BACKGROUND Recurrent pregnancy loss, (RPL) affecting 1%–2% of couples, is defined as ≥3 consecutive pregnancy losses before 20-week' gestation. Women with RPL are routinely screened for etiological factors, but routine screening of male partners is not currently recommended. Recently it has been suggested that sperm quality is reduced in male partners of women with RPL, but the reasons underlying this lower quality are unclear. We hypothesized that these men may have underlying impairments of reproductive endocrine and metabolic function that cause reductions in sperm quality. METHODS After ethical approval, reproductive parameters were compared between healthy controls and male partners of women with RPL. Semen reactive oxygen species (ROS) were measured with a validated inhouse chemiluminescent assay. DNA fragmentation was measured with the validated Halosperm method. RESULTS Total sperm motility, progressive sperm motility, and normal morphology were all reduced in the RPL group vs controls. Mean ±SE morning serum testosterone (nmol/L) was 15% lower in RPL than in controls (controls, 19.0 ± 1.0; RPL, 16.0 ± 0.8; P < 0.05). Mean ±SE serum estradiol (pmol/L) was 16% lower in RPL than in controls (controls, 103.1 ± 5.7; RPL, 86.5 ± 3.4; P < 0.01). Serum luteinizing hormone and follicle-stimulating hormone were similar between groups. Mean ±SE ROS (RLU/sec/106 sperm) were 4-fold higher in RPL than in controls (controls, 2.0 ± 0.6; RPL, 9.1 ± 4.1; P < 0.01). Mean ±SE sperm DNA fragmentation (%) was 2-fold higher in RPL than in controls (controls, 7.3 ± 1.0; RPL, 16.4 ± 1.5; P < 0.0001). CONCLUSIONS Our data suggest that male partners of women with RPL have impaired reproductive endocrine function, increased levels of semen ROS, and sperm DNA fragmentation. Routine reproductive assessment of the male partners may be beneficial in RPL.

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However, the effects of different cancer types on spermatogenic function remain unknown. Total Motile Count (TMC) has emerged as a prognostic indicator of fertility potential, yet there remains very little data reporting the effects of male cancers on TMC. The aim of this study was to assess the effects of male cancers on TMC.METHODS: An analysis of male patients with cancer undergoing sperm cryopreservation at a UK tertiary centre between 1992-2016. Primary measures were semen parameters prior to cryopreservation, including TMC. TMC was calculated: [semen volume]*[sperm concentration]*[total motility]. Patients were categorised according to their cancer diagnosis: testicular, prostate, leukaemia, lymphoma, gastrointestinal, brain and other cancers. Kruskal-Wallis tests with Dunn's pairwise post-hoc analyses were performed to compare variables between groups, and Bonferroni corrections applied to pvalues. Chi-squared tests were used to compare proportions between groups.RESULTS: 3433 cancer patients cryopreserved sperm during the study period. Testicular malignancy was the most frequent indication for sperm cryopreservation. Overall, 30.8% of men cryopreserving sperm had an abnormal sperm concentration. Testicular malignancy was associated with the lowest sperm concentration (p<0.001) and the greatest prevalence of oligozoospermia (<15 x 10 6 mL -1 ) (p<0.001). Patients with leukaemia had the lowest sperm motility (p<0.001). Overall, 29.3% of male cancer patients had an abnormal TMC (<20 x 10 6 ). Patients with testicular malignancy had the lowest TMC of all cancer types (p<0.001). 34.4% had less than 20 million motile sperm in their ejaculate, including 13.4% (n[144) who had a TMC <5 million.CONCLUSIONS: This study represents the largest singlecentre analysis of sperm cryopreservation in men with cancer. We highlight that, according to their TMC, almost 30% of male cancer patients are subfertile before their cancer treatment. Whilst men with testicular malignancy are the most severely affected, a significant proportion of men with all cancer types would likely require the use of Assisted Reproductive Technologies to achieve successful conception (as indicated by TMC <20 million) even prior to potentially gonadotoxic therapy.