Low semen quality and adverse histological changes in testes of adult male mice treated with bee venom (Apis mellifera).

Background: Male infertility has been on the rise since the past seven decades. Recently, in Libya, bee venom therapy (BVT) has become a popular method among alternative healthcare practitioners for treating male infertility. However, a literature search did not find any published studies that investigated the use of BVT for infertility treatment. Aim: To investigate the effect of bee venom on the male reproductive status through measurements of semen quality parameters and testicular histological changes in adult male mice. Methods: A total of 48 male mice were randomly divided into three experimental groups (which were subdivided into two subgroups with eight mice each) as follows: control, bee venom sting (BVS), and bee venom injection (BVI). The normal control subgroup mice were not subjected to any treatment, while the vehicle control subgroup mice were injected (i.p.) with 200 µl of 0.9% saline solution. In the BVS-treated subgroups, each mouse was stung by one live bee for five times (BVS-5) or seven times (BVS-7) every third day for 2 or 3 weeks. While each mouse in the BVI-treated subgroups received 23 µg/kg in a dose volume of 200 µl BVIs (i.p.) for five times (BVI-5) or seven times (BVI-7) every third day for 15 or 21 days. Results: The findings of this study showed that repeated bee venom treatment by sting or injection to adult male mice resulted in a significant decline in testosterone levels, sperm count, sperm motility, and a very significant increase in the percentage of abnormal sperm morphology; also, there were harmful testicular histological changes in the structural organization of seminiferous tubules and degenerative changes in the germinal epithelium compared to control group. Conclusion: The results of this study provide evidence for the low semen quality and adverse testicular histological changes in male mice treated with bee venom. Hence, there is a desperate need for educating alternative healthcare practitioners and infertile couples about the harmful effects of BVT on reproductive status.

Comparison of the Effect of Ceratonia siliqua L. (Carob) Syrup and Vitamin E on Sperm Parameters, Oxidative Stress Index, and Sex Hormones in Infertile Men: a Randomized Controlled Trial.

Herbal products with an antioxidant capacity can boost male reproductive functions. The empiric use of Ceratonia siliqua (carob) for its antioxidant properties is common among infertile men in Iran and Turkey. The objective of this study is to investigate the effects of C. siliqua (carob) on semen parameters, oxidative stress markers, and pregnancy rate in a parallel randomized, controlled study. A total of 60 infertile men with oligozoospermia, asthenospermia, and teratospermia were recruited from April 2018 to March 2019. Participants were divided randomly into the following two groups: carob syrup twice a day or vitamin E 100 mg twice a day for 3 months. Semen analysis was performed and hormonal levels and stress oxidative markers were measured in each treatment arm after 3 months. The quality of semen parameters improved in the carob group compared with Vit E semen count (p = 0.04 Cohen's d = .51), morphology (p = 0.001 Cohen's d = .93) and motility parameters (p = 0.002 Cohen's d = .90) were significantly higher in the carob group. No significant difference can be detected in post-treatment hormonal parameters and oxidative markers between groups, except for total antioxidant capacity(TAC) which was higher after post-treatment in carob group. A significantly higher pregnancy rate was found among the carob group. The administration of carob may be an effective agent for the improvement of semen parameters, probably related both to its involvement in the changing of testosterone level and to its antioxidant properties. Nevertheless, additional studies to evaluate the optimal dose and duration of treatment are needed. The trial has been registered in the Iranian Registry of Clinical Trials (Registration number: IRCT20171209037794N1.

A double-blinded, randomized placebo-controlled trial on the effect of traditional Chinese medicine formula Wuzi Yanzong pill on improving semen qualities in men with suboptimal parameters.

