scholarly journals Sperm selection for assisted reproduction by prior hyaluronan binding: the HABSelect RCT

2019 ◽  
Vol 6 (1) ◽  
pp. 1-80
Author(s):  
Jackson Kirkman-Brown ◽  
Sue Pavitt ◽  
Yacoub Khalaf ◽  
Sheena Lewis ◽  
Richard Hooper ◽  
...  
Keyword(s):  
Dna Fragmentation ◽  
Outcome Measures ◽  
Live Birth ◽  
Intracytoplasmic Sperm Injection ◽  
Primary Outcome ◽  
Sperm Quality ◽  
Clinical Pregnancy ◽  
Research Network ◽  
Sperm Selection ◽  
Selection For

Background Sperm selection for intracytoplasmic sperm injection (ICSI) has traditionally relied on standardised methods of sperm processing combined with subjective sperm selection (motility/morphology). In 2012, live birth rates (LBRs) stood at ≈24% per cycle started (32% per cycle reaching embryo transfer). Objective(s) The main clinical objective was to determine the benefits of a hyaluronan (HA)-based sperm selection process for physiological intracytoplasmic sperm injection (PICSI). A parallel, mechanistic objective evaluated sperm chromatin integrity and the potential of PICSI to compensate for poor sperm quality. Design A Phase III, parallel-arm, blinded randomised controlled trial (RCT) of efficacy of PICSI versus ICSI alongside mechanistic evaluation. Setting The RCT ran from February 2014 to August 2016, involving NHS (n = 14) and private (n = 2) UK hospital or satellite clinics. Mechanistic work was conducted in three university-based research laboratories and a partnering small–medium enterprise from June 2015 to December 2017. Participants Couples undergoing an ICSI procedure using freshly ejaculated sperm with female partners aged between 18 and 43 years and male partners aged between 18 and 55 years. Intervention Health and Care Professions Council-registered embryologists used the Medicines and Healthcare products Regulatory Agency-registered (HA-coated) PICSI™ dish (Origio, Måløv, Denmark) to select a single sperm for injection. Control couples received standard care. Main outcome measures Clinical – the primary outcome was full-term live birth (≥ 37 weeks’ gestation). Secondary outcome measures were confirmed clinical pregnancy (CP), miscarriage following confirmation and preterm live birth (< 37 weeks’ gestation). Mechanistic – measurement models were designed for deoxyribonucleic acid (DNA) fragmentation, compaction and HA binding [HA binding score (HBS)]. Results A total of 2772 couples were randomised and 2752 couples were included in the primary analysis (PICSI, n = 1371; and ICSI, n = 1381). Clinical – primary outcome: 379 out of 1381 (27.4% PICSI) and 346 out of 1371 (25.2% ICSI) couples who were randomised (up to 24 hours before treatment) into the trial achieved a term live birth ≥ 37 weeks’ gestation [odds ratio (OR) 1.12, 95% confidence interval (CI) 0.94 to 1.34; p = 0.18]. Subgroup analyses did not reveal differences in treatment effects for HBS, maternal age, previous miscarriage, follicle-stimulating hormone or anti-Müllerian hormone levels and paternal sperm concentrations. Secondary outcomes: CP was achieved for 487 out of 1382 (35.2% PICSI) and 491 out of 1375 (35.7%, ICSI) couples (OR 0.98, 95% CI 0.84 to 1.15; p = 0.80). Miscarriage affected 60 out of 1381 (4.3% PICSI) and 96 out of 1371 (7.0% ICSI) of couples (OR 0.61, 95% CI 0.43 to 0.84; p = 0.003). Preterm LBRs were 46 out of 1381 (3.3% PICSI) and 45 out of 1371 (3.3% ICSI) (OR 1.02, 95% CI 0.67 to 1.55; p = 0.94). Mechanistic: in the subset of samples examined, HBS correlated with sperm motility, concentration, fertilisation rate and DNA fragmentation. Sperm DNA compaction was weakly associated with clinical pregnancy rates (CPRs), but neither HBS nor DNA fragmentation was predictive of any clinical outcome. Limitations Embryologists were not blinded and limited data were available from poorer samples and non-random sample selection in the mechanistic cohort. Prepared rather than raw semen was used for tests of DNA integrity. Conclusions PICSI offered no clear advantage in relation to the primary outcome. PICSI led to a reduced miscarriage risk, but had no effect on CPR or preterm LBR. Future work Re-evaluate PICSI focusing on CP and miscarriage rates and consider aspects of sperm quality that PICSI favours. Trial registration Current Controlled Trials ISRCTN99214271. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. The research is also supported by the NIHR Infrastructure at Leeds and the NIHR Clinical Research Network.

