Scholarly article on topic 'The effects of traditional Korean medicine in infertile male patients with poor semen quality: A retrospective study'

The effects of traditional Korean medicine in infertile male patients with poor semen quality: A retrospective study Academic research paper on "Health sciences"

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Abstract of research paper on Health sciences, author of scientific article — Junyoung Jo, Ui Min Jerng

Abstract Introduction Approximately fifteen percent of couples have difficulty conceiving, with male infertility being the contributory factor for about half of all cases of infertile couples. This retrospective study was designed to evaluate the pregnancy rates of couples after infertile men with poor semen quality had received traditional Korean medicine (TKM). Methods This study was performed at a private Korean medicine hospital in Seoul, Republic of Korea between November 2013 and March 2015. Seventeen infertile male patients with poor semen quality, with spouses under the age of 35 and without known female infertility factors were treated with Korean herbal medicine and/or acupuncture for at least six weeks. Data were obtained from the patients’ medical records and through telephone interviews, 6 months to 12 months after TKM treatment. Results Of the seventeen patients who continued unprotected intercourse after TKM treatment, twelve had spouses that subsequently conceived spontaneously (70.5%) within a year after TKM. Two patients had babies after intra uterine insemination (IUI) and in vitro fertilization (IVF), respectively. Conclusions TKM may provide an effective option for infertile male patients with poor semen quality. Further prospective studies with larger populations as well as randomised controlled trials are needed to confirm these results.

Academic research paper on topic "The effects of traditional Korean medicine in infertile male patients with poor semen quality: A retrospective study"

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Title: The effects of traditional Korean medicine in infertile male patients with poor semen quality: A retrospective study

Author: Junyoung Jo Ui Min Jerng

PII: DOI:

Reference:

S1876-3820(16)30007-5 http://dx.doi.org/doi:10.1016/j.eujim.2016.01.007 EUJIM 504

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Received date: 9-11-2015

Revised date: 28-1-2016

Accepted date: 28-1-2016

Please cite this article as: Jo Junyoung, Jerng Ui Min.The effects of traditional Korean medicine in infertile male patients with poor semen quality: A retrospective study.European Journal of Integrative Medicine http://dx.doi.org/10.1016Zj.eujim.2016.01.007

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The effects of traditional Korean medicine in infertile male patients with poor semen quality: a retrospective study

Junyoung Jo, K.M.D., Ph.D a and Ui Min Jemg, K.M.D., Ph.D.b

a Department of Korean Obstetrics and Gynecology, Conmaul Hospital, Seoul, Republic of Korea b Clinical Research Division, Korea Institute of Oriental Medicine, Daejon, Republic of Korea

Correspondence: Ui Min Jerng, KMD, PhD

Address: 1672 Yuseongdae-ro,Yuseong-gu, Daejeon, 305-811, Republic of Korea Tel.: +82-2-3475-7000; Fax: +82-2-586-2630; E-mail: breeze@kiom.re.kr

Abstract

Introduction: Approximately fifteen percent of couples have difficulty conceiving, with male infertility being the contributing factor about half of all cases of infertile couples. This retrospective study was designed to evaluate the pregnancy rates of couples after infertile men with poor semen quality receiving Traditional Korean medicine (TKM).

Methods: This study was performed at a private Korean medicine hospital in Seoul, Republic of Korea between November 2013 and March 2015. Seventeen infertile male patients with poor semen quality with spouses under the age of 35 and without known female infertility factors were treated with Korean herbal medicine and/or acupuncture for at least six weeks. Data were obtained from the patients' medical records and through telephone interviews, 6 months to 12 months after TKM treatment.

Results: Of the seventeen patients who continued unprotected intercourse after TKM treatment, twelve had spouses that subsequently conceived spontaneously (70.5%) within a year after TKM. Two patients had babies after intra uterine insemination (IUI) and in vitro fertilization (IVF), respectively. Conclusions: TKM may provide an effective option for infertile male patients with poor semen quality. Further prospective studies with larger populations as well as randomised controlled trials are needed to confirm these results.

