Can Acupuncture Affect Overall Sperm Quality?

Original title: Can Acupuncture Affect the Overall Sperm Quality in Infertile Males?

Abstract

Primary infertility affects 8-15% of couples worldwide. Although historically the woman was thought to be the cause of infertility, it is now known that men are equally as likely to contribute to infertility as women. Further, there is evidence that male infertility has been on the rise.

Currently, western treatments for male infertility are limited. However, previous studies have shown that traditional Chinese medicine, with the use of acupuncture and moxibustion can improve semen quality in infertile males. Therefore, it would be beneficial to evaluate the efficacy of using acupuncture treatment as a potential therapy to improve sperm quality and quantity in men thus reducing overall infertility rates.

The aim of this study is to consolidate acupuncture and traditional Chinese medicine treatment as a possible option for infertility solutions in males through a high quality Randomized Controlled Trial.

Introduction

Primary infertility, defined as an unachieved pregnancy after 12 months of unprotected sexual intercourse, affects 8-15% of couples worldwide.¹ Infertility can have devastating effects on the mental health and overall well-being of infertile couples,² and thus has health effects extending far beyond the ability to conceive. Historically, when a couple could not conceive it was thought to be the fault of an infertile woman. However, men and women are just as likely to contribute to the couple’s infertility, and there is evidence that male infertility may be on the rise.³

Male-type infertility deals with an alteration in sperm concentration and/or motility and/or morphology.⁴ To qualify as infertility this change in sperm production must be present in at least one of two sperm samples that will be collected at one and four weeks apart.⁴ In 2010, the World Health Organization (WHO) revised the reference ranges of what constitutes normal sperm values; men with sperm/semen parameters such as total sperm number or sperm concentration below the normal range are considered to have male factor infertility.⁴ 

Infertility in males is estimated to be present at a rate of 7%,⁵ and is a reported factor in 40-50% of couples’ infertility cases.¹ To highlight the prevalence, one study reported that approximately 30 million males worldwide are infertile.⁶ Male infertility is influenced by both the health of the sperm and the health of the male that produces the sperm.⁷ Semen irregularities include decreased sperm count, low concentration of sperm, reduced vitality, motility problems, and DNA fragmentation disorder.⁵ Factors specific to men’s health that affect sperm quality are urogenital infections, obstructions in the reproductive tract, environmental toxins burdening the male’s vitality, and physiological irregularities.⁸

A systematic review and meta-analysis evaluating the trends in sperm count over time showed a significant overall decline in both sperm concentration (SC) and total sperm count (TSC).⁹ In fact, this study reported a 52.4% decline in sperm concentration and a 59.3% decline in total sperm count from 1973 to 2011 in North America, Europe, Australia and New Zealand.⁹ A current study sampling sperm from North America, Europe, and Africa recorded a substantial 57% reduction in average sperm concentration over the past 35 years.¹⁰

Currently, the western treatment for male infertility is limited.¹¹ A study published in 2003 that evaluated the effects of acupuncture and moxa on semen quality in patients with semen abnormalities found that these traditional Chinese medicine (TCM) techniques significantly increased the percentage of normal-form sperm in infertile patients with oligoasthenoteratozoospermia without apparent cause.¹² In an earlier study from 1997 the effect of acupuncture on sperm parameters in men with low sperm counts was studied. Semen samples were analyzed prior to and 1 month after a 5-week treatment regime consisting of 2 treatments per week for 5 weeks. In the acupuncture treated group, the fertility index increased significantly (p < or = .05) and improvement was demonstrated in total functional sperm fraction, percentage of viability, total motile spermatozoa per ejaculate, and integrity of the axonema (p < or = .05). Thus, the study concluded that reduced sperm activity may benefit from acupuncture treatment.¹³ Therefore, it would be useful to further evaluate the use of acupuncture to improve sperm quality and quantity in men and potentially improve overall fertility rates.

Type of Study

Prospective Randomized Control Trial (RCT).

Groups

1. Experimental Group: Traditional acupuncture needle treatment.
2. Control Group: No treatment.

Time Parameters

16 weeks: Treatment 1x/week; Follow up every 3 weeks (weeks 3, 6, 9, 12 & 15)

• • Admitted to study– Week “0”

Patient has signed consent and enrolled (assigned a subject identification number).

• • Treatments in Progress – Weeks 1-12;

– The subject is currently receiving acupuncture protocol specific treatments.

– Weekly acupuncture treatments and lab evaluation every 3 weeks.