P–058 The effect of sperm DNA fragmentation on intracytoplasmic sperm injection (ICSI) outcome

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Arafa ◽  
H Elbardisi ◽  
S AlSaid ◽  
H Burjaq ◽  
T AlMazooqi ◽  
...  
Keyword(s):  
Dna Fragmentation ◽  
Live Birth ◽  
Intracytoplasmic Sperm Injection ◽  
Male Fertility ◽  
Birth Rate ◽  
Live Birth Rate ◽  
Clinical Pregnancy ◽  
Sperm Dna Fragmentation ◽  
Reproductive Outcomes ◽  
Sperm Dna

Abstract Study question Does the sperm DNA fragmentation (SDF) level impact the clinical outcome of couples undergoing intracytoplasmic sperm injection (ICSI)? Summary answer No significant effect was observed for SDF on the reproductive outcome of couples undergoing ICSI. What is known already Sperm DNA Fragmentation (SDF) has emerged as an important biomarker in the assessment of male fertility potential. It is currently being used as one of the advanced sperm function tests along with other conventional methods in male fertility evaluation. The impact of SDF on the reproductive outcomes of ICSI remains to be controversial. Evidence extracted from three meta-analyses have indicated that higher SDF is not associated with a negative impact on ICSI outcomes. On the contrary, another meta-analysis revealed that SDF can have a significant impact on the pregnancy rate of ICSI with an OR of 1.31. Study design, size, duration This is a retrospective cohort study carried out in the assisted conception unit of a tertiary medical center. The study duration was over a 5-year period from August 1st, 2014 to August 1st, 2019. The charts of 1922 patients who underwent ICSI were screened for inclusion in the study. Inclusion criteria were patients who underwent ICSI using ejaculate spermatozoa and had a recorded SDF test done within a week before ICSI (n = 390). Participants/materials, setting, methods Sperm chromatin dispersion was used to evaluate SDF utilizing the Halosperm G2 test kit (Halotech, Madrid, Spain). All patients performed the ICSI trial using ejaculated spermatozoa. Patients were divided according to the SDF level into 3 groups; SDF &lt;20% (n = 148), SDF 20–30% (n = 133), and SDF &gt;30% (n = 109). Female partner fertility status was recorded and couples were grouped into 2 groups based on age and AMH levels; (1) favorable female and (2) unfavorable female status. Main results and the role of chance Overall, clinical pregnancy occurred in 45% of cases, live birth rate was 33.60%, and 1.30% of patients had miscarriage. A significant negative correlation between SDF and sperm count (r–0.232), motility (r–0.469), progressive motility (r–0.312) and normal morphology (r–0.297) was detected (p &lt; 0.001 for all). Fertilization rate, clinical pregnancy and live birth rate were greater in patients with lower SDF than those with higher SDF in both favorable and unfavorable groups, however the difference was not statistically significant (Table 1). Limitations, reasons for caution The main limitation of our study was the retrospective nature of the study where some data may be missing or incomplete. The data was also retrieved from one ART center, therefore our data lacked diversity within methodologies for IVF and SDF testing. Wider implications of the findings: SDF was found to be significantly correlated with conventional semen parameters highlighting its significance as a robust diagnostic test during male fertility evaluation. In this study, while patients with higher SDF values had worse reproductive outcomes with ICSI, the results did not reach statistical significance. Trial registration number NA

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–025 Sperm selection using a modified “swim up” technique in absence of sperm centrifugation improve sperm DNA fragmentation and decreases miscarriage rate

