Improved embryonic development and utilization rates with EmbryoScope: a within-subject comparison versus a benchtop incubator.

The objective of this study was to investigate whether, in consecutive intracytoplasmic sperm injection (ICSI) cycles, embryonic development in an incubator with a time-lapse imaging (TLI) system is better than the previous one obtained in a benchtop incubator (G-185) with similar cultivation characteristics. The study was of a retrospective within-subject design, in which each cycle served as its own control. Data were obtained via the chart review of patients undergoing ICSI in a private university-affiliated in vitro fertilization (IVF) centre who fulfilled the following criteria: second ICSI attempt in which embryos were cultured in a TLI incubator system (TLI group, n = 71), preceded by a first ICSI attempt in which embryos were cultured in a benchtop incubator (Control group, n = 71). Embryonic development up to the fifth day of development, oocyte utilization rate (OUR; transferred embryos plus frozen embryos per total number of retrieved oocytes) and embryo utilization rate (EUR; transferred embryos plus frozen embryos per normally fertilized oocyte) were compared between the groups. There were significant differences in the day 2 non-cleavage rate, day 5 embryo rate, blastocyst development rate, frozen blastocyst rate, OUR, and EUR, in favour of the TLI group. Embryonic development, frozen blastocyst rate, OUR and EUR in the second ICSI cycle were significantly improved when the culture was performed in the EmbryoScope, compared with those rates obtained with culture in a G-185 in the first ICSI cycle of the same patients. The results may also lead to higher cumulative pregnancy outcomes following embryo thawing and transfer.

Paternal ageing impacts blastulation and the outcomes of pregnancy at different levels of maternal age: A clustering analysis of 21,960 oocytes and 3837 ICSI cycles.

The objective of this cross-sectional study was to investigate the impact of paternal age on the outcomes of intracytoplasmic sperm injection (ICSI) cycles at different values of maternal age. A total of 21,960 injected oocytes deriving from 3837 ICSI cycles performed between January 2014 and October 2020, performed in a private university-affiliated in vitro fertilization centre was included. The main effects of maternal and paternal age, as well as the effect of their product (interaction term) on embryo development and pregnancy outcomes were investigated considering the clustering of data. The coefficients for the interaction term were statistically significant for blastocyst development, top-quality blastocyst, implantation, pregnancy, miscarriage, and live-birth rates. For every 1-year increase in paternal age, the odds ratio of live-birth reduces by 1% in females aged 37 years, 1.6% in those aged 38 years, 2.4% in 39-year-old females, 5% in 42-year-old females and so on. An increase in the interaction term by 1 year decreases the pregnancy rate by 0.4% and live-birth rate by 0.8 and increases the miscarriage rate by 1.2%. The slopes of maternal age on blastulation, blastocyst quality, and implantation, pregnancy, miscarriage, and live-birth rate significantly changed (worsened) for every year increase in paternal age.

Early and late paternal contribution to cell division of embryos in a time-lapse imaging incubation system.

The objective of this study was to investigate the impact of male age, semen quality and days of ejaculatory abstinence on embryo morphokinetics. A total of 1,220 zygotes obtained from 139 couples in a private in vitro fertilisation centre were analysed. The timing of specific events from the point of insemination, such as timings to pronuclei appearance and fading, to two, three, four, five, six, seven and eight cells and to blastulation were recorded. Multivariate linear regression analysis was used to evaluate the influence of paternal factors on embryo morphokinetic events. Paternal age was positively correlated with delayed cell cleavage and blastulation, and negatively associated with implantation rate, and clinical pregnancy and live-birth chances. The ejaculatory abstinence was inversely correlated with the implantation rate. Inverse relationships were observed between semen parameters (sperm count, progressive sperm motility, total motile sperm count and morphology) and the timing of specific events during embryo development. Sperm morphology was also positively associated with implantation rate and pregnancy and live-birth chances. Increased paternal age and ejaculatory abstinence, and poor semen quality correlate with delayed cell cleavage and blastulation and negatively impact intracytoplasmic sperm injection outcomes.

Strategies for the management of OHSS: Results from freezing-all cycles.

