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Impact of Whole Systems Traditional Chinese Medicine on In Vitro Fertilization Outcomes

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Patients undergoing IVF may receive 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, lifestyle recommendations. In this retrospective cohort study, 1231 IVF patient records were reviewed to assess the effect of adjuvant WS-TCM on IVF outcomes compared among three groups: IVF with no additional treatment; IVF and elective acupuncture on day of embryo transfer; or IVF and elective WS-TCM. The primary outcome was live birth. Of 1069 non-donor cycles, WS-TCM was associated with greater odds of live birth compared with IVF alone (adjusted odds ratio [AOR] 2.09; 95% confidence interval [CI] 1.36 to 3.21), or embryo transfer with acupuncture only (AOR 1.62; 95% CI 1.04 to 2.52). Of 162 donor cycles, WS-TCM was associated with increased live births compared with all groups (odds Ratio [OR] 3.72; 95% CI 1.05 to 13.24, unadjusted) or embryo transfer with acupuncture only (OR 4.09; 95% CI: 1.02 to 16.38, unadjusted). Overall, IVF with adjuvant WS-TCM was associated with greater odds of live birth in donor and non-donor cycles. These results should be taken cautiously as more rigorous research is needed. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
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ARTICLE
Impact of whole systems traditional Chinese
medicine on in-vitro fertilization outcomes
Lee E Hullender Rubin a,b,c,*, Michael S Opsahl d, Klaus E Wiemer d,
Scott D Mist b, Aaron B Caughey b
aOregon College of Oriental Medicine, 75 NW Couch St, Portland, OR, 97210, USA; bOregon Health and Science University,
Portland, OR, USA; cPortland Acupuncture Studio, Portland, OR, USA; dPoma Fertility, Northwest Center for
Reproductive Sciences, Kirkland, WA, USA
* Corresponding author. E-mail address: lrubin@ocom.edu (LE Hullender Rubin).
Lee Hullender Rubin, DAOM, MS, LAc, FABORM, is a clinician and researcher specializing in reproductive medi-
cine, women’s health and vulvar pain. She graduated with her master’s degree from Bastyr University in 2001,
and her doctorate from the Oregon College of Oriental Medicine (OCOM) in 2009. Dr Hullender Rubin was OCOM’s
first postdoctoral research fellow funded by a National Institutes of Health educational grant. She teaches the
doctoral infertility module and is Adjunct Research Faculty at OCOM, and Visiting Research Faculty at Oregon
Health and Science University. She currently practices at her clinic, the Portland Acupuncture Studio, in Port-
land, Oregon.
Abstract Patients undergoing IVF may receive 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, life-
style recommendations. In this retrospective cohort study, 1231 IVF patient records were reviewed to assess the effect of adjuvant
WS-TCM on IVF outcomes compared among three groups: IVF with no additional treatment; IVF and elective acupuncture on day of
embryo transfer; or IVF and elective WS-TCM. The primary outcome was live birth. Of 1069 non-donor cycles, WS-TCM was associ-
ated with greater odds of live birth compared with IVF alone (adjusted odds ratio [AOR] 2.09; 95% confidence interval [CI] 1.36 to
3.21), or embryo transfer with acupuncture only (AOR 1.62; 95% CI 1.04 to 2.52). Of 162 donor cycles, WS-TCM was associated with
increased live births compared with all groups (odds Ratio [OR] 3.72; 95% CI 1.05 to 13.24, unadjusted) or embryo transfer with acu-
puncture only (OR 4.09; 95% CI: 1.02 to 16.38, unadjusted). Overall, IVF with adjuvant WS-TCM was associated with greater odds of
live birth in donor and non-donor cycles. These results should be taken cautiously as more rigorous research is needed.
© 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
KEYWORDS: acupuncture, Chinese herbal medicine, embryo transfer, in-vitro fertilization, live births, traditional Chinese medicine
http://dx.doi.org/10.1016/j.rbmo.2015.02.005
1472-6483/© 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Reproductive BioMedicine Online (2015) 30, 602
612
www.sciencedirect.com
www.rbmonline.com
Introduction
Women undergoing IVF commonly pursue adjuvant comple-
mentary and alternative health approaches to support their
cycles. Given that early studies have found that acupunc-
ture significantly improves IVF pregnancy rates, patients in-
creasingly choose adjuvant acupuncture to optimize their
chances of pregnancy and live birth (De Lacey et al., 2009).
Utilization rates are unclear. In a survey of 428 Northern Cali-
fornian couples, 22% reported using acupuncture (Smith et al.,
2010), but of 118 Boston-area women surveyed, 47% women
reported using acupuncture and 17% used herbs during their
assisted reproduction technique cycle (Domar et al., 2012).
Another survey of 77 patients found that 92% reported using
acupuncture to support their IVF cycle (Aelion et al., 2009).
A patient may seek an acupuncturist’s support by self-
referral, or her IVF physician may refer her, but it is also pos-
sible that IVF physicians may not be aware of patient use of
these additional therapies (Boivin and Schmidt, 2009).
Investigations into the effect of acupuncture on IVF out-
comes largely focus on a limited number of standardized treat-
ments, usually two, on or around embryo transfer compared
with no acupuncture, sham acupuncture or a placebo needle.
Initial studies suggested that acupuncture on or around embryo
transer improved IVF outcomes (Dieterle et al., 2006; Paulus
et al., 2002; Smith et al., 2006; Westergaard et al., 2006),
and, in a meta-analysis of seven trials, acupuncture in-
creased the odds of clinical pregnancy by 65% (Manheimer
et al., 2008). As more trials were completed, the equivocal
effects were found when this narrow dose of only two or three
acupuncture sessions were compared to controls. In a review
of 14 trials, two to three acupuncture treatments adminis-
tered around embryo transfer did not improve clinical preg-
nancy rates compared with controls (Cheong et al., 2013b).
Another review of 16 trials confirmed these findings, but the
covariate of baseline pregnancy rate was found to be a sig-
nificant mediator of acupuncture’s effect (Manheimer et al.,
2013). Additionally, a clear need exists for an adequate acu-
puncture control, as penetrating or non-penetrating ‘sham or
placebo’ acupuncture controls are likely to be impractical and
may have physiological effects (Manheimer, 2011; Vickers
et al., 2012).
With the advent of two standardized acupuncture ses-
sions as a complete investigational intervention, acupunc-
ture providers thereby question whether it is a sufficient dose
(Craig et al., 2014; Shen et al., 2015). In clinical practice, acu-
puncture treatment is not standardized and instead consid-
ers the patient singularly; treatment is individualised. A course
of treatment can range from six to 24 treatments depend-
ing on the complexity of the case. Furthermore, if an IVF
patient seeks adjuvant acupuncture treatment in the period
before the day of embryo transfer, it is possible that the
patient, her parnter, or both, will receive a complex inter-
vention at the acupuncturist’s office, such as whole-systems
traditional Chinese medicine (WS-TCM). This is a multi-
dimensional intervention that can include any combination
of modalities classified under the system of traditional Chinese
medicine. These include any combination of acupuncture (the
insertion of sterile, filiform needles in the body) (Cochrane
et al., 2014), moxibustion (the burning of processed herb,
artemesia argyi, on or near the body) (Nedeljkovic et al.,
2013), Chinese herbal medicine (Cao et al., 2013; Ried and
Stuart, 2011; Tan et al., 2012), Chinese medical massage with
a tool (guasha) or without (tuina), Chinese medicine-based
dietary recommendations, breathing exercises (Qi Gong), or
movement exercises (Tai Chi) (Noll and Wilm, 2009). It may
also include recommendations for vitamins, supplements, or
both, depending on the training and licensure of the pro-
vider. Beyond a published case study (Hullender Rubin, 2010)
and expert texts (Liang, 2003; Lyttleton, 2004; Noll and Wilm,
2009), the effectiveness of the multi-dimensional WS-TCM ap-
proach on IVF outcomes is unclear.