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Y Cabell. Vives ◽  
P Belchin ◽  
C Lopez-Fernandez ◽  
M Fernandez-Rubio ◽  
J Guerrero-Sanchez ◽  
...  
Keyword(s):  
Dna Fragmentation ◽  
Sperm Quality ◽  
P Value ◽  
Sperm Dna Fragmentation ◽  
Sperm Selection ◽  
Male Factor ◽  
Miscarriage Rate ◽  
Sperm Dna ◽  
Group 2

Abstract Study question Is it useful to avoid sperm centrifugation in laboratory routine work to improve sperm quality and reproductive outcome in Assisted Reproduction Techniques (ART)? Summary answer Exclusion of sperm centrifugation for sperm selection using neat sperm samples (IO-lix), increases sperm quality in the collected subpopulation decreasing miscarriage rate after using ICSI. What is known already Inclusion of sperm centrifugation in ART is an aggressive intervention for sperm selection with ineludible production iatrogenic damage affecting sperm integrity. The application of IMSI, PICSI or microfluidic devices avoid sperm centrifugation and may improve the quality of the subsample obtained. However, these methodologies may result time consuming, expensive or producing poor results when the quality of the sperm is limited. We have already shown that a modified swim-up avoiding centrifugation (called IO-lix) is a low-cost and efficient alternative to microfluidic devices, recovers 100 times more concentration and reduces sperm DNA fragmentation with no significant differences to other methodologies. Study design, size, duration This is a retrospective study from 2018 to 2020 which includes patients with an average of age of 38.2 years using their own oocytes with ICSI as fertilization technique. Two aleatory groups of patients were made: Group 1: 88 cycles with 503 fertilized oocytes and 206 blastocysts were obtained with sperm samples processed by IO-lix and Group 2: 303 cycles, 1451 fertilized oocytes and 591 blastocysts using a standard “swim up” technique to process sperm. Participants/materials, setting, methods A total of 391 ICSI cycles were included in this retrospective study. The male factor was similar in both groups and they showed altered SDF previously to the cycle. We compared data of the motility and SDF of sperm samples before and after applying IO-lix and we analyzed by X2 contingence test differences on miscarriage rates between groups 1 and 2. Main results and the role of chance General sperm parameter changes after IO-lix showed that averaged sperm concentration observed in neat ejaculated samples was 62M/SD=46.4. Values obtained after IO-lix in the same samples were 12.3M/SD8.0. Averaged sperm motility in neat samples was 54%/SD=9.3 and 70.9%/SD=13.2 after IO-lix. Finally, sperm DNA fragmentation in neat samples was 35.8%/SD17.3, while these values decreased to 9.2%/SD=3.9 after IO-lix. About reproductive outcome results, significant differences were not obtained on the development to blastocyst stage rate comparing both groups (X2=0.003; p value = 0.954; Alpha 0.05). In the case of IO-lix processed samples, the pregnancy rate was 59.42% in Group 1 and 44.72% in Group 2 (X2=0.651; p value =0.419; Alpha 0.05). A total of 9 miscarriages of 41 clinical pregnancies (21.95%) were observed after IO-lix, while this number increases to 59 out of 123 clinical pregnancies, which means the 47.96% of the embryo transfers, when “swim-up” was used. In this case significant differences were obtained (X2=3.935; p value = 0.0.047; Alpha 0.05). Limitations, reasons for caution Being a pilot study aimed to understand the results of IO-lix in ART, correlations have not been stablished between the levels of sperm improvement after IO-lix and paired results of ART. This study would be necessary, specially to identify the possible origin of miscarriage associated to the male factor. Wider implications of the findings: Elimination of sperm centrifugation using a combined strategy of gradients and “swim-up” for sperm isolation, reduce miscarriage rate and produce equivalent results of blastocyst development to those obtained with “swim-up”. Being a cost-effective and improving laboratory workload, its use for sperm selection is recommended. Trial registration number Not applicable

P–084 Microfluidic Sperm Sorting (MFSS) technique versus Physiological Intracytoplasmic Sperm Injection (PICSI) technique in high DNA fragmentation index sperm samples