Keywords: male infertility, semen quality, pregnancy rate, herbal medicine, acupuncture, Korean

Traditional Medicine

1. Introduction

Approximately fifteen percent of couples have difficulty conceiving, and male infertility contributes to

approximately 30 percent of these cases [1]. Another 20 percent of the infertility cases result from a

combination of male and female factors, but male factors contribute to approximately half of all cases of

infertility [1]. Thirty to forty-five percent of abnormal semen parameters are idiopathic. Although male

infertility due to some other causes is treatable, treatment for idiopathic poor semen quality remains

empirical with little evidence [2-4]. The use of assisted reproduction technology (ART) is usually the

ultimate option for these situations [5]. However, approximately half of the couples undergoing

consultation for male infertility discontinued ART treatment, mainly because of the physical and

emotional pain resulting from the treatment [6]. Additionally, there is some concern that the infants

conceived using ART, including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI),

have an increased risk of birth defects [7].

Acupuncture and herbal medicines have been widely used to treat male infertility [8, 9]. Although the

evidence is insufficient, a recent systematic review suggests that acupuncture might significantly improve

sperm motility and sperm concentration [8]. Herbal medicines have also been shown to significantly

improve both the quality and the quantity of sperm [10-12]. Traditional Korean Medicine (TKM),

including acupuncture, pharmacopuncture, and herbal medicines, has been widely used in patients with

male infertility in Korea [10, 13, 14]. However, to the best of our knowledge, there have been no studies

on evaluating the pregnancy rates of couples after TKM in infertile men with poor semen quality. The

aim of the present study was to investigate the effects of TKM on pregnancy rates of couples with infertile male patients with poor semen quality. 2. Materials and Methods 2.1. Subjects

We performed a retrospective chart review of male patients with poor semen quality who presented at the Department of Gynecology of Korean Medicine, Conmaul Hospital, Seoul, Republic of Korea, from November 2013 to March 2015. Written informed consent was obtained from each patient. The institutional review board of the Korea Institute of Oriental Medicine approved this retrospective observational study (IRB No.I-1510/005-004).

The eligibility criteria for inclusion were men with infertility problems for a period of >1 year and poor semen quality who had been treated by Korean herbal medicine, acupuncture, and/or pharmacopuncture for at least six weeks based on previous studies [15, 16]. Poor semen quality was defined by abnormal semen parameters performed within three months visiting our hospital, which included oligozoospermia (O), asthenozoospermia (A), teratozoospermia (T) or a combination of these three parameters, according to the 2010 WHO guidelines [17]. We included patients with varicocele but excluded patients with severe general diseases, endocrinopathies, a history of cancer chemotherapy, and testosterone or anti-androgen use. Other exclusion criteria were Y chromosome deletions, abnormal karyotypes and azoospermia. There were no restrictions in terms of age or body mass index. Additionally, patients with a spouse under the age of 35 without known female infertility factors were included. The reason for limiting spousal age is

that the fecundability of women drops significantly after 35 years of age [18]. Patients who have a spouse with endometriosis, polycystic ovarian syndrome, and/or diminished ovarian reserves were excluded. 2.2. Therapeutic interventions

The patients received herbal medicine, acupuncture, and/or pharmacopuncture treatments for at least 6 weeks. Acupuncture and pharmacopuncture treatments were provided once per week on the same day. Acupuncture needles (0.25 mm in diameter and 40 mm in length, Dong Bang, Gyeonggi-do, Republic of Korea) were manually applied to a depth of 15-20 mm, depending on the region of the body in which the needles were inserted. The needles were rotated manually to evoke the Deqi sensation. According to a previous study of male subfertility [19], the following acupoints were mainly chosen: SP6 (bilateral), KI3 (bilateral), LR3 (bilateral), ST29 (bilateral), SP36 (bilateral), CV4, and CV6. Electrical stimulation was applied at 10 Hz for 10 minutes at ST29 (bilateral) to increase testicular blood flow [20]. Acupuncture was maintained for 20 min.

Materials for pharmacopuncture were distilled Cervi pantotrichum cornu and mixed herb extracts which were composed of Calculus bovis, Fel ursi, and Moschus (BUM). Distilled Cervi pantotrichum cornu was applied into CV4 and BL23 (bilaterally), and BUM pharmacopuncture was applied into ST30 and BL32 in a volume of 0.1 cc using a sterile insulin syringe (29 gauge and 1/2 inch, Shinchang, Gyeongsangbuk-do, Republic of Korea). All materials were prepared in a laboratory at the Korean Pharmacopuncture Institute (KPI).

