Description of the condition
The definition of subfertility remains a subject of debate (Gnoth 2005) and confusion between the definition of infertility and subfertility often occurs. Evers (Evers 2002) and He (He 2004) have stated that infertility is the absolute inability to conceive, whilst subfertility is not described as irreversible but rather as any form or grade of diminished ability to conceive over a prolonged time (usually at least six menstrual cycles) (Gnoth 2005). The International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) in their revised terminology document state that the clinical definition of infertility is "a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse" (Zegers-Hochschild 2009). Many women with clinical subfertility will eventually conceive spontaneously; for example, after 12 unsuccessful cycles the live birth rate among untreated couples with subfertility will reach nearly 50% in the following 36 months, which is equivalent to slightly reduced fertility. However, approximately 5% of these couples have little chance of falling spontaneously pregnant in the next 48 months and these are defined as infertile or sterile (Gnoth 2005). Fertility, subfertility, infertility and sterility are therefore not dichotomous (Evers 2002; Gnoth 2005).
Subfertility without any prior pregnancy is termed 'primary subfertility', whilst 'secondary subfertility' is when couples are unable to conceive the number of children desired (He 2004). There is a strong trend towards increased subfertility as women increasingly delay having children until a time when their natural capacity to conceive is in decline (Boivin 2007; Evers 2002).
The main factors which contribute to subfertility are ovulation dysfunction, tuboperitoneal diseases and male factors, such as azoospermia or oligospermia (absent or low sperm count); subfertility may also be unexplained (Evers 2002). Endometrial and uterine factors, as well as advancing female age, probably also contribute to impaired fertility (Adamson 2003).
The diagnosis of subfertility varies, depending upon the cause. With respect to unexplained subfertility, it is a diagnosis of exclusion of abnormalities through standard investigations of both members of a couple (Athaullah 2002). There are also several prediction models which have been developed to make accurate predictions of a couple's chance of conceiving naturally (Van Geloven 2012; Verhoeve 2011).
Treatment such as assisted reproductive technologies (ART), including intra-uterine insemination (IUI), with or without controlled ovarian hyperstimulation (COH) and in vitro fertilisation (IVF), are often recommended upon a diagnosis of subfertility. Treatments include COH with IUI for ovulation dysfunction and unexplained subfertility; surgery for pelvic adhesions, endometriosis and myomas; and IVF for severe tubal factors or failure to conceive with standard infertility treatment (Adamson 2003; Evers 2002). However, determining the effectiveness of treatment is difficult given that few well-designed and analysed studies have been carried out in reproductive medicine (Adamson 2003).
The aim of this systematic review is to investigate the effectiveness and safety of acupuncture for the management of subfertility based on the results of randomised controlled trials (RCTs). Acupuncture trials with a focus on primary clinical outcomes other than fertility should be investigated in separate systematic reviews.
Description of the intervention
Acupuncture, as one of the main forms of traditional Chinese medicine (TCM), has been practised within the Chinese healthcare system for thousands of years (Qiu 1993). Since the late 20th century, the demand for acupuncture has been growing steadily in many Western nations (Hamilton 2008; Harkin 2007; Zhu 2009; Qiu 1993; Schmincke 2008). In 2006, an interview survey conducted by the National Institutes of Health in the United States indicated that 1.1% of their population (representing 2.13 million Americans) reported recent use of acupuncture (Burke 2006). Subfertility is one of the common problems which cause people to seek acupuncture treatment (Ng 2008).
There are several different forms of acupuncture including body acupuncture, electroacupuncture, auricular acupuncture and scalp acupuncture (Qiu 1993).
Body acupuncture is defined as needling acupuncture points on the human body along the traditional meridians and excludes cranial and ear points (Lan 1997).
Electroacupuncture is the stimulation of acupuncture points by electrical current (Qiu 1993).
Auricular acupuncture is a micro system within TCM and involves stimulation of acupuncture points in the ear (Qiu 1993).
Scalp acupuncture is the parallel insertion of needles along the scalp for treating neurological conditions (Qiu 1993).
Although subfertility was not recorded explicitly in the classical texts as a defined entity, the word subfertility is often used interchangeably with infertility (Xia 1994). Contemporary TCM researchers acknowledge the two types of impaired fertility: the absolute inability to conceive and the relative diminished ability to conceive, which is the focus of TCM practice (Song 2008).
According to the TCM philosophical framework, there is a natural pattern of vital energy (Qi) throughout the body; a disruption in this flow of energy indicates disease (Maciocia 1998). The key pathology of subfertility is impeded function of the kidneys (the kidneys are the main organ in charge of reproduction within the TCM framework). Subfertility also results from impairment or obstruction of the flow of energy in the Chong and Ren meridians, which are associated with the uterus and ovaries. It is believed that a constitutional deficiency is the underlying pathology. The principle of the application of acupuncture is to strengthen the impaired organ and channels and unblock the obstruction in the related channels (Luo 1986; Xia 1994).
How the intervention might work
The mechanism of action of acupuncture in the treatment of female subfertility remains largely unclear. However, emerging literature suggests that acupuncture mediates and alters specific hormone levels. Modern researchers have revealed that the effect of acupuncture in relation to fertility might be mediated through central neurotransmitters including ß-endorphin and serotonin, resulting in the release of gonadotropin-releasing hormone (GnRH) and thereby influencing pituitary gonadotropin secretion, ovarian follicular growth and finally ovulation (Chang 2002; Petti 1998). Studies of auricular and body acupuncture have also indicated that ovulation induction might occur through the mediation of the hypothalamic-pituitary ovarian axis (Cai 1997; Chen 2007; Xiang 2002).
In addition, Westergaard and co-workers conducted a randomised trial and concluded that acupuncture significantly improves the reproductive outcome of IVF/intracytoplasmic sperm injection (ICSI) on the day of embryo transfer compared with no acupuncture. They therefore postulated that acupuncture might have a general sympathoinhibitory effect, which in turn increases uterine and ovarian blood flow (Westergaard 2006). Acupuncture appears to have a favourable safety profile (Highfield 2006).
Why it is important to do this review
Subfertility is a prevalent problem, despite significant advances in the techniques available in the field of reproductive medicine. And there are still opportunities to explore the optimisation of treatment modalities. Treatments should have proven effectiveness with low risk (Gnoth 2005). At present, reproductive treatment leads to large financial, social and psychological burdens for couples and the community (Myers 2008), with increased risks of multiple pregnancy, miscarriages and ovarian cancer (Bensdorp 2007; Hughes 2010).
Acupuncture has been used recently in the management of subfertility (Ng 2008). Investigations of the use of acupuncture in assisted reproduction are increasing, in particular in the industrial developed countries. The main attractions for patients and health professionals of using acupuncture for fertility problems are that in general it is inexpensive and relatively painless, with no known adverse side effects if performed by qualified personnel. While public interest in the use of acupuncture for the improvement of fertility arises from time to time, there is demand for evidence of proven effectiveness (Domar 2006). A systematic review of the use of acupuncture for female subfertility to determine effectiveness and safety will address these needs and demands.