Non-male Factor Infertility Research Articles

A method for determining potential parental contamination: linkage disequilibrium-based log-likelihood ratio analysis for IVF-PGT

BackgroundAt present, embryologists are attempting to use conventional in vitro fertilization (cIVF) as an alternative to intracytoplasmic sperm injection (ICSI) for preimplantation genetic testing (PGT). However, the potential parental contamination origin of sperm cells and cumulus cells is considered the main limiting factor in the inability of cIVF embryos to undergo PGT.MethodsIn this study, we established an IVF-PGTA assay for parental contamination tests with a contamination prediction model based on allele frequencies and linkage disequilibrium (LD) to compute the log-likelihood ratio (LLR) under competing ploidy hypotheses, and then verified its sensitivity and accuracy. Finally, comparisons of the effectiveness of SNP-based analysis and LLR-based IVF-PGTA among 40 cIVF embryos was performed, based on both statistical analysis of the parental contamination rate and chromosomal ploidy concordance rate between TE biopsy and ICM isolations.ResultsWith IVF-PGTA assay, biopsies with 10% maternal contamination could be detected accurately, and contamination caused by sperm cells could be eliminated completely. Utilizing LLR-based or single Nucleotide Polymorphism (SNP) -based analyses, our comprehensive examination of 40 clinically discarded fresh cIVF embryos revealed an absence of paternal contamination. Strikingly, the LLR-based analysis uniquely revealed a mere instance of 24% maternal contamination within the trophectoderm cell (TE) biopsy of 5* embryo. Furthermore, it was solely through this analysis that embryo (9-F) was identified as a triploid of paternal origin.ConclusionsIn this study, we developed a new bioinformatics analysis method for identifying parental contamination during IVF-PGT, especially for couples with nonmale factor infertility.

The impact of intracytoplasmic sperm injection versus conventional in vitro fertilization on the reproductive outcomes of couples with non-male factor infertility and frozen-thawed embryo transfer cycles

This study was aimed to investigate the impact of intracytoplasmic sperm injection (ICSI) on reproductive outcomes in couples with non-male factor infertility and frozen-thawed embryo transfer (FET) treatment. This retrospective cohort study involved a total of 10,143 cycles from 6206 couples who underwent FET at the Third Affiliated Hospital of Zhengzhou University between January 2016 and September 2022. Patients were categorized into two groups based on the insemination methods of transferred embryos. Clinical and neonatal outcomes were compared between ICSI and conventional in vitro fertilization (cIVF) groups. The results showed that ICSI was not associated with improved clinical outcomes compared to cIVF. However, ICSI was associated with lower birthweight when twins were born. In conclusion, although subgroup analysis showed that ICSI was associated with slightly improved live birth rate for infertile couples with non-male factor infertility compared to cIVF, the regression analysis showed that ICSI did not demonstrate any improvement of the reproductive outcomes. The infertile women with twin pregnancies should be further informed of the lower birthweight and lower birth length when their oocytes were inseminated with ICSI. The findings of this study provide valuable insights for clinicians when discussing the benefits and risks of ICSI in patients with non-male factor infertility.

P-126 The impact of ICSI versus IVF on the reproductive outcomes of couples with non-male factor infertility and frozen-thawed embryo transfer cycles