• • Treatments cease – The end of study treatment for any reason (please note that off treatment date may not be the same date as last treatment). Full course of treatment is 12 weeks.
  • Follow-up – Week 15

– All post-treatment visit data that is collected per protocol (including adverse effects, SOC assessments, efficacy, etc.).

• • Off Study – Week 16

– The subject has fully completed treatment and follow up.

STUDY PROTOCOL

Acupuncture Treatment Protocol (according to STRICTA guidelines)

1. Acupuncture rationale

1a) Style of acupuncture: traditional Chinese medicine

1b) Reasoning: TCM will be used based on results from a past study¹² and because practitioners with expertise in TCM are accessible. Using a single style of acupuncture increases the homogeneity of treatments among all study participants. Point selection is based on TCM acupuncture techniques, using acupoints previously reported as being effective in oligospermia.¹²

1c) Extent to which treatment was varied: The acupuncture protocol consists of 8 standardized points indicated for infertility, augmenting the qi and supplementing kidney yang, and is based on the work of Gurfinkel et al., 2003. In order to limit potential confounding variables, moxibustion, cupping, herbs, and electroacupuncture will not be permitted. In each individual treatment session, 8 acupuncture points will be utilized. The points used will be: SP 4, SP 6, ST 30, ST 36, LI 4, LIV 3, KI 3, and PC 6.

2. Details of needling

2a) Number of needle insertions per subject per session: 16

See Table 1 for names of acupoints, insertion details and the TCM Rationale.

*All points needled bilaterally.

Table 1 Acupuncture points selected for use in this study.¹²

2b) Response sought: To obtain “Deqi” needling sensation (“Deqi” translates from pinyin to English as “arrival of qi,” and refers to the sensations felt at the location of needling point characterized by the sensory perceptions experienced¹⁴ at each point.

2c) Needle stimulation: Manual needle stimulation and tonification on each acupuncture point. Manual stimulation refers to needle manipulation techniques including rotation, lifting, and thrusting the needle at insertion.¹⁵ Tonification is often referred to as “stimulation” or “activation” and describes the act of generating or bringing qi to a deficient area or meridian and can be done with needle stimulation, herbs, acupressure, and Moxa.¹⁶ Manual stimulation will be rotation of needles clockwise for 5 seconds at insertion and again prior to removal.

2d) Needle retention time: Each session consists of a 25-minute treatment period with acupuncture needles retained for 25 minutes..

2e) Needle type (size & brand): 0.25mm x 30mm – DBC Brand; Stainless steel disposable needles.

3. Treatment regimen

3a) Number of treatment sessions: One acupuncture needling treatment per week utilizing the above 8-point protocol for 12 weeks.

4. Other components of treatment

4a) Details of other interventions administered to the acupuncture group: To isolate the effects of acupuncture, no moxibustion, cupping, herbs, exercises, or lifestyle advice will be given.

4b) Setting and context of treatment: Treatment exam rooms will be single table rooms with one participant per room. Needles will be retained with the door shut and lights dimmed. Practitioners will be instructed to identify the predetermined standardized points and follow the treatment protocol. Practitioners may welcome questions from patients and adjust or remove needles if the participant reports discomfort.

5. Practitioner background

4 US-trained and licensed acupuncturists with a median of 6 years of experience (range 5–20 years) will provide study treatments in the clinic setting. One lead investigator will train the acupuncturists in the study procedures, protocol, and monitor compliance with the protocol throughout the study. Acupuncturists must be DACM/DAOM graduates, CALE/NAACOM licensed, with a minimum 5+ years of experience.

6. Control or comparator interventions

Because “sham” and placebo acupuncture have been shown to elicit measurable responses in past studies,^17,18 the study design uses a ‘no treatment’ group as the control.

STUDY SAMPLE

Target Population

The target population will be comprised of males with insufficient sperm quality for fertilization and inability to achieve conception. Successful conception is defined as the ability to achieve clinical pregnancies or live births.

Study Sample

This study sample will consist of 100+ males with sperm abnormalities as defined below. Race will be identified by each study applicant.

