CASE REPORT

SEMEN QUALITY IMPROVEMENT IN A MAN WITH IDIOPATHIC INFERTILITY TREATED WITH TRADITIONAL KOREAN MEDICINE: A CASE REPORT Junyoung Jo, KMD1,2, Sun Haeng Lee, KMD3 Jin Moo Lee, KMD, PhD1 and Ui Min Jerng, KMD, PhD4,#

Approximately 45–50% of the cases of infertility result from deficiencies associated with male factors, and 30–45% of these deficiencies are idiopathic. A standardized approach for the treatment of idiopathic male infertility remains elusive. In Korea, male infertility has been treated with either acupuncture, herbal remedies, or pharmacopuncture. We report a case of male idiopathic infertility in which the patient’s semen quality improved through traditional Korean medicine (TKM) therapies, which was evaluated according to the 2010 World Health Organization (WHO) standards. A 35year-old infertile man visited the Conmaul Hospital from August 2013 to December 2013. He was diagnosed with asthenoteratozoospermia. The patient received 3 TKM therapies—acupuncture, pharmacopuncture, and herbal remedies —for 3 months. After 3 months of treatment, a second semen analysis of the patient was conducted. The sperm motility

INTRODUCTION Approximately 45–50% of the cases of infertility result from deficiencies associated with male factors, and 30–45% of these deficiencies are idiopathic.1 A standardized approach for the treatment of idiopathic male infertility remains elusive. Empirical drugs have been used, but the evidence of their efficacy is insufficient.2 A systematic review suggests that dietary antioxidant supplements may be beneficial for improving semen quality.3 However, the review also reports that the evidence of their efficacy is insufficient because of the small number of subjects included for analysis in each trial and a lack of information about improved pregnancy rates.3 In Korea, male infertility has been treated with acupuncture, herbal remedies, or pharmacopuncture, which is the

1 Department of Korean Gynecology, Graduate School of Kyung Hee University, Seoul, Republic of Korea 2 Department of Korean Gynecology, Conmaul Hospital, Seoul, Republic of Korea 3 Department of Korean Pediatrics, Graduate School of Kyung Hee University, Seoul, Republic of Korea 4 Clinical Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea # Correspondence to:1672 Yuseongdae-ro, Yuseong-gu, Daejeon 305811, Republic of Korea. e-mail: [email protected]

& 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). ISSN 1550-8307/$36.00

increased by 13%, and the normal sperm morphology increased by 4% over 3 months. In addition, the total motile sperm count was 2.5 times higher than that before treatment. The results of the present study support the clinical potency of treatment with acupuncture, pharmacopuncture, and herbal remedies in idiopathic infertile men, especially for the improvement of sperm motility and morphology. Further large-scale randomized controlled trials with elaborate designs should be performed to verify the clinical effect of TKM therapies. Key words: Sperm quality, sperm motility, traditional Korean medicine, acupuncture, herbal medicine (Explore 2015; ]:]]]-]]] & 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NCND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

subcutaneous injection of specific herbal extracts into specific acupoints. Some studies suggest that each of these treatments improves semen quality.4–6 However, there have been no published studies in which these treatments were used simultaneously for the treatment of idiopathic male infertility. We report a case of male idiopathic infertility in which the patient's semen quality improved through traditional Korean medicine (TKM) therapy, which was evaluated according to the 2010 World Health Organization (WHO) standards.

