moxibustion was applied to Shenque (CV 8) and acupuncture was to Zhongji (CV 3), Guanyuan (CV 4), Qihai (CV 6), Zigong (EX-CA 1), Xuebai (SP 10), etc. till the transfer time for one session of treatment. Totally, 3 sessions were required. In the control group, no intervention of acupuncture and moxibustion was applied. The endometrial morphology, subendometrial blood flow index, the levels of serum estradiol (E2), progesterone (P) and luteinizing hormone (LH) on the day of injection of human chorionic gonadotropin (hCG), the dosage and time of gonadotropin (Gn), oocyte count, high-quality embryo number, embryo cultivation rate and clinical pregnant rate were observed in the two groups. At the conclusion of the study, researches found in IVF-ET treatment, acupuncture and moxibustion affect estrogen level on hCG day, improve high-quality embryo rate, endometrial blood flow state and morphology so that the endometrial receptivity is increased and the method is expected to be the assistant therapeutic approach for the improvement of IVF-ET outcome.72