Given this background, we sought to compare the repro-
ductive outcomes of women who elected WS-TCM treat-
ment in addition to their usual IVF care, and compared them
with those who received the usual IVF care alone and to those
who received two standardized acupuncture treatments on
the day of embryo transfer acupuncture only. Our main ob-
jective was to compare the three groups on the primary
outcome of live birth.
Materials and methods
Study design
This was a retrospective cohort study of WS-TCM effects on
IVF reproductive outcomes compared with two groups: those
who received acupuncture treatments only on the day of
embryo transfer (ACU); and those who received IVF usual care
alone. The Oregon College of Oriental Medicine Institu-
tional Review Board approved this study on 11 January 2011
(IRB reference number 09
028). Reproductive outcomes data
were obtained from a single, private IVF centre, the North-
west Center for Reproductive Sciences (NCRS), Kirkland,
Washington.
Patient criteria
Of 1509 patient charts, only NCRS patients who underwent
IVF with fresh donor or non-donor embryos transferred
between August 2005 and December 2010 were included, re-
gardless of embryo quality. Additionally, women who under-
went pre-implantation genetic screening testing or
intracytoplasmic sperm injection cycles were also included.
To further reduce selection bias, all biomedical diagnoses were
included. Diminished ovarian reserve was diagnosed if FSH was
12 mIU/ml or more, antral follicle count total less than 10,
and anti-Müllerian hormone less than 1.0 ng/ml, or any com-
bination of these measures. Since the mean age of the WS-
TCM was higher than the other groups, this most likely
accounted for the increased incidence of diminshed ovarian
reserve diagnosis. All patients who underwent transfers with
frozen embryos (n=251) or embryos from frozen oocytes
(n=27, research cycles) were excluded.
All included patient data (n=1231) were reviewed to iden-
tify patients who received ACU, and then reviewed a second
time to identify and tabulate patients who received WS-
TCM, as all WS-TCM patients received ACU as part of their
treatment plans. The data were de-identified and assigned
unique identifiers. The key was only available to the primary
investigator. Visit data were then independently abstracted
603Whole-systems TCM and IVF cohort study
from acupuncture clinic financial records and confirmed via
scheduling calendars by two research assistants. A third party
was consulted to resolve any conflicts.
Interventions
Usual care
Non-donor. IVF cycle management was individualized to each
patient according to biomedical diagnosis. In general, pa-
tients were treated with either a gonadotrophin-releasing
hormone (GnRH) agonist (Cramer et al., 1999) or antagonist
(Felberbaum et al., 1995; Olivennes et al., 1998) IVF proto-
col. Oral contraceptive pills were taken on the first day of
menses and continued from 1
3 weeks. Once ovarian sup-
pression was confirmed, ovarian stimulation was initiated. Go-
nadotrophin medications were administered twice daily in
variable doses based on age and antral follicle count, for up
to 12 days, and included follitropin alpha (Gonal-f, EMD Serono,
Geneva, Switzerland), follitropin beta injection (Follistim;
Merck, New Jersey, US), injectable menotropins (Menopur,
Ferring, Saint-Prex, Switzerland), or a combination of go-
nadotrophins. When three to four lead follicles measured a
minimum of 17
18 mm on ultrasound, a patient was trig-
gered with HCG (HCG; Novarel; Ferring, Siat-Prex, Switzer-
land). Within 36 h of trigger, transvaginal ultrasound-guided
oocyte retrieval was carried out under conscious sedation.
Once recovered from retrieval, patients were administered
intramuscular progesterone in oil injections (Watson Labo-
ratories, Parsippany, NJ, USA; West-Ward Pharmaceutical,
Eatontown, NJ, USA; or Fresenius Kabi, Lake Zurich, IL, USA),
50 mg/ml twice daily until embryo transfer.
All recovered oocytes were fertilized within the embry-
ology laboratory by either conventional insemination or in-
tracytoplasmic sperm injection. Fertilization was visually
confirmed by the presence of two pronuclei 17
22 h after fer-
tilization. Embryos were cultured in 5% oxygen incubators and
were evaluated every 24 h before embryo transfer. All embryos
were individually cultured in 20
30 µl droplets of Global
Medium (IVF Online, Guildford, CT, USA), supplemented with
10% human serum albumin and covered with 5.5 ml of equili-
brated oil. Embryo culture was carried out in 35 mm Nunc
dishes (Thermo Scientific Fisher, San Rafael, CA, USA). For
blastocyst culture, embryos were moved to new culture dishes
on day 3 of development. Day of embryo transfer was based
on the cause of patient infertility, number and quality of
embryos, as well as patient age. Blastocyst culture and trans-
fer was attempted whenever possible. When pre-implantation
genetic diagnosis or screening was planned, blastomere biopsy
was carried out on cleavage-stage embryos on day 3 of de-
velopment, and embryo transfer occurred on day 5.
Day 3 embryo(s) or day 5 blastocyst(s) embryo transfer was
undertaken with all patients with a full bladder using a Wallace
catheter (Smiths Medical International, Kent, UK) with ul-
trasound guidance by one out of four physicians and accord-
ing to SART guidelines (SART and ASRM, 2006; SART and ASRM,
2008; SART and ASRM, 2009). After transfer, Prometrium (pro-
gesterone, AbbVie Inc., Chicago, IL, USA), 200 mg supposi-
tories were inserted vaginally twice daily. Serum HCG was
collected to determine pregnancy 14 days after retrieval. If
pregnant, progesterone supplementation continued to ges-
tational week 10. If not pregnant, progesterone was
discontinued.
Donor. Egg donors underwent ovarian stimulation using similar
protocols as non-donors. Donor egg recipients underwent an
endometrial development cycle timed to correspond to the
ovarian stimulation of the donor. Donor recipients began the
oral contraceptive pill on the first day of their menses and
continued from 1
3 weeks. Once suppression was con-
firmed, Vivelle-Dot patches (Novartis, Basel, Switzerland) and
Estrace (Bayer-Schering, Berlin, Germany) were incremen-
tally increased for up to 11
15 days depending on oestrogen
levels and endometrial thickness. Once the endometrial thick-
ness achieved 8 mm or thicker, and the donor eggs were re-
trieved, the donor recipient proceeded with the same
progesterone protocol and embryo transfer as non-donor
patients.
Acupuncture group
In addition to the IVF usual care, patients could elect to receive
two standardized acupuncture treatments on the day of
embryo transfer (ACU). The IVF nurse notified patients that
acupuncture treatment was available to them. All ACU treat-
ment protocols were based on previous published research
(Craig et al., 2014; Paulus et al., 2002), and the treatment
methods were previously described (Hullender Rubin et al.,
2012a,b 2013c). Patients received two standardized acupunc-
ture treatments on the same day as the embryo transfer.
Treatments were administered onsite at the IVF centre by
one of nine state-licensed acupuncturists, certified in acu-
puncture by the National Certification Commission of Acu-
puncture and Oriental Medicine (NCCAOM). The acupuncturists’
experience ranged from 1
9 years. All were trained to carry
out the treatments in the same manner, and a treatment
manual was provided. Refresher training to ensure continu-
ity of methods occurred annually.
