Epidemiology and trends in male subfertility

The incidence and the causes of male infertility and male reproductive ill-health (in general) are important issues that remain poorly characterised. There does not appear to be a worldwide decline in semen quality but changes are more apparent in some regions than others. Furthermore, though the incidence of testicular cancer and congenital genital malformations had been increasing, the rate of increase has seemingly slowed over the past decade. Demographic data on UK fertility rates also provide scant evidence to suggest that infertility is increasing. Though this incidence data is reassuring, male infertility has been associated with an ever-increasing number of putative risk factors, including current exposures or parental exposures to occupational, lifestyle or environmental factors. It is currently unclear to what extent such risk factors (and others such as DNA damage) influence male infertility. Better characterisation of risk factors will aid our understanding of what is happening to male infertility. This brief review examines recent trends in male infertility and summarises the extent to which knowledge in this area has improved significantly.     

The risk of endometriosis after exposure to endocrine-disrupting chemicals: a meta-analysis of 30 epidemiology studies

Endocrine-disrupting chemicals (EDCs) are suspected to be associated with endometriosis (EMs). This study aimed to synthesize published data and evaluate the relationship between four classic EDCs exposure and the risk of EMs. A systematic literature search for original peer reviewed papers was performed in the databases PubMed, EMBASE, and Web of Science based on inclusion criteria up to January 2018. Subsequently, a total of 20 papers conducting 30 studies fulfilled the eligibility criteria and were included in this meta-analysis (four studies for bisphenol A (BPA), 12 studies for polychlorinated biphenyls (PCBs), eight studies for organochlorine pesticides (OCPs), and six studies for phthalate esters (PAEs)). The overall odds ratio (OR) across all exposures and EMs was 1.41 (95% confidence interval (CI): 1.23–1.60). When assessing four specific chemicals, respectively, consistent increases in the risk of EMs were found in PCBs group (OR = 1.58; 95% CI: 1.18–2.12), OCPs group (OR = 1.40; 95% CI: 1.02–1.92) and PAEs group (OR = 1.27; 95% CI: 1.00–1.60), while BPA showed no significant association with EMs. Besides, in the di-(2-ethylhexyl)-phthalate (DEHP) group – the most commonly used PAEs, significant risk was also found (OR = 1.42; 95% CI: 1.19–1.70). The current meta-analysis strengthens the evidence that specific EDCs or their metabolites may promote the occurrence of EMs.     

Comparing the pregnancy rates of one versus two intrauterine inseminations (IUIs) in male factor and idiopathic infertility

Purpose : To compare the effectiveness of double IUI with single IUI in male factor and idiopathic infertility patients undergoing controlled ovarian hyperstimulation (COH). Methods : A prospective randomized study of 1257 COH-IUI cycles was performed. Total 1270 patients with mild or moderate male factor infertility (n = 776) and idiopathic infertility (n = 494) were enrolled in this study, and 767 with male factor infertility and 490 with idiopathic infertility completed clomiphene citrate (CC)/human menopausal gonadotrophin (hMG) COH cycles and IUI. Categorized on the basis of the causes of infertility (male factor, M; idiopathic infertility, I), patients were randomized into one of the following groups: Single IUI group (M₁/I₁) received single insemination 34 h post hCG administration, and double IUI group (M₂/I₂) received two inseminations 18–24 and 36–48 h post hCG injection, respectively. Results : The overall pregnancy rates were 15.43%. Pregnancy rate for single and double IUI group was 11.06 and 19.87% (p < 0.05), respectively. There was a significant statistical difference in cycle fecundity between M₁ and M₂ group (11.34% vs. 24.93%, p < 0.05), and between I₂ and M₂ group (11.93% vs. 24.93%, p < 0.05), but there was no significant difference between I₁ and I₂ (10.53% vs. 11.93%, p > 0.05). Conclusions : Double IUI increases the pregnancy rate significantly in patients with male factor infertility, and single IUI acts as efficient as double IUI in patients with idiopathic infertility.Part of the data have been orally presented at the 21st Annual Meeting of the European Society of Human Reproduction and Embryology in Copenhagen, 2005.     

