Therapeutic potential of rutin in male infertility: A mini review / 中西医结合学报

Male infertility has become a problem worldwide, and recent research has emphasized the development of more effective therapy options. Among natural compounds, rutin has been widely studied for its potential to treat dysfunction related to male infertility, including a reduction in sperm quality, spermatogenesis disruption and structural disruption in the testis. A thorough review of scientific literature published in several databases, including Google Scholar, PubMed/MEDLINE and Scopus, was used to synthesize the present state of research on the role of rutin in male reproductive health. Rutin has been shown to possess antiapoptotic, antioxidant and anti-inflammatory activities, among others, which are crucial in the management of male infertility. Numerous investigations have shown that rutin protects against male infertility and have explored the underlying mechanisms involved. The present review, therefore, assesses the therapeutic mechanisms involved in male infertility treatment using rutin. Rutin was able to mitigate the induced oxidative stress, apoptosis, inflammation, and related physiological processes that can cause testicular dysfunction. Please cite this article as: Rotimi DE, Elebiyo TC, Ojo OA. Therapeutic potential of rutin in male infertility: A mini review. J Integr Med. 2023; 21(2): 130-135.

The combined effect of lifestyle intervention and antioxidant therapy on sperm DNA fragmentation and seminal oxidative stress in IVF patients: a pilot study

ABSTRACT Purpose: Sperm DNA fragmentation (SDF) and seminal oxidative stress are emerging measurable factors in male factor infertility, which interventions could potentially reduce. We evaluated (i) the impact of lifestyle changes combined with oral antioxidant intake on sperm DNA fragmentation index (DFI) and static oxidation-reduction potential (sORP), and (ii) the correlation between DFI and sORP. Materials and Methods: We conducted a prospective study involving 93 infertile males with a history of failed IVF/ICSI. Ten healthy male volunteers served as controls. Semen analysis was carried out according to 2010 WHO manual, whereas seminal sORP was measured using the MiOXSYS platform. SDF was assessed by sperm chromatin structure assay. Participants with DFI >15% underwent a three-month lifestyle intervention program, primarily based on diet and exercise, combined with oral antioxidant therapy using multivitamins, coenzyme Q10, omega-3, and oligo-elements. We assessed changes in semen parameters, DFI, and sORP, and compared DFI results to those of volunteers obtained two weeks apart. Spearman rank correlation tests were computed for sORP and DFI results. Results: Thirty-eight (40.8%) patients had DFI >15%, of whom 31 participated in the intervention program. A significant decrease in median DFI from 25.8% to 18.0% was seen after the intervention (P <0.0001). The mean DFI decrease was 7.2% (95% CI: 4.8-9.5%; P <0.0001), whereas it was 0.42% (95%CI; -4.8 to 5.6%) in volunteers (P <0.00001). No differences were observed in sperm parameters and sORP. Based on paired sORP and DFI data from 86 patients, no correlation was observed between sORP and DFI values (rho=0.03). Conclusion: A 3-month lifestyle intervention program combined with antioxidant therapy reduced DFI in infertile men with elevated SDF and a history of failed IVF/ICSI. A personalized lifestyle and antioxidant intervention could improve fertility of subfertile couples through a reduction in DFI, albeit controlled trials evaluating reproductive outcomes are needed before firm conclusions can be made. Trial registration number and date: clinicaltrials.gov NCT03898752, April 2, 2019.

Improvement of fertility parameters with tribulus terrestris and anacyclus pyrethrum treatment in male rats

