Multicentric, prospective observational data show sperm capacitation predicts male fertility, and cohort comparison reveals a high prevalence of impaired capacitation in men questioning their fertility.

RESEARCH QUESTIONS: Can a previously defined relationship between sperm capacitation and the probability of a man generating pregnancy within three cycles, prospectively predict male fertility in diverse clinical settings? A second study asked, what is the prevalence of impaired sperm fertilizing ability in men questioning their fertility (MQF), and does this relate to traditional semen analysis metrics? DESIGN: In the multicentric, prospective observational study, data (n = 128; six clinics) were analysed to test a published relationship between the percentage of fertilization-competent, capacitated spermatozoa (Cap-Score) and probability of generating pregnancy (PGP) within three cycles of intrauterine insemination. Logistic regression of total pregnancy outcomes (n = 252) assessed fit. In the cohort comparison, Cap-Scores of MQF (n = 2155; 22 clinics) were compared with those of 76 fertile men. RESULTS: New outcomes (n = 128) were rank-ordered by Cap-Score and divided into quintiles (25-26 per group); chi-squared testing revealed no difference between predicted and observed pregnancies (P = 0.809). Total outcomes (n = 252; 128 new + 124 previous) were pooled and the model recalculated, yielding an improved fit (P < 0.001). Applying the Akaike information criterion found that the optimal model used Cap-Score alone. Cap-Scores were performed on 2155 men (with semen analysis data available for 1948). To compare fertilizing ability, men were binned by PGP (≤19%, 20-29%, 30-39%, 40-49%, 50-59%, ≥60%). Distributions of PGP and the corresponding Cap-Scores were significantly lower in MQF versus fertile men (P < 0.001). Notably, 64% of MQF with normal volume, concentration and motility (757/1183) had PGP of 39% or less (Cap-Scores ≤31), versus 25% of fertile men. CONCLUSIONS: Sperm capacitation prospectively predicted male fertility. Impaired capacitation affects many MQF with normal semen analysis results, informing diagnosis versus idiopathic infertility.

Glycodelin levels in uterine flushings and in plasma of patients with leiomyomas and polyps: implications for implantation.

BACKGROUND: Glycodelin, a glycoprotein, is present in both blood plasma and uterine flushings. It has been implicated in the process of implantation and angiogenesis. During the secretory phase, progesterone secretion is related to glycodelin production. METHODS AND RESULTS: We obtained uterine flushings, prospectively, from 47 infertile patients during the proliferative phase. Patients were recruited from our university practice. Transvaginal ultrasound and sonohysterography permitted the stratification of patients into control, leiomyoma or polyp groups. Total plasma and uterine flushing glycodelin was measured with enzyme-linked immunosorbent assay. Blood was also analysed for progesterone. Uterine flushing glycodelin levels were significantly increased in patients with polyps when compared with controls. An increase in uterine flushing glycodelin levels was noted in patients with leiomyomas compared with controls, though not statistically significant. Plasma glycodelin levels were significantly increased in patients with leiomyomas and polyps when separately compared with controls. There was a significant relationship between plasma glycodelin production and progesterone levels in patients with polyps. CONCLUSIONS: Leiomyomas and polyps are growing tumours and thus produce significant plasma glycodelin levels. Uterine glycodelin flushings are elevated in patients with both polyps and leiomyomas. Elevated glycodelin levels in the follicular and peri-ovulatory period may impair fertilization and implantation.