P–066 Does microfluidic sperm sorting (MSS) affect embryo euploidy rates in couples with high sperm DNA fragmentation (SDF)?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Keskin ◽  
E G Pabuçcu ◽  
A Tufan ◽  
D.Ö Demirkıran ◽  
R Pabuçcu
Keyword(s):  
Dna Fragmentation ◽  
Live Birth ◽  
Embryo Quality ◽  
Gradient Centrifugation ◽  
Small Sample ◽  
Sperm Dna Fragmentation ◽  
Birth Rates ◽  
Live Birth Rates ◽  
Sperm Dna ◽  
Euploidy Rates

Abstract Study question Does MSS (microfluid chip-sorted spermatozoa selection) provide improvement on embryo quality and euploidy rates in couples with high SDF (sperm DNA fragmentation) and previous failed in vitro fertilization/ intracystoplasmic sperm injection (IVF/ICSI) cycles? Summary answer Use of MSS technique provides higher number of top quality blastocysts compared to density gradient centrifugation (DGC), however euploidy and live birth rates weren’t improved. What is known already Previously it has been reported that sperm DNA damage leads to poor embryo development and there is a significant association between SDF and high embryo aneuploidy rates. Recently this fact raised attention to sperm selection techniques such as MSS to enhance embryo quality, miscarriage rates and embryonic euploidy rates. Study design, size, duration This was a retrospective electronic medical record (EMR) analysis of a tertiary assisted reproduction center between 2016 and 2020. All EMR were reviewed to select eligible cases as; couples undergoing a new IVF/ICSI cycle with PGT-A (preimplantation genetic testing for aneuploidies). In total, data from 243 patients were obtained for the analysis that accounts for 688 embryos. Participants/materials, setting, methods Patients had at least 2 previous failed IVF cycles and males had at least 20% SDF. In their new cycles, MSS was offered, preceding ICSI and PGT-A. Couples who accepted the technique were assigned to MSS group (92 cycles with 310 embryos) and the rest were managed with DGC and assigned as controls (151 cycles with 378 embryos). Azoospermia cases and women with age>43, uterine abnormalities, trombophilia were excluded. Biopsies were performed at blastocyst stage. Main results and the role of chance Two groups were comparable in terms of demographic data including women and men age, SDF, sperm parameters and cycle characteristics. There was no difference between groups in terms of fertilization rates (MSS 85% vs DGC 79% p = 0.9), euploidy rates (MSS 53.2% vs DGC 50.7% p = 0.3), mean no of euploid embryo per patient (MSS 1.09 vs DGC 0.95 p = 0.3), positive pregnancy test (MSS 50% vs DGC 38.4% p = 0.06), clinical miscarriage (MSS 7.6% vs DGC 6.6% p = 0.7) and live birth rates (LBR)(MSS 42.4% vs DGC 31.7% p = 0.09). Total no of blastocysts and top quality blastocysts were significantly higher in MSS group than in DGC (3.9 vs 2.5 p < 0.01 and 1.6 vs 0.8 p < 0.001 respectively). Limitations, reasons for caution Retrospective design, small sample size, lack of proper randomization and power analysis are the main limitations. Wider implications of the findings: Offering PGT-A to couples with unexplained repeated IVF failures and high SDF seems feasible. MSS for such cases improves embryonic division process as improved blastulation rates were documented. However, euploidy rates were not improved in MSS group revealing that other factors influence comprehensive chromosomal status of an embryo. Trial registration number Not applicable

Sperm DNA fragmentation measured by sperm chromatin dispersion impacts morphokinetic parameters, fertilization rate and blastocyst quality in ICSI treatments

Zygote ◽  
2021 ◽  
pp. 1-8
Author(s):  
Shikai Wang ◽  
Weihong Tan ◽  
Yueyue Huang ◽  
Xianbao Mao ◽  
Zhengda Li ◽  
...  
Keyword(s):  
Dna Fragmentation ◽  
Embryo Quality ◽  
Fertilization Rate ◽  
Sperm Chromatin ◽  
Sperm Dna Fragmentation ◽  
Blastocyst Formation ◽  
High Quality ◽  
Morphokinetic Parameters ◽  
Sperm Dna ◽  
Blastocyst Quality