The first acupuncture session took place 1 h and 15 min
before embryo transfer, and the second no more than 30 min
after the embryo transfer. The Craig acupuncture protocol
was used on both cycle types between 2005 and 2007 (Craig
et al., 2014), and the following points were needled. Before
embryo transfer: GV-20/Baihui; PC-6/Neiguan; CV-6/Qihai;
ST-29/Guilai; SP-8/Diji; LR-3/Taichong; right ear (uterus, en-
docrine); left ear (Shenmen, Brain) After embryo tranfer: LI-
4/Hegu; SP-10/Xuehai; ST-36/Zusanli; SP-6/Sanyinjiao; KI-
3/Taixi; right ear (Shenmen, Brain); and left ear (uterus,
endocrine). Between 2008 and 2009, the modified Craig pro-
tocol was used in both cycle types, with the only modifica-
tion being acupoint KI-3/Taixi was removed from the protocol
(Hullender Rubin et al., 2012a,b). In 2010, the acupuncture
protocol was adjusted according to cycle type owing to pre-
liminary retrospective analysis suggesting fresh, non-donor
cycles benefitted from the modified Craig (Hullender Rubin
et al., 2012a), and donor cycles benefitted from the Craig pro-
tocol (Hullender Rubin et al., 2012b, 2013a). Patients could
also elect to listen to soft music or a guided meditation during
the acupuncture sessions. No other recommendations were
provided.
Whole-systems traditional Chinese medicine group
In addition to the usual IVF care and acupuncture on the day
of embryo transfer as described above, patients could elect
604 LE Hullender Rubin et al.
to pursue adjuvant whole-systems traditional Chinese Medi-
cine (WS-TCM) treatment. Patients were either referred by
the IVF doctor or self-referred. Flyers describing care with
the acupuncturist were available in the IVF clinic lobby.
One of three Washington state-licensed acupuncturists with
3
4 years of master’s level training in acupuncture and Chinese
herbal medicine provided the WS-TCM treatment. All three
acupuncturists were nationally certified by the NCCAOM in acu-
puncture, one (LHR) was NCCAOM certified in herbs, and one
was certified in herbs by the California state licensing exam.
All pursued postgraduate continuing education in reproduc-
tive medicine and infertility, and one (LHR) was board cer-
tified in reproductive medicine by the American Board of
Oriental Reproductive Medicine.
At the initial visit, the patient’s biomedical chart was re-
viewed. The patient was assessed according to TCM theory,
an accepted form of medicine (WHO, 2007). A detailed WS-
TCM treatment plan was provided outlining the dose and fre-
quency of acupuncture, electro-acupuncture, Chinese
medicine-based dietary suggestions, lifestyle recommenda-
tions, and any recommended nutritional supplements.
Patient visits were typically once a week and increased
in frequency to twice a week from the start of IVF suppres-
sion medications to oocyte retrieval. Needles sizes ranged
from 0.18 mm to 0.25 mm in diameter and 30
40 mm in
length for body points, and 0.16 mm x 15 mm for ears. Size
and length were selected based on patient’s tolerance,
acupoint location and body size. Needles used were Vinco
brand (China), Sierin brand (Japan), and DBC brand (Korea).
Electroacupuncture stimulator used was ES-2 (Heliomed,
China) between 2005 and 2007, and Electrostimulator 4c.Pro
(Pantheon Research, Venice, CA, USA) was used between
2007 and 2010. Treatment could also include the following
modalities: warming Far Infrared Mineral lamp (TDP CQ-27,
FIRARD II, China), Chinese medical massage (tuina) and in-
direct moxibustion stick (Hoist Wuyan Jiutiao, Smokeless
Moxa Stick, China). All customized Chinese herb formulas
were dispensed in granular form and manufactured by KPC
herbs (Taiwan). All herbal tablets were made of standard-
ized Chinese herbal formulas and manufactured by Golden
Flower Chinese Herbs (Taiwan). Recommended nutritional
supplements included prenatal vitamins, essential fatty acids,
antioxidants and probiotics.
Acupuncture and herbal treatment was based on TCM
pattern diagnosis and phase of menstrual cycle. According to
Chinese medicine, regulating the menstrual cycle is consid-
ered a central treatment approach to female reproduction
(Cochrane et al., 2014). This approach was previously de-
scribed in several case studies (Hullender, 2009; Hullender
Rubin, 2010; Hullender Rubin and Marx, 2012; Hullender Rubin
et al., 2013b), but in general, treatment was divided into four
phases: menses (cycle days 1
4, follicular [cycle days 5
11],
ovulation [cycle days 12
16], and luteal [cycle days 17 to onset
of menses]). During menses, treatment was directed at regu-
lating menses and reducing of dysmenorrhoea pain, if present
(Smith et al., 2011). Follicular phase treatment was di-
rected at regulating reproductive hormones (Chen, 1997;
Napadow et al., 2008), and endometrial (Stener-Victorin et al.,
1996) and follicular development (Rashidi et al., 2013). Ovu-
lation phase treatment was directed at inducing ovulation
(Jedel et al., 2011; Johansson and Stener-Victorin, 2013;
Johansson et al., 2013; Stener-Victorin et al., 2012). Luteal
phase treatment focused on regulating hormones (Cochrane
et al., 2014). Throughout the entire cycle, treatment had a
sub-aim of reducing stress (De Lacey et al., 2009; Kovarova
et al., 2010; Madaschi et al., 2010). During the IVF cycle, WS-
TCM treatments were individualized according to patient needs
and TCM pattern diagnosis, but aimed to support the goals
of the IVF phase. Treatment could also include Chinese
medicine-based dietary and lifestyle recommendations. During
down-regulation and ovarian stimulation, treatment was aimed
to improve ovarian and uterine blood flow (Magarelli et al.,
2009; Stener-Victorin et al., 1996), improve oocyte quality
(Rashidi et al., 2013) and reduce stress. Acupuncture was op-
tional on the day of oocyte retrieval to manage pain (Gejervall
et al., 2005; Humaidan et al., 2006; Stener-Victorin, 2005),
or postoperative nausea, vomiting, or both (Cheong et al.,
2013a), which was used by only six patients. One more visit
was suggested 5
7 days after embryo transfer to reduce stress.
Outcome measures
The primary outcome measure was live birth after 24 weeks’
gestation. Secondary outcome measures were biochemical
pregnancies, spontaneous abortions, ectopic pregnancies, ges-
tational age, singleton, twin and triplet pregnancy. Biochemi-
cal pregnancy was defined as a positive serum beta-HCG and
pregnancy that failed to develop to the clinically identifi-
able stage on ultrasound evaluation. Spontaneous abortion is
defined as the spontaneous loss of a pregnancy with an
ultrasound-confirmed gestational sac before 20 gestational
weeks.
Statistical analysis
Treatment groups were counted and differentiated by donor
or non-donor cycle type. Demographics and descriptive sta-
tistics were computed by group in the following variables for
non-donor cycles: age, FSH, primary infertility, cause of in-
fertility, cycle number, method of fertilization, pre-
implantation genetic screening, total antral follicle count,
number of days stimulated, total gonadotrophin dose, peak
oestradiol, endometrial thickness, number of mature oocytes
obtained, number of embryos transferred, day of embryo
transfer (day 3 or 5), ovarian hyperstimulation syndrome
(OHSS) and gestational age. For donor cycles, the same
covariates were compared with the exception of age, FSH,
total antral follicle count, number of days stimulated, total
gonadotrophin dose and OHSS.
Outcomes of live birth, biochemical pregnancy, sponta-
neous abortion, singleton, twins and triplet pregnancy were
tabulated by group and cycle type. Differences in outcomes
were calculated using logistic regression and adjusted by
covariates associated with outcomes.
Data were analysed in the following ways: (i) compara-
bility of demographics between group; (ii) differences in out-
comes with chi-squared (when groups numbered 10 or greater)
or Fisher’s exact (when groups numbered less than 10). Means
were compared via analysis of variance and proportions were
compared by chi-squared; and (iii) in order to control for po-
tential confounding, the magnitude of effects on pregnancy
605Whole-systems TCM and IVF cohort study
outcomes was assessed using multivariable logistic regres-
sion analyses and presented as adjusted odds ratios (AOR) with
95% confidence intervals (CI). Results were considered sta-
tistically significantly different if P <0.05. Stata. (StataCorp,
2011, USA) was used to carry out all tests.