Preparation process for Cervi Pantotrichum Cornu pharmacopuncture under the supervision of a doctor of

Korean medicine (KMD) was according to a set of rules as follows: 300 g of powdered Cervi

Pantotrichum Cornu was extracted with 2000 mL of distilled water for 3 h. The extract was filtered

through an 8-^m pore-sized filter paper (Whatman®, United States), and was evaporated at 70°C for 3 h in a rotary evaporator (Eyela®, Japan). The solution was mixed with 100 mL of 95% ethanol after being

cooled down to room temperature. The supernatant of the stirred solution was evaporated and filtered to

remove the second sediment. The second supernatant was mixed with 100 mL of 85% ethanol, evaporated,

and filtered to remove the third sediment. The third supernatant was mixed with 100 mL of 75% ethanol,

evaporated, and filtered to remove the ethanol. The acidity of the remaining solution was regulated with

hydrochloric acid to a pH value between 7 and 8, and refrigerated for 24 h. The solution was sterilized

after removing a small amount of suspended matter through filtering.

Preparation process for BUM pharmacopuncture was as follows: Calculus bovis 85 g, Fel ursi 10 g, and

Moschus 5 g were pulverized in a mortar in a clean room. After they were mixed with 1000 mL of distilled water in an electromagnetic stirrer (TOPS®, Korea) for 3 h, the solution was divided into the first

supernatant and the sediment. The process for stirring the sediment with distilled water and dividing into

a supernatant and sediment were repeated two more times. The first, second, and third supernatant were evaporated at 70°C for 3 h in a rotary evaporator (Eyela®, Japan) all together, after filtering through an 8-^m pore-sized filter paper (Whatman®, United States). The process of mixing with ethanol (90%, 80%,

70% concentration, respectively), filtering through an 8-^m pore-sized filter paper, and evaporating in the

rotary evaporator were repeated. The remaining solution was evaporated with distilled water in the rotary

evaporator to remove the ethanol. This solution was lyophilized in a freeze dryer (IlShinBioBase®, Korea) after filtering through a 0.1-^m pore-sized cellulose nitrate membrane filter (Whatman®, United States).

The herbal prescriptions were customized to individual pattern diagnosis, but mainly for refreshing the

'kidney ' deficiency. Detailed compositions of the Korean herbal prescriptions are shown in Table 1.

Each plant material was mixed and decocted with purified water in Conmaul hospital. Raw materials of

medicinal herbs were identified whether these were obtained from precise medicinal herbs. They were

also tested as heavy metals, toxins, or microbes in the herbs by the licensed herbal distributor before they

were stocked in the hospital. These processes are based on the pharmacopoeia and the regulation on herbs

Codex published in the Korean authority (Ministry of Food and Drug Safety). This herbal remedy was

administered 3 times per day, once after each meal. The patient did not receive any conventional

treatments while receiving the above treatments. The acupuncture, pharmacopuncture, and herbal

medicine treatments were administered by a KMD (Junyoung Jo) with seven years of clinical experience.

When patients visited the clinic for acupuncture or herbal medicine treatment, they were asked about any

adverse events and uncomfortable symptoms which may have been associated with TKM treatment.

2.3. Data collection and analysis

The primary outcome with respect to the efficacy of TKM was spontaneous pregnancy rates, while the

secondary outcome was time to pregnancy (TTP). Information on clinical characteristics, the occurrence

of spontaneous pregnancies, adverse events, and TTP were retrieved from the patients' medical records

and through telephone interviews, 6 months to 12 months after TKM treatment.

Pregnancies after TKM treatment following any other ART were excluded for computing the

spontaneous pregnancy rate. Patients who did not report a pregnancy during follow-up period in the clinic,

did not give to a telephone interview, or did not get a phone call were considered as unable to get

pregnant.

The TTP of each patient was calculated by estimating the fertilization day by considering the

gestational age. Cumulative probability curves of TTP were drawn in a '1 year-survival rate'-like form

using the Kaplan-Meier method. Patients who did not report a pregnancy or did not agree to a telephone

interview were censored.

SPSS 19.0 for Windows (SPSS Inc., Chicago, IL, USA) was used for data management and statistical

analysis. All continuous variables were expressed as the mean ± standard deviation (SD).