Summary To determine the effects of sperm DNA fragmentation (SDF) on embryo morphokinetic parameters, cleavage patterns and embryo quality, this retrospective study analyzed 151 intracytoplasmic sperm injection (ICSI) cycles (1152 embryos collected) between November 2016 and June 2019. SDF was assessed using sperm chromatin dispersion. The cycles were divided into two groups based on the SDF rate: SDF < 15% (n = 114) and SDF ≥ 15% (n = 37). The embryo morphokinetic parameters, cleavage patterns, and embryo quality were compared between the two groups. The morphokinetic parameters tPNf, t2, t3, t4, t5, t6, and t8 were achieved significantly earlier in the SDF < 15% group compared with in the SDF ≥ 15% group. The fertilization and 2PN rates seemed to be significantly higher in the SDF < 15% group compared with in the SDF ≥ 15% group, while the abnormal cleavage rates were similar. However, a significantly higher rate of chaotic cleavage (CC) was observed in the SDF ≥ 15% group. The D3 high-quality embryo and available embryo rates were similar between the two groups. The blastocyst formation, high-quality blastocyst, and available blastocyst rates in the SDF < 15% group were significantly higher than those in the SDF ≥ 15% group. With an increase in SDF level, the chemical pregnancy, clinical pregnancy and implantation rates tended to decrease, while the miscarriage rate increased. This study demonstrated that SDF ≥ 15% reduces the fertilization rate of ICSI cycles and affects certain morphokinetic parameters. A higher SDF level can also induce a higher rate of CC, with subsequent decreases in the blastocyst formation rate and blastocyst quality.

O-212 MACS vs TESA for raised sperm DNA fragmentation index – a RCT

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
K C Mantravadi ◽  
D R Gedela
Keyword(s):  
Dna Fragmentation ◽  
Live Birth ◽  
Trial Registration ◽  
Sperm Dna Fragmentation ◽  
Sperm Selection ◽  
Reproductive Outcomes ◽  
Fragmentation Index ◽  
Sperm Dna ◽  
Sperm Dna Fragmentation Index ◽  
Dna Fragmentation Index

Abstract Study question In Individuals with raised Sperm DNA Fragmentation Index (SDF), will sperm selection by magnetic activated cell sorting (MACS) or surgical retrieval of testicular sperms (TESA) optimize the reproductive outcomes? Summary answer Couples with failed implantation raised SDF, TESA /MACS offer similar results. This RCT doesn’t prove superiority or added benefit with any of the above interventions. What is known already It is evident that raised SDF negatively affects the reproductive outcomes. Management for raised SDF to optimize reproductive outcomes is still elusive. Study design, size, duration This was a Randomized Control Trial (RCT) with prior approval from institutional Ethical Committee and trial registration. Couples undergoing stimulation with raised SDF were randomized to MACS (n = 75) and TESA (n = 75) for sperm selection between April2019 & February2020. Participants/materials, setting, methods Couples with history of one failed IVF had SDF testing and SDF&gt;30% were recruited. SDF test done with SCSA method and randomized using software. ICSI was the method of insemination. Extended embryo culture till blastocyst was done and freeze all policy was opted. Two Blastocysts that showed 100% survival were transferred in a Frozen Embryo transfer (FET) cycle. Embryonic and Reproductive outcomes were compared between both groups. Live birth and Miscarriage were the primary outcomes. Main results and the role of chance Reproductive Outcomes of MACS Vs TESA were: Average Blastocyst conversion - 32% Vs 39% (RR 1.22, CI1.00 to 1.50) Implantation rate (IR) - 50% Vs 35% (RR - 0.71, CI 0.51 to 0.98) Miscarriage rate (MR) - 5.3% Vs 11% (RR1.6333, CI 0.5227 to 5.1039) Multiple Pregnancy rate (MPR) - 8% Vs 4% Live birth Rate (LBR) per Intention to treat (ITT) - 41.3% Vs 44% (RR 0.95, 95% CI 0.72 to 1.26) LBR per ET cycle - 63% Vs 56% (RR 1.23, 95% CI 0.77 to 1.94) Our preliminary results suggest that despite greater availability of blastocysts for transfer in the TESA group, no difference in ART outcomes was observed between the groups. Though the IR was statistically low with TESA, our primary outcomes LBR and MR were comparable. TESA or MACS seem to offer similar outcomes. Considering the invasiveness with TESA, MACS can be offered for better sperm selection for couples with raised sperm DFI & failed implantation. Limitations, reasons for caution Small sample size. TESA is a surgical intervention Wider implications of the findings Optimal intervention for management of SDF still needs further research. Trial registration number CTRI/2019/07/020140