ABSTRACT Objective Anacyclus Pyrethrum (AP) and Tribulus Terrestris (TT) have been reported as male infertility treatment in several studies; however, in Iranian traditional medicine these two plants are prescribed simultaneously. In this study, we aimed to determine the effects of AP and TT extracts both separately and simultaneously on the male Wistar rat fertility parameters. Materials and Methods 32 male Wistar rats were divided into 4 groups: Control, TT, AP, and AT treated groups. Treatment continued for 25 days and rats were weighed daily. Their testes were dissected for histological studies. Sperm analysis including sperm count, viability and motility were performed. Serum was obtained to evaluate testosterone, LH and FSH levels. Histological studies were conducted to study Leydig, and Sertoli cells, spermatogonia and spermatid cell numbers, and to measure seminiferous diameter and epithelium thickness. Results Sperm count increased in all the treatment groups. Sperm viability and motility in AT and AP groups were elevated. TT and AT groups showed significantly increased testosterone level compared to control group (P=004, P=0.000, respectively) and TT, AP and AT treatment groups showed increased LH level (P=0.002, P=0.03 and P=0.000, respectively) compared to control, while only AT group showed increased FSH (p=0.006) compared to control. Histological studies showed significant increase of spermatogonia, Leydig and Sertoli cell numbers and epithelial thickness in AT group compared to other groups. All the treatment groups had higher number of Leydig, spermatogonia and spermatid cells. Conclusion TT and AP improved sexual parameters; however, their simultaneous administration had higher improving effects on studied parameters.

Fertility Enhancing Potency of Omega-3 Fatty Acids in Male Rats

Abstract Cases of some grave side effects of some allopathic medicines used in treatment of infertility has caused a global need for alternatives with minimal or no side effect, hence the demand to evaluate the fertility enhancing potential of omega-3 fatty acids (O3FA) in male rats. This study evaluated the fertility enhancing potential of omega-3 fatty acids (O3FA) in male rats. Seventy-two sexually mature male albino rats 11-13 weeks of age, weighing between 171 - 180 g were assigned into six groups (I - VI) fed graded doses of O3FA. Administration of O3FA lasted twenty-eight days at 48 hour intervals. At the end of the treatment, organosomatic index of testes, testicular and epididymis sperm cells counts and testicular histology were assessed following standard methods. The actual and relative testicular weights, testicular and epididymis sperm counts of all O3FA treated rats were significantly increased (p < 0.05) when compared with the control group rats. The photomicrographs of testes in O3FA treated rats showed normal spermatogonial cell layers and active spermatogenesis with appearance of spermatids in the lumen of some tubules. The findings of this study depicts that O3FA possesses the potency of enhancing various fertility indices in male rats with regards to absolute and relative testicular weights as well as sperm counts.

Comparing clomiphen citrate plus HMG with clomiphen citrate plus rFSH in IUI cycles in couples with unexplained or male factor infertility: a prospective randomized study

Different protocols are used for controlled ovarian hyper stimulation [COH], but the optimal method has not yet been determined. The aim of this study was to compare the outcome of controlled ovarian stimulation [COS] using clomiphen citrate [CC] plus HMG versus CC plus rFSH in intra uterine insemination cycles [IUI]. 144 women with unexplained or male factor infertility undergoing IUI cycles were randomized [72 patients in CC plus rFSH group and 72 patients in CC plus HMG group] and included in this single blind study from October 2006 to June 2010. The primary outcomes were clinical and ongoing pregnancy rates. The number of dominant follicles, mean of follicular size, endometrial thickness on the day of HCG administration, total dose of gonadotropins and duration of stimulation with gonadotropins were secondary outcomes. Clinical and ongoing pregnancy rates were not significantly different in the two groups .There was a significant higher multiple pregnancy rate in CC plus rFSH group [33.3%] versus CC plus HMG group [12.5%; p<0.005]. There were no statistically significant differences in the secondary outcomes between the two groups. According to our results it seems that CC plus HMG is a more suitable and cost-effective regimen than CC plus rFSH in IUI cycles in patients with unexplained or male factor infertility

Carnitine supplement: does it worth trial to improve semen quality among infertile Sudanese men?