Results
A total of 1231 fresh cycles took place, in which an embryo
transfer occurred. Non-donor cycles numbered 1069 and donor
cycles numbered 162 (Table 1). In the non-donor cycles, 580
patients were in the usual care group, 370 in the ACU group
and 119 in the WS-TCM group. The mean (±SD) number of WS-
TCM visits was 12.0 (±12.4). The three groups were compa-
rable on all reproductive variables at the start of the cycle,
except diagnosis of diminished ovarian reserve (P=0.01), di-
agnosis of cause of infertility as ‘other’ (P=0.03); cycle
number (P=0.004) and total antral follicle count (P=0.0497).
Significant differences were found in cycle characteristics:
number of mature oocytes obtained (P=0.02); number of
embryos transferred (P=0.003) (Table 2).
The proportion of live births was significantly higher in the
WS-TCM group (61.3%) compared with either the usual care
Table 1 Demographic characteristics.
Non-donor cycles WS-TCM Usual care ACU P-value
Group N 119 580 370
Age a,b 35.0 ±4.0 34.3 ±4.3 34.9 ±4.3 NS
FSHa,b 10.9 ±3.4 10.7 ±3.1 11.2 ±3.9 NS
Total antral follicle counta,b,f 8.0 ±2.4 8.3 ±2.5 7.9 ±2.6 0.0497
Primary infertilityc,d 48.0 51.4 52.7 NS
Cause of infertilityc,d
Male 40.0 36.6 35.4 NS
Diminished ovarian reservef31.1 20.9 27.3 0.01
Endometriosis 10.1 11.9 12.7 NS
Ovulatory dysfunction 17.7 20.7 21.6 NS
Tubal 15.1 15.9 13.0 NS
Uterine 6.7 5.9 5.2 NS
Otherf13.5 7.8 6.0 0.03
Unknown 8.4 14.5 14.3 NS
Multiple diagnoses 34.5 31.4 30.8 NS
Cycle number c,d
First cyclef57.4 72.6 70.0 0.004
Repeated cyclef42.6 27.4 30.0 0.004
Donor cycles WS-TCM Usual care ACU P-value
Group N 21 104 37
Primary infertilityc,d 47.6 34.6 45.9 NS
Cause of infertility
Malec,e 19.0 16.3 10.8 NS
Diminished ovarian reservec,d 81.0 92.3 89.2 NS
Endometriosisc,e 0.0 16.3 10.8 NS
Ovulatory dysfunctionc,e 9.5 1.0 2.7 NS
Tubalc,e 9.5 6.7 5.4 NS
Uterinec,e 9.5 7.6 5.4 NS
Otherc,e 4.8 9.6 8.1 NS
Unknownc,e 0.0 0.0 0.0 NS
Multiple diagnosesc,e,f 28.6 42.3 24.3 0.02
Cycle number
First cyclec,e 57.1 51.0 67.6 NS
Repeated cyclec,e 42.9 49.0 32.4 NS
aData are mean ±SD.
bAnalysis of variance.
cData are proportion.
dChi-squared.
eFisher’s exact.
fSignificant findings (P<0.05).
ACU =women receiving acupuncture on day of embryo transfer; NS =not statistically signifi-
cant; WS-TCM =Whole-systems traditional Chinese medicine.
606 LE Hullender Rubin et al.
(48.2%) or ACU groups (50.8%, P=0.03 (Table 3). Fewer spon-
taneous abortions (P=0.02) occurred in the WS-TCM group
compared with the other groups. On the outcome of bio-
chemical pregnancies, there was no difference between
groups, but WS-TCM trended toward significantly fewer than
the other groups (P=0.05). No ectopic pregnancies occurred
in the WS-TCM group, but this was not a significant differ-
ence than compared with the usual care or ACU groups. Mean
gestational age, and the proportions of live birth on or after
37 gestational weeks, singleton, twin and triplet pregnan-
cies were not different between groups.
The WS-TCM group was associated with more live births
compared with both groups when adjusted for the covariates
of previous IVF cycle, age, and gonadotrophin dosage (AOR
1.93; 95% CI 1.27 to 2.92) (Table 4). More live births were
associated with WS-TCM compared with embryo transfer acu-
puncture only, adjusted for age and gonadotrophin dosage
(AOR 1.62; 95% CI 1.04 to 2.52), and when compared with IVF
alone, adjusted for previous IVF and gonadotrophin dosage
(AOR 2.09; 95% CI 1.36 to 3.21). Live births were not signifi-
cantly affected in patients who received acupuncture only
on the day of embryo transfer compared with IVF usual
care.
When compared with both groups, WS-TCM was associ-
ated with fewer biochemical pregnancies (odds ratio [OR] 0.27;
95% CI 0.08 to 0.86). Decreased biochemical pregnancies were
also associated with WS-TCM compared with embryo trans-
fer acupuncture alone unadjusted (OR 0.25; 95% CI 0.07 to
Table 2 Cycle characteristics.
Non-donor cycles WS-TCM Usual care ACU P-value
Group, n119 580 370
Number of days stimulateda,b 9.8 ±1.2 9.9 ±1.2 9.9 ±1.3 NS
Total gonadotrophin dose, IUa,b 3959.3 ±1503.6 3721.6 ±1515.6 3932.1 ±1580.1 NS
Peak oestradiol, pg/mla,b 3153.7 ±1781.8 3211.0 ±1644.0 3017.0 ±1634.0 NS
Endometrial thickness, mma,b 10.9 ±2.4 11.2 ±2.4 11.2 ±2.2 NS
Number of mature oocytes obtaineda,b,f 14.0 ±8.7 15.7 ±9.1 14.2 ±8.0 0.02
OHSS c,d 8.4 9.5 7.1 NS
Fertilization methodc,d
Conventional 47.1 51.0 46.3 NS
ICSI 48.7 46.2 49.3 NS
Mixed 4.2 2.8 4.3 NS
Pre-implantation genetic screeningc,d 13.5 9.3 6.5 NS
Number of embryos transferreda,b,f 2.9 ±1.2 2.6 ±1.1 2.8 ±1.1 0.003
Day of embryo transferc,d
Day 3 64.7 59.7 65.7 NS
Day 5 35.3 40.3 34.3 NS
Mean number of acupuncture visitsa12.0 ±12.4
Donor cycles
Group, N 21 104 37
Peak oestradiol, pg/mla,b 4303.9 ±2130.5 4250.3 ±2035.4 4428.4 ±2660.4 NS
Endometrial thickness, mma,b 9.7 ±2.0 10.5 ±2.1 10.0 ±2.0 NS
Number of mature oocytes obtained from donora,b,f 18.6 ±8.0 21.7 ±8.7 26.4 ±11.2 0.005
Fertilization method
Conventionalc,d 57.1 60.6 67.6 NS
ICSIc,e 38.1 33.7 27.0 NS
Mixedc,e 4.8 5.8 5.4 NS
Pre-implantation genetic diagnosis Testingc,e 4.8 10.6 8.3 NS
Number of embryos transferred a,b 2.2 ±0.7 2.2 ±0.7 1.9 ±0.6 NS
Day of embryo transfer
Day 3c,e 23.8 38.5 24.3 NS
Day 5c,d 76.2 61.5 76.7 NS
Mean number of acupuncture visitsa10.6 ±13.6
aData are mean ±SD.
bAnalysis of variance.
cData are proportions.
dChi-squared.
eFisher exact.
fSignificant findings (P<0.05).