Abstract Study question Does Intracytoplasmic Sperm Injection (ICSI) improve reproductive outcomes in patients with non-male factor infertility undergoing Frozen-Thawed Embryo Transfer (FET) treatment? Summary answer ICSI showed slightly improved clinical outcomes compared to IVF, but was associated with higher preterm birth rates and low birthweight when twins were born. What is known already The use of ICSI has seen a significant surge globally, particularly in Europe and the USA, as a solution for fertilization failure resulting from male factor infertility. FET presents a viable option for those considering additional children. Numerous studies have investigated the effectiveness of ICSI in couples with non-male factor infertility undergoing fresh embryo transfer in ovarian stimulation cycles. However, there is a dearth of evidence demonstrating whether ICSI, compared to conventional IVF (cIVF), could influence reproductive outcomes in couples with non-male factor infertility undergoing FET treatment. Study design, size, duration This retrospective cohort study included 10,143 cycles from 6,206 couples who underwent FET at the Third Affiliated Hospital of Zhengzhou University between January 2016 and September 2022. Participants/materials, setting, methods Patients were categorized into two groups based on the insemination methods used for the transferred embryos. Patients were excluded if : 1) Embryos were biopsied and tested; 2) Oocytes had been vitrified; 3) Embryos were derived from donor oocytes, AOA treatment, or rescue ICSI; 4) Embryos that were not transferred; and 5) They had undergone fresh embryo transfer. PSM at a ratio of 1:1 was utilized to ensure comparability of reproductive outcomes. Main results and the role of chance Post-PSM, the general characteristics were comparable across both groups. The clinical pregnancy rates (37.6% vs 40.0%, P = 0.311), miscarriage rates (21.4% vs 23.1%, P = 0.597), and live birth rates (28.2% vs 30.4%, P = 0.329) exhibited no significant disparity post-PSM between the two groups. Notably, a marginally elevated live birth rate was observed in the ICSI group when blastocysts were transferred to the women (39.8% vs 48.3%, P = 0.050). However, the GEE models indicated that ICSI did not enhance the likelihood of clinical pregnancy, miscarriage, and live birth relative to IVF in women with non-male factor infertility. Following adjustments for variables, ICSI yielded consistent OR values [1.14(0.92-1.42), P = 0.241; 1.08(0.72-1.61), P = 0.703; and 1.16(0.92-1.46), P = 0.220, respectively]. The perinatal outcomes were similar between the two grousps. However, a significantly higher incidence of preterm birth was observed in the ICSI group compared to the cIVF group (20.0% vs 12.5%, P = 0.026). While pregnancy complications were comparable between the two groups, neonates born as twins in the ICSI group exhibited significantly reduced live birth-weight [2520.8(572.9) vs 2691.9(423.7), P = 0.043] and birth length [47.5(2.8) vs 48.5(2.3), P = 0.031]. Correspondingly, the rate of low birthweight was significantly higher in the ICSI group (38.9% vs 21.0%, P = 0.025). Limitations, reasons for caution The retrospective design may lead to selection bias among the included patients. The use of ICSI in ART has been strictly regulated in our country, limiting the sample size and potentially reducing the statistical power. Wider implications of the findings The value of ICSI should be thoroughly discussed with patients with non-male factor infertility before ovarian stimulation. Further research is needed to better understand the impact of ICSI on reproductive and neonatal outcomes in this population. Trial registration number 2021YFC2700602

Developmental outcomes of children born through ICSI versus conventional IVF (cIVF) in couples with non-male factor infertility.

In non-male factor infertile couples, are there any differences in the developmental outcomes between children born through ICSI and conventional IVF (cIVF)? In this preliminary study, ICSI and cIVF seem to have a comparable effect on developmental outcomes after 12 months in children born to non-male factor infertile couples. ICSI, an invasive technique, has raised concerns about potential developmental abnormalities in children. Limited data are available regarding the developmental outcomes of ICSI-conceived infants born to non-male factor infertile couples. This prospective cohort study involved a follow-up of all children aged 12 months or older who were born from pregnancies resulting from either ICSI or cIVF as part of a previous randomized controlled trial (RCT) (NCT03428919). In the original RCT, 1064 women were randomly assigned to the ICSI or cIVF groups (532 women for each group). Follow-up was conducted with 155 couples (195 children) in the ICSI group and 141 couples (185 children) in the cIVF group. The Vietnamese version of the Ages & Stages Third Edition Questionnaires (ASQ-3) and the Development Red Flags questionnaires were completed by the participants. A total of 141 (90.1%) women (177 children) in the ICSI group and 113 (80.1%) women (145 children) in the cIVF group returned fully completed questionnaires. The primary outcomes were the developmental outcomes based on responses to the ASQ-3 and the Red Flags questionnaire. The mean age of children at follow-up was 19.5 ± 5.0 months in the ICSI group and 19.3 ± 5.5 months in the cIVF group. The mean height and weight of children in both groups were similar. The overall proportion of children with any abnormal ASQ-3 score did not differ significantly between the ICSI and cIVF groups (16.9% vs 13.1%, P = 0.34). The proportion of children with Red Flag signs was also comparable between the two groups (6.2% vs 9.2%, P = 0.36, ICSI vs cIVF, respectively). Despite a reasonably high follow-up response rate, there is a potential risk of sampling bias, and overall, the number of children with developmental abnormalities was very small. The study relied solely on questionnaires as screening tools, rather than incorporating additional behavioral observations or physical developmental tests; this may have affected the statistical power and the significance of between-group comparisons. The current findings contribute to the existing evidence and support the comparative safety of ICSI and cIVF regarding early childhood development. However, more extensive and prolonged follow-up data for these children are needed to draw definitive conclusions. No external funding was received for this study, and no authors reported conflicting interests. NCT04866524 (clinicaltrials.gov).

Economic evaluations of assisted reproductive technologies in high-income countries: a systematic review.