Carnitine supplement proves to upgrade the quality of semen by increasing sperm count and motility. In this study we have determined the level of L - carnitine in the seminal plasma of men with normal and abnormal seminal analysis. L - carnitine levels among the normal group was significantly higher than the abnormal group. We recommend trials of carnitine supplements to evaluate its usefulness in correcting some infertility cases. A total of 52 men, recruited from fertility centers in Khartoum, were included in this study. Colorimetric carnitine determination kits were used for estimation of L - carnitine in seminal plasma. Collectively, men with normal values of semen analysis had significantly higher mean seminal plasma carnitine levels compared to abnormal values [p = 0.028]. Oligospermic men had significantly lower levels of carnitine compared to normal [p = 0.046]. Seminal plasma carnitine level seems to correlate with seminal quality and its deficiency may be a reason for infertility among some Sudanese men

Carnitine supplement: Does it worth trial to improve semen quality among infertile Sudanese men?

Carnitine supplement proves to upgrade the quality of semen by increasing sperm count and motility. In this study we have determined the level of L - carnitine in the seminal plasma of men with normal and abnormal seminal analysis. L - carnitine levels among the normal group was significantly higher than the abnormal group. We recommend trials of carnitine supplements to evaluate its usefulness in correcting some infertility cases. Subjects and methods: A total of 52 men; recruited from fertility centers in Khartoum ;were included in this study. Colorimetric carnitine determination kits were used for estimation of L - carnitine in seminal plasma. Results: Collectively; men with normal values of semen analysis had significantly higher mean seminal plasma carnitine levels compared to abnormal values (p = 0.028). Oligospermic men had significantly lower levels of carnitine compared to normal (p = 0.046). Conclusion: Seminal plasma carnitine level seems to correlate with seminal quality and its deficiency may be a reason for infertility among some Sudanese men

A study of the antioxidant effect of alpha lipoic acids on sperm quality

OBJECTIVE: Assisted reproductive techniques are useful in helping infertile couples achieve successful conception. Initial studies have shown that sperm cryopreservation, one step in assisted reproduction, causes a dramatic reduction in sperm quality. This has been attributed to, among other things, free radical activities. The aim of the present study was to minimize this oxidative attack by adding an antioxidant into the sperm microenvironment. Alpha lipoic acids were selected for this purpose for their efficient free radical scavenging properties and solubility in lipid and aqueous phases. METHODS: For this investigation, semen from six Boer bucks was pooled. Seminal analysis of the baseline prior to incubation of samples with different concentrations of Alpha lipoic acids (0.00625, 0.0125, 0.025, 0.05, 0.1 mmol/ml) was performed, and post-seminal analysis was conducted after a one-hour incubation. The comet assay was used to observe the effect of Alpha lipoic acids on sperm DNA integrity. Statistical analysis using an unpaired t-test with a significance level of p<0.05 was then performed. RESULTS: Our results indicate that the sperm motility rate was improved after incubation with Alpha lipoic acids at a concentration of 0.02 mmol/ml. This concentration was also capable of reducing DNA damage. CONCLUSION: In conclusion, Alpha lipoic acids renders cryoprotection to sperm, thereby improving sperm quality.

Sperm morphological studies of the west African dwarf buck treated with pumpkin plant (Cucurbita pepo) / Estudio morfológico del esperma de la cabra enana del oeste africano tratado con planta de calabazas (Cucurbita pepo)

Four healthy bucks of the West African Dwarf breed aged between 24 and 30 months were used for this study. The bucks were first used as control and later as experimental animals upon being fed daily with oiled pumpkin plant for the period of six months. The objective of the study was to investigate the effect of the pumpkin plant on the morphology of the spermatozoa of the bucks. There were significant differences (p< 0.05) between the control and experimental values for both primary and secondary morphological spermatozoa abnormalities: the pyriform head has a control value of 6 (0. 42 percent) and post-feeding value of 0 (0 percent), the beat tail; 14(0.97 percent) and 2 (0.16 percent) for the control and post feeding values respectively. The curved mid piece: 17 (1.18 percent) and 1 (0.08 percent) for the control and post-feeding values respectively. The bent mid piece also differed significantly (p<0.05) between control value of 16 (1.11 percent) and post feeding value of 3 (0.23 percent). All through the stages of the study, there were significant reductions in the number of sperm cells with abnormalities consequent upon daily feeding of the animals with pumpkin plant. The plant is therefore recommended for both prevention and treatment of make infertility in man and animals.