ACU =day of embryo transfer acupuncture only; ICSI =intracytoplasmic injection; NS =not significant; OHSS =ovarian hyperstimulation syndrome;
WS-TCM =whole-systems traditional Chinese medicine.
607Whole-systems TCM and IVF cohort study
0.82), or standard IVF when adjusted for FSH and gonado-
trophin dosage, (AOR 0.28; 95% CI 0.09 to 0.91). No differ-
ence was observed between the ACU and usual care groups
on this outcome.
No differences were detected between groups on the
outcomes of spontaneous abortion, ectopic pregnancies,
singleton, twin, triplet pregnancies or gestational
age.
Table 3 Reproductive outcomes.
Non-donor cycles WS-TCM Usual care ACU P-value
Group, n119 580 370
Live birtha,b,f 61.3 48.2 50.8 0.03
Biochemical pregnancya,c,f 2.5 8.4 9.5 NS
Spontaneous abortiona,c,f 5.8 10.7 7.3 0.02
Ectopica,c 0 1.0 0.8 NS
Singletona,b 60.3 63.2 57.0 NS
Twinsa,b 38.4 33.2 40.3 NS
Tripletsa,b 1.4 3.2 2.2 NS
Gestational aged,e 37.8 ±2.7 37.8 ±2.8 37.4 ±3.3 NS
Live birth on or after 37.0 weeksa,b 64.4 72.9 67.6 NS
Donor cycles
Group, n21 104 37
Live birthc,d 85.7 62.5 59.5 NS
Biochemical pregnancy a,c 4.8 8.7 8.1 NS
Spontaneous abortiona,c 4.8 11.5 16.2 NS
Ectopica,c 0.0 1.0 0.0 NS
Singleton a,b 55.6 54.0 54.6 NS
Twinsa,c 38.9 45.3 45.5 NS
Tripletsa,c 4.8 1.6 0.0 NS
Gestational aged,e 37.7 ±3.3 36.9 ±3.1 36.8 ±3.7 NS
Live birth on or after 37.0 weeksa,b 72.2 60.0 63.6 NS
aData are proportions.
bChi-squared.
cFisher’s exact.
dData are mean ±SD.
eAnalysis of variance.
fSignificant findings (P<0.05).
ACU =day of embryo transfer acupuncture only; NS =not significant; WS-TCM =whole-
systems traditional Chinese medicine.
Table 4 Reproductive outcomes logistic regression analysis (odds ratio and 95% confidence interval).
Outcome Cycle type WS-TCM versus all WS-TCM versus usual care WS-TCM versus ACU ACU versus usual care
Live birth Non-donor 1.93, 1.27 to 2.92a,h 2.09, 1.36 to 3.21b,h 1.62, 1.04 to 2.52c,h 1.24, 0.94 to 1.64d
Donor 3.72, 1.05 to 13.24e,h 3.6, 1.00 to 13.01e4.09, 1.02 to 16.38e,h 0.74, 0.35 to 1.58e
Biochemical
pregnancy
Non-donor 0.27, 0.08 to 0.86e,h 0.28, 0.09 to 0.91f,h 0.25, 0.07 to 0.82e,h 1.30, 0.83 to 2.03e
Donor 0.54, 0.07 to 4.36e0.55, 0.06 to 4.74g0.57, 0.06 to 5.82e1.01, 0.26 to 3.90e
Spontaneous
abortion
Non-donor 0.60, 0.27 to 1.34e0.50, 0.22 to 1.13e0.79, 0.34 to 1.87e0.72, 0.45 to 1.14e
Donor 0.34, 0.04 to 2.70e0.38, 0.05 to 3.12e0.26, 0.03 to 2.31e1.67, 0.59 to 4.75e
aAdjusted odds ratio comparing WS-TCM with all groups with previous IVF, age and gonadotrophin dosage as covariates.
bAdjusted odds ratio comparing WS-TCM with usual care, with previous IVF and gonadotrophin dosage as covariates.
cAdjusted odds ratio comparing WS-TCM with ACU with age and gonadotrophin dosage as covariates.
dAdjusted odds ratio comparing usual care with ACU with prior IVF, age, and gonadotrophin dosage as covariates.
eUnadjusted odds ratio.
fAdjusted odds ratio comparing WS-TCM with usual care, with FSH, and gonadotrophin dosage as covariates.
gAdjusted odds ratio comparing WS-TCM with usual care, with number of embryos transferred as covariate.
hSignificant outcomes.
ACU =day of embryo transfer acupuncture only; usual care, usual IVF care; WS-TCM =whole-systems traditional Chinese medicine.
608 LE Hullender Rubin et al.
Of the donor cycles, 104 recipients usual care group re-
ceived an embryo transfer, 37 in the ACU group and 21 in the
WS-TCM group. The mean (±SD) number of WS-TCM visits was
10.6 (±13.6). The three groups were comparable on the vari-
ables of incidence of primary infertility; cause of infertility
due to male factors; diagnosis of diminished ovarian reserve;
endometriosis; ovulatory dysfunction; tubal issues; uterine
issues; unknown reasons; other diagnosis; male only factors;
female only factors; male and female factors; cycle number;
incidence of pre-implantation genetic screening; fertiliza-
tion method; number of days stimulated; peak oestradiol; en-
dometrial thickness; day 3 or day 5 embryo transfer (Tables 1
and 2). Groups were different for the following variables:
multiple diagnoses (P=0.02) and number of mature oocytes
obtained (P=0.005).
On the outcome of live births, 85.7% of the WS-TCM group,
62.5% of the usual care and 59.5% of the ACU group had a live
birth (Table 3). No differences were observed between groups
for biochemical pregnancies or spontaneous abortions. No
ectopic pregnancies occurred in the WS-TCM group for this
cycle type, but this was not significantly fewer than usual care
or ACU groups. Gestational age, singleton, twin, and triplet
pregnancies were also not different between groups.
Significantly greater odds of live birth was associated with
adjuvant WS-TCM compared with all groups (OR 3.72; 95% CI
1.05 to 13.24), and when compared with the ACU group (OR
4.09; 95% CI 1.02 to 16.38). When WS-TCM was compared with
usual care, an association of increased odds trended towards
significance (OR 3.6; 95% CI 1.00 to 13.01, unadjusted). The
small sample size and exceedingly broad confidence inter-
vals, however, indicate the weaknesses of these associa-
tions. No difference was found between the ACU and usual
care groups on this outcome.
Outcomes of biochemical pregnancy or spontaneous abor-
tion was not significantly affected by WS-TCM, regardless of
comparison group in the donor cycles.
Discussion
To the best of our knowledge, this is the first adequately
powered study of the effect of adjuvant WS-TCM on IVF re-
productive outcomes. This is meaningful for its public health
impact on infertility treatment and management, prelimi-
nary evidence of the need for an optimized acupuncture dose
and demonstration that WS-TCM, a multidisciplinary inter-
vention that includes acupuncture, was associated with more
live births than two standardized acupuncture treatments on
the day of embryo transfer or usual IVF care alone. These find-
ings suggest WS-TCM could make significant contributions to
the public health issue of infertility ( Macaluso et al., 2010;
CDC, 2010; CDC, 2014), if provided in an effective dose. Al-
though IVF live births increase with advances in patient man-
agement and laboratory procedures, success is not guaranteed.
Couples often must undergo several IVF cycles engendering
extensive emotional distress and economic costs (Cousineau
and Domar, 2007).