Inclusion Criteria

This study will include men aged 21-50 years old, living within a 50 mile radius of the study site. Each man will be selected based on one or more of the following preexisting infertility factors: low sperm quality factors including oligozoospermia or oligospermia, motility problems, abnormal spermatozoa, low sperm count with combined motility and abnormalities. Definition of each infertility factor is as follows:

• Oligozoospermia or oligospermia: sperm concentration is low, fewer than 15 million per ml.
• Motility problems: asthenozoospermia or asthenospermia — less than 40% of the sperm are moving, and less than 32% are swimming progressively.
• Abnormal spermatozoa: teratozoospermia – less than 4% of the sperm are normally shaped.
• Low sperm count combined with motility and abnormalities: Oligoasthenoteratozoospermia (sometimes referred to as OATS) – fewer than 15 million sperm per ml where less than 4% are normally shaped.
• Necrospermia:  all sperm are dead.
• Poor viability: less than 58% are alive.¹⁹

Exclusion Criteria

The following pre-existing conditions (or development thereof within the study period), interventions, lifestyle, and social factors will disqualify prospective subjects from inclusion in this study:

• • Conditions: congenital or physiological deformities and abnormalities such as history of cryptorchidism, seminal vesiculitis, testicular cancer, BPH, prostate cancer, acute or chronic prostatitis, current sexually transmitted infection (STI), active genitourinary infections (cystitis, urethritis, pyelonephritis, etc.), impotence/Erectile Dysfunction, autoimmune disorders, diabetes, obesity, sickle cell disease, chronic kidney disease hemochromatosis, mumps, smallpox, orchitis, urethritis, Obstruction or absence of vas deferens, varicocele, radical pelvic surgery, anejaculation, spinal cord injury, Y chromosome microdeletions (YCMD), karyotypic abnormalities.
  • Interventions: Testosterone supplements, anabolic steroids, corticosteroids, hormone replacement therapy, chemotherapy, radiation therapy, FDA-approved drugs having the potential to impair human spermatogenesis, vasectomy.
  • Lifestyle and Social Factors: Alcohol consumption (no more than 2 alcoholic drinks in 1 day and no more than 4 alcoholic drinks in 1 week), smoking cigarettes, illicit or recreational drug use, and any history of diagnosed sleep disorder.

Outcome Measures

Primary Outcome Measure: Sperm Concentration and Total Sperm Count

Sperm abnormalities are a critical factor in male infertility. Male infertility is evaluated by physical examination and semen analysis. As stated in a published clinical assessment of male fertility, “…standardized semen analyses depend on the descriptive analysis of sperm motility, morphology, and concentration, with a threshold level that must be surpassed to be considered a fertile spermatozoon”.²⁰

The primary biometric outcomes that will be evaluated in this study are sperm concentration (SC), total sperm count (TSC) and sperm motility (SM). One method of calculating the sperm count is to use the following equation: sperm concentration × 2ml/6cm. Normal volume is equal to 1.5 milliliters or greater.⁵ There are several potential causes for error in the semen analysis process; semen analysis is imperfect and errors in specimen collection can arise from abstinence, anxiety, failure to collect the entire specimen, container toxicity and delay in analysis, all of which can affect the sperm count and concentration.²¹

Semen analysis looks at the concentration, morphology, motility, total number, vitality and volume of sperm.⁴ Normal total sperm count is 39 million sperm per ejaculate.⁵ Normal sperm concentration is more than 15 million spermatozoa per milliliter.⁵ A concentration of less than 15 million per milliliter is considered oligozoospermia and is characterized as a “low sperm count”.⁴

To achieve fertilization, sperm must pass through the cervical mucus. This depends on motility which is defined as the percentage of sperm moving in a forward progression of at least 25 μm/s. A normal semen analysis contains at least 50% progressively motile spermatozoa. Persistent poor sperm motility is a predictor of failure in fertilization.⁴

In this proposed study the semen samples of all participants will be evaluated by complete semen analysis (CSA). The CSA will provide the desired values of semen concentration (SC), total sperm count (TSC) and sperm motility (SM). The samples will be collected and processed at a commercial sperm bank laboratory. A qualified andrology lab technician will calculate the semen values according to the World Health Organization (WHO) criteria to ensure accurate results and a consistently high standard of evaluation across all participants in the study.

Secondary Outcome Measures:

a. Patient Vital Signs

Standard patient vital signs are utilized as a secondary outcome measure in this study. According to the WHO’s 5th edition criteria for sub-fertile semen values , impairment of semen volume, sperm concentration, and total motile count is more common in hypertensive men.²² Therefore, improvement of blood pressure and other vital signs in the course of this study may be associated with an overall improvement in sperm production. For example, during the course of the study, blood pressure readings that normalize to within the acceptable reference range may suggest a positive outcome based upon the experimental treatment. Improvement in vital signs can thus provide insight into how acupuncture affects subjects’ biomarkers of sperm concentration and motility.

