Nutritional Interventions And Male Infertility

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Infertility, defined as the inability of sexually-potent, non-contracepting couple to conceive following a year of regular intercourse without using contraceptive methods, occurs in 10-15% of couples [Baba>>1-4]. Despite the absence of reliable figures of the worldwide rate of infertility [Kuma>>3], it’s suggested that fertility issues occur in approximately 72.4 million couple worldwide [Kumar>>4], while 60-80 million couples being currently affected by infertility as reported by the WHO [Kumar>>5].

Male infertility is defined as the male’s incapacity to impregnate his partner. Practically, it is the result of disturbance in sperm concentration, motility, morphology, or a combined effect observed in one of two sperm samples drawn a month apart [Kumar>>20]. It represents 40-50% of infertility [Kumar>>21-23+ Baba>>7,9], overall, with 7% of all men being affected by it [Kumar>>24]. Male factor infertility is diagnosed in those with sperm parameters lowers than the normal values reported by the WHO [Kumar>>26], the most important of which are low sperm concentration (oligospermia), limited motility (asthenospermia), and abnormal morphology (teratospermia). Other elements (i.e., semen volume or seminal markers) are associated with male infertility to a lesser degree [Kumar>>27], as 90% of contributing factors to ‘male factor’ infertility are associated with changes in the total sperm count, with a noticeable correlation between both total sperm count and semen-related parameters [Kumar>>28]

Etiologies of male infertility can be broadly classified into five categories: (1) hypothalamic-hypophyseal tract disorders (i.e., pituitary insufficiency or tumors, hyperprolactinemia, Kallmann syndrome, or hemochromatosis); (2) testicular diseases (i.e., infections, atrophy, Klinefelter syndrome, chromosomal deletion abnormalities, or systemic disorders); (3) seminal tract disorders (i.e., retrograde ejaculation or obstructive azoospermia); (4) immunological condition; (5) psychosomatic etiology [Ghuman]. Noteworthy, varicocele is considered one of the leading yet correctable causes of male infertility [Mahat>>48], both in the general (14.8%) and azoospermic populations (10.9%) [guidelines>>10].

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Various factors have been reported to have an effect on sperm parameters, including several comorbidities (i.e., renal diseases, hepatic insufficiency, chronic pulmonary disorders, cystic fibrosis, and multiple sclerosis) [Fainberg]. Of note, male infertility has been reported in many obese men, probably due to alterations in their hormone levels secondary to the increased extent of adipose tissue in their bodies. In a large population study, it was noted that male infertility is inversely associated with body mass index (BMI) as regards several sperm parameters, including testosterone level, testosterone-to-estradiol ratio, sperm concentration, and sperm morphology [Faiberg.>>6]. Compared to individuals with normal BMI, azoospermia and oligospermia have been reported to occur in 12.7% and 31.7% of obese individuals (high BMI), respectively. In addition, it was observed that the time to conceive is prolonged in couples with obese men (high BMI) and normal-weight female partners [Faiberg>>7].

In recent years, it has been observed that healthy dietary patterns/habits and nutritional modifications are associated with improved sperm quality and other sperm-related parameters, including quantity, concentration, motility, morphology, and DNA fragmentation [Skoracka>>6,7,20,26]. In this context, various dietary and nutritional interventions have been investigated for their efficacy in improving sperm parameters in infertile men.

In a recent meta-analysis, 25-hydroxyvitamin D has been observed to be of higher levels in fertile men compared to infertile peers, with a significant correlation with sperm motility and motility [Arab]. In another meta-analysis of three randomized controlled trials (RCTs), it was noted that omega-3 fatty acid in combination with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) improved sperm motility, with the three trials showing increased sperm concentration with these combined interventions. [Hosseini]. Coenzyme Q10 (CoQ10) has been studies in a number of meta-analyses and it has been shown to have a significant impact on semen parameters in infertile men, being associated with a significant increase in sperm count [Lafuente + Salas], total sperm concentration [Salas], sperm motility [Lafuente], and sperm morphology [Salas]. It has been shown effective in patients with oligospermia and asthenozoospermia [Buhling]. Selenium is an essential element for spermatogenesis [Boitani]. In a meta-analysis of seven RCTs, it was found that selenium resulted in a significant improvement in semen parameters in patients with oligozoospermia and asthenozoospermia [Buhling], with increased total sperm count, total sperm motility, and sperm morphology [Salas]. Meanwhile, L-carnitine and acetyl-L-carnitine have been shown to have beneficial outcomes related to asthenozoospermia [Buhling]. L-carnitine has been shown to be associated with significant increase in sperm motility and morphology [Salas]. Moreover, various RCTs have shown beneficial effects of vitamin C [Cyrus+ Abel], vitamin E [El-Sheikh + Kessopoulo+ Ghanem], and vitamin D [Jensen] on various clinical (increased pregnancy rates) [Ghanem] and semen-related parameters, including improved sperm motility, morphology, and total sperm concentration.

Despite the presence of many meta-analyses in this regard, the small number of included trials along with the small overall sample size limits generalizability of such findings. Moreover, to date, there has been no study to investigate the comparative efficacy of all of these nutritional interventions in a single network meta-analysis model to determine which intervention in superior to others in terms of semen parameters among infertile men. 

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