Sperm quality and paternal age: effect on blastocyst formation and pregnancy rates
The aim of this retrospective study was to assess the effect of paternal age and of sperm concentration and progressive motility before preparation on the blastulation and clinical pregnancy rates.
In IVF, progressive motility lower than 32% affected significantly the fertilization rate (p?0.0001), but not the blastulation, clinical pregnancy and early miscarriage rates. This is in agreement with the work by Chen et al. [12] who did not find any significant difference concerning sperm concentration, total motility, progressive motility and rapid progressive motility between the clinical pregnancy and non-pregnancy groups. Differently from our study where sperm analysis was performed on fertilization day, in the study by Chen et al., sperm was analysed in the 6 months before the attempt.
In ICSI, sperm concentration before preparation did not affect the cycle outcomes (clinical pregnancy or early spontaneous miscarriage). Similarly, rapid progressive motility ( or 32%) did not affect the blastocyst formation, clinical pregnancy and early miscarriage rates. The effect of sperm concentration and rapid progressive motility on the fertilization rate with ICSI (Table 5) could be explained by the bias linked to the association between asthenozoospermia and oligozoospermia. Borges et al. [13] reported that sperm concentration before preparation influences the fertilization rate in ICSI (OR 3.994, p?=?0.015), but not the rate of blastocyst formation. However, in this study, patients were classified only in two groups (concentration??or 15 M/ml), which did not allow highlighting the effect of severe oligozoospermia on the rate of blastocyst formation found in our study (Table 4).
In our analysis, we did not take into account the percentage of normal forms on fertilization day. This bias is, however, limited because the literature is not unanimous on the effect of teratozoospermia on the outcome of ART attempts. Zhu et al. [14] suggested that isolated teratozoospermia (4% of normal forms according to the Kruger’s classification [15]) justifies the use of ICSI versus IVF to improve the fertilization rate. Conversely, according to Lockwood et al. [16], teratozoospermia is not a parameter to be taken into account for the choice of ART technique and allows even intra-uterine inseminations. These results confirm those reported by Fan et al. [17]. Many other groups also previously demonstrated the absence of effect of isolated teratozoospermia on IVF results [18–21].
In our study, sperm concentration lower than 0.2 M/ml was the only sperm-related factor that influenced negatively the blastocyst formation rate after ICSI. This is in agreement with the study by Miller and Smith [22] who also found a higher blastulation rate in IVF than in ICSI, which was performed only in the case of reduced sperm motility or of 4???normal forms. In the same study, increasing paternal age influenced the blastocyst formation rate, independently of the used fertilization technique. We found a similar effect when paternal age was higher than 50 years, but only in the IVF subgroup. In our study, rapid progressive motility did not have any effect on the blastulation rate (both techniques), differently from what reported previously [22, 23].
The effect of severe oligozoospermia on the fertilization and blastulation rates after ICSI could be partially explained by an elevated DNA fragmentation rate (i.e., DNA strand breaks). Many studies have tried to determine the effect of DNA fragmentation on the fertilization, pregnancy and spontaneous miscarriage rates. At low level, these breakages are repaired in the oocyte after fertilization. Beyond a certain level, they cannot be efficiently repaired to allow normal embryo development. Many studies have observed the absence of links between the DNA fragmentation index (DFI) and the quality of embryos generated with ICSI [24–30]. Moreover, according to Evenson et al. [31], improving sperm chromatin structure during ART is not associated with higher fertilization and embryo quality rates. The absence of correlation between DFI and embryo quality could be partially explained by the fact that better quality spermatozoa are chosen for ICSI [30]. However, other studies have highlighted the existence of an association between the level of sperm DNA fragmentation and degree of embryo fragmentation after ICSI [32–39]. Guérin et al. [40] never obtained a successful pregnancy, when sperm DFI was higher than 45%, whatever the ART technique used. Larson et al. [41] found that if more than 27% of spermatozoa show DNA denaturation, no pregnancy can be obtained after ICSI. For Simon et al. [42], increased sperm DNA fragmentation is associated with abnormal protamination and results in lower fertilization rates, poorer embryo quality and reduced pregnancy rates.
New approaches are needed for sperm selection. A very interesting study by Muratori et al. [43] provides the evidence that the density gradient centrifugation procedure produces an increase in sperm DNA fragmentation in some subjects undergoing IVF/ICSI, who then show a much lower probability of pregnancy, raising concerns about the safety of this selection procedure. Alternative sperm selection strategies are recommended for those patients.
Unfortunately, we did not record male body mass index (BMI) in our study. This is obviously a limitation for our results interpretation as more and more studies have highlighted to role of BMI of men on fertility issues. In 2013, Anifandis et al. [44] showed that even if male BMI did not correlate with sperm parameters, the groups with the highest BMI had the lowest embryo quality. Moreover, the combination of BMI and age of both men and women had a negative effect on pregnancy rate. A more recent systematic review with thirty papers included [45] confirm these results. Men obesity does not influence conventional sperm parameters but is associated with reduction of live birth rate per cycle and an increase of DNA fragmentation.
The effects of paternal age are difficult to interpret due to the maternal age bias. Indeed, paternal age is strictly correlated with that of the female partner. Our univariate analysis did not allow determining the incidence of paternal age «alone» on the different parameters under study. Nevertheless, our results suggest that from the age of 51 years, paternal age negatively affects the rates of blastocyst formation (IVF) and of clinical pregnancy (ICSI). For both techniques, the rate of early miscarriage was slightly higher (but not significantly) in the age group 51 years. The pregnancy rate reduction associated with increasing paternal age has been already described by Hassan and Killik [46] and De La Rochebrochard and Thonneau [47]). Increasing paternal age also has an effect on the rate of early miscarriages. De La Rochebrochard et al. [48] reported that in the case of maternal age over 35 years and paternal age over 40 years, the risk of early miscarriage is increased. For Kleinhaus [49], this risk is present from the age of 40 years, also after adjustment for maternal age (OR 1.6 vs 25 years). Finally, Slama [50] found that the risk of early miscarriage is higher starting from the paternal age of 35 years. Finally, there is probably a cumulative effect of increasing paternal and maternal age. According to our results, we consider as threshold ages 37 years for women and 51 for men.