P–080 Higher sperm DNA fragmentation reduces the proportion of good quality embryos at day 5 on IVF and ICSI cycles from unselected males

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
I Hervá. Herrero ◽  
A Pacheco ◽  
R Rivera-Egea ◽  
M Gi. Julia ◽  
A Navarro-Gomezlechon ◽  
...  
Keyword(s):  
Dna Fragmentation ◽  
Embryo Quality ◽  
Blastocyst Stage ◽  
Dna Integrity ◽  
Embryo Morphology ◽  
Sperm Dna Fragmentation ◽  
Cleavage Stage ◽  
Sperm Dna ◽  
Embryo Fragmentation ◽  
The Impact

Abstract Study question Does sperm DNA fragmentation (SDF) reduce the ratio of good-quality embryos in day 3 (D3) and day 5 (D5) of embryonic development? Summary answer High sperm DNA fragmentation (SDF &gt;15%) is associated with poor embryo quality at blastocyst-stage per cycle in unselected patients undergoing IVF and ICSI. What is known already It has been shown that the proportion of spermatozoa with DNA fragmentation is higher in infertile men than in semen from fertile men. However, the controversy regarding the impact that sperm genome damage can have on IVF or ICSI treatments is evident in the published literature. The effects of SDF would become evident after activation of the embryonic genome at 8-cell stage, compromising not only the quality of the embryos obtained, but also the reproductive outcomes, as reduced implantation rates, higher miscarriages rates and thus, a decreased chance of pregnancy. Study design, size, duration This multicentric observational retrospective study included 1339 couples who underwent 2759 IVF-ICSI cycles using autologous oocytes from January 2000 to March 2019. All men have an SDF test in their ejaculated spermatozoa by TUNEL assay (Terminal deoxynucleotidyl transferase dUTP nick end labeling). The subjects were divided into two groups according to their sperm DNA integrity: low (≤15%) (n = 2287 cycles) or high (&gt;15%) (n = 472) SDF. Participants/materials, setting, methods Embryo quality was assessed complying morphological standards at cleavage-stage on D3 and at blastocyst-stage on D5 (inner cell mass (ICM) and trophectoderm (TE) grade (A, B, C or D)) in according to ASEBIR’s embryo selection criteria, being embryos of good quality those categorized as A+B. The outcomes were calculated in relation to the total number of zygotes obtained. The results were compared by Student t test; p value &lt;0.05 was considered significant. Main results and the role of chance The SDF average of the low group was 5.8% (95% CI 5.6–5.9) whereas in high group was 23.7% (95% CI 23.0–24.4). The female age was equal, 37.1 years (95%CI 37.0–37.2) and 37.1 years (95% CI 36.8–37.4) respectively. A total of 9796 embryos were evaluated. The optimal cleavage-stage embryo rate per cycle was 25.0% (95% CI 21.7–28.3) (8.0 average cells number, 1.5 embryo fragmentation average, symmetry 1, mononucleated cells) versus 26.7% (95%CI 19.1–34.2) (7.9 average cells number, 1.8 embryo fragmentation average, symmetry 1, mononucleated cells) when comparing between groups (p &lt; 0.001). Blastocyst-stage arrival rate (number of embryos at D5) per cycle was 55.8% (95% CI 54.3–57.2) in ≤ 15% SDF group (embryo quality score was ICM A:12.1%, B:69.5%, C:8.8%, D:4.5%; TE A: 7.5%, B:42.2%, C:42.2%, D:8.1%) and 55.9% (95% CI 52.8–59.1) in the &gt;15% SDF group (ICM A:12.0%, B:68.7%, C:10.6%, D: 5.2%; TE A:9.1%, B:44.8%, C:37.8%, D:8.3%) (p &lt; 0.001). The good quality blastocyst rate per cycle was significantly higher in the group with SDF ≤15%, 27.7% (95%CI 26.5–29.0) versus SDF &gt;15% (27.4% (95%CI 24.6–30.2)). Of the total number of blastocysts, the proportion of A+B blastocyst was 60.5% (95% CI 58.3–62.7) and 64.2% (95% CI 59.2–69.2) (p &lt; 0.001), respectively. Limitations, reasons for caution The retrospective and multicenter nature of this study leads to uncontrolled biases derived from the clinical practice. Although the results were not adjusted for female’s age, it was not statistically different between groups. Embryo morphology evaluation was performed by senior embryologists, it still remains a subjective evaluation, though. Wider implications of the findings: In this study, a higher amount of data was compiled so that a large number of embryos were analyzed. The DNA integrity of the sperm may be an important consideration when poor quality embryos were obtained in the previous cycle when deciding on the next clinical strategy to apply. Trial registration number NA