OBJECTIVE: To compare the use of GnRH agonist (GnRHa) or hCG trigger in potential OHSS patients undergoing freeze-all programs. We also compared the clinical outcomes when fresh versus freeze-thawed embryo transfers were performed in cycles with a high number of retrieved oocytes. METHODS: The study included potential OHSS patients who received GnRHa (n=74) or hCG (n=49) trigger. The protocols were compared with respect to the clinical outcomes. We also compared the clinical outcomes of cycles in which hCG trigger was used and more than 20 MII oocytes were retrieved when: fresh embryo transfer protocol (n=153) or freeze-all protocol (n=123) were performed. RESULTS: A decreased serum estradiol level, a decreased number of retrieved oocytes, an increased MII retrieved rate, and decreased fertilization rate was observed in the hCG when compared with the GnRHa group. No significant differences were noted concerning clinical outcomes. When fresh cycles were compared with frozen-thawed cycles, the estradiol serum level and the number of cryopreserved embryos were higher in the frozen-thawed cycles. The clinical pregnancy rate was higher among freeze-all cycles, as well as the implantation and cumulative pregnancy rates, when compared with fresh embryo transfer cycles. CONCLUSION: The use of GnRHa trigger may be a good alternative to prevent the OHSS in patients presenting an extreme ovarian response to COS, leading to similar clinical outcomes, when compared with the traditional hCG trigger. Moreover, our findings demonstrated that the strategy of freezing-all embryos not only decreases the risk of OHSS but also leads to a better pregnancy rate.

Endometriosis Affects Oocyte Morphology in Intracytoplasmic Sperm Injection Cycles?

OBJECTIVE: To identify associations between presence of endometriosis and oocyte defects, embryo developmental potential, and cycle outcomes. METHODS: This study looked into the impact of endometriosis on oocyte and embryo quality, and blastocyst formation probability. Endometriosis was also correlated with cycle characteristics. In order to avoid age-related bias, in the first analysis only patients aged 36 years or younger were included, and the cycles were split into endometriosis infertility cycles (n=431; 3172 oocytes) and other cycles (n=2510; 24480 oocytes). RESULTS: The number of retrieved oocytes (10.6±21.2 vs. 14.6±21.1, P<0.001), oocyte yield (68.1±20.0% vs. 70.6±19.6%, P=0.015), and embryos obtained (6.1±4.43 vs. 7.8±5.12, P<0.001) were lower among patients with endometriosis. Implantation rates (28.1%±38.9% vs. 33.9±42.7, P<0.001) were lower among patients with endometriosis, but fertilization, pregnancy, miscarriage and cycle cancelation rates were not different. There was a significant increase in the incidence of extra-cytoplasmic, but not intra-cytoplasmic, oocyte defects among patients with endometriosis. The quality of embryos (45.3% vs. 47.3%, P=0.037) collected from patients with endometriosis was lower, but blastocyst formation rates were unaltered. CONCLUSION: A possible explanation for the lower implantation rates seen in patients with endometriosis is the poorer quality of the oocytes and embryos observed in this group of patients.

Sperm morphological normality under high magnification predicts laboratory and clinical outcomes in couples undergoing ICSI.

The objective of this study was to evaluate whether 'motile sperm organelle morphology examination' (MSOME) is correlated with the outcome of ICSI. A total of 14400 spermatozoa from 72 couples undergoing ICSI were analysed by MSOME (x6600) and graded into four groups: grade I, normal form and no vacuoles; grade II, normal form and lesser than or equal to 2 small vacuoles; grade III, normal form greater than 2 small vacuoles or at least one large vacuole and grade IV, large vacuole and abnormal head shapes or other abnormalities. The correlations between the proportion of morphologically normal spermatozoa (grade I + II) and ICSI outcomes were assessed. The proportion of grade I+ II spermatozoa was lower in patients with oligoasthenoteratozoospermia (OAT) compared to patients with other types of semen alterations (10.6% vs. 17.0%, p = 0.001). The proportion of grade I+ II spermatozoa was positively correlated with blastocyst formation (S = 8.31, R(2):13.5%, p = 0.014) and implantation rates (S = 8.32, R(2): 7.9%, p = 0.030). The proportion of grade I + II spermatozoa was higher in patients with ongoing pregnancy in comparison with those who had a miscarriage (23.2% vs. 10.8%, p = 0.007). Sperm morphological normality was lower in oligoasthenoteratozoospermia patients but correlated with blastocyst formation, implantation and miscarriage rates in couples undergoing ICSI. MSOME may be valuable in predicting ICSI outcomes.

Sperm morphological abnormalities visualised at high magnification predict embryonic development, from fertilisation to the blastocyst stage, in couples undergoing ICSI.