Which assited reproductive technology (ART) interventions in high-income countries are cost-effective and which are not? Among all ART interventions assessed in economic evaluations, most high-cost interventions, including preimplantation genetic testing for aneuploidy (PGT-A) for a general population and ICSI for unexplained infertility, are unlikely to be cost-effective owing to minimal or no increase in effectiveness. Approaches to reduce costs in order to increase access have been identified as a research priority for future infertility research. There has been an increasing number of ART interventions implemented in routine clinical practice globally, before robust assessments of evidence on economic evaluations. The extent of clinical effectiveness of some studied comparisons has been evaluated in high-quality research, allowing more informative decision making around cost-effectiveness. We performed a systematic review and searched seven databases (MEDLINE, PUBMED, EMBASE, COCHRANE, ECONLIT, SCOPUS, and CINAHL) for studies examining ART interventions for infertility together with an economic evaluation component (cost-effectiveness, cost-benefit, cost-utility, or cost-minimization assessment), in high-income countries, published since January 2011. The last search was 22 June 2022. Two independent reviewers assessed publications and included those fulfilling the eligibility criteria. Studies were examined to assess the cost-effectiveness of the studied intervention, as well as the reporting quality of the study. The chosen outcome measure and payer perspective were also noted. Completeness of reporting was assessed against the Consolidated Health Economic Evaluation Reporting Standard. Results are presented and summarized based on the intervention studied. The review included 40 studies which were conducted in 11 high-income countries. Most studies (n = 34) included a cost-effectiveness analysis. ART interventions included medication or strategies for controlled ovarian stimulation (n = 15), IVF (n = 9), PGT-A (n = 7), single embryo transfer (n = 5), ICSI (n = 3), and freeze-all embryo transfer (n = 1). Live birth was the mostly commonly reported primary outcome (n = 27), and quality-adjusted life years was reported in three studies. The health funder perspective was used in 85% (n = 34) of studies. None of the included studies measured patient preference for treatment. It remains uncertain whether PGT-A improves pregnancy rates compared to IVF cycles managed without PGT-A, and therefore cost-effectiveness could not be demonstrated for this intervention. Similarly, ICSI in non-male factor infertility appears not to be clinically effective compared to standard fertilization in an IVF cycle and is therefore not cost-effective. Interventions such as use of biosimilars or HMG for ovarian stimulation are cheaper but compromise clinical effectiveness. Lack of both preference-based and standardized outcomes limits the comparability of results across studies. The selection of efficacy evidence offered for some interventions for economic evaluations is not always based on high-quality randomized trials and systematic reviews. In addition, there is insufficient knowledge of the willingness to pay thresholds of individuals and state funders for treatment of infertility. There is variable quality of reporting scores, which might increase uncertainty around the cost-effectiveness results. Investment in strategies to help infertile people who utilize ART is justifiable at both personal and population levels. This systematic review may assist ART funders decide how to best invest to maximize the likelihood of delivery of a healthy child. There was no funding for this study. E.C. and R.W. receive salary support from the National Health and Medical Research Council (NHMRC) through their fellowship scheme (EC GNT1159536, RW 2021/GNT2009767). M.D.-T. reports consulting fees from King Fahad Medical School. All other authors have no competing interests to declare. Prospero CRD42021261537.

Comparison of outcomes between intracytoplasmic sperm injection and in vitro fertilization inseminations with preimplantation genetic testing for aneuploidy, analysis of Society for Assisted Reproductive Technology Clinic Outcome Reporting System data

To evaluate whether insemination via intracytoplasmic sperm injection provides any benefit over in vitro fertilization for non-male factor infertility with respect to pre-implantation genetic testing results and pregnancy outcome. Retrospective Cohort Study of the Society for Assisted Reproductive Technology database. Patients undergoing in vitro fertilization or intracytoplasmic sperm injection in non-male factor pre-implantation genetic testing for aneuploidy cycles. In vitro fertilization vs. intracytoplasmic sperm injection MAIN OUTCOME MEASURES: Primary outcomes were percentage of embryos suitable for transfer and live birth rates. Secondary outcomes included subgroup analysis for embryos suitable for transfer on cycles from patients ≥ 35 y/o vs. < 35 y/o, ≤ 6 oocytes retrieved vs. > 6 oocytes retrieved, and unexplained infertility. Additionally, gestational age at delivery and birthweight between in vitro fertilization and intracytoplasmic sperm injection were evaluated. A total of 30,446 non-male factor preimplantation genetic diagnosis for aneuploidy cycles were evaluated, of which 4867 were in vitro fertilization and 25,579 were intracytoplasmic sperm injection. Following exclusion criteria and adjustment for any necessary confounding variables, no significant differences existed in embryos suitable for transfer between in vitro fertilization and intracytoplasmic sperm injection cycles, 41.6% (40.6%, 42.6%) vs. 42.5% (42.0%, 42.9%), respectively or live birth rates, 50.1% (37.8, 62.4%) vs. 50.8% (38.5%, 62.9%), respectively. There were no significant differences in the rates of embryos suitable for transfer and live birth rates between in vitro fertilization and intracytoplasmic sperm injection in non-male factor cycles undergoing pre-implantation genetic testing for aneuploidy.

