The Therapeutic Effects of Bu Shen Yi Jing Pill on Semen Quality in Sub Fertile Males: a Randomized Controlled Trial

Study Overview
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Brief Summary
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This study aims to evaluate the safety and efficacy of Bu Shen Yi Jing (BSYJ) Pill , a type of traditional Chinese medicine, in improving male subfertility and semen parameters.

Detailed Description
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Subfertility is defined as a failure to conceive after 1 year of regular unprotected intercourse. Impaired fertility affects 10 to 15% of couples and male factor is the cause of subfertility in 25 to 40% of couples. With increasing paternal age, semen volume, sperm motility and the percentage of sperm with normal morphology decreases. The majority of men who present with subfertility have either abnormal sperm density, motility or morphology, or a combination of the above, and treatment for this condition is varied and empirical. There is a paucity of studies and randomized controlled trials to guide treatment of male factor subfertility. Various antioxidant formulations and multivitamins have been used empirically but have not been shown consistently to improve sperm counts and viability. When treatment fails, assisted reproduction will be the last resort. All assisted reproduction treatments are associated with medical, financial and emotional burden. Given the lack of proven treatment options in Western Medicine, Traditional Chinese Medicine (TCM) may provide a viable complementary treatment option. One such option is the Bu Shen Yi Jing (BSYJ) pill. A clinical observational study conducted by the team in Singapore Thong Chai Medical on subfertile male patients with poor sperm quality and a body constitution of Kidney Deficiency showed that 2 courses of BSYJ pill over a 6 months' duration resulted in successful conception of 33% of azoospermic male patients (n = 60). In a subgroup of patients where serial sperm analysis was available (n=10), the percentage of sperm with grade A motility increased from a median of 22.6 ± 2.4% pre-treatment to 35.1 ± 3.2% post treatment (p < 0.05); and the hyaluronic binding assay improved from 33.2 ± 2.4% to 72 ± 4.6% (p < 0.05). This suggests that BSYJ pills possibly works on improving the motility of the sperms in patients having the Kidney deficiency body constitution. As such, this study aims to validate these hypotheses and anecdotal evidence by conducting a safety and efficacy study of the BSYJ pill on a prospective cohort.

Official Title
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The Therapeutic Effects of Bu Shen Yi Jing Pill on Semen Quality in Sub Fertile Males: a Randomized Controlled Trial

Conditions
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Male Infertility, Infertility, Traditional Chinese Medication (TCM), Reproductive Issues

Intervention / Treatment
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* Drug: Bu Shen Yi Jing Pill
* Drug: Placebo Drug


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Duration of subfertility (both primary and secondary) ≥ 1 year; Any or combination of the three abnormal semen parameters, defined according to the 2010 WHO criteria, including Oligozoospermia, with sperm concentration less than 15 x 10^6, Teratozoospermia, with normal sperm morphology less than 4%, and Asthenozoospermia, with total sperm motility less than 40%, or progressive sperm motility less than 32%. Diagnosed with TCM syndrome of Kidney Deficiency Based on a prominent TCM diagnosis textbook known as TCM Diagnostics, the main symptoms patients need to fulfil for Kidney Deficiency are either nocturnal polyuria or lower back pain. In addition, patients need to fulfil any 1 of the secondary symptoms, including fatigue; dizziness; tinnitus or deafness; memory loss; excessive urination; low libido; wet dreams; premature ejaculation; presence of feverish palms and soles or night sweats; dry mouth or throat; cold intolerance or preference for warmth; poor sleep quality. Presence of both 1 main symptom and 1 secondary symptom allows for the diagnosis of the Kidney Deficiency syndrome. Patients who meet all three criteria mentioned above will be included in the study. Exclusion Criteria: Azoospermia and severe oligoasthenoteratozoospermia; Aspermia; Varicocele; Recent urogenital infections; Y chromosome deletions; Abnormal karyotypes History of chemotherapy and / or radiotherapy; Patients on fertility supplements or supplements marketed to improve fertility; Patients with uncontrolled diabetes or/and hypertension; with uncontrolled chronic medical conditions Patients currently already on BSYJ pills treatment

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a double-blinded randomised control trial. Participants will be randomised using block randomization by a pre-determined randomisation schedule generated by a biostatistician in block size of 4. Enrolment and assignment of intervention will be carried out by an investigator. The investigators will perform block randomization of the subjects in blocks of 4 in the ratio of 1:1 such that 2 will be assigned to treatment and 2 will be assigned to placebo.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Patients in this arm will be given a placebo pill that resembles the actual Bu Shen Yi Jing Pill. | Drug: Placebo Drug<br>* Placebo contains the ingredients: grounded black rice and permitted colouring. The ingredients are encapsulated within a gelatine capsule. Dosage of the study drug is as follows: 3 pills each time, for 3 times a day, taken for 6 days every week for 1 year<br>* Other names: Control drug;|
| Active Comparator: Bu Shen Yi Jing Pill<br>Patients in this arm will be given the BSYJ Pill. | Drug: Bu Shen Yi Jing Pill<br>* Bu Shen Yi Jing Pill contained Radix Pseudostellaria, Fructus Lycii, Radix Et Rhizoma Salviae, Rhizoma Dioscorea, Semen Plantaginis, Semen Cuscuta, Patriniae Herba, Herba Epimedii, Radix Ophiopogonis, Fructus Rubi, Fructus Corni, Bupleurum roots, Fructus Schisandrae Chinensis, Radix Et Rhizoma Glycyrrhizae. Dosage of the study drug is as follows: 3 pills each time, for 3 times a day, taken for 6 days every week for 1 year<br>* Other names: BSYJ Pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the change in sperm volume from baseline after treatment with BSYJ pill | From sperm samples analyses | 1 year | 
| To determine the change in sperm morphology from baseline after treatment with BSYJ pill | From sperm samples analyses | 1 year | 
| To determine the change in sperm motility from the baseline after treatment with BSYJ pill | From sperm samples analyses | 1 year | 
| To determine the change in sperm concentration from the baseline after treatment with BSYJ pill | From sperm samples analyses | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the clinical pregnancy rate and successful delivery rate after BSYJ pill | Defined by the number of pregnancies and subsequent actual births after commencement of BSYJ pill | 2 year | 
| To study the safety and determine the changes in blood profile after treatment with BSYJ pill | Defined by changes in participant's full blood count, renal panel, liver function test and hormone profile. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infertility, Sperm, Traditional Medicine