THE IMPACT OF SOME FACTORS ON OOCYTE MATURATION IN PATIENTS UNDERGOING IN VITRO FERTILIZATION AT HANOI MEDICAL UNIVERSITY HOSPITAL

Serum unconjugated bisphenol A concentrations in women may adversely influence oocyte quality during in vitro fertilization

Expression and localization of opioid receptors during the maturation of human oocytes

Involvement of anticentromere antibody in interference with oocyte meiosis and embryo cleavage

The efficiency of progesterone vaginal gel versus intramuscular progesterone for luteal phase supplementation in gonadotropin-releasing hormone antagonist cycles: a prospective clinical trial

Despite advances in assisted reproductive technologies, predicting outcomes of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) remains difficult. Hormonal status, oocyte maturity, and ovarian reserve contribute to treatment variability. This study examined correlations among demographic, endocrine, and embryological parameters in women undergoing IVF and ICSI whose partners had normal semen profiles, and evaluated the effect of follicle-stimulating hormone (FSH) levels on outcomes. A retrospective analysis was performed on 488 women aged 18 to 45 years who underwent IVF and ICSI between 2022 and 2024. Data included age, body mass index (BMI), infertility duration, and levels of FSH, luteinizing hormone, anti-Müllerian hormone (AMH), thyroid-stimulating hormone, and fasting blood sugar. Embryological variables were oocyte yield, maturity stages (germinal vesicle, metaphase I, and metaphase II [MII]), and embryo count. Pearson correlations and the Kruskal-Wallis test were used to compare groups stratified by FSH (<10, 10-20, >20 mIU/mL). BMI and infertility duration showed weak correlations with embryological outcomes. AMH correlated positively with embryo count (r=0.29, p<0.01). MII oocytes correlated strongly with oocyte yield (r=0.90, p<0.01) and moderately with embryo count (r=0.46, p<0.01). Women with FSH <10 mIU/mL had significantly higher oocyte yield, MII oocyte numbers, and embryo counts than those with FSH ≥10 mIU/mL (p<0.001). Lower FSH and higher AMH are associated with better oocyte maturity and embryo yield. These markers may support individualized stimulation strategies to improve IVF and ICSI outcomes.

“Rescue” Intracytoplasmic Sperm Injection (ICSI) Can Result in Acceptable Pregnancy Rates in In Vitro Fertilization (IVF) Patients with Complete Fertilization Failure

D. T. Carrell, A. Nyboe Andersen and D. J. Lamb Departments of Surgery (Urology), Obstetrics and Gynecology, and Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA, The Fertility Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark, and The Center for Reproductive Medicine, Scott Department of Urology and the Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