Acupuncture on or around day of embryo transfer does sig-
nificantly reduce stress in IVF patients in both randomized con-
trolled trials (RCTs) (Domar et al., 2009; Isoyama et al., 2012;
Smith et al., 2006) and observational studies (Balk et al., 2010;
De Lacey et al., 2009). Initial RCTs found that acupuncture
improved IVF pregnancy rates (Dieterle et al., 2006; Paulus
et al., 2002; Westergaard et al., 2006). As more studies were
conducted, the effect became less clear as subsequent studies
failed to reproduce those outcomes, with one RCT finding live
births were lower in the acupuncture group compared with
control (Craig et al., 2014). Craig et al. (2014) suspected the
location of treatment offsite from the IVF centre and study
population of acupuncture naïve women may have contrib-
uted to this finding (2014). Further, two standardized acu-
puncture sessions administered on day of embryo transfer
alone were an insufficient acupuncture dose to improve IVF
birth outcomes in two of the most recent systematic reviews
(Cheong et al., 2013b; Manheimer et al., 2013).
We observed that, in addition to embryo transfer acu-
puncture, an average of 12 WS-TCM visits for non-donor cycles
and 11 visits for donor cycles were associated with greater
odds of live birth. The combined approach of WS-TCM treat-
ment before starting IVF with the two treatments on the day
of embryo transfer acupuncture may be an optimal interven-
tion to improve IVF birth outcomes in addition to stress re-
duction. An increased acupuncture dose, ie. more acupuncture
sessions, is consistent with the effectiveness reported in other
studies. Uterine blood flow was improved with eight electro-
acupuncture sessions (Stener-Victorin et al., 1996). Nine
electro-acupuncture sessions plus embryo transfer day acu-
puncture were correlated with an increase in serum cortisol
and prolactin and improved IVF outcomes in prospective clini-
cal trial (Magarelli et al., 2009). Fourteen sessions of low-
frequency electro-acupuncture significantly reduced androgens
and improved menstrual frequency over physical exercise or
no treatment in women with polycystic ovary syndrome in an
RCT (Jedel et al., 2011). Ovulation was induced in another
RCT with 24 visits over 3 months in women with polycystic
ovary syndrome (Johansson et al., 2013) using the same in-
tervention described by Jedel et al. (2011).
In our study, every patient undergoing WS-TCM received
a multidisciplinary intervention, of which all patients re-
ceived acupuncture, electro-acupuncture, or both, in addi-
tion to lifestyle and dietary recommendations. Prenatal
vitamins, essential fatty acids, antioxidants, probiotics, and
Chinese herbs were also commonly suggested. Because of the
nature of individualized care, recommendations were tai-
lored to the patient’s need and varied considerably within the
group. Further, some patients elected to only pursue acu-
puncture to support their cycles. This is representative of TCM
treatment in the real world. An objective of whole-systems
research is to evaluate the combined effects of a complex in-
tervention (Elder et al., 2006; Ritenbaugh et al., 2003). It is
not intended to evaluate the single ingredients of a complex
intervention, as it may over or underestimate the single in-
gredient’s influence and cannot account for the confound-
ing or mediating effects of the other component(s).
This retrospective study has three limitations. First, owing
to the nature of a retrospective cohort study, there is limited
internal validity. Study groups were not randomly allo-
cated, so the groups differed on several variables. We at-
tempted to minimize potential bias from these differences
by adjusting for covariates associated with pregnancy out-
comes through multivariable logistic regression analysis. We
also acknowledge the difference in the number of embryos
transferred between groups may influence our findings. During
dataset analysis, however, this covariate did not signifi-
609Whole-systems TCM and IVF cohort study
cantly impact outcomes. We therefore question the bio-
logic plausibility that the difference contributed, in part, to
our results. Further, women elected which treatment to
pursue. Women who elected WS-TCM, ACU, or both, could
differ in unknown ways that may affect outcomes.
Secondly, it was also possible that women in the usual care
groups received WS-TCM or day of embryo transfer acupunc-
ture at another site, or patients in the ACU group received
WS-TCM elsewhere leading to misclassification bias. Comple-
mentary and alternative medicine use is common in IVF pa-
tients (Smith et al., 2010) and not always reported to their
IVF practitioners (Boivin and Schmidt, 2009). Such bias,
however, would have been towards the null suggesting that
our estimates of effect would only underestimate the actual
effect of WS-TCM.
Finally, embryo quality may have differed between groups.
Although embryo quality is a known predictor of IVF success
(Heitmann et al., 2013; Vernon et al., 2011), only the highest
quality embryos available were selected for transfer. As more
women in the WS-TCM group were diagnosed with dimin-
ished ovarian reserve, it is more likely that the WS-TCM group
would have had lower quality embryos, which may mean the
effect of WS-TCM is underestimated by our study.
In conclusion, despite these potential limitations, this study
provides evidence that the addition of WS-TCM to non-
donor IVF cycles may increase the odds of achieving a live birth
over usual IVF care alone or two standardized treatments ad-
ministered around embryo transfer. The effects of WS-TCM
were less clear compared with usual donor IVF care alone but
showed a non-significant trend towards increased odds of a
live birth in this cycle type. This retrospective cohort study
suggests that WS-TCM as an adjuvant IVF treatment may be
associated with improved live birth rates. More rigorous, com-
parative effectiveness research is needed to substantiate these
findings and determine an optimal number of WS-TCM visits
compared with an adequate and validated time-attention
control, such as a mind
body programme to confirm these
findings.
Acknowledgements
Sincere thanks to the NCRS patients, doctors, embryology, and
nursing staff. LHR formerly owned the acupuncture prac-
tice. Whole-systems traditional Chinese medicine was pro-
vided by primary investigator (LHR); Roxane Geller, MS, LAc;
and Holly Fritz, LAc. Day of embryo transfer acupuncture was
provided by the primary investigator (LHR), HF; Melissa
Rosenberger MS, MAcOM, LAc; Janci Karp, ND, LAc, LMP;
Heather Stadler, MAc, LAc; Nicole Hidaka, MS, LAc; Lindsay
A. Staker, MS, LAc; and Elaina Greenberg, MS, LAc. Chart data
abstraction completed by Patrick Allen, MAcOM, LAc, and
Angela Humphrey, MAcOM, LAc.
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612 LE Hullender Rubin et al.
... Now, TCM has become the mainstream of reproductive health care in the East Asia by virtue of its prominent efficacy, rich resource, and less toxicity (Yang et al., 2013;Li et al., 2016). Studies have shown that TCM can effectively increase the levels of estrogen and progesterone (Li et al., 2012), improve endometrial receptivity (Yu et al., 2011), and ultimately improve pregnancy outcome (Zhu et al., 2014;Hullender et al., 2015). Shoutai Pill (Chinese Dodder Seed, Himalayan Teasel Root, Chinese Taxillus Twig, and Donkey-hide Glue) is a famous prescription derived from Qing Dynasty, and its efficacy in URSA has been verified by a recent meta-analysis which shows that the addition of Shoutai Pill is superior to western medicine alone in preventing abortion in the first trimester of URSA (Li et al., 2020). ...
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... [15] Treatment of infertility when the cause is limited to decreased ovarian reserve is empirical at present except for oocyte donation. [16] In recent years, Traditional Chinese medicine (TCM) [17][18][19][20][21][22] have made some progress in improving the outcome of IVF in those patients that were diagnosed with DOR. It is of some academic value to make a meta-analysis to make people more clear about the effectiveness and safety of traditional Chinese medicine in preconditioning patients with diminished ovarian reserve that would undergo In Vitro Fertilization. ...
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... Frequency and total number of treatments are an important part of the total 'dose' of acupuncture [9,50] both in research and in clinical practice. Given that both frequency and total number of treatments plays a role in acupuncture's effectiveness for conditions such as depression [51], and the total number of treatments is a key factor in positive outcomes for acupuncture and IVF [13,52], failure to deliver enough treatment may mean that maximum therapeutic benefit is not achieved [53]. ...