Efficacy of intracytoplasmic sperm injection in women with non-male factor infertility: A systematic review and meta-analysis.

The use of intracytoplasmic sperm injection (ICSI) has dramatically increased in patients with non-male factor infertility during the last decades. However, whether ICSI provides a significant benefit over invitro fertilization (IVF) in these patients is still controversial. In this study, we aimed to investigate the efficacy of ICSI on reproductive outcomes with non-male factor infertility and to provide updated evidence for clinical practice. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to March 2023. Randomized controlled trials (RCTs) comparing the efficacy between ICSI and IVF in patients with non-male factor infertility were included. The main outcomes were the live birth rate (LBR), fertilization rate (FR), and total fertilization failure (TFF). The pooled estimates were calculated using the random-effects models as relative risk (RR) with 95% confidence intervals (CIs). This systematic review and meta-analysis was registered in PROSPERO (CRD42023427004). We included 18 RCTs with 3249 cycles and 30 994 oocytes. The results demonstrated that ICSI reduced the risk of TFF (RR = 0.26, 95% CI: 0.13-0.50, I2 = 58%) and increased FR per oocyte inseminated/injected (RR = 1.14, 95% CI: 1.08-1.20, I2 = 69%), but it did not improve LBR (RR = 1.11, 95% CI: 0.94-1.30, I2 = 0%) or other outcomes compared with IVF. However, the difference in fertilization failure reduction between ICSI and IVF may be explained by different randomization methods (randomization based on patients vs. sibling oocytes). When considering only studies with randomization based on patients, we found no evidence of the difference between the groups (RR = 0.72, 95% CI: 0.48-1.06, I2 = 0%). Furthermore, no differences were observed in subgroup analyses based on other factors, including female age, study period, and controlled ovarian stimulation protocols. Our findings suggest that ICSI leads to no difference in reproductive outcomes compared to IVF in patients with non-male factor infertility. Considering the cost and safety of ICSI, we have no evidence to support the routine use of ICSI in these populations. High-quality RCTs with large sample sizes will be needed to confirm our results and explore clinical and neonatal outcomes.

Comparisons of conventional in vitro fertilization versus intracytoplasmic sperm injection in women with thyroid autoimmunity and non-male factor infertility, a propensity score matching analysis

The aim of the study is to compare the outcomes between the insemination methods of conventional in vitro fertilization and intracytoplasmic sperm injection in infertile women with thyroid autoimmunity and non-male factor infertility. This was a retrospective cohort study which included women with thyroid autoimmunity and non-male factor infertility. Reproductive outcomes such as embryo development parameters and clinical outcomes were compared between the two groups. The propensity score matching was applied to balance the general characteristics with significant differences between the two groups. Generalized estimating equations were used to explore the impact of ICSI on the embryo development potential of the inseminated oocytes. Sensitivity analysis using E-values was used to account for unknown confounders. After 1:2 propensity score matching, the general characteristics were all comparable. The good cleavage embryo rate, blastocyst utilization rate, and good blastocyst rate were significantly lower in the intracytoplasmic sperm injection group than those in the conventional in vitro fertilization group. After controlling for the confounding factors, intracytoplasmic sperm injection was significantly negatively associated with development of usable blastocysts and good blastocysts, while showed no impact on fertilized oocytes, usable cleavage embryos and good cleavage embryos. Although limited by the limited sample size, there were comparable clinical and obstetrical outcomes between conventional in vitro fertilization and intracytoplasmic sperm injection groups. Intracytoplasmic sperm injection neither improved the embryo development potential nor increased the clinical pregnancy and live birth rates compared to conventional in vitro fertilization in the studied population. Prospective studies that randomly divide the studied population in two the two groups and compare the reproductive outcomes are warranted.

Compared With Conventional Insemination, Intracytoplasmic Sperm Injection Provides No Benefit in Cases of Nonmale Factor Infertility as Evidenced by Comparable Euploidy Rate

(Abstracted from Fertil Steril 2023;120(2)) Intracytoplasmic sperm injection (ICSI) has dramatically improved fertilization rates for couples with male factor infertility and those with prior failed in vitro fertilization (IVF) cycles. Although several international academic organizations and the cumulative evidence do not suggest the routine use of ICSI for nonmale factor infertility, it is now used frequently for all cases of IVF regardless of the indication.

