scholarly journals A Novel Assisted Oocyte Activation Method Improves Fertilization in Patients With Recurrent Fertilization Failure

Author(s):  
Meng Wang ◽  
Lixia Zhu ◽  
Chang Liu ◽  
Hui He ◽  
Cheng Wang ◽  
...  

Total fertilization failure (TFF) occurs in 1–3% of total intracytoplasmic sperm injection (ICSI) cycles and can reoccur in subsequent cycles. Despite the high success rate with the application of assisted oocyte activation (AOA), there is still a small number of couples who cannot obtain fertilized eggs after conventional calcium (Ca2+) ionophores-based ICSI-AOA. Six couples experiencing repeated TFF or low fertilization (<10%) after ICSI and conventional ICSI-AOA were enrolled in this study. Compared with the regular ICSI group and the conventional ICSI-AOA group, the new AOA method, a combination of cycloheximide (CHX) and ionomycin, can significantly increase the fertilization rate from less than 10 up to approximately 50% in most cases. The normal distribution of sperm-related oocyte activation factor phospholipase C zeta (PLCζ1) in the sperms of the cases indicated the absence of an aberrant Ca2+ signaling activation. The results of the whole-embryo aneuploidies analysis indicated that oocytes receiving the novel AOA treatment had the potential to develop into blastocysts with normal karyotypes. Our data demonstrated that CHX combined with ionomycin was able to effectively improve the fertilization rate in the majority of patients suffering from TFF. This novel AOA method had a potential therapeutic effect on those couples experiencing TFF, even after conventional AOA, which may surmount the severe fertilization deficiencies in patients with a repeated low fertilization or TFF.

2021 ◽  
Vol 10 (12) ◽  
pp. 2616
Author(s):  
Tanya L. Glenn ◽  
Alex M. Kotlyar ◽  
David B. Seifer

Intracytoplasmic sperm injection (ICSI) was originally designed to overcome barriers due to male factor infertility. However, a surveillance study found that ICSI use in non-male factor infertility increased from 15.4% to 66.9% between 1996 and 2012. Numerous studies have investigated fertilization rate, total fertilization failure, and live birth rate per cycle (LBR), comparing the use of ICSI versus conventional in vitro fertilization (IVF) for non-male factor infertility. The overwhelming conclusion shows no increase in fertilization rate or LBR per cycle with the use of ICSI for non-male factor infertility. The overuse of ICSI is likely related to the desire to avoid a higher rate of total fertilization failure in IVF. However, data supporting the benefit of using ICSI for non-male factor infertility is lacking, and 33 couples would need to be treated with ICSI unnecessarily to avoid one case of total fertilization failure. Such practice increases the cost to the patient, increases the burden on embryologist’s time, and is a misapplication of resources. Additionally, there remains conflicting data regarding the safety of offspring conceived by ICSI and potential damage to the oocyte. Thus, the use of ICSI should be limited to those with male factor infertility or a history of total fertilization factor infertility due to uncertainties of potential adverse impact and lack of proven benefit in non-male factor infertility.


1995 ◽  
Vol 4 (2) ◽  
pp. 75-86 ◽  
Author(s):  
Susan E Lanzendorf

Mammalian fertilization, whether it takes place within the female reproductive tract or within a laboratory dish, is comprised of many processes which must follow a specific sequence. The spermatozoon must bind to and pass through the zona pellucida, fuse with the oolemma and become incorporated into the cytoplasm of the oocyte. Fusion of the two gametes triggers oocyte activation, resulting in exocytosis of the cortical granules and completion of the second meiotic division of the oocyte. A block in one or more of these processes, due either to abnormalities in the spermatozoon or oocyte, may result in fertilization failure.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
E Seo. Pe. Yin