Role of varicocele repair for male infertility in the era of assisted reproductive technologies

Varicocele is an abnormal condition characterized by dilatation of the pampiniform plexus veins draining the testis and is present in 15 % of men. Varicoceles have an adverse effect on spermatogenesis and are the most common cause of male infertility. Approximately 35 % of infertile men and more than 70 % of men with secondary infertility were reported to have varicoceles. Although data on methods of varicocele repair are accumulating, there remains controversy regarding the indications and techniques for varicocele repair. In addition, the role of varicocele repair in this era of assisted reproductive technologies continues to be debated. In this study, we performed a comprehensive PubMed search in order to review the current status of varicocele repair for male infertility. We reviewed English‐language studies published from 1992 through 2013. After reviewing the articles, we identified a recent meta‐analysis of four randomized controlled trials, which found that varicocele repair for oligozoospermic men was associated with better pregnancy rates as compared with observation. Our review of prospective studies showed that all semen parameters, including sperm concentration, motility, and progressive motility, were significantly improved after varicocele repair. We also summarize the findings of recent studies reporting beneficial effects of varicocele repair, i.e., decreased oxidative stress and sperm DNA fragmentation after varicocele repair and superior cost effectiveness versus in vitro fertilization/intracytoplasmic sperm injection alone, which may be important in the era of assisted reproductive technologies. Varicocele repair is a widespread, well‐established procedure that can improve semen parameters in men with infertility. The effect of such treatment on the pregnancy rate is unclear because evidence is limited due to difficulties in recruiting patients for studies. Among the repair techniques, microsurgical repair using a subinguinal approach is potentially the best practice, although this procedure requires training in microsurgery. All these topics require further research in studies with sufficient patient enrollment and follow‐up.     

Sperm DNA fragmentation and male fertility: a retrospective study of 5114 men attending a reproductive center

PurposeThe sperm DNA fragmentation index (DFI) was quantitatively measured and its relationship with age, semen quality, and infertility conditions was investigated.MethodsSemen routine test and sperm DFI were performed in 2760 infertile male and 2354 male whose spouse experienced at least one unexplained miscarriage to analyze the correlation between sperm DNA damage, semen routine parameters, and age.ResultsSperm DFI was significantly lower from patients whose wife experienced unexplained miscarriage compared to infertility males (p = 0.000). An inverse correlation between sperm DFI and sperm progressive motility was observed (r_s = − 0.465, p = 0.000) and sperm DFI was positively correlated with age (r_s = 0.255, p = 0.000). However, the correlation between sperm DFI and sperm concentration, semen volume, total sperm count, and motile sperm count were not proved.ConclusionsSperm DFI is an important indicator for evaluating the quality of semen. Sperm DNA integrity testing is preferentially recommended to those who have decreased sperm progressive motility, especially older men. An integrative analysis of sperm DFI, sperm progressive motility, age, and infertility conditions can provide a more comprehensive assessment of male fertility.     

Current options for preservation of fertility in the male

Modern cancer therapies have greatly improved survival rates in men of reproductive age and younger; however, surgery, chemotherapy, and irradiation may lead to male infertility. Men with cancer should be counseled about fertility preservation before initiating therapy, when possible. Currently, options for male fertility preservation include cryopreservation of semen or testicular tissue. However, prepubertal boys pose a special problem in this area.     