Intracytoplasmic sperm injection does not improve the outcome of IVF treatments in patients with advanced maternal age or low oocyte number: A randomized controlled trial.

Intracytoplasmic sperm injection (ICSI) was introduced to achieve fertilization in cases of severe male factor infertility. However, ICSI is often used in cases of non-male factor infertility, such as advanced maternal age or low oocyte number, but the clinical benefit of the method in these indications has not been proven. A prospective randomized study was conducted in a university clinic between 2018 and 2020. Patients with ≥40 years of age and/or ≤4 oocytes with non-sever male factor infertility were randomized into conventional IVF or ICSI groups. Fertilization rate, embryo quality, implantation, clinical pregnancy and live birth rates were compared. A total of 336 IVF cycles (169 conventional IVF and 167 ICSI) were involved in the study. The fertilization rate was higher in the conventional IVF group compared to the ICSI group (IVF: 61.7%, ICSI: 53.4%, P=0.001). Embryo development and morphology did not show considerable difference between groups. Implantation, clinical pregnancy and live birth rate were 13.1%, 24.3% and 11.4% in the conventional IVF and 10.4%, 19.0%, 12.0% in the ICSI group. The differences were not significant. Subgroup analysis showed a significantly better clinical outcome following conventional IVF when advanced maternal age was accompanied by low oocyte number (Implantation: 11.7% vs 2.6%, P=0.027; Clinical pregnancy: 18.5% vs 4%, P=0.020). A significantly higher fertilization rate, a tendency for higher clinical pregnancy rate was found in conventional IVF treatments compared to ICSI. When advanced maternal age was associated with low oocyte number, ICSI resulted in a substantially lower chance of fertilization and clinical pregnancy. These data suggest that ICSI offers no advantage over conventional IVF in terms of fertilization, embryo quality, implantation and pregnancy rates for couples with advanced maternal age or with low oocyte number.

Conventional IVF is feasible in preimplantation genetic testing for aneuploidy.

To investigate the feasibility of the application of conventional in vitro fertilization (cIVF) for couples undergoing preimplantation genetic testing for aneuploidies (PGT-A) with non-male factor infertility. To evaluate the efficiency of sperm whole-genome amplification (WGA), spermatozoa were subjected to three WGA protocols: Picoplex, ChromInst, and multiple displacement amplification (MDA). In the clinical studies, 641 couples who underwent PGT-A treatment for frozen embryos between January 2016 and December 2021 were included to retrospectively compare the chromosomal and clinical outcomes of cIVF and intracytoplasmic sperm injection (ICSI). Twenty-six couples were prospectively recruited for cIVF and PGT-A treatment between April 2021 and April 2022; parental contamination was analyzed in biopsied samples; and 12 aneuploid embryos were donated to validate the PGT-A results. Sperm DNA failed to amplify under Picoplex and ChromInst conditions but could be amplified using MDA. In frozen PGT-A cycles, no significant differences in the average rates of euploid, mosaic, and aneuploid embryos per cycle between the cIVF-PGT-A and ICSI-PGT-A groups were observed. The results of the prospective study that recruited couples for cIVF-PGT-A treatment showed no paternal contamination and one case of maternal contamination in 150 biopsied trophectoderm samples. Among the 12 donated embryos with whole-chromosome aneuploidy, 11 (91.7%) presented uniform chromosomal aberrations, which were in agreement with the original biopsy results. Under the Picoplex and ChromInst WGA protocols, the risk of parental contamination in the cIVF-PGT-A cycles was low. Therefore, applying cIVF to couples with non-male factor infertility who are undergoing PGT-A is feasible.

P-251 Differences in fertilization, blastocyst, and ploidy rates in intracytoplasmic sperm injection (ICSI) versus conventional insemination for patients undergoing in vitro fertilization (IVF)