CASE PRESENTATION The institutional review board of Kyung Hee University Korean Medicine Hospital at Gangdong approved this retrospective observational study, and the requirement of patient approval or informed consent for the review of medical records was waived (KHNMCOH 2014-06-002). A 35-year-old infertile man visited the Conmaul Hospital from August 2013 to December 2013. He had been trying to have a child for four years, but he was unsuccessful. He had a normal serum follicle stimulating hormone (FSH) level and a normal testicle size at his first visit. He had not undergone any previous surgeries. Semen analysis was performed in the laboratory of Maria Hospital in Korea, which specializes in infertility, according to the 2010 WHO standards. He was diagnosed with asthenoteratozoospermia (Table 1). The patient received three TKM therapies—acupuncture, pharmacopuncture, and herbal remedies—for three months. EXPLORE ] 2015, Vol. ], No. ] http://dx.doi.org/10.1016/j.explore.2015.04.007

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6 92 215 43

SM (%) TMS (106) TSC (106) TM (%) Count (10 )

After Treatment

43 5.0 36 118.4 30 32 3.7 Patient

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TM ¼ total motility; TSC ¼ total sperm count; TMS ¼ total motile sperm; SM ¼ strict morphology.

SM (%) TMS (10 ) TM (%) Count (10 ) Volume (mL)

6

Before Treatment

6

TSC (10 )

6

2

Volume (mL)

6

Semen Parameters

Table 1. Effects of a Combined Therapy of Acupuncture, Pharmacopuncture, and Herbal Remedy on Semen Parameters

2

Acupuncture and pharmacopuncture treatments were provided once a week on the same day. Acupuncture needles (0.25 mm in diameter and 40 mm in length from Dong Bang, Gyeonggi-do, Korea) were manually applied to a depth of 15– 20 mm, depending on the region of the body into which the needles were inserted. The needles were rotated manually to evoke the Deqi sensation. The following acupoints were chosen according to previous acupuncture studies on improving semen quality in male infertility: SP6 (bilateral), KI3 (bilateral), LR3 (bilateral), ST29 (bilateral), SP10 (bilateral), CV4, and CV6.6,7 Additionally, an electrical stimulation of 10 Hz was applied for 10 min to the acupuncture needles that were inserted into acupoint ST29. This manipulation was based on another study which reported that electrical stimulation of ST29 increased testicular blood flow.8 Acupuncture was maintained for a duration of 20 min. For pharmacopuncture, 0.1 cc of distilled Cervi Pantotrichum Cornu extract was injected into subcutaneous tissues located on acupoints BL23, BL33, and BL52 (bilateral injections at all points). A sterile insulin syringe (29 Gauge and 1/2 inch from Shinchang, Gyeongsangbuk-do, Korea) was used for injection. Distilled Cervi Pantotrichum Cornu extract was prepared in a laboratory at the Korean Pharmacopuncture Institute. The herbal remedy was a decoction of Cuscuta chinensis Lam. 13.3 g, Lycium chinense Mill. 13.3 g, Cornus officinalis Sieb. 13.3 g, Morinda officinalis How 13.3 g, Epimedium koreanum Nakai 13.3 g, Cynomorium songaricum Rupr. 13.3 g, Rehmannia glutinosa Libosch. 10.7 g, Achyranthes japonica Nakai 10.7 g, Rubus coreanus Miq. 8 g, Panax ginseng C. A. Mey. 6.7 g, Poria cocos Wolf 6.7 g, Paeonia suffruticosa Andr. 6.7 g, Alisma canaliculatum ALL. 6.7 g, Angelica gigas Nakai 6.7 g, Cnidium officinale Makino 6.7 g, Schisandra chinensis Baill. 4 g, and Plantago asiatica L 4 g. Each plant material was mixed and decocted with purified water. This herbal remedy was administered three times a day, once after each meal. The patient did not receive any conventional treatment while receiving these three treatments. After three months of treatment, a second semen analysis of the patient was conducted—in the same laboratory by the same technician in Maria Hospital in Korea—according to the 2010 WHO standards.9 The outcomes before and after TKM therapies are shown in Table 1. The total sperm motility and sperm morphology of the patient before treatment were below the lower limit of the 2010 WHO standards. After treatment, the total sperm motility was normal. In addition, the total motile sperm count was 2.5 times higher than that before treatment. The sperm morphology also increased to 6%, which was normal, after treatment. No adverse effects were observed during the treatment.