Cuatro cabras de la raza enana del oeste de África, con edades comprendidas entre los 24 y 30 meses, fueron utilizadas para este estudio. Las cabras sirvieron primero como control y, posteriormente, como animales de experimentación los que se alimentaron diariamente con aceite de planta de calabaza por un período de seis meses. El objetivo del estudio fue investigar el efecto de la planta de calabaza sobre la morfología de los espermatozoides de las cabras. Hubo diferencias significativas (p <0,05) entre los valores control y experimental en las anomalías morfológicas primarias y secundarias de los espermatozoides: la cabeza tuvo un valor de control de 6 (0,42 por ciento) y post alimentación valor 0 (0 por ciento), el movimiento de la cola un valor de 14 (0,97 por ciento) y 2 (0,16 por ciento) para el control y post alimentación, respectivamente. La curvatura media: valores de 17 (1,18 por ciento) y 1 (0,08 por ciento) para el control y post-alimentación, respectivamente. La inclinación media también difería significativamente (p <0,05), con un valor entre 16 (1,11 por ciento) el control y 3 (0,23 por ciento) post-alimentación. Hasta el final de las etapas del estudio, hubo una reducción significativa en el número de células de esperma con anomalías como consecuencia de la alimentación diaria de los animales con la planta de calabaza. Por lo tanto, la planta se recomienda para la prevención y el tratamiento de la infertilidad en hombres y otros animales.

Effect of clomiphene citrate on sperm density in male partners of infertile couples.

Infertility is on the rise in today's world. A subnormal sperm count is frequently encountered in infertile couples. Clomiphene citrate, 1-[p-(beta-diethyl aminoethoxy) phenyl]-1,2-diphenyl chloroethylene, is an orally active nonsteroidal agent distantly related to diethylstilbestrol. It is thought to stimulate pituitary gonadotropin release by excluding estradiol from hypothalamic receptor sites. This interaction neutralizes the normal negative feedback control of estrogen and results in enhanced secretion of LH-RH, FSH-RH and gonadotropins. Testosterone is produced by the Leydig cells in response to LH secretion. The concentration of testosterone in the tubular environment is believed to maintain the gametogenic function of the testis. Clomiphene citrate in the dose of 25 mg daily for 25 days with five days rest was administered to 25 extreme oligozoospermic men (group I) and 40 moderate oligozoospermic men (group II) the cycle being continued for three months). Repeat semen analysis was done at the end of three months and all the routine seminal parameters were reevaluated. The data thus obtained was analyzed using Student's paired 't' test. The mean sperm count in Group I increased from 3.84 +/- 0.32 to 8.2 +/- 1.58 (P < 0.05) and in Group II from 13.05 +/- 0.48 to 24.55 +/- 1.73 (P < 0.001). The mean motile sperm count in Group I increased from 1.74 +/- 0.25 to 3.92 +/- 0.83 (P < 0.05) and in Group II from 8.27 +/- 0.40 to 10.05 +/- 0.56 (P < 0.01). Thus clomiphene citrate exerts its effect on spermatogenesis by raising the endogenous serum FSH, LH and testosterone levels to initiate and maintain gametogenesis (10). Researchers opined that this increase in endogenous gonadotrophins manifests itself in improving the sperm count, sperm motility and to certain extent morphology of the sperms, when there is no end-organ pathology.

Medical management of male infertility.

Management of male infertility is always a difficult task. In recent years booming of artificial reproductive technologies (ART) has put infertologists and andrologists in front of a million dollar question whether to treat the person or the gametes. A basic andrology laboratory at present has become part and parcel of an infertility clinic. Hence treatment of male infertility has become institutional and collective for clinicians and basic scientists. The basic approach towards management of male infertility includes confirmation of diagnosis and to find out the cause for which pathological, endocrinological and biochemical tests are essential. In this series specific defects causing seminopathy has been found in 18% cases where treatment is straightforward and towards the cause. The main bulk of idiopathic seminal defects (82%) really poses challenge to the infertologists so far management is concerned. In this study commonest seminal defect has been found to be oligoasthenozoospermia which amounts to 63% cases. For medical management purpose drugs commonly used are clomiphene, gonadotrophins, bromocriptine, L-thyroxine, vitamin E, B12, etc. When they fail the main approach remains to be intra-uterine insemination (IUI) and ART eg, in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI).