Abstract Study question Are there differences in fertilization, blastocyst development, or euploidy rates when comparing ICSI versus conventional insemination among patients with male and non-male factor infertility? Summary answer Fertilization rate was lower for male factor ICSI. There were no differences in blastocyst development. Euploidy rate was lower for non-male factor ICSI. What is known already ICSI was developed for male factor infertility due to its requirement for a very small number of viable sperm. Its use has expanded beyond male factor due to some studies suggesting enhanced fertilization, and lower risks of failed fertilization or inadvertent contamination of embryo biopsy specimens. There are potential risks associated with ICSI, including imprinting disorders, birth defects, and significantly increased cost. It is also unclear whether ICSI contributes to genetic abnormalities by bypassing the egg’s natural sperm selection and potentially disrupting the meiosis apparatus. Study design, size, duration This retrospective cohort study of 576 patients was conducted at a single clinic from January 2021 to December 2021. Patients were grouped into (1) ICSI with male factor (n = 201), (2) ICSI with non-male factor (n = 160), and (3) conventional insemination with non-male factor (n = 215). Primary outcome was ploidy status, determined by calculating the percentage of euploid, aneuploid, and mosaic (both low and high mosaic) among the three groups. Secondary outcomes included fertilization and blastocyst development rates. Participants/materials, setting, methods Patients undergoing autologous IVF at a single clinic, with PGT-A performed at a single lab were included. Fertilization rate was defined as the percentage of 2PNs per number of mature eggs injected/inseminated. Blastocyst rate was defined as the percentage of blastocysts per 2PNs. Ploidy rate was defined as the percentage of euploid/aneuploid/mosaic blastocysts per total biopsied blastocysts for which a result was obtained. Percentage data was compared using N-1 Chi-squared test. Main results and the role of chance There were no significant differences in patient age, number of oocytes retrieved, or number of mature oocytes among the three groups. Fertilization rate for male factor ICSI was significantly lower compared to both non-male factor ICSI (74.2% vs 77.8%, p = 0.005) and conventional insemination (74.2% vs 76.8%, p = 0.018). There was no significant difference in fertilization rate between non-male factor ICSI and conventional insemination. There were no significant differences between blastocyst rates on Day 5, 6, or 7, or total blastocyst rate among the three groups. The euploidy rate for conventional insemination was significantly higher than that for non-male factor ICSI (53.4% vs 46.8%; p = 0.008). Non-male factor ICSI yielded lower euploidy rate than male factor ICSI (46.8% vs 52.4%, p = 0.034). Aneuploidy rate for non-male factor ICSI was significantly higher than both male factor ICSI (36.1% vs 31.0%, p = 0.041) and conventional insemination (36.1% vs 31.0%, p = 0.030). Mosaicism levels were similar between the three groups. There were no significant differences in number of biopsied embryos with no results: 5 for ICSI male factor group (0.59%), 6 for ICSI non-male factor (0.96%), and 10 for conventional insemination (0.89%). Limitations, reasons for caution This was a retrospective analysis of patients from a single clinic, with a relatively small sample size so results may not be generalizable to all populations. Extensive demographic information and baseline characteristics (including reason for ICSI performed among non-male factor patients) were not analyzed so there may be confounding factors. Wider implications of the findings This is the first study that we are aware of to investigate the ploidy status of embryos created among non-male factor patients undergoing ICSI. Conservative use of ICSI can significantly decrease the cost of IVF. Larger studies are needed to further elucidate the role for ICSI among these patients. Trial registration number not applicable

P-456 Economic evaluations of assisted reproductive technology in high income countries - a systematic review

Abstract Study question In high-income country settings, what is the evidence supporting economic evaluations of in vitro fertilisation (IVF) interventions? Summary answer Most interventions associated with IVF are high cost for minimal improvement in effectiveness, leading to excessively high acceptability thresholds. What is known already The economic burden of infertility, and approaches to reduce costs and increase access have been identified in the top 10 research priorities for future infertility research. Meanwhile, there has been exponential growth in use of ART for infertility, especially in high-income countries. Therefore, it is important to map the landscape of economic evaluations in IVF research to inform health policy and future research. Study design, size, duration A systematic review of studies of an IVF intervention together with an economic evaluation conducted in high income countries between 2011 and 2022 was completed. Seven electronic databases were searched for eligible studies (MEDLINE, PUBMED, EMBASE, COCHRANE, ECONLIT, SCOPUS or CINAHL). Participants/materials, setting, methods Studies assessing a component of IVF with a cost effectiveness, cost benefit, cost utility or cost minimization assessment were included. Studies were examined to assess their chosen outcome measure, perspective, completeness of reporting and cost effectiveness of the intervention studied. Cost data were converted to USD, taking inflation into consideration. Main results and the role of chance Of the 40 included studies, 62% evaluated an unselected population and 68% used livebirth as the effectiveness outcome measure. Modelling studies predominated (65%) over those alongside trials. Most (80%) spoke from a health funder perspective. There were 11 IVF interventions assessed together with an economic evaluation. The incremental cost effectiveness ratio was greatest for those interventions where the intervention did not improve efficacy significantly. The intervention of PGT-A was assessed as either less effective and more expensive, or more effective, but costing up to $600,000 USD for each additional livebirth. Likewise, intracytoplasmic sperm injection for non-male factor infertility, conferred minimal benefit but cost up to $72000 USD per additional livebirth. Choice of agents for ovarian hyperstimulation were assessed in 15 included papers. Recombinant FSH is more effective and slightly more expensive than biosimilars. The direction of effect of the cost effectiveness findings was the same for the groups of studies assessing IVF, ICSI, PGT-A and embryo transfer number, increasing confidence in the findings across different settings and funding models. Limitations, reasons for caution Systematic reviews of economic evidence rely on assumptions of evidence in included studies. The data on health outcomes (e.g. pregnancy rates) were sometimes optimistic compared with findings in evidence from large trials or systematic reviews. There is variable reporting quality which might increase uncertainty around the cost effectiveness results. Wider implications of the findings Economic evaluation of IVF interventions is important for state funders and individuals who pay for treatment. Awareness of the real price per outcome allows consideration for funding to be applied more effectively. Multi-faceted decision making is needed. Cost effectiveness alone should not champion interventions that may otherwise have adverse consequences. Trial registration number not applicable

