Diagnosis of Partial Retrograde Ejaculation in Non-Azoospermic Infertile Men with Low Semen Volume

Abstract

In non-azoospermic patients with low semen volume (LSV), looking for partial retrograde ejaculation (PRE) by searching sperm in the postejaculatory urine (PEU) is required. The use of a retro-ejaculatory index (R-ratio) was suggested to define PRE, but none of the studies indicated a specific threshold above which PRE must be considered. Our objective was to propose a threshold value for the R-ratio as indicative of PRE in patients with LSV selected to be devoid of any known causes or risk factors for retrograde ejaculation or LSV. Among our data base (2000-2009) including 632 patients with PEU, 245 male patients from infertile couples who had had a first semen analysis with LSV (< 2mL) and a second semen analysis associated with PEU, were selected on the previous criteria. A prospective control group was randomly constituted (2007-2008) of 162 first consulting male patients from infertile couples, with a normal semen volume (≥ 2mL) on a first semen analysis and who accepted to collect PEU with their usual second semen analysis, selected on the previous criteria. To define an R-ratio threshold indicative of PRE, we used a ROC curve analysis and a regression tree based on a classification and regression tree (CART) algorithm. Of the 245 LSV patients, 146 still presented low semen volume (< 2 mL) on the second semen analysis. From the use of the CART algorithm, two low (1.5% and 2.8%) and two high R-values (7.1% and 8.3%) were defined, according to the lower reference limit for semen volume of 2.0 mL (WHO 1999) or 1.5 mL (WHO 2010) respectively. As only one or no patient with normal semen volume was observed above the two high R-values, we suggest an R-value higher than the range of [7.1-8.3]% as indicative of PRE until confirmation by a prospective multicenter study.

Fig 1. Flowchart and design of the study.

Fig 2. Semen and post ejaculatory urine characteristics as function of the R-value thresholds obtained from the CART procedure in 162 patients with normal semen volume (NSV) and 146 patients with observed low semen volume < 2 mL (LSV).

Values are mean ± SD (median); 1.5% and 7.1%, thresholds values of R determined by the CART procedure on the 308 (162 plus 146) patients; % corresponds to number of patients/total number of patients with NSV or LSV. Three ranges of R-value classified patients: 80% of NSV patients (129/162) and 27% of LSV patients (39/146) were under an R-value of 1.5%, 20% of NSV and 38% of LSV were comprised between 1.5% and 7.1%, and less than 1% of NSV and 35% of LSV had an R-value ≥ 7.1%. R (%), [uTSC divided by (uTSC plus sTSC)] multiplied by 100 uVolume, urine volume (ml) uSC, urine sperm count (10⁶/ml) uTSC, urine total sperm count (uVolume multiplied by uSC; 10⁶) Abst Delay, abstinence delay (days) sVolume, semen volume (ml) sSC, semen sperm count (10⁶/ml) sTSC, semen total sperm count (sVolume multiplied by sSC; 10⁶) TAS, total amount of sperm (uTSC plus sTSC; 10⁶) ^a p < 0.05 between 129 NSV and 39 LSV ^b p < 0.05 between 32 NSV and 56 LSV ^c p < 0.05 between 129 NSV (R < 1.5%) and 32 NSV (1.5 ≤ R < 7.1%) ^d p < 0.05 between 39 LSV (R < 1.5%) and 56 LSV (1.5 ≤ R < 7.1%) ^e p < 0.05 between 56 LSV (1.5 ≤ R < 7.1%) and 51 LSV (R ≥ 7.1%) ^f p < 0.05 between 39 LSV (R < 1.5%) and 51 LSV (R ≥ 7.1%)

Fig 3. Distribution of patients according to R-values and semen volume.

Reference lines were drawn on x-axis to represent WHO lower reference limits for semen volume (1.5 mL [20] and 2 mL [16]) and on y-axis to represent low and high R-value thresholds obtained from CART procedure (1.5% and 2.8%, 7.1% and 8.3% respectively). + (green), 146 patients with observed low semen volume (<2 mL) × (red), 99 patients with normalized semen volume (≥ 2 mL) * (blue), 162 patients with normal semen volume (≥ 2 mL).