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
G Kant ◽  
K D Nayar ◽  
H Sharma ◽  
S Gupta ◽  
S Mishra ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Dna Fragmentation ◽  
Embryo Development ◽  
Intracytoplasmic Sperm Injection ◽  
Development Rate ◽  
Clinical Pregnancy ◽  
Sperm Dna Fragmentation ◽  
Fragmentation Index ◽  
Sperm Dna ◽  
Dna Fragmentation Index

Abstract Study question To evaluate the effectiveness of using Microfluidic Sperm Sorting (MFSS) technique and Physiological Intracytoplasmic Sperm Injection (PICSI) technique in patient with high DNA fragmentation index (DFI) sperm samples. Summary answer Sperm selected by microfluidic sorting are associated with significant increase in day 3 grade A embryo development rate, clinical pregnancy rate over PICSI. What is known already DNA damage is unrecognisable in living sperm prior to insemination and an increased sperm DNA fragmentation index has been associated with lower fertilization rates, impaired embryo development and reduced pregnancy rates. Standard semen processing techniques are associated with centrifugation, which may induce reactive oxygen species and DNA damage. In strategies to minimize sperm DNA fragmentation, Physiological ICSI can relatively reduce sperm DNA fragmentation by 67.9% (Parmegiani et al., 2010) while new technique Microfluidic sperm sorter technique also demonstrate sperm selection with significantly reduced DNA damage. Study design, size, duration A prospective randomised study was conducted from 1st August 2019 to 31st December 2020. Two hundred patients were randomised by computer generated list and divided into 2 groups. Group A (n = 100) , in which sperm were processed by microfluidic sperm sorter (MFSS) while in group B (n = 100), sperm were selected by Physiological Intracytoplasmic Sperm Injection (PICSI) technique and morphologically normal motile sperm were injected by Intracytoplasmic sperm injection (ICSI) technique in all mature oocytes. Participants/materials, setting, methods The study period included all normozoospermic patients with high DNA fragmentation index (&gt;25% ) while oligospermic, asthenozoospermic samples, patients with poor ovarian reserve and advanced age were excluded from the study. All A grade embryos were vitrified and transferred in frozen embryo replacement cycle. Both groups were compared on the basis of fertilisation rate, day 3 grade A embryo development rate , clinical pregnancy rate and miscarriage rate. Main results and the role of chance Cycle characteristics (female age, length of stimulation, gonadotrophin dose, number of oocytes and number of transferred embryos) were similar in both groups. Between the 2 groups, There was a significant increase observed in day 3 grade A embryo development rate (60% vs. 42%, p–0.016) and clinical pregnancy rate (62% vs. 46%, p–0.049), while no statistical significant difference observed in fertilisation rate (82% vs. 78%, p–0.80) and miscarriage rate ( 12% vs. 11%, p- 1). Limitations, reasons for caution: Larger randomised control studies are needed to strengthen these results. Wider implications of the findings: We have demonstrated that sperm sorted by microfluidic helps in selection of sperm with better DNA integrity over Physiological ICSI. Using it in routine practice can help in reducing the negative effect of reactive oxygen species and thus improve pregnancy rate and live birth rate. Trial registration number MCDH/2019/31

scholarly journals Variation of DNA Fragmentation Levels During Density Gradient Sperm Selection for Assisted Reproduction Techniques

Medicine ◽  
2016 ◽  
Vol 95 (20) ◽  
pp. e3624 ◽  
Author(s):  
Monica Muratori ◽  
Nicoletta Tarozzi ◽  
Marta Cambi ◽  
Luca Boni ◽  
Anna Lisa Iorio ◽  
...  
Keyword(s):  
Dna Fragmentation ◽  
Density Gradient ◽  
Assisted Reproduction ◽  
Sperm Selection ◽  
Assisted Reproduction Techniques ◽  
Selection For

scholarly journals Outcomes of Intracytoplasmic Sperm Injection Cycles for Complete Teratozoospermia: A Case-Control Study Using Paired Sibling Oocytes