Reaçäo acrossômica na exploraçäo de infertilidade masculina em fecundaçäo in vitro / Place of acrosomal reaction in the exploration of male infertility in in vitro fertilization

O acrossoma, vesícula de origem golgiana, tem um papel essencial no desenvolvimento da fecundaçäo, tanto in vivo com in vitro. Neste artigo estudaram diferentes métodos de induçäo da reaçäo cromossômica (RA). Os indutores como o líquido folicular, a progesterona e o cálcio iônico permitem a exploraçäo da dinâmica da RA e a análise dos espermatozóides aptos a realizar esta RA. Este trabalho mostra o interesse destas exploraçöes nos casos de infertilidade masculina em Reproduçäo Assistida.

Growth hormone treatment in infertility: a short review.

In cultured animal granulosa cells, insulin-like growth factor 1 (IGF-1) and growth hormone (GH) have been shown to have a functional role. With the recent availability of recombinant GH, clinical studies have followed using GH in ovulation induction in patients resistant to stimulation by gonadotrophins alone. So far, patient numbers have been small in the studies conducted but the results suggest that GH may improve ovulation induction and reduce gonadotrophins requirement. However, patients with GH deficiency are not infertile. Thus the evidence suggests that the role of GH treatment in infertility is probably facilitative and not obligatory.

Efecto de la infección seminal asintomática y su tratamiento sobre la calidad del semen de hombres infertiles / Effect of asymptomatic seminal infection and its treatment on sperm quality in infertile men

Se estudió el semen de 17 pacientes con infección seminal asintomática, tratados durante un mes con 3 antibióticos (10 días cada uno);ampicilina, tetraciclina y sulfaprim, en forma secuencial. Se les realizó espermograma, fructosa y fosfatasa ácida seminal, así como cultivo bacteriológico del semen, durante la infección, y a los 3 y 6 meses después de tratamiento. Se utilizaron los criterios de infección de la OMS. A los 3 meses persistió la infección en 4 pacientes y a los 6, en 2. Al detectar la infección, los que tenían anormalidad del volumen eyaculado, de la movilidad, de la morfología y de la concentración de espermatozoides por mL fueron 3,9,3,6 y 5 respectivamente. En los pacientes en los que desapareció la infección. Los resultados indican que el tratamiento de la infección seminal asintomática no mejora los indicadores estudiados del espermograma

Respuesta testicular a la gonadotropina coriónica humana en pacientes infértiles atendiendo al patrón histológico testicular / Testicular response to human chorionic gonadotropin in infertile patients. According to testicular histology standard

Se estudió la respuesta testicular a 6,000 UI de HCG intramuscular determinando testosterona (T) y estradiol (E2) plasmáticos, en pacientes infértiles, de acuerdo al patrón histológico testicular y se compararon sus resultados con los obtenidos en hombres normales. En los normales la T presentó un incremento inicial a las 2-4 horas y un incremento máximo entre 48-96 horas post-HCG. El E2 presentó un incremento máximo a las 24 horas post-HCG, regresando al nivel basal a las 192 horas. En los pacientes infértiles con hipoespermatogénesis y aplasia germinal, la T repondió a la HCG en forma similar a los normales, pero el E2 disminuyó más rápido en los últimos, lo que sugiere una disminución de la capacidad de sintetizar y/o liberar E2. Aquellos con hialinización tubular no presentaron la respuesta bifásica de T y los incrementos de T y E2 se encontraron disminuidos significativamente. Finalmente, los pacientes con Síndrome de Klinefelter no respondieron a la estimulación con HCG. Se concluye que los pacientes infértiles presentan una respuesta diferente a la HCG si son clasificados según el patrón histológico de los testículos