1 TCM TREATMENT FOR AUTOIMMUNE THYROIDITIS CAUSING INFERTILITY Effectiveness of Acupuncture and/or Moxibustion for Fertility Treatment in Women with Autoimmune Thyroid Dysfunction. A Literature Review By Jung Hwa Sarah Park A Capstone Project Presented in partial fulfillment of the requirements for the Doctor of Acupuncture and Oriental Medicine Degree Yo San University Los Angeles, California April, 2017 2 TCM TREATMENT FOR AUTOIMMUNE TH YROIDITIS CAUSING INFERTILITY Approval Signature Page 3 TCM TREATMENT FOR AUTOIMMUNE TH YROIDITIS CAUSING INFERTILITY Acknowledgements Past two years of struggling in many ways to stay in the program and finish the capstone was really hard. Thank you, my husband Joe and my father-in-law Young Park for your tremendous support and encouragement with love. I have to say that I would not be able to finish this without my lovely and patient children, Isaac and Lauren who were the source of the love while completing this program. I also want to thank my father Harry, my brother Sam, and sister-in-law Kathy for encouraging me with unconditional love and cheers. I send thanks to my brother-in-law Jason and sister-in-law Sandy for caring heart in many ways. The most special thanks go to Jamie and Sam who never ceased helping me throughout the program by nourishing me physically and spiritually. My Cohort 6 fellows, Julie G., Nefertiti, Romi, Elif, Pam, Kyle, Veronica, Julie C., Rachel were the most encouraging people along the 2-year of tough journey. Lastly, I am honored to have Dr. Murchison, Dr. Crampton, and Dr. Ramsey for always keeping me on the right track and strengthening me with loving advice and guidance. Without all of the love and care, I wouldn’t be able to finish this challenging yet precious journey. May God bless you all abundantly! 4 TCM TREATMENT FOR AUTOIMMUNE TH YROIDITIS CAUSING INFERTILITY Abstract Immune related infertility refers to an inability of conception or to sustain a live- birth due to some aspect of immune dysfunction. Thyroid dysfunction with immunological factors increase the risk of miscarriage, premature labor, or low birth weight as compared to a normal pregnancy in women with normal thyroid function. However there is no specific western treatment for Hashimoto’s Thyroiditis besides thyroid medication. The purpose of this research is to maximize the effects of alternative fertility treatments for women who are dealing with autoimmune thyroid dysfunction. After a thorough review, Acupuncture can be used as a treatment of thyroid dysfunction induced infertility, where by anti-inflammatory treatment has shown modulation of Th1 and Th2 balance. Some studies have shown that Moxibustion also has an effect on immunomodulation in normal condition and autoimmune status by elevating CD3+ and CD4+ T-lymphocytes in normal patients and decreasing CD8+ T-lymphocytes. This Literature review may show the possible effectiveness of Acupuncture and/or Moxibustion to reduce possible miscarriage due to Autoimmune Thyroid condition and increase pregnancy rate. However, studies about Acupuncture and/or Moxibustion treatment for autoimmune related female infertility were limited. Therefore, further case studies about Acupuncture and/or Moxibustion for infertility due to Autoimmune Thyroiditis will be helpful to confirm the hypothesis. 5 TCM TREATMENT FOR AUTOIMMUNE TH YROIDITIS CAUSING INFERTILITY Table of Contents Chapter 1: Introduction Definition Key Ter…m…s …a…nd… G…l…os…s…ar…y… o…f A…b…b…r…ev…ia…t…io…n…s ………………....………………….. 6 C hapter 2: Literature review …………………………………… 17 Chapter 3: Methodology …………………………………………………...…………….…….................. 22 Chapter 4: Results .…...………..……………………….…………………..……………………………..... 41 Chapter 5: Discussi…on… .…………..……………………………………………………………………………….... 43 References …………….…………………………………………………………………………....…... 53 Appendices… ………………………..………………………………………………………………………………....…. 56 • Data A…b…st…r…ac…ti…o…n …Ta…b…le…s. …………………………………………………………………………….....