The role of traditional and complementary medicine to improve fertility and emotional well-being

THE FERTILITY SOCIETY OF AUSTRALIA - The role of traditional and complementary medicine to improve fertility and emotional well-being

Traditional and Complementary Medicine (T&CM) is a broad set of healthcare practices
that sit outside conventional medicine in many countries [1]. They are described by users as
preventative and holistic, aimed to treat illness, promote health and well-being and used due
to personal beliefs, preferences and resonance with traditions and cultural practices [2]. Common
therapies include acupuncture, naturopathy and physical and manual therapies such as yoga,
and massage [3]. Complementary medicines sold in pharmacies and health-food shops including
herbs, vitamins, minerals and nutritional supplements are regulated under the Therapeutic
Goods Act 1989. Few high-quality studies of the effect of T&CM on fertility have been
undertaken. Of the published studies, most have focused on female fertility. Existing evidence
of the effects of T&CM on subfertility and infertility-related distress is reviewed.

EVIDENCE REVIEW

- Acupuncture and female subfertility and ART outcomes
Acupuncture is a Chinese medical treatment that involves insertion of
fine sterile metal needles into prespecified areas of the body or acupuncture
points. Auricular acupuncture is an acupuncture variant, where needles
are inserted into acupuncture points on the outer ear. Another related
treatment is acupressure, where sustained pressure is applied to
acupuncture points [4].
A systematic review and meta-analysis of eight randomised controlled
trials (RCTs) including 1,546 women with anovulatory infertility due to
polycystic ovary syndrome (PCOS) was published in 2019 [5]. It found
that acupuncture may improve restoration of regular menstrual periods.
However, the overall quality of the evidence was low or very low and the
authors concluded that there is currently insufficient evidence to support
the use of acupuncture for treatment of ovulation disorders in women
with PCOS.
An overview of 11 systematic reviews (SRs) (210 RCTs and 44,619
women undergoing IVF) found that despite increased clinical pregnancy
rates (RR 1.12 95% CI 1.08 to 1.16, 7 SRs), there was no evidence that
acupuncture had any effect on rates of live birth, ongoing pregnancy, or
miscarriage regardless of whether acupuncture was performed around the
time of oocyte retrieval or around the day of embryo transfer [6].
A subsequent systematic review included subgroup analyses that compared
results from RCTs of acupuncture against no adjunctive treatment,
against trials using sham controls [7]. There was evidence of increased
chance of pregnancy when acupuncture was compared to no adjunctive
treatment (RR 1.32, 95% CI 1.07–1.62, 12 trials, 2230 women). This
positive effect was also seen with ongoing pregnancies (RR 1.42, 95%
CI 1.17–1.73, 6 trials, 1144 women) and live births (RR 1.30, 95%
1.00–1.68, 9 trials, 1,980 women). No evidence of clinical benefit was
found for acupuncture when it was compared to sham controls. This was
also the case in a recent RCT of 848 women undergoing IVF where
administration of acupuncture vs sham acupuncture at the time of ovarian
stimulation and embryo transfer resulted in no significant difference in
live birth rates [8].
Adverse effects of acupuncture were reported in six trials and included
nausea, dizziness, tiredness, drowsiness, headache, chest pain, pain/itching
at needle site [7].

- Acupuncture to improve wellbeing in subfertile women
There is low quality evidence for the effect of acupuncture in reducing anxiety
in women with infertility. A systematic review of four RCTs involving 595
infertile women [9] found a statistically significant reduction in anxiety for
acupuncture compared to no treatment in two studies.

- Acupuncture and male subfertility
Acupuncture may improve sperm quality and fertilisation rates in ICSI
although effects on pregnancy and live birth rates have not been
demonstrated. A systematic review and meta-analysis of four RCTs
including 500 men with oligozoospermia or asthenozoospermia examined
the effect of acupuncture on sperm quality. Men receiving acupuncture
between 27 days and three months had significantly higher sperm
concentration (mean difference (MD) 6.42 x 106 per ml, 95% CI 4.91
– 7.92) and rapid sperm motility (MD 6.35%, 95% CI 4.38 – 8.32, 3
RCTs, n=278) compared to controls, however this did not translate into
increased clinical pregnancy rates [10]. None of the studies reported any
adverse events; however, it was unclear whether data on adverse events
were collected or reporting was inadequate.
There is very low-quality evidence of a small but consistent positive effect
of acupuncture on sperm parameters in subfertile men. In a summary
of six prospective studies [11], acupuncture for 10 days to 12 weeks was
found to improve sperm viability [12, 13], concentration [12] motility
[14, 15], percentage of normal morphology [16, 17], and possibly
improve pregnancy rates [12]. The mechanism by which acupuncture
may improve sperm quality remains unknown.