3. Results

Twenty-seven men with abnormal semen parameters according to the 2010 WHO guidelines visited

our clinic from November 2013 to March 2015. We screened the medical records of all 27 patients, and

six patients with their spouses were over the age of 35 and four patients with female infertility factors

were excluded. Finally, 17 patients with poor semen quality (A=2, T=2, AT=9, OA=1, OAT=3) were

included. Of these patients, four patients had varicocele, one had a varicocelectomy, one had a history of

cryptorchidism, two had failed IVF and one had a failed intrauterine insemination (IUI). Of seventeen

patients, three patients (OAT=2, AT=1) were lost at follow-up and could not be reached by phone. The

baseline descriptive parameters of all of the patients are shown in Table 2.

The duration of treatment was from 6 weeks to 20 weeks. The mean duration of treatment and TTP was

11.18 and 11.57 weeks, respectively. Twelve patients impregnated their spouse spontaneously within a

year after TKM treatment. The spontaneous pregnancy rate of all included patients was 70.5%. Nine of

the twelve patients had a spouse that gave birth, and the other patients had spouses with pregnancies over

20 weeks of gestational age. Two couples had a baby after TKM treatment following IUI and IVF,

respectively. The cumulative probability curves of TTP were drawn as '1 year-survival rate'-like form

using the Kaplan-Meier method (Figure 1). No adverse events were observed during or following the

treatment.

4. Discussion

Following TKM treatment with herbal remedies, acupuncture and/or pharmacopuncture, twelve of

seventeen patients (70.5%) with poor semen quality reported that they had successfully impregnated their

spouse spontaneously within a year, and nine of the twelve patients had a spouse that subsequently gave

birth to a healthy full-term infant.

Evidence now suggests that 30-80 percent of poor semen quality is believed to be due to the damaging

effects of oxidative stress [21]. Oxidative stress occurs when reactive oxygen species (ROS) overcome

semen's natural antioxidant defense and cause cellular damage to the sperm [21]. ROS are thought to

cause infertility by two principal mechanisms. First, ROS damage the sperm membrane, which in turn

reduces the sperm's motility and ability to fuse with the oocyte. Second, ROS directly damage sperm

DNA, compromising the paternal genomic contribution to the embryo [21]. Antioxidants are known to

scavenge and dispose of ROS, suppress their formation, and act to oppose the actions of ROS [4].

Although there have been four small randomized controlled trials suggesting that antioxidant

supplementation in subfertile males may improve live birth rates for couples, they are insufficient to

confirm the effects of antioxidants [4].

Herbal remedies are known to be effective in improving sperm count, sperm motility, and sperm

morphology [9, 12, 22]. Cornus officinalis Sieb. Et Zucc, Schizandra chinensis Baillon, Rubus coreanus

Miquel, Cuscuta chinensis Lam, and Lycium chinense Mill are herbs that are frequently used in TKM to

treat male infertility. Each of these five herbs exhibits antioxidant properties [22], and the combination of

these herbs has been shown to improve both sperm count and sperm activity [22]. An in vitro study has

shown that oligosaccharides from Morinda officinalis acted as a protective agent for the oxidative

damaged sperm DNA [23]. Extracts of Epimedium koreanum Nakai had shown antioxidant activities,

which included free radical- and ferric-reducing power and lipid peroxidation inhibition [24], and

improved erectile function in aged rats [25]. Cynomorium songaricum Rupr showed significant increases

in epididymal sperm counts and absolute testes in rat testes [26]. All of these effects might be a result of

their antioxidative properties, which help restore the imbalance in excessive levels of ROS.

Various studies have also reported the effects of acupuncture treatment on male infertility. Although

most of the previous studies were based on uncontrolled trials, the evidence suggests that acupuncture

improves sperm count [13, 15, 27], sperm motility [13, 19], and sperm morphology [13, 16, 28]. Although

the mechanism by which acupuncture improves semen quality is unknown, it is possible that acupuncture will enhance blood supply in the testicular arteries, decrease testicular temperature by heat exchange in the pampiniform plexus, and interrupt the peroxidation process [15, 28]. These mechanisms might also potentially reduce ROS [28].

In TKM, male infertility is recognized as resulting mainly from a 'kidney' deficiency. The term 'kidney' in TKM embraces more functions than the concept of kidney in conventional western medicine. It is considered that abundant 'kidney' qi increases sperm motility in TKM [29]. The acupuncture points used in this study are related to the spleen, liver, and kidney meridians. These three meridians are recognized to govern reproductive functions. Further, the herbal medicine used in this study is believed to improve the semen quality by refreshing the 'kidney' yin and yang [10].

