The effect of cult-active medium on pregnancy outcomes after intracytoplasmic sperm injection in azoospermic men: A case-control study

Background: Failed oocyte activation following intracytoplasmic sperm injection (ICSI) as a result of calcium deficiency is a major challenge. Objective: We compared the effect of cult-active medium (CAM) on ICSI outcomes in obstructive azoospermia cases. Materials and Methods: The present study was conducted with 152 ICSI cases, classified into CAM and control groups. The injected oocytes in the control group were cultured in the cleavage medium, while in the artificial oocyte activation group, oocytes were chemically activated through exposure to 200 µL of CAM for 15 min. Fertilization and cleavage rates, quality of embryos, and biochemical pregnancy and live birth rates were assessed in both groups. Results: There were significant differences between the groups in terms of fertilization and cleavage rates after using the CAM in the percutaneous epididymal sperm aspiration (PESA) subgroup (p = 0.05, p ≤ 0.001) and in the testicular sperm extraction subgroup (p = 0.02, p = 0.04), compared to their control groups. Also, the pregnancy rate was significantly higher in the PESA-CAM subgroup (p = 0.03). The PESA-CAM subgroup demonstrated a significant difference in embryo quality after ICSI (p = 0.04). Unsuccessful embryo transfer and abortion were lower in both subgroups compared to the control groups, but this difference was not significant. Surprisingly, live birth rate was higher in the PESA-CAM subgroup (p = 0.03). Conclusion: CAM treatment could improve fertilization and cleavage rates in obstructive azoospermia participants. It had a significant effect on embryo quality, and pregnancy and live birth rates in PESA cases. Key words: Calcium ionophore, Obstructive azoospermia, Fertilization, ICSI.

Oocyte cryopreservation review: outcomes of medical oocyte cryopreservation and planned oocyte cryopreservation

Background The utilization of oocyte cryopreservation (OC) has become popularized with increasing numbers of reproductive-aged patients desiring to maintain fertility for future family building. OC was initially used for fertility preservation in postmenarchal patients prior to gonadotoxic therapies; however, it is now available to patients to circumvent age-related infertility and other diagnoses associated with early loss of ovarian reserve. The primary aim of this paper is to provide a narrative review of the most recent and robust data on the utilization and outcomes of OC in both patient populations. Summary OC results in similar oocyte yield in patients facing gonadotoxic therapies and patients undergoing planned OC. Available data are insufficient to predict the live birth rates or the number of oocytes needed to result in live birth. However, oocyte yield and live birth rates are best among patients < 37.5 years old or with anti-mullerian hormone levels > 1.995 ng/dL, at the time of oocyte retrieval. There is a high ‘no use’ rate (58.9%) in patients using planned OC with 62.5% returning to use frozen oocytes with a spouse. The utilization rate in medical OC patients is < 10%. There is currently no data on the effects of BMI, smoking, or ethnicity on planned OC outcomes. Conclusion It is too early to draw any final conclusions on outcomes of OC in medical OC and planned OC; however, preliminary data supports that utilization of OC in both groups result in preservation of fertility and subsequent live births in patients who return to use their cryopreserved eggs. Higher oocyte yield, with fewer ovarian stimulation cycles, and higher live birth rates are seen in patients who seek OC at younger ages, reinforcing the importance of age on fertility preservation. More studies are needed in medical OC and planned OC to help guide counseling and decision-making in patients seeking these services.

Cumulative Live Birth Rates for Low-Prognosis Women Over 5 Years or 9 Frozen-Thawed Embryo Transfer Cycles

Background: For heterogeneous populations of low-prognosis women, it remains unclear as to how long individuals should continue undergoing ART when attempting to have a baby, as there have been insufficient studies to date tracking the cumulative live birth rates (CLBRs) for these women over the entire course of their ART treatment, particularly over extended time periods. Methods: This was a retrospective analysis of 17,698 women at a tertiary care academic medical center who had begun undergoing IVI/ICSI cycles using a PPOS approach between January 2013 and January 2019. Low-prognosis patients were stratified into four groups based upon POSEIDON criteria, with patients exhibiting normal or high ovarian reserves and response to stimulation (defined as AFC ≥5, >9 oocytes retrieved) being included as controls (group 5). The CLBR within 5 years or 9 FET cycles from the OPU day of the first cycle was the primary endpoint for this study, including all repetitive oocyte retrieval cycles and subsequent FET cycles. Optimistic and conservative approaches were used for the analysis of CLBRs and the depiction of cumulative incidence curves.Results: Under both optimistic and conservative model analyses, patients in group 5 exhibited the highest CLBR within 5 years or 9 FET cycles, followed by POSEIDON group 1, group 3, group 2, and group 4. Upward trends in CLBRs were evident across the five groups with the prolongation of time or an increase in FET cycle counts. Within the first 2 years or 3 FET cycles, the CLBRs rose rapidly, followed by more moderate increases over the following 2-3.5 years or 4-6 cycles, with the patients in group 3 and group 4 exhibiting the most obvious improvements. Patients in all groups reached a CLBR plateau after 3.5 years or 6 FET cycles.Conclusions: All low-prognosis women should undergo ART treatment for a minimum of 2 years or 3 FET cycles, and exhibit better outcomes when extending ART treatment to 3.5 years or 6 FET cycles (particularly for POSEIDON groups 3 and 4), but should consider ceasing further treatment thereafter due to a lack of apparent benefit.

