Current evidences and clinical practice -a combined meeting with Reproductive Endocrinology

1. TCM on Patients undergoing IVF
Current evidences and clinical practice
Center for Traditional medicine, Taipei Veterans General Hospital
Chu-Feng Wu M.D.
2021.12.08

2. TCM Utilization rates are unclear
• 428 Northern Californian couples, 22% reported using acupuncture
(Smith et al., 2010)
• 118 Boston-area women surveyed, 47% women reported using
acupuncture and 17% used herbs during their assisted reproduction
technique cycle (Domar et al., 2012)
• 77 patients found that 92% reported using acupuncture to support
their IVF cycle (Aelion et al., 2009)

3. More than we think
• Self-referral
• IVF physician may refer
• IVF physicians may not be aware of patient use of these additional
therapies (Boivin and Schmidt, 2009)

4. Fresh embryo transfer
新鮮胚胎植入
中西醫整合IVF

5. Inclusion 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, regardless of
embryo quality.
• Women who underwent pre-implantation genetic screening testing
or intracytoplasmic sperm injection cycles were also included.
• To further reduce selection bias, all biomedical diagnoses were
included.

6. Exclusion criteria
• All patients who underwent transfers with frozen embryos (n = 251)
or embryos from frozen oocytes (n = 27, research cycles) were
excluded.
The Oregon College of Oriental Medicine Institutional
Review Board approved this study on 11 January 2011
(IRB reference number 09–028).

9. Whole-systems traditional Chinese medicine
(WS-TCM)
• At the initial visit, the patient’s biomedical chart was reviewed.
The patient was assessed according to TCM theory.
• Patient visits were typically once a week and increased in
frequency to twice a week from the start of IVF suppression
medications to oocyte retrieval.
• One more visit was suggested 5–7 days after embryo transfer to
reduce stress.
• 精卵的成熟、成熟卵泡的排出、黃體支持、妊娠維持

10. Treatment is individualized 辨證論治
• Acupuncture and herbal treatment was based on TCM pattern
diagnosis and phase of menstrual cycle.
• A detailed WS-TCM treatment plan was provided outlining the dose
and frequency of acupuncture, electro-acupuncture, Chinese
medicine-based dietary suggestions, lifestyle recommendations,
and any recommended nutritional supplements.
• A course of treatment can range from six to 24 treatments
depending on the complexity of the case.
• All customized Chinese herb formulas were dispensed in granular
form and manufactured by KPC herbs (Taiwan).

12. 調周法
• Regulating the menstrual cycle is considered a central treatment
approach to female reproduction (Cochrane et al., 2014)
• 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]

13. “心（腦）-腎-子宫軸”學說
• 中醫理論將心定為“五臟六腑之大主，神明出焉”，對其他臟腑發揮
主宰指揮作用，與子宮和衝任督脈、足少陰腎經、手少陰心經直接或
間接地關聯，使此形成“心-腎-子宮”連貫，尤重心（腦）統一管理
作用，是調節女性生殖內分泌的核心所在，陰陽平衡，氣血調暢，無
不關乎於此。
• 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).

14. 排卵前
• During menses, treatment was directed at regulating menses and
reducing of dysmenorrhea pain, if present(Smith et al., 2011).
• Follicular phase treatment was directed at regulating reproductive
hormones (Chen, 1997; Napadow et al., 2008), and endometrial
(Stener-Victorin et al., 1996) and follicular development (Rashidi
et al., 2013).注重陰分。歸芍地黃湯, 養精種玉丹, 補天種玉丹

15. 排卵後
• Ovulation 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).氤氳之候，活
血通絡。補腎促排卵湯, 健脾促排卵湯
• Luteal phase treatment focused on regulating hormones (Cochrane
et al., 2014).黃體功能不全是腎陽虛不孕症常見類型，溫腎助陽。毓
麟珠-溫腎健脾法

16. During the IVF cycle
• 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 optional 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)

17. Acupuncture on the day of
embryo transfer (ACU)
• 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.
• Before embryo transfer: GV-20/Baihui; PC-6/Neiguan; CV-6/Qihai;
ST-29/Guilai; SP-8/Diji; LR-3/Taichong; right ear (uterus,
endocrine); left ear (Shenmen, Brain).
• After embryo transfer: LI-4/Hegu; SP-10/Xuehai; ST-36/Zusanli;
SP-6/Sanyinjiao; KI-3/Taixi; right ear (Shenmen, Brain); and left
ear (uterus, endocrine).

18. • In this retrospective
study, adjuvant WS-TCM
and IVF was associated
with increased odds of
live birth in women aged
38 to 42 years old.
Outcomes
Live births in women who integrate whole
systems traditional Chinese medicine with
IVF does age matter?

19. Frozen-thawed
embryo transfer
(FET)
冷凍胚胎植入
中西醫整合IVF

20. Patients
• Extracted data from charts from their community clinics of shared
fertility clinic patients who added acupuncture therapy prior to
embryo transfer (ET).
• Cycles with gestational carriers, donor eggs, no transfer, or
embryos without chromosomal screening were excluded.

21. Interventions and Comparison
• UC group: usual care for women who completed FET alone
• ET Acu group: UC and ET Acu of two standardized acupuncture
sessions before and after ET
• TCM group: UC, ET Acu and acupuncture therapy received in the
community prior to ET that included Traditional Chinese Medicine
therapies such as diet and lifestyle modifications, warming
therapy, or if appropriate, Chinese herbal therapy.

