Introduction

In the past three decades, an increasing number couples have been in need of the services of human reproduction clinics in order to diagnose and manage the problems associated with infertility. According to the World Health
Orga-nization, 8-10% of couples may experience fertility problems during the reproductive age (1).

Infertility intensifies psychological distress, and evidence suggests that stress could adversely affect the outcomes of infertility treatment (2). For many women, infertility is accompanied by substantial emotional and psychological challenges. Furthermore, it is considered a remarkably distressful experience for women, which might lead to psychological morbidity in the form of anxiety, depression, and chronic stress (3).

On the other hand, assisted reproductive technology (ART) could be a predisposing factor for emotional and physical stress in infertile women (4). Today, it is well established that emotional and behavioral disorders lead to immune system damage (5).

Women show different reactions to
ineffe-ctive pregnancy attempts; such examples are disappoi-ntment, annoyance, and significant psychological distress. Emotional responses to infertility have been associated with feelings of grief, depression, anxiety or chronic stress, which adversely affect the hypothalamic-pituitary axis and even the possibility of a successful pregnancy following in-vitro fertilization (6). In-vitro fertilization (IVF) has been shown to be a stress-causing procedure, giving rise to anxiety in most of the cases. Moreover, waiting for treatment results and uncertainty of success may appear as other sources of stress, anxiety, and even depressive symptoms in infertile women (1).

Considering the significant emotional and financial stress associated with IVF, many women are in search of alternative therapies to diminish stress and achieve higher IVF success rates (7). Currently, various psychological interventions are implemented for individuals who are under emotional pressure regarding their response to infertility or subfertility treatments. These interventions are mostly focused on particular therapeutic approaches, such as psychodynamic-analytic interventions, mind/body-oriented
rela-xation, cognitive-behavioral therapies, training and education, and online counseling (6).

Acupuncture and traditional Chinese medicine have been widely used as a key remedy for mental disorders since 1100 BC (1). The first reports on the application of acupuncture in infertility treatment were published during 1960s (8). According to statistics, anxiety and depression are prevalent disorders in female populations, with the incidence twice higher compared to male populations. Management of these psychological disorders is rather complex considering the high prevalence rates and medication side effects.

In this regard, evidence supports the
effectti-veness of acupuncture to overcome the limitations of current therapeutic approaches (9). Use of acupuncture in the treatment of psychological disorders has been on a rising trend, and several studies have denoted the reduction of anxiety level following acupuncture (1, 10, 11).

Previous studies have investigated the
possi-bility of alleviating anxiety and stress through sympathoinhibitory exclusivity and impact on β-endorphin levels (12, 13). Furthermore, evidence suggests that acupuncture could remarkably improve debilitated immune functions in anxious women, while diminishing increased immune parameters (e.g., superoxide anion levels and lymphoproliferation) (5).

According to the literature, acupuncture enhances IVF outcome through four feasible mechanisms, including the adjustment of
neuro-endocrinological factors, increasing blood flow to the uterus and ovaries, modulation of cytokines, and alleviating stress, anxiety, and depression (14, 15).

In this regard, findings of So et al. were indicative of decreased anxiety levels in both study groups receiving real and placebo acupuncture (16). However, in another study by Isoyama et al., mean score of Hamilton Anxiety Rating Scale after a tentative period was significantly lower in the experimental group compared to the control group (1). In a research by Balk et al., women who received an acupuncture treatment regimen had lower stress scores before and after embryo transfer compared to other subjects (17).

With this background in mind, a systematic review is required in order to reconcile these contradictory findings. This study aimed to investigate the effects of acupuncture on anxiety in infertile women receiving ART.

Materials and Methods

This systematic review was conducted via searching in databases such as MEDLINE, PubMed, Cochrane Library, and PsycINFO, as well as clinical trial registries (clinicaltrials.gov) and reference lists. Related articles that were published since the initiation of each database until March 2015 were included in this study. Keywords and medical subject headings used in the literature search were as follows: acupuncture AND infertility AND (depression OR anxiety OR stress).

Titles and abstracts of all the retrieved articles were reviewed, and relevant studies were obtained in full text. Inclusion criteria were randomized controlled trials and studies published in English. Reference lists of the eligible articles were reviewed for replication.

We also carried out a forward citation searching in the selected articles via Google Scholar, and studies using acupuncture in cases with IVF or intracytoplasmic sperm insemination were included in this review. Process of article selection is illustrated in Figure 1 (18).

Article selection

Two reviewers independently assessed each article in order to determine their eligibility. All randomized controlled trials performed to investigate the effects of acupuncture on the anxiety of infertile women were included in this study. For the trials to be qualified, data on the final outcome of anxiety level were extracted, as obtained based on Spielberger’s State-Trait Anxiety Inventory (STAI) (8), shortened version of the 20-item STAI (10 items) (6), Hamilton Anxiety Scale (HAS) (1), and the Chinese version of STAI questionnaire (16).

Data extraction and quality assessment

One investigator abstracted the details regarding the author(s), year of study,
rando-mization, interventions, follow-ups and results, while the second investigator reviewed the obtained data in terms of accuracy. Any disagreement in this process was evaluated based on the expert opinion of the third
resear-cher. In addition, possible duplicate publications were conferred.Quality of the selected articles was assessed based on the checklist of Oxford Center for Evidence-Based Medicine (19), which consists of four main sections, as follows: 1) randomized assignment of patients to treatment groups and similarity of groups at the beginning of the trial, 2) additional treatments and intention-to-treat analysis, 3) placebo or sham treatment, and 4) statement of the results. Results of the quality assessment of the selected studies are presented in Table 1.

Outcome measures

In one of the selected articles, anxiety level was considered as the outcome measure (1). In two other studies, in addition to anxiety level, other outcome measures were evaluated, including overall pregnancy rate, implantation rate, clinical pregnancy rate, ongoing pregnancy rate, live birth rate, endometrial and subendometrial vascularity, cortisol concentration (16), perceived stress using the fertility problem inventory, and infertility self-efficacy based on the infertility self-efficacy scale (6). Moreover, outcome measures were not clarified in one study, while the authors noted factors such as pregnancy rate, anxiety level, and personal differences in optimism and pessimism using the Life Orientation Test Revised (LOT-R) (8).