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Nigel Pereira ◽  
Queenie V. Neri ◽  
Jovana P. Lekovich ◽  
Steven D. Spandorfer ◽  
Gianpiero D. Palermo ◽  
...  
Keyword(s):  
Live Birth ◽  
Intracytoplasmic Sperm Injection ◽  
Sperm Morphology ◽  
Male Partner ◽  
Clinical Pregnancy ◽  
Semen Parameters ◽  
Birth Rates ◽  
Spontaneous Miscarriage ◽  
Sibling Oocytes ◽  
Live Birth Rates

Objective. To investigate the outcomes of intracytoplasmic sperm injection (ICSI) cycles where sibling oocytes from a single donor were split between two recipients based on strict sperm morphology.Methods. Retrospective cohort study. All ICSI cycles had one donor’s oocytes split between two recipients in a 1 : 1 ratio based on strict sperm morphology, that is, one male partner had morphology of 0% and the other had morphology of >1%. Fertilization, positive hCG, clinical pregnancy, spontaneous miscarriage, and live birth rates of the aforementioned groups were compared.Results. The baseline characteristics of the two groups (n=103), including semen parameters of the male partners, were comparable. There was no difference in the fertilization rates when comparing the 0% group to the >1% group (78.7% versus 81.6%;P=0.66). The overall positive hCG, clinical pregnancy, spontaneous miscarriage, and live birth rates for the 0% group were 61.2%, 49.5%, 10.7%, and 38.8%, respectively. The corresponding rates in the >1% group were positive hCG (63.1%), clinical pregnancy (55.3%), spontaneous miscarriage (7.77%), and live birth (46.6%).Conclusions. The fertilization and pregnancy outcomes of ICSI cycles for strict sperm morphology of 0% versus morphology of >1% are equivalent. These results can provide reassurance to couples undergoing ICSI for severe teratospermia.

scholarly journals Sperm selection by rheotaxis improves sperm quality and early embryo development

Reproduction ◽  
2021 ◽  
Vol 161 (3) ◽  
pp. 343-352 ◽  
Author(s):  
Jon Romero-Aguirregomezcorta ◽  
Ricardo Laguna-Barraza ◽  
Raúl Fernández-González ◽  
Miriama Štiavnická ◽  
Fabian Ward ◽  
...  
Keyword(s):  
Membrane Fluidity ◽  
Dna Fragmentation ◽  
Density Gradient ◽  
Embryo Development ◽  
Sperm Quality ◽  
Early Embryo ◽  
Control Group ◽  
Sperm Selection ◽  
Foetal Development ◽  
Development Rates

The objective of this work was to elucidate whether a sperm selection method that combines rheotaxis and microfluidics can improve the selection of spermatozoa over density gradient and swim-up. For this purpose human sperm selected by rheotaxis were compared against density gradient, swim-up and a control group of non-selected spermatozoa in split frozen-thawed (FT) and fresh (F) semen samples. Sperm quality was assessed in terms of motility, morphology, DNA fragmentation index (DFI), viability, acrosome integrity and membrane fluidity. Using a mouse model, we compared fertilisation and embryo development rates after performing ICSI with spermatozoa, sorted using rheotaxis or swim-up. Selection by rheotaxis yielded a sperm population with reduced DFI than the control (P < 0.05), improved normal morphology (P < 0.001) and higher total motility (TM; P < 0.001) than the other techniques studied in F and FT samples. Swim-up increased TM compared to density gradient and control in FT or F samples (P < 0.001), and yielded lower DFI than the control with F samples (P < 0.05). In FT samples, selection by rheotaxis yielded sperm with higher viability than control, density gradient and swim-up (P < 0.01) while acrosomal integrity and membrane fluidity were maintained. When mouse spermatozoa were selected for ICSI using rheotaxis compared to swim-up, there was an increase in fertilisation (P < 0.01), implantation (P < 0.001) and foetal development rates (P < 0.05). These results suggest that, in the absence of non-destructive DNA testing, the positive rheotaxis can be used to select a population of low DNA fragmentation spermatozoa with high motility, morphology and viability, leading to improved embryo developmental rates.

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