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BuShen HuoXue decoction (BSHXD) has been used to treat patients with unexplained recurrent spontaneous abortion (URSA). However, the chemical compounds and mechanism by which BSHXD exerts its therapeutic and systemic effects to promote the proliferation of decidual stromal cells (DSCs) has not been elucidated. This work sought to elucidate the cellular and molecular mechanism of BSHXD in terms of inflammatory factors IL-17A in DSCs in vitro because of the critical roles of inflammation, apoptosis, and immunity in the development and progression of pregnancy loss. Twelve migratory chemical compounds from BSHXD extract were qualitatively analyzed by high-performance liquid chromatography (HPLC). DSCs were collected from normal early pregnancy (NEP) and URSA to determine whether BSHXD affects IL-17A/IL17RA via the PI3K/AKT pathway. Abnormal apoptosis and activated p-AKT were observed in URSA DSCs. RhIL-17 A, LY294002 (a PI3K pathway inhibitor), and BSHXD were individually or simultaneously administered in NEP DSCs, suggesting that BSHXD restored cell proliferation without excessive stimulation and IL-17A promotes proliferation via the PI3K/AKT pathway. Using the same intervention in URSA DSCs, qRT-PCR measured the upregulated mRNA levels of IL-17 A/IL-17RA, PI3K, AKT, p-AKT, PTEN, Bcl-2, and Bcl-xL and downregulated mRNA levels of BAD and ACT1 after treatment with BSHXD. We demonstrated that BSHXD affected IL-17A/IL-17R via PI3K/AKT pathway to promote the proliferative activity of DSCs in URSA. These results provide a new insight to further clarify the relationship between inflammation and apoptosis and the mechanism of imbalance in the dynamic equilibrium between Th17/Treg immune cells at the maternal-fetal interface.
Chapter
While assisted reproductive technology has given so many people the ability to bear children, it is still far from a cure-all for fertility issues. Two traditional medical systems, traditional Chinese medicine (TCM) and Ayurveda have been using a very different, more holistic approach to help couples enhance fertility for millennia. This chapter explains how TCM and Ayurveda approach infertility issues. Specifically, it discusses the fundamental principles of both systems, the importance of focusing on foundation health and creating balance in the body, and how these systems personalize treatment. Both systems believe that proper preparation for pregnancy can set the stage for a healthier pregnancy and better long-term health for the future child. TCM refers to this as “tilling the soil before planting the seed.” The basic elements of diagnosis, patterns of imbalance, treatment approaches including acupuncture, herbal medicine, diet, panchakarma, and research on the efficacy of these approaches are discussed.
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Maximising access to and the success of fertility treatments should be a priority for global reproductive health, as should overall patient well-being. The demand for in vitro fertilization (IVF) and other assisted fertility treatments has increased over the past decade and is likely to further increase in years to come. Nevertheless, there is still considerable unmet demand for infertility support worldwide. Moreover, the high emotional, physical and financial burden experienced by individuals undergoing IVF cycles can be a risk for their mental and physical health, which in turn can influence treatment continuation and the likelihood of IVF success. Studies from various parts of the world show that most individuals undergoing IVF also use adjunct alternative medicines and procedures, the most common being traditional Chinese medicine (TCM). The complementary and synergistic role of TCM for individuals undergoing IVF is an area that merits further attention and research, both for its potential positive effects on IVF success rates and for its broader physical and mental health benefits. However, much of the existing evidence is not sufficiently robust or consistent for findings to be adopted with confidence. This commentary argues that much work must be done to understand the efficacy and clinical best practices for these integrated approaches. This can be achieved in part by developing more robust and clinically relevant randomized controlled trial protocols, collecting and triangulating evidence through a variety of study designs and methods, and strengthening the collection and pooling of clinic-level data.
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Objective: To assess the efficacy of the Zishen Yutai Pill compared with placebo on live birth rates among women after fresh embryo transfer cycles. Methods: We conducted a double-blind, multicenter, placebo-controlled, randomized trial to investigate whether administration of the Zishen Yutai Pill would improve pregnancy outcomes among women undergoing fresh embryo transfer after in vitro fertilization or intracytoplasmic sperm injection. The primary outcome was live birth rate. Secondary outcomes were rates of implantation, biochemical pregnancy, clinical pregnancy, pregnancy loss, cycle cancellation, and maternal, fetal, and neonatal complications. A total sample size of 2,265 women (1:1 in two groups) was used to detect a live birth rate difference between the Zishen Yutai Pill and placebo. Participants were enrolled and randomized to receive 5 g of the Zishen Yutai Pill or placebo orally, three times per day during the study. Results: Recruitment was completed between April 2014 and June 2017, with 2,580 patients screened. Two thousand two hundred sixty-five patients were randomized: 1,131 to the Zishen Yutai Pill and 1,134 to placebo. Characteristics were similar between groups. In intention-to-treat analysis, the rates of live birth in the Zishen Yutai Pill (ZYP) group and placebo group were 26.8% and 23.0% (rate ratio [RR], 1.16; 95% CI 1.01-1.34; P=.038), respectively. The implantation rates were 36.8% and 32.6% in the ZYP and placebo groups, respectively (RR 1.13; 95% CI 1.01-1.25; P=.027). The biochemical pregnancy rate for the ZYP group was 35.5% compared with 31.1% in the placebo group (RR 1.14; 95% CI 1.02-1.28; P=.026). The rates of clinical pregnancy in the ZYP and placebo groups were 31.2% compared with 27.3%, respectively (RR 1.14; 95% CI 1.00-1.30; P=.043). There were no significant between-group differences in the rates of pregnancy loss, maternal, or neonatal complications (all P>.05). Conclusion: The Zishen Yutai Pill increased the rate of live birth after fresh embryo transfer compared with placebo. Clinical trial registration: Chictr.org.cn, Chictr-TRC-14004494.
Article
Background The effects of acupuncture on in-vitro fertilization outcomes remain controversial. This study aimed to perform a meta-analysis to assess the effectiveness of acupuncture as an adjuvant therapy to embryo transfer compared to sham-controls or no adjuvant therapy controls on improving pregnancy outcomes in women undergoing in-vitro fertilization. Methods A systematic literature search up to January 2021 was performed and 29 studies included 6623 individuals undergoing in-vitro fertilization at the baseline of the study; 3091 of them were using acupuncture as an adjuvant therapy to embryo transfer, 1559 of them were using sham-controls, and 1441 of them were using no adjuvant therapy controls. They reported a comparison between the effectiveness of acupuncture as an adjuvant therapy to embryo transfer compared to sham-controls or no adjuvant therapy controls on improving pregnancy outcomes in women undergoing in-vitro fertilization. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated assessing the effectiveness of acupuncture as an adjuvant therapy to embryo transfer compared to sham-controls or no adjuvant therapy controls using the dichotomous method with a random or fixed-effect model. Results Significantly higher outcomes with acupuncture were observed in biochemical pregnancy (OR, 1.98; 95% CI, 1.55–2.53, p < 0.001); clinical pregnancy (OR, 1.70; 95% CI, 1.46–1.98, p < 0.001); ongoing pregnancy (OR, 1.78; 95% CI, 1.41–2.26, p < 0.001); and live birth (OR, 1.58; 95% CI, 1.15–2.18, p = 0.005) compared to no adjuvant therapy controls. However, no significant difference were found between acupuncture and no adjuvant therapy controls in miscarriage (OR, 0.96; 95% CI, 0.48–1.92, p = 0.91). No significant difference was observed with acupuncture in biochemical pregnancy (OR, 1.16; 95% CI, 0.65–2.08, p = 0.62); clinical pregnancy (OR, 1.13; 95% CI, 0.83–1.54, p = 0.43); ongoing pregnancy (OR, 1.04; 95% CI, 0.66–1.62, p = 0.87); live birth (OR, 1.02; 95% CI, 0.73–1.42, p = 0.90), and miscarriage (OR, 1.16; 95% CI, 0.86–1.55, p = 0.34) compared to sham-controls. Conclusions Using acupuncture as an adjuvant therapy to embryo transfer may improve the biochemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth outcomes compared to no adjuvant therapy controls. However, no significant difference was found between acupuncture as an adjuvant therapy to embryo transfer and sham-controls in any of the measured outcomes. This relationship forces us to recommend the use of acupuncture as adjuvant therapy in women undergoing in-vitro fertilization and inquire further studies comparing acupuncture and sham-controls to reach the best procedure.