BACKGROUND: In Hong Kong, one of six couples is affected by subfertility problems. Male infertility contributes to half of the infertility cases. In male infertility, there is no effective treatment for patients with idiopathic infertility/poor semen parameters. Recent meta-analysis results suggest that a traditional Chinese medicine (TCM) formula - Wuzi Yanzong pill - showed a curative effect on male fertility. However, the heterogeneity of the studies could not draw a definitive conclusion on the therapeutic effect of this formula. The aim of this study is to conduct a well-designed randomized controlled trial to investigate the effect of TCM formula Wuzi Yanzong pill on improving semen qualities in men with suboptimal parameters. METHODS: This study is a double-blinded, randomized placebo-controlled trial conducted in a public hospital in Hong Kong. Participants will be randomized, using computer-generated random numbers, with a 1:1 ratio to either the Wuzi Yanzong pill formula group or the placebo group. Both groups will be administered the drugs for 12 weeks. Participants will have a total of four visits for their semen and blood assessments for a 6-month period, and we will follow up for another 6 months to record their conception outcome. The primary outcome is to compare the total motile sperm count, natural conception rate, and pregnancy outcome to those under placebo treatment. Secondary objectives are sperm functions and assisted reproductive technology outcome. DISCUSSION: To date, there are no studies using the disclosed Wuzi Yanzong formula or double-blinded, randomized trials. The Wuzi Yanzong TCM formula may provide a good clinical solution for subfertile males for which contemporary western medicine has no cure. Therefore, a well-designed randomized trial for evaluating the effect of Wuzi Yanzong TCM formula is urgently needed. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR-INR-17010790 . Registered on 27 February 2017. Centre for Clinical Research and Biostatistics - Clinical Trials Registry, CUHK_CCRB00548 . Registered on 27 February 2017.

The cardiometabolic effect of current management of polycystic ovary syndrome: strategies of prevention and treatment.

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder amongst women of reproductive age, which is characterized by reproductive and cardiometabolic disturbances with long-term health repercussions. Insulin resistance (IR), impaired glucose tolerance, type 2 diabetes mellitus (DM2), obesity and dyslipidemia occur more in women with PCOS than in age-comparable women without PCOS. Long term data regarding risks or benefits of medical intervention for metabolic dysfunction of PCOS are lacking. Therapies, such as oral contraceptives (OCPs) and anti-androgenic medications used to manage the reproductive manifestations of PCOS, may themselves be the cause of cardiometabolic perturbations. Hence, strategies regarding the management of reproductive issues in PCOS encompass a patient-specific tailored approach. Factors that influence the cardiometabolic side effects arising during treatment of the reproductive manifestations of PCOS (hirsutism/anovulation) are also discussed in this paper in order to build future strategies to minimize the overall cardiometabolic risk.

Challenges of Obtaining Evidence-Based Information Regarding Medications and Male Fertility.

In the clinic, the existing literature is insufficient to counsel our infertile men on medication use. Most studies have flaws that limit their application to evidence-based practice. In this chapter, we discuss the limitations of the current literature and the challenges to designing more useful studies. Among the most important weaknesses of existing studies is lack of power; that is, too few men are included to draw conclusions about the existence and size of medication effects. Adequate power is particularly important when confirming an absence of medication effect. Bias is also a problem in most studies. Early studies were rarely randomized, placebo-controlled, or blinded; a common example is patients receiving different medication regimes based on the severity of their symptoms-making it impossible to attribute differences between treated and untreated men to the medications. Additional bias is introduced by failing to include other factors that influence the outcome in the experimental design. A uniform population amenable to randomization and placebo-control are experimental species, and useful information has been gained from these models. However, application to humans is limited by differences from other species in route of drug administration, absorption of the drug, concentration in the male genital tract tissues, and genital tract physiology. To a lesser degree, there is variation among individual men in their response to drugs. In addition, drugs in the same class may have different effects, limiting the applicability of data across drugs of a single class. Complicating matters further, a toxic medication may seem to improve fertility endpoints by improving a disease condition that diminishes fertility. Finally, drug interactions have not been studied, and actual fertility data (pregnancy/fecundity) in humans are rare. A healthy dose of skepticism is warranted when evaluating studies of medications and male reproductive health.

Short-term buserelin administration induces apoptosis and morphological changes in adult rat testes.