22. Outcomes
• There was no difference in live births between UC (67.7%) and TCM (64.6%,
p=0.35), but both groups were associated with significantly more live births
over ET Acu (55.3%, p=0.005 and 0.05, respectively).
• The rate of miscarriage was also similar between UC (6.6%) and TCM (8.9%,
p=0.20), but again, both were associated with significantly less than ET Acu
(15.3%, p=0.001 and 0.03, respectively).
• Patients who chose ET Acu and TCM differed on important variables that
may predict birth outcomes thereby limiting interpretation.

24. Repeated implantation failure (RIF)
• Main reasons as follows:
• limited potential development of embryos (e.g., abnormal chromosomes
and blood types, abnormal male sperm quality);
• impaired endometrial receptivity;
• compatibility between the embryo and endometrium
• However, even when there are high quality embryos, some
maternal factors such as age, pelvic environment, intrauterine
factors, endometrial receptivity, and hydrosalpinx and
psychological factors will still lead to the occurrence of RIF.
• Consider TCM for Endometrial Preparation

25. Inclusion Criteria
• RIF with three or more implantation failures in previous IVF/ICSI
cycles.
• High-quality embryos were subjected to cryopreservation by
vitrification, and were still in good condition after being thawed.
• CM standard was in accordance with deficiencies in Spleen and
Kidney functions.

27. Endometrial Mechanical Stimulation
• Hysteroscopic examinations to exclude organic endometrial
problems
• Intrauterine device (IUD) was removed after 2 months and then
the endometrium was stimulated softly again.
• Hysteroscopy was performed using a digital camera (Tricam SLII,
Germany, Carl Stortz, Tuttlingen, Germany).

28. The sequential therapy of (Yupei Qisun) in CM
• The first stage started 60 days before FET. Bushen Jianpi Recipe
(補腎健脾方) was given to invigorate the Spleen and Kidney.
• The second stage started about 19 to 30 days before FET according
to the various methods of endometrial preparation. Bushen Jianpi
Recipe and the modified Erzhi Pill (加味二至丸) were given.
• The third stage started from 14 to 60 days after FET depending on
the pregnancy result. Bushen Jianpi Recipe and Shoutai Pill (壽胎
丸) were given.安胎並舉
• All herbs were boiled by the Pharmacy of Shuguang Hospital.

29. • Sixty-six infertile patients with Kidney-yin deficiency syndrome undergo in
vitro fertilization-embryo transfer (IVF-ET).
• The dosage and duration of Gn were significantly lower in the treatment
group than that in the control group (P<0.05).
• The high quality oocyte and embryo rates, and clinical pregnancy rate were
all higher in the treatment group than those in the control group (P<0.05).

30. Outcomes
• The mean endometrial thickness in the CM group was greater than in the
hysteroscopy group, but the difference was not statistically significant.
• The increased level of DNMT1 protein expression after treatment may
lead to the enhanced endometrial receptivity.
• No statistically significant difference in the abnormal pregnancy rate
among the groups.

32. Clinical Cases in VGH
• 32 y/o, MARRIED FOR 4 YEARS, G0P0, WANT A BABY(AIHX3 W/ CLOMID -GONA-F-
HCG OR PROFASI FAIL AT NTUH)
• D/I: 5-7/24-26, moderate amount, blood clot(-), low back soreness,
menorrhagia associated with headache and nausea, LMP:2007-9/24, Hx of
POLYPECTOMY+ D&C ON 2001, TVS: EM: 9.1 mm, LEFT CHOCOLATE CYST;MYOMA
2CM; LAPAROSCOPY: BIL. TUBES OCCLUSION, R/O ENDOMETRIOSIS OF OVARY
• SEMEN=93M;M=56% NF 55%;HSG;+/+,SUGGEST IVF BY DR. YANG
• FSH: 10.30
• E2: 28.95
• PRL: 11.87
• AMH:>1.0
• Impression: IDIOPATHIC INFERTILITY R/O ENDOMETRIOSIS 血瘀證receptivity?

33. 中西醫整合治療 SINCE 2007-5/24
• Rx. Utrogestan 100 mg TID, Leuprolide acet.*inj5mg/ml 2.8ml
• FET x3 preceding with Leuplin 6M discomfort(++)
• Low abdominal fullness and low back soreness, some vaginal spotting, acne,
constipation, dry mouth, shallow sleep with lots of dreams, high stress due
to family factors…
• TCM 補腎調周法(測量基礎體溫)+逐瘀+療程症狀治療
• 若需停服中藥期間可單用Acupuncture (see another case)
• 2008-08 EMBRO TRANSFER x2, 2008-9/1 HCG+, LIVE BIRTH x1
(EDC on 2009-05)
TCM IVF cycle：預處理階段、啟動階段、板機日間、取卵後進入健黃體治療時期

34. Take Home Messages
• The retrospective studies suggest that TCM as an adjuvant IVF
treatment may improve live birth rates in patients undergoing
fresh or frozen embryo transfer.
• 中醫在心腎陰陽，肝脾氣血，衝任督帶及子宮的總體調控下，達成女
性生理功能規律變化，減少IVF療程中的不適感。
籌辦中

35. 門診時間
臺北榮總 傳統醫學部 針灸科四診
每週四下午1:30至5:30
https://zhufngwu.blogspot.com/2020/02/blog-post.html