… 65 • Copy of IRB approval Letter 6 TCM TREATMENT FOR AUTOIMMUNE TH YROIDITIS CAUSING INFERTILITY Chapter 1: Introduction According to the World Health Organization (WHO) declares infertility as a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse (Brazdova et al., 2014). Regardless of age, Infertility has been reported to be one of the most universal chronic disorder (Brazdova et al., 2014). Fertility dysfunction is affecting couples worldwide as many as 186 million people (Inhorn & Patrizio, 2015). Female fertility dysfunction has become a major medical issue in Gynecological clinics although male infertility contributing to about half of all cases (Inhorn & Patrizio, 2015). Estimates on the number of couples having fertility issues vary from onee tin a slix to one in ten, with 9% currently cited as the probable global average (Cochrane ., 2016). In women’s menstrual cycle and in achieving fertility affecting the actions of follicle-stimulating hormone and luteinizing hormone is controeltle adl .b, y specific triiodothyronine on oocytes affecting reproduction (Medenica 2015). Also Pregnant women who affected by Subclinical Hypothyroidism or Autoimmune Thyroid antibodies have an increased risk of preeclampsia, perinatal mortality, and miscarriage (Sarkar, 2012). Throughout the last twenty years, Thyroid disease related to pregnancy dysfunction has rapidly increased. Thyroid dysfunction interferes with human reproductive physiology and it reduces the possibility of pregnancy while adversely affecting pregnancy outcomes (Sarkar, 2012). Autoimmune Thyroid disease is present in about 4% of young females, and up to 15 % of females are Thyroid antibody positive (Sarkar, 2012). In one 7 TCM TREATMENT FOR AUTOIMMUNE TH YROIDITIS CAUSING INFERTILITY et al. prospective cohort study by Liu (2014) screened 3315 women and demonstrated that women with Subclinical Hypothyroidism and Thyroid autoimmunity are found to have the highest risk and earlier gestational ages of miscarriage and at an inetc raela.,s ed risk of miscarriage between four and eight gestational weeks (Liu 2014). The worldwide annual incidence of Hashimoto's Thyroiditis is estimated to be 0.3-1.5 cases per 1000 persons (Iddah & Macharia, 2013). Also more women than men and older women than younger women tend to have Hashimoto’s Thyroiditis (Iddah & Macharia, 2013). Women who have euthyroid function in early pregnancy and who have asymptomatic autoimmune thyroid disorders are at a significant ertis akl of developing hypothyroidism progressively during gestation (Feldthusen ., 2015). And the presence of Thyroid Peroxidase antibody (TPO Ab) in pregnant women significantly increases the risk of preterm delivery as an immune dysfunction bye dt yaslregulating activity of the immune system at the fetal- maternal interface (He ., 2012). As a biomedical response to infertility, In Vitro Fertilization (IVF) has become onee to f Aalssisted Reproductive Technology (ART) commonly used to support fertility (Cochrane ., 2016). However, patients with Thyroid Peroxidase Antibody (TPO Ab) or Thyroglobulin Antibody (TGB Ab) have significantly lower fertilization rate, implantation rate, pregnancy rate, and higher risk for miscarriage following In Vitro Fertilization- Eetm ablryo Transfer (IVF-ET) when compared with women without TPO Ab or TGB Ab (Zhong ., 2012). Cho (2015) demonstrated that altered thyroid hormone levels are associated 8 TCM TREATMENT FOR AUTOIMMUNE TH YROIDITIS CAUSING INFERTILITY with disturbed folliculogenesis, a lower fertilization rate, and lower embryo quality (Cho, 2015). Also women who plan to undergo Controlled Ovarian Hyper stimulation should be treated with L-thyroxine if they have positive results for serum anti-thyroid antibodies and TSH levels higher than 2.5 mIU/L (Cho, 2015). Another study shows that Ovarian stimulation used in the preparation of an ART procedure is known to increase the need of thyroid hormones in women with TAI and those with Hety palothyroidism for risk reduction in the miscarriage rate and premature delivery (Unuane ., 2012). These studies show that Fertility is related to Thyroid hormones and Thyroid antibodies. However, due to the unavailability and unaffordability of IVF in majority of the world, Traditional Chinese Medicine (TCM) including Acupuncture, Moxibustion (Moxa), aetn adl Chinese Herbal Medicine (THM) has been used to treat fertility dysfunction (Cochrane ., 