Randomized allocation of oocytes to IVF or ICSI for IVF-naïve cases with unexplained infertility in an IVF-ICSI Split protocol favors ICSI to optimize live birth outcomes

In assisted reproduction treatments (ART), applying the ICSI method for fertilization of oocytes rather than traditional IVF method, is regarded as controversial for two reasons, namely utility and safety. Our study examines an IVF-ICSI Split model for couples with unexplained infertility, where male factor is meticulously excluded and ART is conducted by a strict algorithm, a commitment to blastocyst culture, along with single embryo transfers and a high commitment to cryopreservation. From 242 treatment cycles, 3346 oocytes recovered (13.8 per OPU) were randomly allocated to IVF or ICSI and the fertilization rates standardized to the number of 2PNS arising from each group applying the metaphase II oocyte number identified for the ICSI group, as the denominator for both groups. The fertilization rates were significantly higher overall for ICSI (83.2% vs 65.4%; p<0.0001), being most pronounced for women under 40 years. The resultant embryos had equivalent implantation rates in both fresh ET and frozen (FET) cycles with no significant differences in pregnancy rates, miscarriage rates or live birth outcomes indicating equivalent embryo quality. However, there were significantly higher numbers of ICSI-generated embryos cryopreserved and subsequent FET procedures showed higher live birth rates (21 births vs 6 births; p<0.005) and potential livebirths (214 births vs 104 births; p<0.0001). No congenital fetal abnormalities were detected in any of the 199 babies delivered during the study period to December 2020, neither IVF-generated nor ICSI-generated. Whilst the data strongly favors ICSI, there were 2 women (from 26 with fertilization in one arm only) who demonstrated fertilization only in the IVF arm of the study. We conclude that the IVF-ICSI Split model should be undertaken on all IVF-naïve women with unexplained infertility to determine the appropriate fertilization mode, albeit ICSI will be safely preferred for >90% of cases.

Comparison of the C Umulative Live Birth Rates After One ART Cycle Including All Subsequent Frozen–thaw Cycles in Women Undergoing IVF Using Progestin Primed Ovarian Stimulation Versus Long GnRH Agonist Protocol

Background: The efficacy and reproductive outcomes of progestin primed ovarian stimulation protocol (PPOS) were previously compared to rarely used ovarian stimulation protocol and also the live birth rate were reported by per embryo transfer rather than cumulative live birth rates (CLBRs). Does the use of PPOS improve the cumulative live birth rates (CLBRs) and shorten time to live birth when compared to long GnRH agonist protocol in women with normal ovarian reserve?Methods: A retrospective cohort study was designed to include women aged<40 with normal ovarian reserve (regular menstrual cycles, FSH <10 IU/L, antral follicle count >5) undergoing IVF from January 2017 to December 2019. The primary outcome was cumulative live birth rates (CLBRs) within 18 months from the day of ovarian stimulation.Results: A total of 995 patients were analyzed. They used either PPOS (n=509) or long GnRH agonist (n=486) protocol at the discretion of the attending physicians. Both groups had almost comparable demographic and cycle stimulation characteristics except for duration of infertility which was shorter in the PPOS group. In the GnRH agonist group 372 cases (77%) completed fresh embryo transfer, resulting into 218 clinical pregnancies and 179 live birth. The clinical pregnancy rate, ongoing pregnancy, and live birth per transfer were 58.6%, 54.0%, 53.0% respectively. In the PPOS, no fresh transfer was carried out. During the study period, the total number of initiated FET cycles with thawed embryos was 665 in the PPOS group and 259 in the long agonist group. Of all FET cycles, a total of 206/662 (31.1%) cycles resulted in a live birth in the PPOS group versus 110/257 (42.8%) in the long agonist group (OR: 0.727; 95% CI: 0.607–0.871; p<0.001) .The implantation rate of total FET cycles was also lower in the PPOS group compared with that in the agonist group 293/1004 (29.2%) and 157/455 (34.5%) (OR: 0.846; 95% CI: 0.721–0.992; p= 0.041). Cumulative live birth rates after one complete IVF cycle including fresh and subsequent frozen embryo cycles within 18 months follow up were significantly lower in the PPOS group compared that in the long agonist group 206/509 (40.5%) and 307/486 (63.2%), respectively (OR: 0.641; 95% CI: 0.565-0.726). The average time from ovarian stimulation to pregnancy and live birth was significantly shorter in the long agonist group compared to the PPOS group (p<0.01) In Kaplan-Meier analysis, the cumulative incidence of ongoing pregnancy leading to live birth was significantly higher in the long agonist compared in the PPOS group(Log rank test, p<0.001). Cox regression analysis revealed stimulation protocol adopted was strongly associated with the cumulative live birth rate after adjusting other confounding factors (OR =1.917 (1.152-3.190), p=0.012) .Conclusion: Progestin primed ovarian stimulation was associated with a lower cumulative live birth rates and a longer time to pregnancy / live birth than the long agonist protocol in women with a normal ovarian reserve.