P–237 The good, the fast and the slow: which is better? Live birth rate following single blastocyst frozen embryo transfer

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
P Sokol ◽  
E Clu. Obradó ◽  
M Sol Inarejos ◽  
M Parrieg. Beltrán ◽  
F Martíne. Sa. Andrés ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Embryo Transfer ◽  
Live Birth ◽  
Embryo Quality ◽  
Frozen Embryo Transfer ◽  
Birth Rates ◽  
Live Birth Rates ◽  
Actual Effect ◽  
Blastocyst Quality ◽  
The Impact

Abstract Study question Are embryo quality and day of vitrification (Day 5, 6 or 7) associated with live birth rates (LBR) following single blastocyst transfer (SBT) in frozen embryo transfer cycle (FET)? Summary answer Both blastocyst quality and day of vitrification are significantly associated with LBRs, with very low LBR when poor quality embryos are frozen on day 6. What is known already Evidence suggests that chromosomal status (ploidy) is strongly associated with blastocyst morphology and good quality embryos are more likely to be euploid. Furthermore, previous studies have shown a relationship between the time that embryos need to reach blastocyst stage and their euploidy rate with slowly developing blastocysts showing higher rate of aneuploidy. Nonetheless, despite all this evidence little is known about the actual effect of the combination of blastocyst quality and day of its vitrification. The scope of this study was to quantify the actual effect of the embryo quality and day of vitrification on live birth rates following FET. Study design, size, duration Retrospective analysis of 1546 FET cycles with SBT conducted between 2017 and 2019 in the university-affiliated private clinic. The embryos used for FET were obtained from IVF/ICSI: with PGT (FET-PGT) or without PGT (FET0) or from donated oocytes (FET-DON). Participants/materials, setting, methods FET with natural, natural-modified and completely medicated cycles to prepare endometrial lining were included. Blastocysts were classified according to Spanish Association for the Study of Reproductive Biology (ASEBIR) classification, ranging from A (the highest) to D (the lowest). The impact on LBR of different subgroups, formed within FET-PGT, FET0, FET-DON groups due to different day of vitrification and blastocyst quality, was assessed, using logistic regression after adjusting for age, day of vitrification and embryo quality. Main results and the role of chance We included 1546 FET cycles. Of those, 543 (35%) corresponded to FET-PGT; 648 (42%) to FET0 