- Acupuncture for improved wellbeing in subfertile men
Infertility can have a negative impact on men’s psychological wellbeing
and sexual function. A systematic review reported a higher prevalence of
depression and anxiety in men with infertility compared to fertile men, and
a higher incidence of erectile dysfunction and premature ejaculation [18].
Whilst there is very limited evidence for any interventions to improve the
sexual health and wellbeing of infertile men, evidence from a meta-analysis
of two RCTs (59 men) found no difference between acupuncture and sham
acupuncture in improved erectile function (RR 2.73, 95% CI 0.42 to
17.78, p = 0.29, two RCTs n= 59) [19].

- Chinese herbal medicine and female subfertility
Traditional Chinese herbal medicine (CHM) has a history of being used for
female infertility in south-east Asian countries. CHMs are often polyherbal
formulations containing a large number of herbal, mineral, or animal
derived ingredients, with most formulas averaging between 10 and 15
components [20]. These formulas are usually tailored to traditional Chinese
medicine diagnosis. A Delphi study reached consensus on proposed clinical
practice guidelines for best CHM practice in the treatment of infertility due
to PCOS in a Western healthcare context [21]. CHM formulas are often
taken for three to six months pre-conceptually to improve fertility.
A meta-analysis of systematic reviews of CHM for women with infertility
as a result of anovulation, PCOS, endometriosis, fallopian tube blockage or
unexplained infertility included 40 RCTs and 4,247 women [22]. Compared
to Western pharmaceutical treatments, CHM increased pregnancy rates
(OR 3.14, 95% CI 2.72-3.62), decreased the risk of miscarriage and
improved cervical mucous scores, biphasic temperatures and endometrial
thickness. No significant side effects of CHM were reported. The quality of
the included studies was assessed as low due to variation in the formulations
of CHM, treatment protocols and due to variable comparators.
A systematic review of CHM treatments to improve outcomes for women
with endometriosis included two RCTs (n=158) [23]. In one trial, no
difference in pregnancy rates between CHM alone and gestrinone
(antiprogesterone) subsequent to laparoscopic surgery, was found (RR
1.18, 95% CI 0.87-1.59). In the second trial, CHM administered orally
and in combination with a herbal enema was compared with danazol (an
androgen). Women taking CHM and those taking CHM in combination
with a herbal enema were more likely to experience symptom relief than
women taking danazol (RR 5.06, 95% CI 1.28-20.05 and RR 5.63, 95%
CI 1.47-21.54, respectively).
A systematic review of CHM for women with anovulatory infertility due
to PCOS included five trials (n=441 women) [24]. In three of these trials
(n=300 women), increased pregnancy rates were found for CHM plus
clomiphene, compared with clomiphene alone (OR 2.62, 95% CI 1.65-4.14).
In the other two trials there were no statistically significant differences in
pregnancy rates between CHM and clomiphene, or between CHM plus
aparoscopic ovarian drilling (LOD) and LOD alone. Studies were of low
quality as live birth rates were not reported and only one study assessed
adverse effects.