ICSI for non-male factor infertility: time to reappraise IVF?

Intracytoplasmic sperm injection (ICSI) was initially introduced to overcome problems due of severe male factor infertility not being solved with conventional in-vitro fertilization (cIVF). However, recent years have witnessed an increasing use of ICSI by most assisted reproductive technique laboratories for non-male factor indications. Examples of the latter include previous fertilization failure after cIVF, few or poor-quality oocytes, immature oocytes, advanced maternal age, preimplantation genetics test (PGT), cryopreserved oocytes, and unexplained infertility. The replacement of cIVF with ICSI in several non-male factor infertility cases is probably because some reproductive specialists consider that ICSI is associated with better reproductive outcomes. Unfortunately, data on reproductive outcomes in favor of ICSI over cIVF are limited or absent. Therefore, the factors that can help define the use of one technique over the other should be identified. These should include the likelihood of fertilization failure, potential risks of the procedure, and its costs. In this review, we aim to highlight the current guidelines, advantages, and limitations of the use of cIVF/ICSI for infertility treatment. Additionally, we provide a comprehensive review of the use of ICSI in indications other than severe male factor infertility.

Compared with conventional insemination, intracytoplasmic sperm injection provides no benefit in cases of nonmale factor infertility as evidenced by comparable euploidy rate

To evaluate if differences in euploidy rates exist between intracytoplasmic sperm injection (ICSI) and conventional insemination (CI) in non-male factor infertility cases. Retrospective cohort study. Single, academically affiliated infertility center in the U.S. A total of 3,554 patients who underwent in-vitro fertilization (IVF) cycles from January 2014 to December 2021. All cycles that had pre-implantation testing for aneuploidy (PGT-A) performed by trophectoderm biopsy and had a post preparation sperm concentration >4 million total motile sperm per milliliter were included. The primary outcome was embryo euploidy rate per embryo biopsied in the ICSI versus CI group. Secondary outcomes included fertilization rate and number of embryos biopsied. Generalized estimating equations with a Poisson distribution was used to estimate the euploid rate ratio (with total embryos biopsied as an offset), while accounting for multiple retrievals per patient. To adjust for confounding, a propensity score model was fit for ICSI using 14 baseline female and male characteristics. Oocytes retrieved and number of embryos biopsied were similar in both groups, while fertilization rate per oocyte retrieved was significantly lower with ICSI (0.64 vs 0.66, p=0.04). The proportion of euploid embryos in the ICSI group was significantly lower when compared to CI (0.47 vs 0.52), with a euploid rate ratio of 0.89 (p<0.001). Interestingly, when accounting for variation in PGT reference laboratories over the study time period, adjusting for date of procedure did not change the relationship between ICSI and euploid rate (RR=0.89, p<0.001); however, after adjusting for PGT reference laboratory, the relationship between ICSI and euploid rate was no longer significant (RR=0.97, p=0.07). In the setting of non-male factor infertility, ICSI resulted in a lower fertilization rate and an 11% lower embryo euploid rate compared to CI. Although the data is not statistically significant when adjusted for PGT reference laboratory, we can still conclude that ICSI does not provide any benefit. This data supports the recommendation that CI should be the preferred methodology of fertilization in non-male factor infertility cases.

Clinical characteristics and offspring developmental malformation of 126 patients with septate uterus.

Clinical characteristics and offspring developmental malformation of 126 patients with septate uterus.

Duration of infertility and assisted reproductive outcomes in non-male factor infertility: can use of ICSI turn the tide?