Association of phthalate esters with endometriosis in Indian women

OBJECTIVE: To evaluate the possible association between phthalate esters (PEs) and the occurrence of endometriosis. DESIGN: Case-control study. SETTING: Department of Reproductive Medicine, Bhagawan Mahavir Medical Research Centre, Maternal Health and Reproductive Institute and Department of Analytical R&D, Hetero Research Foundation, Hyderabad, Andhra Pradesh, India. SAMPLE: Blood samples were collected from 49 infertile women with endometriosis (study group); 38 age-matched women without endometriosis (control group I) but with infertility related to tubal defects, fibroids, polycystic ovaries, idiopathic infertility and pelvic inflammatory diseases diagnosed by laparoscopy and a further group of 21 age-matched women (control group II) with proven fertility and no evidence of endometriosis and other gynaecological disorders during laparoscopic sterilisation. METHODS: Concentrations of PEs were measured using gas chromatography. MAIN OUTCOME MEASURES: Evaluation of PEs concentrations in women with endometriosis compared with women free from the disease. RESULTS: Women with endometriosis showed significantly higher concentrations of di-n-butyl phthalate (DnBP), butyl benzyl phthalate (BBP), di-n-octyl phthalate (DnOP) and diethyl hexyl phthalate (DEHP) (mean 0.44 [SD 0.41]; 0.66 [SD 0.61]; 3.32 [SD 2.17]; 2.44 [SD 2.17] micrograms/ml) compared with control group I (mean 0.08 [SD 0.14]; 0.12 [SD 0.20]; 0; 0.50 [SD 0.80] micrograms/ml) and control group II (mean 0.15 [SD 0.21]; 0.11 [SD 0.22]; 0; 0.45 [SD 0.68] micrograms/ml). The correlation between the concentrations of PEs and different severity of endometriosis was strong and statistically significant at P < 0.05 for all four compounds (DnBP: r=+0.73, P < 0.0001; BBP: r=+0.78, P < 0.0001; DnOP: r=+0.57, P < 0.0001 and DEHP: r=+0.44, P < 0.0014). CONCLUSIONS: This study suggests that PEs may have an aetiological association with endometriosis.     

Life-table analysis of artificial insemination pregnancy rates for couples with male factor and idiopathic infertility

Background :  In the summer of 2002, standard guidelines for the application of assisted reproductive technology were reported by a research group of the Ministry of Health, Labor and Welfare. The present study aimed to examine the relationship between the number of cycles of artificial insemination and the cumulative pregnancy rates according to the cause of infertility.
Methods :  Patients who experienced their first cycle of artificial insemination during the period of January 1999–December 2002 were included in the study and were divided into a male factor infertility group and an idiopathic infertility group. Cumulative pregnancy rates resulting from artificial insemination with the husband's semen were calculated by the life-table approach.
Results :  During the study period, 139 couples entered the assisted reproduction program and underwent 581 cycles. Significant differences were observed in cumulative pregnancy rates between the two groups.
Conclusion :  It is recommended that couples with male factor infertility and who fail to conceive within six or seven cycles of intrauterine insemination, consider a modification of treatment strategy such as in vitro fertilization, because cumulative pregnancy rates of this group were reached at a plateau within six or seven cycles. In contrast, patients with idiopathic infertility, the cumulative pregnancy rates appeared to increase constantly with each subsequent cycle. It is important to consider modifications of treatment strategy in the light of the cause of infertility. (Reprod Med Biol 2004; 3 : 27–31)     

Effects of Anethum graveolens L. on fertility in male rats

ABSTRACT

Objectives The effects of Anethum graveolens seed extract on fertility of male rats were investigated.

Methods Male Wistar rats were divided into five groups according to the treatment they received during 42 days: control, low dose (0.5 g/kg) and high dose (5 g/kg) of aqueous extracts, and low dose (0.045 g/kg) and high dose (0.45 g/kg) of ethanol extracts of Anethum graveolens seed. Sperm count and motility and testosterone concentration were measured. Sections of the testes, epididymis, and seminal vesicles were stained with peroxidase-conjugated lectins of Ulex europaeus agglutinin, peanut agglutinin, Dolichos biflorus agglutinin, soy bean agglutinin and concanavalin A. The treated male rats were mated with females and the crown-rump lengths and weights of their newborn pups were measured.

Results No significant differences in sperm count, sperm motility or testosterone concentration were observed in the experimental groups. However, female rats did not become pregnant after mating with rats given the high dose of the ethanol extract. The distribution of terminal sugars on the epithelial surface of the reproductive structures decreased in the experimental groups.

Conclusion Anethum graveolens extract decreased fertility rate by modifying some terminal sugars on the cell surface of male reproductive organs involved in sperm maturation, capacitation and oocyte recognition.