Abstract Study question Will artificial activation of oocytes alter the ploidy status of the resultant blastocysts? A sibling-oocytes pilot study Summary answer AOA-ICSI does not increase the risk of having aneuploidy blastocysts and can improve the fertilization rate in patients with sperm factor deficiency. What is known already Despite introducing ICSI as an aid to improve chances of fertilization, fertilization failure can still occur in 2–3% of ICSI cycles. Fertilization is a complex process triggered by a cascade of events following calcium (Ca2+) oscillations. Evidence suggests that the deficiency, localization or altered structure of the sperm-derived protein PLCζ in oocyte activation may be a reason for meiotic II arrest in the oocyte. Artificial oocyte activation has been proposed to compensate for the lack of calcium oscillation and resumes meiotic progression. There are however insufficient studies to determine its effect on the chromosomal status of the resultant blastocysts. Study design, size, duration This is a prospective, randomized study conducted at our Center from August-October 2020. A total of 20 couples intended for ICSI + Preimplatation Genetic Testing for Aneuploidy (PGT-A) cycles were recruited based on fulfilling one of the following criteria: 1) previous total fertilization failure (TFF), 2) history of low fertilization rate (<30%), 3) more than 2 cycles of failed IVF cycles (no implantation) 4) poor embryo development (no blastocysts formed) and 5) severe male factor. Participants/materials, setting, methods A total of 231 MII oocytes underwent randomization in a 1:1 ratio between AOA-ICSI and control group. All oocytes are subjected to ICSI treatment. Oocytes in the AOA-ICSI group are treated in 25μl droplets 10μM ready to use bicarbonate buffered calcium ionophore (Kitazato, Japan) for 15 minutes post-ICSI. The blastocysts were biopsied and subjected to PGT-A. Primary outcome was the aneuploidy rate and secondary outcomes were fertilization rate and blastocyst rate. Main results and the role of chance There were 11 out of 40 (27.5%) aneuploid blastocysts in the AOA-ICSI group and 7 out of 23 aneuploid blastocysts (30.4%) in the control group [odds ratio (OR) = 0.87; 95% confidence interval (CI) 0.28–2.68, p = 0.8040). There was no statistically significant difference between both groups. However, fertilization rate of the AOA- ICSI group was significantly higher than the fertilization rate in the control group (68.6% vs 49.6% respectively, OR = 2.22; 95% CI, 1.31–3.81, p = 0.0034). There were 40 blastocysts formed in the AOA-ICSI group and 23 blastocysts formed in the control group. It was found that the AOA-ICSI group yielded a higher blastocyst rate (49.4%) compared to the control group (41.1%) (OR = 1.40; 95% CI, 0.71 to 2.78, p = 0.3379) but the difference was not statistically significant. Limitations, reasons for caution The possibility of TE cells biopsied may not be representative of the whole blastocyst makes it possible to have false clinical data. The dosage and time were also not evaluated in this study as exposure time was found to be a critical factor of fertilization rate in a previous study. Wider implications of the findings: This study showed that AOA-ICSI does not increase the risk of having aneuploidy blastocysts and can improve the fertilization rate in patients with sperm factor deficiency. Additional studies involving a larger number of patients with more specific indication can further justify the benefits of AOA as a therapeutic application. Trial registration number NA


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
G Lópe. Ruiz ◽  
C Olmed. Illueca ◽  
M Bare. Gómez ◽  
S Roy. Bolea ◽  
L Aba. d. Velasco ◽  
...  

Abstract Study question Does Calcymicin improve reproductive outcomes of ICSI cycles in cases of fertilization failure and/or embryo blockage indications? Summary answer The application of the Calcymicin after ICSI improves reproductive outcomes, especially in cases with clinical indication of fertilization failure. What is known already According to the bibliography, deficiencies in the oocyte activation process frequently lead to failed ICSI cycles, and these can be corrected by increasing initial levels of calcium (Ca2+) in the oocyte using assisted oocyte activation techniques (AOA), such as the use of Ca2+ ionophores. Ca2+ Ionophores have been shown to trigger an initial Ca2+ spike in the ooplasm that activates Ca2+/Calmodulin dependent protein kinase II, which initiates the cascade of cellular events leading to oocyte activation. Previous results suggest that Ca2+ ionophore treatment can give live offspring after failed ICSI cycles. Study design, size, duration 270 oocytes collected from 17 patients who presented cycles with low fertilization rates and/or embryo blockage or poor quality embryos (according to ASEBIR’s embryo classification criteria) were retrospectively analyzed. Oocytes were divided into two groups, a control group that underwent conventional IVF/ICSI and another group that underwent an ICSI cycle with AOA. Study groups were defined according to clinical indications and subgroups according to AOA or control. All data were collected from 2017 until 2020. Participants/materials, setting, methods Among the 270 oocytes of the study sample, 142 belonged to the control group and 128 belonged to the AOA group. The AOA group oocytes were activated for 15 minutes immediately after ICSI using a prepared solution containing the Ca2+ ionophore A23187, CultActive© (Gynemed, Germany). Fertilization rate and type, blastocyst formation rate, blastocyst quality, embryo kinetics, and pregnancy rates were analyzed, all of them were compared to FIV/ICSI cycles without oocyte activation (control group). Main results and the role of chance In the analyses of the whole sample of oocytes, the AOA treatment gave a fertilization rate of 72.5%, which was significantly higher compared to 53.8% of the control cycles (p = 0.002). Good quality blastocysts and pregnancy rates were also significantly higher than the control (p = 0.01). In the group with an indication of fertilization failure, a significantly higher fertilization rate was recorded compared to the control (65% and 33%, respectively). A higher rate of abnormal embryos with three pronuclei was also found compared to the control (p < 0.001). There were no significant differences in blastocyst formation rates, quality, or embryo kinetics (p > 0.05). In the group with an indication of embryo blockage/poor embryo quality, a significantly higher rate of good quality blastocysts and lower blastulation time were recorded compared to the control (p < 0.05). Limitations, reasons for caution The safety of the AOA technique with Ca2+ ionophore has not been fully demonstrated. In our study, none of the newborns had malformations, and gestational weeks and birth weights were normal. However, further studies on the safety of this technique are needed to implement it routinely in human reproduction clinics. Wider implications of the findings: According to these findings, an increase in the initial levels of calcium in the oocyte through the application of the Ca2+ ionophore A23187 after ICSI improves the results of failed assisted reproduction cycles, especially in the case of those diagnosed with fertility failure, which is a clear indication for AOA. Trial registration number Not applicable


Sign in / Sign up

Export Citation Format

Share Document