BackgroundIntracytoplasmic sperm injection (ICSI) is increasingly used among in vitro fertilization (IVF) cycles without male factor infertility. For couples with prolonged infertility duration, the preferred insemination method may vary across laboratories and clinics. We analyzed whether ICSI is effective for non-male factor infertility with long infertility duration.MethodsSeventeen thousand four hundred seventy-seven IVF/ICSI cycles from women with non-male factor infertility were included, of these 4177 women with infertility duration ≥ 5 years were in the final analysis. Primary outcome was the live birth rate after first embryo transfer. Secondary outcomes were rates of clinical pregnancy and fertilization.ResultsA nonlinear relationship was observed between infertility duration and IVF fertilization rate, which decreased with infertility years up to the turning point (4.8 years). 4177 women with infertility ≥ 5 years were categorized by IVF (n = 3806) or ICSI (n = 371). Live birth rate after first embryo transfer was 43.02% in ICSI and 47.85% in IVF group (adjusted odds ratio (aOR), 0.91; 95% confidence interval (CI), 0.72–1.15). Fertilization rate per metaphaseII (aOR, 1.10; 95% CI, 0.86–1.40) and clinical pregnancy rate (aOR, 0.89; 95% CI, 0.71–1.13) were similar between the two groups. Sensitive analyses (women ≥ 35 years) did not show a benefit of ICSI over IVF.ConclusionsWomen with infertility exceeding 4.8 years had decreased incidence of IVF fertilization. The use of ICSI showed no significant improvement in fertilization and live birth rates for non-male factor couples with ≥ 5 years of infertility.

Impact of intracytoplasmic sperm injection in women with non-male factor infertility: A systematic review and meta-analysis.

The purpose of this study is to determine whether intracytoplasmic sperm injection (ICSI) is beneficial in patients with non-male factor infertility. This systematic review and meta-analysis included articles from inception to May 2022. Published studies of non-male factor infertile women undergoing ICSI or in vitro fertilization (IVF) included in PubMed, Embase, web of science, Wanfang Database, and CNKI were searched by computer, without language restrictions. A random-effect model was applied to calculate the risk ratios (RRs) and their 95% confidence intervals (CIs). Letters, case reports, and review articles including meta-analyses and expert opinions were excluded. The primary endpoints were laboratory outcomes and pregnancy outcomes. The Secondary endpoints were neonatal outcomes. Six randomized controlled studies and 20 retrospective cohort studies met the inclusion criteria. In meta-analytic forest plots, compared with IVF, those who received ICSI treatment were not different in fertilization rate (RR = 0.99, 95% CI [0.90-1.09], P = 0.88), total fertilization failure rate (RR = 1.30, 95% CI [1.17-1.45], P < 0.00001), and good quality embryo rate (RR = 0.94, 95% CI [ 0.86-1.02], P = 0.15), clinical pregnancy rate (RR = 0.84, 95% CI [0.70-1.01], P = 0.06), live birth rate (RR = 0.89, 95% CI [0.77-1.03], P = 0.13), miscarriage rate (RR = 1.06, 95% CI [0.78-1.43], P = 0.71), preterm neonatal delivery rate (RR = 0.92, 95% CI [0.67-1.26], P = 0.61), and low neonatal weight rate (RR = 1.13, 95% CI [0.80-1.61], P = 0.48). However, the implantation rate of IVF was better than ICSI (RR = 0.77, 95% CI [0.64-0.93], P = 0.005). In the subgroup analysis of the live birth rate of fresh embryo transfer, IVF performed in those ≥35 years had a higher live birth rate (RR = 0.82, 95% CI [0.78-0.83], P < 0.001). The findings of this study indicate that ICSI is not superior to IVF in the treatment of infertility related to non-male factors. In order to confirm this result, more high-quality clinical studies are needed.

FERTILIZATION BY INTRACYTOPLASMIC SPERM INJECTION (ICSI) IS ASSOCIATED WITH LOWER RATES OF EUPLOIDY IN NON-MALE FACTOR INFERTILITY COMPARED TO CONVENTIONAL INSEMINATION (CI)

The use of ICSI in non-male factor infertility cases has dramatically increased worldwide and in many clinics is used for all cases, regardless of sperm characteristics. The objective of this study was to examine differences in euploidy rates between CI and ICSI in non-male factor infertility cases.

ICSI IS ASSOCIATED WITH LOWER BLASTULATION RATES COMPARED TO CONVENTIONAL IVF AMONG COUPLES WITH NON-MALE FACTOR INFERTILITY AND LOW OOCYTE YIELD

To determine whether intracytoplasmic sperm injection (ICSI) for non-male factor infertility is associated with higher rates of blastulation compared to conventional in vitro fertilization (IVF) cycles with low oocyte yield.