Study question What is the impact of metaphase I (MI) time to mature period (TTM) regarding blastocyst development and ploidy status? Summary answer A short period of TTM (0.1 to 1.0) is related to an increase number of blastocyst formation when compared to longer TTM (1.1 to 3.0). What is known already To achieve meiotic competence, coordinated nuclear and cytoplasmic changes must occur in the oocyte to support fertilization and DNA replication and to ensure correct ploidy of the zygote and embryonic genome activation. Concomitant with chromosome condensation and migration, oocyte maturation goes by cytoplasm reorganization throughout the transitions of MI, polar body extrusion and MII. Despite the optimization of COH protocols, nearly 20% of the retrieved oocytes remain immature at the GV or MI stages. In vitro maturation of MI could increase the number of available embryos; however, longer culture time may affect oocyte quality, resulting in abnormal fertilization and cleavage. Study design, size, duration Prospective cohort study from 244 patients (n = 277 cycles) that had at least 1 MI oocyte after oocyte retrieval (OPU) following controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF) treatment according to medical referral in an single private ART center from January/2019 to November/2022. All MI oocytes were placed in a time-lapse incubator (TL, EmbryoScope, Vitrolife, Sweden) to check the exact time of first polar body extrusion (TTM to MII) before intracytoplasmic sperm injection (ICSI). Participants/materials, setting, methods Three hours after OPU, oocytes were denuded and assessed for maturation. Six-hundred and seven MI oocytes were followed in TL and those that reached the MII stage in a maximum of 6 hours post-OPU, were injected by ICSI (at 6h post-OPU) and stratified according to the TTM (0.1-1.0 hours and 1.1-3.0 hours). Fertilization rate, blastocyst formation, and ploidy were assessed. Kruskal-Wallis, chi-squared and Fisher tests were applied for statistical analysis. p &amp;lt; 0,05 was considered significant. Main results and the role of chance Patient mean age (n = 244) was 38,50 ± 3,40 years. From those, 25 patients (10.3%) had 2 cycles and 4 patients (1.6%) had 3 cycles with at least 1 MI oocyte. Age, anti-Müllerian hormone (AMH), #OPU, #MII, %MII (MII/OPU), #MI and MI% (MI/OPU) mean were not statistically different in patients with 1, 2 or 3 cycles in our cohort. One hundred forty-nine patients (61%) in 165 cycles (59.6%) had at least 1 oocyte that reached MII stage. In total, 248 oocytes were injected after 0.1-1.0h (group 1, n = 104, 41.9%) and 1.1-3.0h (group 2, n = 144 oocytes, 58.1%) of in vitro maturation. Age (38,99 ± 3,01 vs 38,85 ± 3,31), AMH (1,27 ± 1,29 vs 1,63 ± 1,87), #OPU (8,98 ± 4,32 vs 8,90 ± 4,34), #MII (4,41 ± 2,74 vs 4,44 ± 2,178), %MII (47.6% ± 18.8% vs 48.4% ± 17.1%) and %MI that followed to ICSI (59.2% ± 28.5% vs 54.8% ± 29.2%) were not different between groups 1 and 2 respectively. The mean number of MI that followed to ICSI were higher in group 1 (1,28 ± 0,48 vs 1,10 ± 0,32, p = 0.0008). Normal fertilization (2PN) and embryo cleavage were similar between groups (54.8% vs 45.1%, p = 0.157, 96.6% vs 93.3%, p = 0.467, respectively). However, blastocyst formation rate (#blastocyst/#fertilized) was higher in group 1 (n = 33, 55.9% vs n = 26, 34.7%, p = 0.015). Euploidy rates were similar between groups (9/28, 32% vs 4/24, 16%, p = 0.336). Limitations, reasons for caution Besides the retrospective nature of this study, male factor and infertility reason were not considered in this analysis. Due to the low number of blastocyst formation and consequentially ploidy assessment and number of embryo transfer, the results regarding euploidy rate may be underestimated and pregnancy rates were not included. Wider implications of the findings Oocytes that reached maturity up to 1 hour after denudation showed higher blastocyst formation rate, thus increasing embryo availability to transfer. In vitro-matured oocytes exhibit increased spindle and chromosomal abnormalities compared with oocytes matured in vivo, which may explain the lower rates of euploid embryos, especially in group 2. Trial registration number Not applicable.

Clinical outcomes for various causes of infertility with natural-cycle in vitro fertilization combined with in vitro maturation of immature oocytes

Oocyte retrieval versus conversion to intrauterine insemination in patients with poor response to gonadotropin therapy

Antimullerian hormone versus the clomiphene citrate challenge test for evaluation of ovarian reserve prior to in vitro fertilization

Background & objectives:The major cause of fertilisation failure after ICSI is failure of the oocyte to initiate the biochemical processes necessary for activation. This inability could be ascribed to cytoplasmic immaturity of those gametes even if they had reached nuclear maturity. The activation of a mature oocyte is characterised by release from metaphase II (MII) arrest and extrusion of the second polar body, followed by pro-nuclear formation. The aim of this study was to evaluate the fate of in vitro matured (IVM) metaphase I (MI) oocytes subjected to intracytoplasmic sperm injection (ICSI) at different time intervals after extrusion of the first polar body (1PB) in in vitro fertilization (IVF) cycles.Methods:A total of 8030 oocytes were collected from 1400 ICSI cycles, 5504 MII at the time of cumulus retrieval. Four hundred eight metaphase II (MII) (27.1%) matured to MII after in vitro culture for 2-26 h and 5389 sibling MII in the moment of oocyte denudation were injected. On the other hand, 49 ICSI cycles containing only MI oocytes at retrieval were injected at three different time intervals after reaching the MII. The intervals were as follows: 2-6 h (n=10), 8-11 h (n=4) and 23-26 h (n=10). Fertilization and development potential were evaluated in both studies.Results:Fertilization, embryo cleavage and quality were significantly lower in IVM MI compared to MII at time of denudation. Pregnancy rate was higher in group MII. Pregnancy was achieved in three embryo transfers when ICSI was performed within 2-6 h (group I) and 8-11 h (group II) after PB extrusion. One pregnancy was obtained in group I and a healthy neonate was born.Interpretation & conclusions:Immature oocytes from women whose ovaries have been stimulated could be matured, fertilized by ICSI, cleaved in vitro and to give rise to a live birth. However, the developmental competence of embryos derived from immature oocytes is reduced, compared with sibling in vivo matured oocytes. Further, human IVM oocytes need between 2-6h after the 1PB extrusion to complete its maturation.