- Naturopathy and female subfertility
Women planning to conceive are more likely than women who are not,
to consult a naturopath (OR 1.30, 95% CI 1.03-1.64) [3] with the aim
to enhance their fertility, reduce PMS and maintain wellbeing [3, 25].
Naturopathy is a form of medicine recognized by the World Health
Organization [26, 27] that is codified by holistic philosophy and principles
of practice.
A systematic review of naturopathy included one small RCT investigating
reproductive outcomes in a group of overweight women with PCOS
(n=122) [28]. Increased pregnancy rates were found for two herbal
medicine supplements containing extracts of Glycyrrhiza glabra, Paeonia
lactiflora, Cinnamomum verum, Hypericum perforatum and Tribulus
terrestris plus lifestyle coaching compared to lifestyle coaching alone in the
subgroup of women wanting to conceive (RR 3.9, 95% CI 1.1 to 13.1,
p=0.01). The was no evidence of improved live birth rates compared to
lifestyle coaching alone and adverse effects, although few (three per cent),
included dysfunctional menstrual bleeding and flu-like symptoms [29].
Caution interpreting these results is advised due to the small sub-sample of
women and due to the absence of evidence for safety in pregnancy. One of
the extracts used in the study was Hypericum perforatum (St Johns wort)
which can interact negatively with hormone medicines [30] and other
pharmaceuticals.
An RCT compared the effects of a complex supplement containing similar
herbs (extracts of Glycyrrhiza sp., Dioscerea villosa, Camellia sinensis
and Turnera diffusa) plus nutrients (Folic acid, vitamin E, selenium and
omega 3) against folic acid alone, taken for 28 to 56 days before hormone
stimulation for IVF/ICSI on embryo quality (fragmentation and number
of cells) and pregnancy rates in women undergoing IVF/ICSI (n=100)
[31]. Slightly improved embryo quality at three days was found for the
herbal nutrient complex (RR 1.6, 95% CI 1.01-2.60) however this did not
translate to an increased pregnancy rate.
A third RCT evaluated Fertility Blend, a proprietary combination of
herbal medicines (Vitex agnus castus and green tea extracts) and nutrients
(L-arginine; vitamins E, B6, and B12; folate; iron; magnesium; zinc; and
selenium) compared with a placebo [32]. Ninety-three women who had
been trying to conceive for 6 to 36 months completed the study. After
three months, the pregnancy rate was significantly higher in the herbal/
nutritional group (26 per cent vs. 10 per cent, p=0.01).
There is very low-quality evidence for the benefits of herbal and nutritional
antioxidant supplements for women with subfertility [33]. A systematic
review of 50 RCTs found a mild treatment effect for antioxidants
compared to placebo, no treatment or usual care. Live birth rates were
improved in eight RCTs including 651 women (OR 2.13, 95% CI 1.45
to 3.12, p in 26 RCTs including 4,271 women (OR 1.52, 95% CI 1.31 to 1.76,
p disturbances were no more common in women who took antioxidant
supplements than in controls (OR 0.79, 95% CI 0.58 to 1.08, p= 0.14,
18 RCTs, 2,834 women and OR 1.55, 95% CI 0.47 to 5.10, p=0.47, 3
RCTs, 343 women respectively).

- Naturopathy and male subfertility
There is limited low-quality evidence for benefits of naturopathic
(combined herbal nutrient) antioxidant supplements including carnitine,
coenzyme Q10 200mg, vitamin D plus calcium, vitamin E 3-600mg, zinc
and an antioxidant formulation (Menevit® Bayer Australia Ltd) for infertile
men [34]. In a systematic review of 61 RCTs including 6264 men with
infertility due to low sperm concentration and/or low motility or abnormally
shaped sperm (morphology), significantly increased spontaneous clinical
pregnancy rates (OR 2.97, 95% CI 1.91 to 4.63, p 786 men) and live birth rates (OR 1.79, 95% CI 1.20 to 2.67, p= 0.005,
7 RCTs, 750 men) were observed for antioxidant supplements compared
to placebo or no treatment. However, there was no evidence of reduced risk
of miscarriage (OR 1.74, 95% CI 0.40 to 7.60, p= 0.46, 3 RCTs, 247 men).
No evidence of a positive effect on sperm concentration, motility,
morphology or spontaneous pregnancies for antioxidant supplements was
reported in another systematic review [35]. Two RCTs compared vitamin
C (1000mg/day) alternating with E (800mg/day) and vitamin E (600mg)
alone against placebo controls over six to eight weeks [36, 37]. No differences
were found between groups.
There is some evidence that selenium, Co-enzyme Q10 (CoQ10) and
carnitine supplements may improve sperm quality and increase pregnancy
rates for subfertile men. A meta-analysis of seven placebo controlled RCTs
including 644 infertile men, observed improved sperm concentration
for Selenium (1-200mcgs per day for 12-26 weeks) (SMD 0.64%, 95%
CI 0.38 to 0.90, two trials, 245 men) and CoQ10 (2-300mg per day for
12-26 weeks) (SMD 0.95%, 95% CI 0.72 to 1.19, three trials, 314 men)
(35). Naturally conceived pregnancy rates were increased for men taking
selenium (200mcg for 26 weeks) [38], for CoQ10 (200 mg per day for 26
weeks) [39] and for carnitine [40, 4]) compared to placebo controls.
The usefulness of these results is limited due to the very low methodological
quality of studies [35]. Only two trials investigated effects of naturopathy
on pregnancy rates, and none investigated its effects on live birth rates or
assessed adverse effects.