PURPOSE: To investigate the effect of buserelin on gonadal structure and function in adult male rats. METHODS: Twenty-four adult Wistar male rats were divided into three groups: two treated groups and controls. The first and second treated groups received 300 (low dose) and 500 (high dose) µg/kg buserelin, respectively, and the control group received normal saline. All groups were treated subcutaneously for five days. RESULTS: The seminiferous tubular epithelial thickness was significant decreased in the treated groups compared with those in the control. There was a significant increase in apoptotic cell death in high dose treated group compared with low dose treated and control groups. No significant difference in serum testosterone level was observed after one month in the three groups. CONCLUSION: Buserelin induces apoptotic cell death and decreased diameter and epithelium thickness of seminiferous tubules in the adult rat testes.

Short-term buserelin administration induces apoptosis and morphological changes in adult rat testes

Abstract Purpose: To investigate the effect of buserelin on gonadal structure and function in adult male rats. Methods: Twenty-four adult Wistar male rats were divided into three groups: two treated groups and controls. The first and second treated groups received 300 (low dose) and 500 (high dose) µg/kg buserelin, respectively, and the control group received normal saline. All groups were treated subcutaneously for five days. Results: The seminiferous tubular epithelial thickness was significant decreased in the treated groups compared with those in the control. There was a significant increase in apoptotic cell death in high dose treated group compared with low dose treated and control groups. No significant difference in serum testosterone level was observed after one month in the three groups. Conclusion: Buserelin induces apoptotic cell death and decreased diameter and epithelium thickness of seminiferous tubules in the adult rat testes.

Safety assessment of powdered Cistanche deserticola Y. C. Ma by a 90-day feeding test in Sprague-Dawley rats.

Cistanche deserticola (C. deserticola), a holoparasitic plant widely distributed in arid or semi-arid areas in Eurasia and North Africa, has been used as an important tonic in traditional Eastern medicine for centuries. However, little information on the systemic toxicity and safety evaluation of it is available. The purpose of this study was to investigate the potential toxicity of powdered C. deserticola as a novel food ingredient by use of a subchronic toxicity study in Sprague-Dawley (SD) rats. A total of 80 male and female rats were fed with diets containing 8, 4, 2 and 0% (control) powdered C. deserticola for 90 days. A toxicological assessment was performed including mortality, body and organ weight, food consumption, blood biochemistry, hematology, gross necropsy and histopathological examinations. There were no signs of toxicity and treatment-related changes in rats treated with powdered C. deserticola. The no-observed-adverse-effect level (NOAEL) of powdered C. deserticola was 7.8 g kg-1 body weight for males and 8.0 g kg-1 body weight for females of rats under the experimental conditions of this study.

An evidence-based perspective to the medical treatment of male infertility: a short review.

INTRODUCTION: Evidence-based medicine (EBM) is the integration of best research evidence with clinical expertise and patient preferences and values. AIM: This narrative review aims to assist the physicians to make informed decisions based on the best available evidence in the area of male infertility and the patients' own preferences and values. METHODS: In this review we present the current state of knowledge and uncertainties about the medical management of male infertility. We describe the best available evidence from systematic reviews, randomized controlled studies and observational studies where appropriate. RESULTS: Data from the literature suggest that gonadotropin treatment of male infertility can lead to a significant increase in pregnancy rates, however larger studies are needed to confirm such findings. Studies including combinations of antiestrogens, antioxidants and androgens are promising but need confirmation with further research. CONCLUSIONS: Most current combination therapies consist of orphan medications without industry support. Andrology research centers and other dedicated departments and units need to conduct randomized controlled trials of sufficient duration, sample number and robust design for groups most likely to benefit from antiestrogens, L-carnitine, antioxidants, and combination therapy. The ease of administration, low cost and mild side effects of antiestrogens justify their utility despite insufficient evidence of effect as monotherapies. Randomized controlled trials assessing other forms of medical therapy and combination therapy are available but are still in the preliminary stages.

Azoospermia after treatment with clomiphene citrate in patients with oligospermia.