The in vitro maturation (IVM) of human oocytes for in vitro fertilization (IVF): is it time yet to switch to IVM-IVF?

Study question Does a low (≤0.5) or very low Metaphase II (MII) (≤0.25) ratio in the oocyte-cycle cohort impact embryo development, transfer outcomes and live birth rates? Summary answer A low MII ratio is associated with fewer blastocysts and reduced PGT-A utilization, however live birth rates remain comparable when patient characteristics are matched. What is known already The proportion of immature oocytes retrieved during in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), has significant implications for fertility outcomes. The ratio of MII oocytes to immature germinal vesicle (GV) and metaphase I (MI) oocytes reflects the quality of ovarian stimulation and is believed to be associated with fertilization rates, embryo development, and live birth rates. Whether the presence of immature oocytes in the cycle cohort is reflective of overall poor oocyte quality is however disputed. Study design, size, duration This retrospective cohort study analyzed patient ICSI cycles where oocyte maturation was assessed between December 2014 to December 2023. Cycles were categorized into three groups based on the metaphase II (MII) to non-MII oocyte ratios: Very Low MII Ratio group (≤0.25) (N = 360 cycles), Low MII Ratio group (≤0.5) (N = 1,814 cycles), and Perfect MII Ratio group (1:1) (N = 2,400 cycles). Participants/materials, setting, methods The low and very low ratio groups were compared to the perfect MII group. To match the groups Propensity score matching (PSM) was applied in two phases: Matching for age, BMI, gonadotropin dosage, and AMH levels. Matching for age, BMI, gonadotropin dosage, and MII count. Primary and secondary outcomes included: Blastocyst formation, preimplantation genetic testing for aneuploidy (PGT-A) utilization, cryopreservation rates, and live birth rates for both fresh and cryopreserved embryo transfers. Main results and the role of chance Despite retrieving a comparable number of oocytes across groups, the Perfect MII Ratio Group demonstrated consistently better outcomes, including significantly higher blastocyst formation rates in the Perfect MII Ratio Group (3.27 per cycle) compared to the Low MII Ratio Group (1.66 per cycle; p &amp;lt; 0.001) and the Very Low MII Ratio Group (1.32 per cycle; p &amp;lt; 0.001). When PSM was applied in the two phases, cycles with very low MII ratios were still associated with reduced blastocyst formation (≤0.25: 1.32 ± 2.77 vs. 3.10 ± 3.22, p &amp;lt; 0.001) and PGT-A utilization (≤0.25: 10.9% vs. 32.1%, p &amp;lt; 0.001). However, post-PSM analysis revealed no significant differences in live birth rates between groups for both cryopreserved (Very Low MII: 41.6% vs. Perfect MII: 30%, p = 0.68) and fresh embryo transfers (Very Low MII: 46.1% vs. Perfect MII: 38%, p = 0.69). The Low MII group displayed a trend to lower values for cryopreserved transfer rates (44% vs. 53%, p = 0.05), while for fresh transfer, rates remained comparable (30% vs. 26.6%, p = 0.55). Limitations, reasons for caution Limitations of our study include its retrospective design and the possibility that not all potentially relevant variables influencing oocyte maturity and reproductive outcomes were captured. Although PSM was employed to control for confounding factors the influence of gonadotropin receptor sensitivity or oocyte intrinsic quality, could not be accounted for. Wider implications of the findings Although a higher proportion of immature oocytes is associated with fewer blastocysts and reduced PGT-A utilization, live birth rates remain comparable when key patient and number of MII are matched. These findings suggest that cycles with lower MII ratios reflect quantitative rather than qualitative limitations. Trial registration number No

Pregnancies and Births Achieved From in Vitro Matured Metaphase I (M I) Oocytes Retrieved in Patients Undergoing in Vitro Fertilization (IVF)