Although a direct comparison is not appropriate, the pregnancy rate for couples in this study was higher and the TTP was shorter than that from previously published studies using supplementary antioxidants [30, 31] or from expectations related to male infertility [32, 33]. Antioxidant supplements, including selenium-vitamin E and coenzyme Q10, have been used to treat idiopathic male infertility [30, 31]. Using selenium-vitamin E supplementation for 14 weeks showed a spontaneous pregnancy in only 10.8 percent of the participants [31] When coenzyme Q10 supplementations were used, the total pregnancy rate (spontaneous clinical pregnancy) was 34.1 percent, within a mean of 8.4 months [30]. The spontaneous pregnancy rate in couples in which the man had abnormal sperm was 23 percent within a year [33].

There were some limitations to our study. First, our study included a small number of participants; thus,

more cases are needed to confirm the effectiveness of the TKM therapies. Second, this study had the

inherent limitations of retrospective research. Finally, we were unable to follow up on the post-treatment

sperm parameters. As we do not have our own laboratory, we had to obtain the semen analysis results

from patients who were analyzed at another hospital laboratory that has a quality control program for

semen analysis to ensure accurate results. Given this clinical situation, it was not easy to obtain a second

semen analysis.

Despite these limitations, our results might be noteworthy. The goal of infertility treatment is to give

birth to a healthy infant; therefore, our report evaluated pregnancy rates and not semen quality

improvement, and our results could add to the available evidence that TKM therapies might increase male

fertility [9, 19]. The results of the present study support the clinical potency of treatment of idiopathic

male infertility with herbal remedies and/or acupuncture. Further large-scale randomized controlled trials

with more elaborate designs should be performed to verify the clinical effect of TKM therapies on male

infertility.

5. Conclusions

There were twelve men (70.5%) that were successful in fathering a baby spontaneously within a year

after TKM. TKM may provide an effective option for infertile male patients with poor semen quality

whose spouses are younger than 35 years old. Further prospective studies in a large population are needed

to confirm these results.

Conflict of Interests

The authors declare that there is no conflict of interests. Acknowledgments

This study was supported by the "Construction of the infrastructure for traditional Korean medicine clinical trials and establishment of evidence for the efficacy and safety of herbal medicine" (No.K15121) of the Korea Institute of Oriental Medicine.

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Figure 1. Time to pregnancy among infertile male patients and their spouses.

Black arrow: Each couple had a baby after traditional Korean medicine (TKM) treatment following IUI and IVF at 12 weeks and 24 weeks, respectively; red dot: censored patients; IUI: intrauterine insemination; IVF: in vitro fertilization.

Table 1. Compositions of the Korean herbal medicines

Scientific names of the herbs(part of the herb) Dose (gram/ per day)

Cuscuta chinensis Lamark(Semen); Rehmannia glutinosa Liboschitz ex 10

Steudel(Steamed root); and Cornus officinalis Siebold et Zuccarini(Fruit)

Morinda officinalis How(Root); Epimedium koreanum Aakai(Aboveground part);

Astragalus membranaceus Bunge(Root); Cynomorium songaricum Ruprecht(Fleshy 8

stem); and Lycium chinense Mill(Fruit)

Rubus coreanus Miquel(Fruit); Dioscorea batatas Decne(Rhizoma); Cistanche 6

deserticola Y. C. Ma(Fleshy stem); and Panax ginseng C. A. Meyer(Root)

Poria cocos Wolf(Sclerotium); Paeonia suffruticosa Andrews(Root bark); Alisma

orientale Juzepczuk(Rhizoma); Angelica gigas Nakai(Root); Cnidium officinale 4

Makino(Rhizoma); Schizandra chinensis Baillon(Fruit); and Plantago asiatica

Linné(Semen)

Table 2. Clinical characteristics of the patients.

Variables

Patients (n=17) Mean ± SD

Male age (years) Semen parameters

Volume (mL) Count (million/mL) Motility (%) Morphology (%) Spouse age (years) Duration of infertility (month)

32.88 ± 1.87

2.91 ± 1.12 44.39 ± 33.60 28.49 ± 16.41 2.47 ± 1.12 32.35 ± 2.18 25.64 ± 11.45

SD: standard deviation