PURPOSE: To investigate the predictive value of the motile sperm organelle morphology examination (MSOME) on embryo morphology. METHODS: The morphologies of 540 embryos obtained from 60 couples undergoing ICSI were evaluated from days 1 to 5 of development and were examined for associations with the percentages of morphologically normal paternal sperm and of the paternal sperm with large nuclear vacuoles (LNVs) as determined by MSOME. RESULTS: An increased percentage of LNV sperm was associated with increased odds of a zygote presenting with pronuclear abnormalities. It was also associated with decreased odds of (i) normal cleavage on days 2 and 3 of development, (ii) the presence of a high-quality embryo on day 3, (iii) the development of an embryo to the blastocyst stage, and (iv) an embryo possessing a normal trophectoderm and inner cell mass. The calculated areas under the curves differed for the embryos that did and did not develop to the blastocyst stage and for the high- and low-quality blastocysts. The optimal cut-off value for the percentage of LNV sperm that maximised proper blastocyst formation was ≤24.5 %, and the cut-off value that maximised blastocyst quality was ≤19.5 %. CONCLUSIONS: These results suggest a very early onset of paternal influences on embryo development. The evaluation of the incidence of vacuoles by MSOME may significantly improve upon the prognostic information provided by conventional semen analyses.

The prevalence of sperm with large nuclear vacuoles is a prognostic tool in the prediction of ICSI success.

PURPOSE: To investigate if there is a correlation between the prevalence of sperm with large nuclear vacuoles (LNV) and intracytoplasmic sperm injection (ICSI) outcomes. METHODS: Two hundred male patients undergoing ICSI had their sperm morphology evaluated through motile sperm organelle morphology examination (MSOME) and the percentage of LNV sperm was recorded and correlated to the ICSI outcomes. RESULTS: The percentage of sperm with LNV negatively influenced the blastocyst formation (S: 16.9, R(2): 20.5%, p = 0.004) and implantation (S: 34.7, R(2): 26.2%, p = 0.001). There were significant differences in the percentage of sperm with LNV between patients in which pregnancy was achieved or not (22.2% vs. 28.4%, p < 0.001) and in patients with ongoing pregnancy or not (22.4% vs. 28.5%, p < 0.001). The incidence of sperm with LNV was determinant to the decreased odds of pregnancy (OR: 0.74, p < 0.001) and increased odds of miscarriage (OR: 1.46, p < 0.001). The area under the curve (AUC) was sufficient to distinguish between couples which did achieve pregnancy or not (AUC: 0.922, p < 0.001). CONCLUSIONS: The MSOME is a prognostic tool in the prediction of ICSI success and could be used to select patients that should have their sperm selected by MSOME for ICSI.

Intracytoplasmic morphologically selected sperm injection outcomes: the role of sperm preparation techniques.

PURPOSE: To compare the results of intracytoplasmic morphologically selected sperm injection (IMSI) between cycles in which the swim-up (SUP) or the density gradient centrifugation (DGC) techniques were used for sperm preparation. METHODS: We evaluated 70 IMSI cycles performed in women with age ≤ 37 years, undergoing IMSI as result of male factor. The couples were divided into two groups: DGC group (n = 26) and SUP group (n = 44). The groups were compared with regard to IMSI outcomes. RESULTS: There were no significant differences between SUP and DGC groups regarding the number of follicles, oocytes, mature oocytes, oocyte yield and mature oocyte rate. Fertilization rate and high-quality embryos rate on day 5 of development were similar between SUP and DGC groups. Implantation, pregnancy and miscarriage rates were not statistically different between SUP and DGC groups (28.8 vs 33.3 %, 46.2 vs 57.1 % and 8.3 vs 4.2 %, respectively). CONCLUSIONS: Both the SUP and the DGC techniques recover improved sperm fractions and result in similar IMSI outcomes. Further randomized trials analyzing both the quality of sperm through MSOME and the IMSI outcomes are needed to elucidate the role of sperm preparation techniques and morphology on IMSI outcomes.

Body mass index is negatively correlated with the response to controlled ovarian stimulation but does not influence oocyte morphology in ICSI cycles.

OBJECTIVE: To investigate whether or not body mass index (BMI) is associated with oocyte dysmorphisms. STUDY DESIGN: This retrospective study enrolled 1105 patients undergoing intracytoplasmic sperm injection (ICSI). The correlation between BMI and the response to controlled ovarian stimulation (COS) and ICSI outcomes was analysed. Oocyte morphology was determined in metaphase II (MII) oocytes retrieved from all cycles. The influence of BMI on the odds of having oocyte dysmorphism was also studied. RESULTS: A negative correlation was found between BMI and the number of oocytes retrieved, MII oocytes, oocytes injected, embryos obtained, high-quality embryos and oocyte recovery rate. In addition, a trend towards a negative correlation between BMI and implantation rate was observed. However, BMI did not influence oocyte dysmorphisms. CONCLUSIONS: A negative correlation was found between BMI and the response to COS, and a trend towards a negative correlation was observed between BMI and implantation rate in the ICSI cycles. However, oocyte dysmorphisms were not influenced by BMI and, therefore, do not account for the reduced ICSI outcomes.