- Herbal medicine and female subfertility
Two systematic reviews of RCTs examining the effects on fertility of herbal
medicine reported very low-level evidence of benefit for a European herbal
proprietary preparation (Klimadynon®), containing Actea racemosa (black
cohosh), as adjunct therapy to ovulation induction using clomiphene
[42, 43]. One of the reviews (24 RCTs and 1,406 women) found higher
pregnancy rates for women taking adjunct Klimadynon®, compared to no
adjunct controls (OR 2.78 95% CI 1.83-4.23, 1 study, 196 women) [43].
When compared with adjunct Ethinyl oestradiol, women taking black
cohosh had significantly higher oestradiol levels, thicker endometrium and
fewer days to follicular maturation, although these clinical improvements
did not translate to significantly improved pregnancy rates [42].
A more recent RCT, found similar clinical improvements for adjunct black
cohosh in women with anovulatory infertility undergoing clomiphene
induction compared to no adjunct controls (n=100) [44]. Significantly
increased endometrial thickness, and improved hormone profiles (FSH to
LH ratio and higher mid luteal progesterone) were found after one cycle
in women who took the black cohosh. However, there was no statistically
significant improvement in pregnancy rates. There is concern about the
safety of black cohosh during pregnancy, especially in the first trimester,
due to possible hormonal effects [45].

- Herbal medicine for male subfertility
There is very low-quality evidence from RCTs of two herbal medicines
improving sperm characteristics, and no evidence that herbal medicine
improves pregnancy or live birth rates for subfertile men. An RCT investigated
Nigella sativa (black carraway seeds) taken over eight weeks against placebo
in 64 subfertile men [46]. Men taking the black seed extract had significantly
more sperm and higher percentages of motile and normal shaped sperm
compared to controls. A second RCT investigated Withania somnifera
(ashwaganda) against placebo in 46 men with oligospermia [47]. After 90
days, men taking ashwaganda had 167 per cent more sperm, 57 per cent
improved motility and 53 per cent higher semen volume than controls.
Another RCT recruited 260 infertile men with idiopathic infertility in an
investigation of Crocus sativus (saffron) taken for 26 weeks against placebo
[48]. No improvements in sperm density, morphology or motility were
found for saffron. The evidence from these studies is limited by the absence
of reporting of adverse effects.

- Manual therapies and female fertility
There is little evidence of benefit on fertility from manual therapies. In one
RCT reflexology versus sham reflexology was administered to 48 anovulatory
women attending a fertility clinic [49]. Women received eight sessions over
10 weeks of either foot reflexology or sham reflexology with gentle massage.
There were no differences between the reflexology and control groups in
rates of ovulation (42 per cent vs 46 per cent) or pregnancy (15 per cent vs
9 per cent).

- Yoga to improve wellbeing of subfertile women
There is some low-quality evidence from two observational studies for yoga
reducing stress associated with infertility. In a non-randomised study of
women waiting to do IVF, the effects on emotional health of a threemonth yoga program, compared with no yoga, were investigated [50].
No improvements in scores on standardised measures of emotional wellbeing
were observed for women doing yoga compared to those who were not.
Another observational study investigated Hatha yoga over six weeks for
stress associated with infertility among 49 women waiting for IVF [51].
Yoga was found to improve infertility-related quality of life and to reduce
negative feelings and thoughts associated with infertility.
Mind-body therapies to improve wellbeing of subfertile women
Potential benefits on emotional wellbeing of art therapy, and other creative
therapies have not been systematically assessed. Small low-quality studies
report benefits including stress reduction, validation of feelings, and fostering

SUMMARY

There is some evidence of benefit from acupuncture, Chinese herbal
medicine and naturopathy in improving fertility outcomes for women
with specific clinical infertility diagnoses and of acupuncture and antioxidant
supplements in improving sperm quality in infertile men. Acupuncture,
yoga and art therapy may reduce infertility-related distress.
An observational study of women using CAM during 12 months of ART
treatment found a lower live birth rate among those using CAM compared
with non-users (52). These observations were not associated with a specific
CAM modality and may have been due to CAM users having a poorer
fertility prognosis.

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