and 355 (23%) to FET-DON cycles. Overall, 1051 (68%) embryos were frozen on day 5(D5), 472 (30.5%) on day 6(D6) and 23 (1.5%) on day 7(D7). As far as embryo quality was concerned, 215 (13.9%) grade A; 957 (61.9%) B; 371(24%) C and 3(0.2%) D blastocysts were transferred. LBRs were significantly different between different embryos frozen on D5 44.3%; on D6 28.8% and on D7 8.7%, p &lt; 0.001. When blastocyst quality was considered, LBR were 48.4% for grade A; 42.5% for B; 25.1% for C and 0% for D, p &lt; 0.001. After applying logistic regression analysis, the odds ratio (OR) for transferring D6-blastocyst was 1.08, 95% CI[0.45; 2.62] and blastocyst with grade B and C; 0.71, 95% CI[0.51; 1.00]; 0.57,95% CI[0.36; 0.88] respectively. However, after transferring D6-blastocyst graded as C, the OR was 0.33, 95% CI[0.12; 0.90]. Our predictive model showed that the impact of the embryo quality on LBR was sustained across three groups. Transfer of D5/D6 grade A blastocyst resulted in the highest, while D6-C in the lowest LBR in all the groups. In the latter case vitrification on D6 impaired additionally the outcome. Limitations, reasons for caution The study should be interpreted with caution due to its retrospective character and the assessment of blastocyst quality on the day of vitrification and not on the day its transfer. Wider implications of the findings: Our robust findings could be considered a useful tool for counselling couples who seek advice regarding their expected success rates in the setting of FET with SBT. The very low livebirth rates in low quality (C) slow developing (D6) embryos should be communicated to patients prior to planning a FET. Trial registration number Not applicable

Does Microfluidic Sperm Sorting Affect Embryo Euploidy Rates in Couples with High Sperm DNA Fragmentation?

2021 ◽  
Author(s):  
Müge Keskin ◽  
Emre Göksan Pabuçcu ◽  
Tufan Arslanca ◽  
Özgür Doğuş Demirkıran ◽  
Recai Pabuçcu
Keyword(s):  
Dna Fragmentation ◽  
Sperm Dna Fragmentation ◽  
Sperm Dna ◽  
Sperm Sorting ◽  
Euploidy Rates

scholarly journals No effect of ovarian stimulation and oocyte yield on euploidy and live birth rates: an analysis of 12 298 trophectoderm biopsies

2020 ◽  
Vol 35 (5) ◽  
pp. 1082-1089 ◽  
Author(s):  
M Irani ◽  
C Canon ◽  
A Robles ◽  
B Maddy ◽  
V Gunnala ◽  
...  
Keyword(s):  
Live Birth ◽  
Ovarian Stimulation ◽  
Estradiol Level ◽  
Birth Rates ◽  
Live Birth Rates ◽  
Follicle Size ◽  
Estradiol Levels ◽  
Gonadotropin Dosage ◽  
Euploid Embryo ◽  
Euploidy Rates