Vital signs will consist of blood pressure, heart rate, respiration rate, and temperature. The vital signs will be measured at the start of each visit prior to receiving the treatment.

The American Heart Association defines the normal sinus Heart Rate (HR) as between 60 and 100 bpm.²³ The standard respiration rate is 12-20 breaths per minute.²⁴ These values will be measured manually and via a pulse oximeter.

The standard human body temperature is 98.6°F (37°C). Temperatures of each study participant will be measured via infrared temporal artery thermometers.

In addition to patient vital signs, Body Mass Index (BMI) will be measured for each subject. BMI is measured by weighing and measuring the vertical height of subjects and calculated as kg/m2 where kg is a person’s weight in kilograms and m2 is their height in meters squared.²⁵ BMI classification is defined as less than 18.5, indicating an individual is underweight, 18.5-25 indicating an individual is normal weight, 25-30 indicating an individual is overweight, and a BMI greater than 30 is defined as obese.²⁵

Blood pressure (BP) is taken via a digital sphygmomanometer.²³ BP standard levels vary with age, however, a systolic level of 110-129 and a diastolic of 70-89 may be used as universal standards precluding hypertension for our study population. Hypertensive emergency (defined as blood pressure greater than 180/120 mm Hg in the presence of impending or progressive organ damage) will prompt immediate referral for urgent/emergent care and dismissal from participation in the current study.

b. Quality of Life, Stress, Mental Health

As previously stated, infertility can have negative effects on the quality of life (QoL) and well-being of the affected individuals and couples. To assess the infertility-related QoL, a variety of patient-reported outcome (PRO) measures have been proposed and utilized. However, there has been some concern regarding the validity of these psychometric evaluations. One of the measures suggested to be most effective is the “Fertility Quality of Life” or (FertQoL).²⁶

The FertQoL was developed in 2011 and is used internationally to measure QoL in men and women experiencing fertility problems and includes an additional module to assess the patient or couples’ satisfactions with treatment.²⁶ Additionally, this is the most widely used measure to assess QoL in interventional infertility studies.²⁶

In the evaluation of the participants in this male infertility study, the FertiQoL will be utilized as the primary tool to assess the QoL outcome measures. This assessment is composed of 36 factors (or assessment items) that are rated by the patients on a scale of 0-4, with higher scores indicating a better QoL. These factors include emotional, mind-body (i.e., cognitive and physical), relational, and social aspects of the patient’s life.  Additionally, it evaluates the patient’s perception of the treatment environment, treatment tolerability, and their satisfaction with their QoL and general physical health.²⁷

Data Analysis

At the end of every follow up period (weeks 3, 6, 9, 12, & 15) sperm concentration, sperm count, and sperm motility will be collected and used as primary outcomes. Once the trial is complete, the data will be analyzed with a logistic regression analysis using two groups: the sperm improvement group, and no improvement in sperm values group. These groups will serve as the dependent variables in the logistic regression analysis.

The secondary outcome measures of respiration rate, blood pressure, heart rate, and temperature will be used as independent variables with discrete data points. Furthermore, the BMI measurement will be used as a covariate to determine potential effects on variables and the primary outcome.

These secondary outcome measures will be used to determine whether a statistical significance exists between the two groups: those who met the threshold (15 million sperm per ml or more), and those who did not (under 15 million sperm per ml). One secondary outcome measure will be added to the study at a time and reviewed for association on the primary outcome measure.

BMI is unlikely to undergo significant change over a 16-week acupuncture treatment protocol and will be used as covariate in our logistic regression analysis in order to determine whether or not certain conditions such as the underweight or overweight, affect outcomes.

The dependent variable is the sperm count/concentration and motility, and a confidence interval of 95% will be used with a p of <0.05.

Conclusion

There are currently no plans to execute this research yet its completion would further consolidate acupuncture and traditional Chinese Medicine treatments as solid options for couples unable to conceive and demonstrate the importance of males being a more integral part of the infertility treatment process. Current research on this topic depicts promising but inconclusive results. High quality Randomized Controlled Trials (RTC) are necessary to further evaluate and conclude the benefits of acupuncture and traditional Chinese Medicine in assisting with fertility. The importance of efficient, low-cost fertility treatments goes beyond its impact on the healthcare field. The outcome can have repercussions on a single couple being able to achieve pregnancy all the way to the entire future of humanity.

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