2016). Acupuncture is increasingly used as an adjunct to AReTt aalnd widely accepted in the complementary and alternative health care system (Cochrane ., 2016). One study resulted in a significantly higher pregnancy rate when undergoing IVF with acupuncture immediately before and after embryo transfer than without acupuncture (White, 2016). In this capstone study will investigate the connection between Infertility and Autoimmune Thyroid dysfunction. Thyroi d and Thyroid Hormones Thyroid gland is butterfly-shaped gland which is located at the base of the neck in front of the trachea (Ain & Rosenthal, 2011). Physiologically the thyroid gland produces, stores, and releases the hormones: Triiodothyronine with three iodine atoms (T3), 9 TCM TREATMENT FOR AUTOIMMUNE TH YROIDITIS CAUSING INFERTILITY Thyroxine with four iodine atoms (T4), and reverse T3 derived from T4 and T3 (rT3) (Rothfeld & Romaine, 2003). T4 is converted to T3 by the removal of an iodine atom, which occurs mainly in the liver and also in the brain tissues where T3 is functional (Rothfeld & Romaine, 2003). Controlling the thyroid gland, the pituitary gland makes thyroid stimulating hormone (TSH), which stimulates the thyroid gland to increase hormonal production, if needed. Also, depending on the amount of T4 it recognizes, the pituitary will increase or decrease the amount of TSH it releases into the bloodstream (Rothfeld & Romaine, 2003). If the pituitary sees very little T4, then it produces more TSH to stimulate thyroid gland to produce more T4 as a negative feedback system (Rothfeld & Romaine, 2003). Then once the T4 level in the blood stream reaches a certain level, the pituitary will stop producing TSH (Rothfeld & Romaine, 2003). T4 and T3 circulate the body almost entirely bound to specific transport proteins, and there are some situations in which these proteins could change their level in the blood whereby altering T4 and T3 levels which happens frequently during pregnancy or women who take birth control pills (Rothfeld & Romaine, 2003). The thyroid also secretes the hormone calcitonin, which regulates the balance of calcium in the blood stream and in the skeletal system (Rothfeld & Romaine, 2003). Calcium is withdrawn from bones and enters the bloodstream as calcitonin levels go up (Rothfeld & Romaine, 2003). When the calcitonin levels decrease, calcium is then deposited into the skeletal tissue (Rothfeld & Romaine, 2003). 10 TCM TREATMENT FOR AUTOIMMUNE THY ROIDITIS CAUSING INFERTILITY Additionally thyroid hormones helps the body regulate homeostasis by regulating energy use, body temperature and sustains brain, heart, muscle, and other organs function. Therefore when the thyroid function properly, the metabolism is well maintained for the female and for the potentially pregnant female. Subsequently, normal thyroid functeiot na li.s required for normal fetal brain and somatic tissue development in newborn (Beers , 2006). Also protein, carbohydrateet, aaln.,d fat metabolism in the fetus is regulated by the mother's thyroid function (Beers 2006). Thyroid promotes growth hormone production, which regulates growth in infants and children. Thyroid also has a role in the healthy aging of adults (Rothfeld & Romaine, 2003). Thyroid is responsible for cell differentiation, reproduction function, intelligence, and brain development (Ryan, 2015). Also protein, carbohydreatt ea,l .a,nd fat metabolism in the feett uasl is regulated by the mother's thyroid function (Beers 2006). According to Rao . (2008),e Ht yaplothyroidism is significantly correlated with growth and metabolism of the fetus (Rao . 20e0t 8a)l. Early in pregnancy, the mother supplies the fetus with thyroid hormones (Rao . 2008). Thus thyreoti da lhormones for the fetus become deficient because the mother has Hypothyroidism (Rao . 2008). Women with high but in normal range TSH with lack of thyroid hormones during pregnancy can cause fetal brain damage resulting in intellectual impairment, and fertility problems are frequently caused by underactive thyroid (Rothfeld & Romaine, 2003). One study suggests that maternal thyroid underfunction may be associated with an impairment of fetal brain development (Poppe and Glinoer, 2003)