DISCUSSION We report a case in which three TKM therapies (acupuncture, pharmacopuncture, and herbal remedies) were simultaneously applied for idiopathic male infertility. We found that the combination of these treatments improved semen quality in an idiopathic infertile man. Acupuncture has traditionally been used to improve semen quality of men in Korea. Various studies have reported the

Semen Quality Improvement

effects of acupuncture in infertile men.4–6 Although the majority of previous studies are based on uncontrolled trials, they suggest that acupuncture improves sperm count,10 sperm motility,7 and sperm morphology.11 We identified acupuncture points based on the acupuncture studies reported above and used electrical stimulation on acupoint ST29 to maximize the effectiveness of the treatment.8 These points are related to the spleen, liver, and kidney meridians, which are known to theoretically govern reproductive function in TKM. Therefore, it is thought that acupuncture on these points might improve spermatogenesis and sexual activity.5 Although the mechanism by which acupuncture improves semen quality is unknown, it is possible that acupuncture might enhance blood supply in the testicular arteries, decrease testicular temperature, and stimulate systemic immune-regulatory actions.6 Cervi Pantotrichum Cornu pharmacopuncture has been used to regulate the kidney yin and yang in TKM. The extracts also display antioxidant and anti-inflammatory activities.12 Accordingly, this has been used to treat male infertility and sexual dysfunction.4,12 The herbal remedy prescribed to the patient is known to be effective for improving sperm count, sperm motility,5 and sperm morphology.13 It is thought that this remedy theoretically improves the semen quality by refreshing the kidney yin and yang according to TKM.14 Cornus officinalis Sieb. Et Zucc, Schizandra chinensis Baillon, Rubus coreanus Miquel, Cuscuta chinensis Lam, and Lycium chinense Mill are herbs that are popularly used in infertile men in TKM. Preliminary in vivo results have also shown that these five herbs improve sperm count and activity.15 This effect might be a result of their anti-oxidative properties, which help restore the imbalance of excessive levels of reactive oxygen species. In this case, the sperm motility increased by 13%, and the normal sperm morphology increased by 4% over three months. These results were equal to or better than those of previous studies of antioxidants. Antioxidant supplements, including selenium–vitamin E and coenzyme Q10, have been used to treat idiopathic male infertility.16,17 Using selenium– vitamin E supplementation for 14 weeks showed a similar improvement in only 6% of participants.16 It took nearly nine months to obtain similar results with this case when coenzyme Q10 supplementations were used.17 There are some limitations to our study. First, this study is a case report; thus, more cases are needed to confirm the effect of TKM therapies. Second, we used a combination therapy of acupuncture, pharmacopuncture, and herbal remedies; therefore, it is difficult to determine which therapy was the most effective. Nevertheless, combined therapy is used in clinical practice because it affords the best effects.4 Third, the methodological issues related to sperm analysis might affect the outcome. The results of semen analysis can be affected by the analysis method and/or by the technique employed by the evaluator. Even specimens that are extracted under the same conditions can provide very different results. As such, the WHO recommends two semen collections.18 Although the analysis method and the evaluator were well controlled in

Semen Quality Improvement

this case, only one semen analysis was performed before and after treatment. Even though the semen quality of the patient improved, he could not successfully impregnate a female partner during the treatment period of three months. However, the duration of this period is insufficient to enable pregnancy, even in normal healthy couples. In the coenzyme Q10 supplementation study, the pregnancy rates were 0% and 2.8% after three and six months of treatment, respectively.17 Accordingly, long-term follow-up is needed to verify the results. In addition, female factors could not be fully excluded in consideration of post-treatment pregnancy rates. Despite these limitations, this study is worthwhile as the first case report of male idiopathic infertility treated by TKM therapies. The results of the present study support the clinical potency of treatment with acupuncture, pharmacopuncture, and herbal remedies in idiopathic infertile men, especially for the improvement of sperm motility and sperm morphology. Further large-scale randomized controlled trials with elaborate designs should be performed to verify the clinical effect of TKM therapies.