STUDY QUESTION Does ovarian stimulation affect embryo euploidy rates or live birth rates (LBRs) after transfer of euploid embryos? SUMMARY ANSWER Euploidy rates and LBRs after transfer of euploid embryos are not significantly influenced by gonadotropin dosage, duration of ovarian stimulation, estradiol level, follicle size at ovulation trigger or number of oocytes retrieved, regardless of a woman’s age. WHAT IS KNOWN ALREADY Aneuploidy rates increase steadily with age, reaching &gt;80% in women &gt;42 years old. The goal of ovarian stimulation is to overcome this high aneuploidy rate through the recruitment of several follicles, which increases the likelihood of obtaining a euploid embryo that results in a healthy conceptus. However, several studies have suggested that a high response to stimulation might be embryotoxic and/or increase aneuploidy rates by enhancing abnormal segregation of chromosomes during meiosis. Furthermore, a recent study demonstrated a remarkable difference in euploidy rates, ranging from 39.5 to 82.5%, among young oocyte donors in 42 fertility centres, potentially suggesting an iatrogenic etiology resulting from different stimulation methods. STUDY DESIGN, SIZE, DURATION This is a retrospective cohort study that included 2230 in vitro fertilisation (IVF) with preimplantation genetic testing for aneuploidy (PGT-A) cycles and 930 frozen-thawed single euploid embryo transfer (FET) cycles, performed in our centre between 2013 and 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 12 298 embryos were analysed for ploidy status. Women were divided into five age groups (&lt;35, 35–37, 38–40, 41–42 and &gt;42 years old). Outcomes were compared between different durations of stimulation (&lt;10, 10–12 and ≥13 days), total gonadotropin dosages (&lt;4000, 4000–6000 and &gt;6000 IU), numbers of oocytes retrieved (&lt;10, 10–19 and ≥20 oocytes), peak estradiol levels (&lt;2000, 2000–3000 and &gt;3000 pg/mL), and sizes of the largest follicle on the day of trigger (&lt;20 and ≥20 mm). MAIN RESULTS AND THE ROLE OF CHANCE Within the same age group, both euploidy rates and LBRs were comparable between cycles regardless of their differences in total gonadotropin dosage, duration of stimulation, number of oocytes harvested, size of the largest follicles or peak estradiol levels. In the youngest group, (&lt;35 years, n = 3469 embryos), euploidy rates were comparable between cycles with various total gonadotropin dosages (55.6% for &lt;4000 IU, 52.9% for 4000–6000 IU and 62.3% for &gt;6000 IU; P = 0.3), durations of stimulation (54.4% for &lt;10 days, 55.2% for 10–12 days and 60.9% for &gt;12 days; P = 0.2), number of oocytes harvested (59.4% for &lt;10 oocytes, 55.2% for 10–19 oocytes and 53.4% for ≥20 oocytes; P = 0.2), peak estradiol levels (55.7% for E2 &lt; 2000 pg/mL, 55.4% for E2 2000–3000 pg/mL and 54.8% for E2 &gt; 3000 pg/mL; P = 0.9) and sizes of the largest follicle (55.6% for follicles &lt;20 mm and 55.1% for follicles ≥20 mm; P = 0.8). Similarly, in the oldest group (&gt;42 years, n = 1157 embryos), euploidy rates ranged from 8.7% for gonadotropins &lt;4000 IU to 5.1% for gonadotropins &gt;6000 IU (P = 0.3), from 10.8% for &lt;10 days of stimulation to 8.5% for &gt;12 days of stimulation (P = 0.3), from 7.3% for &lt;10 oocytes to 7.4% for ≥20 oocytes (P = 0.4), from 8.8% for E2 &lt; 2000 pg/mL to 7.5% for E2 &gt; 3000 pg/mL (P = 0.8) and from 8.2% for the largest follicle &lt;20 mm to 8.9% for ≥20 mm (P = 0.7). LBRs after single FET were also comparable between these groups. LIMITATIONS, REASONS FOR CAUTION Although this large study (2230 IVF/PGT-A cycles, 12 298 embryos and 930 single FET cycles) demonstrates the safety of ovarian stimulation in terms of aneuploidy and implantation potential of euploid embryos, a multi-centre study may help to prove the generalisability of our single-centre data. WIDER IMPLICATIONS OF THE FINDINGS These findings reassure providers and patients that gonadotropin dosage, duration of ovarian stimulation, estradiol level, follicle size at ovulation trigger and number of oocytes retrieved, within certain ranges, do not appear to significantly influence euploidy rates or LBRs, regardless of the woman’s age. STUDY FUNDING/COMPETING INTEREST(S) No external funding was received and there are no competing interests to declare. TRIAL REGISTRATION NUMBER N/A

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