Article
Introduction: Behavioral factors are the leading cause of ill-health worldwide. Diet, physical activity, smoking, and alcohol consumption are the focus of public health targets on promotion of healthy behavior. The science of behavior change is rapidly growing and has largely evolved within mainstream health care treatments. Traditional Chinese Medicine includes self-care practices that encourage healthy behavior alongside treatments such as acupuncture. Exploring behavior change within traditional acupuncture could potentially highlight new techniques and approaches, and contribute to developing models of behavior change. Aims: In this review, the authors aimed to critically appraise research exploring health behavior change within traditional acupuncture, to highlight gaps in the field, identify questions, and enable theory development. Design/Method: The authors were guided by a critical interpretive synthesis (CIS) method to explore a diverse mixture of research including qualitative and quantitative articles. Eight databases were searched up to October 2017 for articles published in English. Eleven thousand four hundred eighty-eight articles were identified (7,149 after deduplication). Titles and abstracts were screened by one reviewer (10% by a second reviewer). Eligible articles were selected using a Population, Intervention, Comparison, Outcome framework. CIS methods, including purposive sampling of eligible articles and a reflexive, dialectic process of critiquing evidence and theory, were used to synthesize the evidence. Results: Several articles examined the prevalence and patterns of behavior change and support for change, although methods varied and reliability of results was limited. There was more evidence concerning diet/exercise than alcohol/smoking. Aspects of acupuncturists' work identified as potential key elements for promoting behavior change included: individualized advice based on symptoms; holistic/biopsychosocial explanations; therapeutic relationship; simultaneous treatment of behavior-limiting symptoms; and patients' physical involvement with intervention. A logic model of the process of behavior change was developed, proposing that perceived support, mutual understanding, and active participation may facilitate change. Possible moderators included: single/multicomponent acupuncture; setting; patient/practitioner characteristics; treatment experience; timing; and treatment duration. Conclusion: These findings suggest behavior change work is a significant part of traditional acupuncture practice, although more reliable evidence is needed to understand the effectiveness, prevalence, and patterns of this work (in particular the patterns suggesting acupuncturists are more likely to work on changes to diet and physical activity than alcohol and smoking behaviors, and more likely to support changes in long-term compared with acute conditions). The proposed model of behavior change should be developed and tested with a view to refining the model and elaborating the suggested links with a wider theory of behavior and behavior change. This review was preregistered with PROSPERO as "Health behaviour change in traditional acupuncture treatment: a protocol for a critical interpretive synthesis": CRD42018099766.
Article
In late Spring 2012 a group of Chinese and Western medical experts in the treatment of infertility came together in Zurich. The meeting was the result of their collaboration on a forthcoming textbook on the treatment of infertility with Chinese medicine. The primary author, Professor Yuning Wu - one of the most eminent fertility specialists and gynaecologists working in China - is the chief doctor and professor of integrated Chinese and Western medicine at the Beijing Hospital of Traditional Chinese Medicine. The other authors are Michael Haeberle, a reproductive endocrinologist, and Celine Leonard and Esther Denz, both senior students of Professor Wu and clinicians specialising in the Chinese medical treatment of infertility. Finally, Inga Heese, a Chinese medicine practitioner working extensively with infertility, andPeter Deadman, co-editorof the Journal of Chinese Medicine - both editors of the forthcoming book - were on hand to ask questions and engage in the discussion.
Article
The second edition of this popular text systematically addresses all aspects of treatment of infertility using Chinese medicine. Clinically focused and with a new easy-to-navigate design, the book begins by covering all the essential fundamentals you will need to understand and treat infertility, before going on to look at what Chinese medicine offers in the way of treatment for functional infertility in men and women, gynecological disorders which contribute to infertility and relevant lifestyle factors. Jane Lyttleton importantly devotes a large part of the book to discussing ways in which Chinese medicine and Western medicine might work together to overcome infertility, and details the increased experience over the past decade in working with IVF patients and their specialists. Leaps forward have also been made in the understanding of conditions such as Polycystic ovarian syndrome and immune infertility. New Features: Greatly expanded section on the place of Chinese medicine and IVF in treatment of infertility. New information on Polycystic ovarian disease and immune infertility and how Chinese medicine approaches their treatment. Updated and balanced advice on pre-conception care. Clinically focused, with easy-to-navigate design.
Article
This review examined the currently available evidence supporting the use of acupuncture to treat primary dysmenorrhoea. To determine the efficacy and safety of acupuncture in the treatment of primary dysmenorrhoea when compared with a placebo, no treatment, or conventional medical treatment (for example oral contraceptives and non-steroidal anti-inflammatory medication (NSAIDs)). The following databases were searched (from inception until March 2010): the Cochrane Menstrual Disorders and Subfertillity Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), PubMed, CINAHL, PsycINFO, Chinese Biomedical Literature Database (CBM), Chinese Medical Current Content (CMCC), China National Knowledge Infrastructure (CNKI), VIP database, Dissertation Abstracts International, BIOSIS, AMED (The Allied and Complementary Medicine Database), Acubriefs, and Acubase. Inclusion criteria included all published and unpublished randomised controlled trials comparing acupuncture with placebo control, usual care, and pharmacological treatment. The following modes of treatment were included: acupuncture, electro-acupuncture, and acupressure. Participants were women of reproductive age with primary dysmenorrhoea during the majority of the menstrual cycles or for three consecutive menstrual cycles, and moderate to severe symptoms. Meta-analyses were performed using odds ratios (OR) for dichotomous outcomes and mean differences or standard mean differences (SMD) for continuous outcomes, with 95% confidence intervals (CI). Primary outcomes were pain relief and improved menstrual symptoms, measured by self-rating scales. Other outcomes included use of analgesics, quality of life, and absence from school or work. Ten trials were included in the review with data reporting on 944 participants. Six trials reported on acupuncture (n = 673) and four trials (n = 271) reported on acupressure. There was an improvement in pain relief from acupuncture compared with a placebo control (OR 9.5, 95% CI 21.17 to 51.8), NSAIDs (SMD -0.70, 95% CI -1.08 to -0.32) and Chinese herbs (SMD -1.34, 95% CI -1.74 to -0.95). In two trials acupuncture reduced menstrual symptoms (for example nausea, back pain) compared with medication (OR 3.25, 95% CI 1.53 to 6.86); in one trial acupuncture reduced menstrual symptoms compared with Chinese herbs (OR 7.0, 95% CI 2.22, 22.06); and in one trial acupuncture improved quality of life compared with usual care.There was an improvement in pain relief from acupressure compared with a placebo control (SMD -0.99, 95% CI -1.48 to -0.49), and in one trial acupressure reduced menstrual symptoms compared with a placebo control (SMD -0.58, 95% CI -1.06 to -0.10). The risk of bias was low in 50% of trials. Acupuncture may reduce period pain, however there is a need for further well-designed randomised controlled trials.
Article
Based on American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology data available in 2007, ASRM's guidelines for the number of embryos to be transferred in in vitro fertilization cycles have been further refined in continuing efforts to reduce the number of higher-order multiple pregnancies. This version replaces the document of the same name that was published most recently in November 2008. (Fertil Steril (R) 2009;92:1518-9. (C) 2009 by American Society for Reproductive Medicine.)