OBJECTIVE: To describe three cases of azoospermia in patients with oligospermia after clomiphene citrate (CC) intake. DESIGN: Case report. SETTING(S): Academic medical center. PATIENT(S): Three patients with oligospermia. INTERVENTION(S): Three oligospermic men used CC, resulting in azoospermia. MAIN OUTCOME MEASURE(S): Semen analysis after CC use and after discontinuation of CC. RESULT(S): Three patients were sent to our clinic for investigation of their azoospermia after use of CC. They had severe oligozoospermia (sperm concentrations of 3.4, 2.8, and 4.1 x 10(6)/mL, respectively) before treatment with CC. These patients were re-evaluated with two new semen analyses, showing azoospermia. After 3 months without use of the drug, the mean sperm concentration was 2.5 +/- 1.1 x 10(6)/mL. CONCLUSION(S): The benefits of empiric treatment with CC must be balanced with the possible undesirable effects, such as azoospermia.

Liver injury induced by a Japanese herbal medicine, sairei-to (TJ-114, Bupleurum and Hoelen Combination, Chai-Ling-Tang) R1.

The case is reported of a man who showed acute hepatitis with jaundice after he was given a Japanese herbal medicine, sairei-to (TJ-114, Bupleurum and Hoelen Combination, Chai-Ling-Tang). Unusually, the component thought to be responsible for the observed drug-induced liver injury was able to be identified. Lymphocyte migration inhibition testing indicated that the tuber of the perennial herbage Pinellia ternate was the causative agent.

[Mode of action of sildenafil].

Sildenafil is the first oral therapeutic agent for erectile dysfunction. Sildenafil is a selective inhibitor of cGMP-specific phosphodiesterase (PDE-5). Penile erection involves relaxation of the corpus cavernosum, an event mediated by NO and cGMP. The biological actions of cGMP are terminated by phosphodiesterase enzymes and PDE-5 is the major cGMP metabolising enzyme in this tissue. Sildenafil is relatively safe compared to erection injectables because it does not relax on isolated human corpus cavernosum, and does not cause priapism. Due to the tendency of abuse of sildenafil, its adverse cardiovascular associations with myocardial infaraction, ventricular arrhythmia and hypertension need to be alerted.

Nonbacterial pyospermia: a consequence of clomiphene citrate therapy.

OBJECTIVE: Since the development of nonbacterial pyospermia in previously nonpyospermic men treated with clomiphene citrate (CC) has been observed, and nonbacterial prostatitis has been after antiestrogen treatment in an animal model, we sought characterize the occurrence of nonbacterial pyospermia in men treated with CC. PATIENTS AND METHODS: Forty-two nonpyospermic men with low serum testosterone levels treated with 25 mg CC/day were retrospectively compared to 27 untreated nonpyospermic men referred for infertility evaluation. RESULTS: Spontaneous nonbacterial pyospermia developed in CC-treated men [14.3%] at rate nearly twice that observed in controls [7.4%]. Serum testosterone increased in CC-treated men, both pyospermic and nonpyospermic. However, only CC-treated, nonpyospermic men demonstrated improvement in semen characteristics. CC-treated men who developed pyospermia were older than nonpyospermic men [pyospermic, 41.7 +/- 8.1 years; nonpyospermic, 35.6 +/- 4.9 years-P < .01). Men over 35 years of age were over six times as likely to develop pyospermia as men under 35 years of age (P < .05). Eight nonpyospermic, CC-treated men (8/36, 22.2%) have contributed to pregnancies leading to live births, whereas no pyospermic man has done so. CONCLUSION: These findings support an association between a nonbacterial inflammatory response of the human male reproductive tract and CC treatment. This pyospermia may occur without significant deterioration of semen characteristics and with an appropriate response to treatment in terms of serum testosterone level. Men over the age of 35 are statistically more likely to develop pyospermia with this therapy. Our results suggest that clomiphene citrate-associated pyospermia has a negative effect on male fertility.

Carnitine supplementation in human idiopathic asthenospermia: clinical results.

On the basis of reported experimental and clinical studies we investigated the effectiveness of L-carnitine administration in a group of patients with idiopathic asthenospermia. A favourable effect of the compound on sperm motility and rapid linear progression has been shown in 37 out of 47 patients treated. In addition, the total number of sperms increased. L-carnitine was supplemented orally by a daily dosage of 3 g for three months.