Acknowledgments

This study was supported by the oNew Donguibogam4 Compilation Project : for expandation of Korean Medicine Knowledge (No. K15500) of the Korea Institute of Oriental Medicine.

REFERENCES 1. Jungwirth A, Giwercman A, Tournaye H, et al. European Association of Urology guidelines on male infertility: the 2012 update. Eur Urol. 2012;62(2):324–332. 2. Attia AM, Abou-Setta AM, Al-Inany HG. Gonadotropins for idiopathic male factor subfertility. Cochrane Database Syst Rev. 2013;8:CD005071. 3. Showell MG, Brown J, Yazdani A, Stankiewicz MT, Hart RJ. Antioxidants for male subfertility. Cochrane Database Syst Rev.. 2011;1:CD007411. 4. Zheng Z. Analysis on the therapeutic effect of combined use of acupuncture and medication in 297 cases of male sterility. J Tradit Chin Med. 1997;17(3):190–193. 5. Crimmel AS, Conner CS, Monga M. Withered Yang: a review of traditional Chinese medical treatment of male infertility and erectile dysfunction. J Androl. 2001;22(2):173–182. 6. So EW, Ng EH. Acupuncture in reproductive medicine. Womens Health (Lond Engl). 2010;6(4):551–563. 7. Dieterle S, Li C, Greb R, Bartzsch F, Hatzmann W, Huang D. A prospective randomized placebo-controlled study of the effect of acupuncture in infertile patients with severe oligoasthenozoospermia. Fertil Steril. 2009;92(4):1340–1343. 8. Cakmak YO, Akpinar IN, Ekinci G, Bekiroglu N. Point- and frequency-specific response of the testicular artery to abdominal electroacupuncture in humans. Fertil Steril. 2008;90(5): 1732–1738. 9. Cooper TG, Noonan E, von Eckardstein S, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16(3):231–245.

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10. Siterman S, Eltes F, Wolfson V, Lederman H, Bartoov B. Does acupuncture treatment affect sperm density in males with very low sperm count? A pilot study. Andrologia. 2000;32(1):31–39. 11. Pei J, Strehler E, Noss U, et al. Quantitative evaluation of spermatozoa ultrastructure after acupuncture treatment for idiopathic male infertility. Fertil Steril. 2005;84(1):141–147. 12. Korean Pharmacopuncture Institute Science Committee. Pharmacopuncturology. 2nd ed. Seoul: Elsevier Korea; 2011; [3,18,19]. 13. Tempest HG, Homa ST, Zhai XP, Griffin DK. Significant reduction of sperm disomy in six men: effect of traditional Chinese medicine? Asian J Androl. 2005;7(4):419–425. 14. Kwon SK, Lee HY, Kang MJ, Kim DI. Effect of herb-medicine on seminal parameters in male infertility patients. J Orient Obstet Gynecol. 2005;18(3):184–191.

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15. Kim SJ, Kim MR, Hwang SY, et al. Preliminary report on the safety of a new herbal formula and its effect on sperm quality. World J Mens Health. 2013;31(3):254–261. 16. Moslemi MK, Tavanbakhsh S. Selenium—vitamin E supplementation in infertile men: effects on semen parameters and pregnancy rate. Int J Gen Med. 2011;4:99–104. 17. Safarinejad MR. The effect of coenzyme Q10 supplementation on partner pregnancy rate in infertile men with idiopathic oligoasthenoteratozoospermia: an open-label prospective study. Int Urol Nephrol. 2012;44(3):689–700. 18. Sánchez-Pozo MC, Mendiola J, Serrano M, et al. Proposal of guidelines for the appraisal of SEMen QUAlity studies (SEMQUA). Hum Reprod. 2013;28(1):10–21.

Semen Quality Improvement

Semen Quality Improvement in a Man with Idiopathic Infertility Treated with Traditional Korean Medicine: A Case Report.

Approximately 45-50% of the cases of infertility result from deficiencies associated with male factors, and 30-45% of these deficiencies are idiopathi...
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