OBJECTIVE: To investigate the association between a low oocyte maturity ratio from in vitro fertilization cycle and blastocyst euploidy.
METHODS: A total of 563 preimplantation genetic testing (PGT) cycles (PGT cycles with chromosomal structural rearrangements were excluded) were performed between January 2021 and November 2022 at our center (average oocyte maturity rate: 86.4% ± 14.6%). Among them, 93 PGT cycles were classified into the low oocyte maturity rate group (group A, < mean - 1 standard deviation [SD]), and 186 PGT cycles were grouped into the average oocyte maturity rate group (group B, mean ± 1 SD). Group B was 2:1 matched with group A. Embryological, blastocyst ploidy, and clinical outcomes were compared between the two groups.
RESULTS: The oocyte maturity (metaphase II [MII oocytes]), MII oocyte rate, and two pronuclei (2PN) rates were significantly lower in group A than in group B (5.2 ± 3.0 vs. 8.9 ± 5.0, P = 0.000; 61.6% vs. 93.0%, P = 0.000; 78.7% vs. 84.8%, P = 0.002, respectively). In group A, 106 of 236 blastocysts (44.9%) that underwent PGT for aneuploidy were euploid, which was not significantly different from the rate in group B (336/729, 46.1%, P = 0.753). However, euploid blastocysts were obtained only in 55 cycles in group A (55/93, 59.1%), which was lower than the rate in group B (145/186, 78.0%, P = 0.001). The clinical pregnancy rate in group B (73.9%) was higher than that in group A (58.0%) (P = 0.040).
CONCLUSIONS: Our results suggest that a low oocyte maturity ratio is not associated with blastocyst euploidy but is associated with fewer cycles with euploid blastocysts for transfer, lower 2PN rates, and lower clinical pregnancy rates.

UNASSIGNED: To evaluate the efficacy of peri-trigger female reproductive hormones (FRHs) in the prediction of oocyte maturation in normal ovarian reserve patients during the in vitro fertilization-embryo transfer (IVF-ET) procedure.
UNASSIGNED: A hospital database was used to extract data on IVF-ET cases from January 2020 to September 2021. The levels of female reproductive hormones, including estradiol (E2), luteinizing hormone (LH), progesterone (P), and follicle-stimulating hormone (FSH), were initially evaluated at baseline, the day of the trigger, the day after the trigger, and the day of oocyte retrieval. The relative change in E2, LH, P, FSH between time point 1 (the day of trigger and baseline) and time point 2 (the day after the trigger and day on the trigger) was defined as E2_RoV1/2, LH_RoV1/2, P_RoV1/2, and FSH_RoV1/2, respectively. Univariable and multivariable regression were performed to screen the peri-trigger FRHs for the prediction of oocyte maturation.
UNASSIGNED: A total of 118 patients were enrolled in our study. Univariable analysis revealed significant associations between E2_RoV1 and the rate of MII oocytes in the GnRH-agonist protocol group (p < 0.05), but not in the GnRH-antagonist protocol group. Conversely, P_RoV2 emerged as a potential predictor for the rate of MII oocytes in both protocol groups (p < 0.05). Multivariable analysis confirmed the significance of P_RoV2 in predicting oocyte maturation rate in both groups (p < 0.05), while the association of E2_RoV1 was not significant in either group. However, within the subgroup of high P_RoV2 in the GnRH-agonist protocol group, association was not observed to be significant. The C-index was 0.83 (95% CI [0.73-0.92]) for the GnRH-agonist protocol group and 0.77 (95% CI [0.63-0.90]) for the GnRH-antagonist protocol group. The ROC curve analysis further supported the satisfactory performance of the models, with area under the curve (AUC) values of 0.79 for the GnRH-agonist protocol group and 0.81 for the GnRH-antagonist protocol group.
UNASSIGNED: P_RoV2 showed significant predictive value for oocyte maturation in both GnRH-agonist and GnRH-antagonist protocol groups, which enhances the understanding of evaluating oocyte maturation and inform individualized treatment protocols in controlled ovarian hyperstimulation during IVF-ET for normal ovarian reserve patients.

OBJECTIVE: To analyze the pregnancy outcomes in patients with positive anti-centromere antibodies (ACA) receiving in vitro fertilization (IVF)-embryo transfer (ET) and natural conception.
METHODS: A case-control study was used to retrospectively analyze the clinical data of 3955 patients who received IVF-ET therapy and had the results of antinuclear antibody (ANA) spectrum at Zhejiang Provincial People\'s Hospital from June 2016 to June 2023. Patients with positive ACA and negative ACA were matched at a ratio of 1∶3 using propensity score matching. Embryo outcomes of IVF were compared between the two groups, and the impact of different fertilization methods and the use of immunosuppressants on pregnancy outcomes were analyzed using self-matching. The natural conception and disease progress were followed up for ACA-positive patients after IVF failure.
RESULTS: The ACA-positive patients accounted for 0.86% of all IVF patients (34/3955) and 2.51% of total ANA-positive IVF patients. Regardless of whether patients received conventional IVF (c-IVF) or intracytoplasmic sperm injection (ICSI), the ACA-positive group exhibited significant differences in oocyte maturity and fertilization compared to the ACA-negative group (both P<0.01). Moreover, the ACA-positive group had a decreased number of D3 suboptimal embryos and D3 optimal embryos (both P<0.05). In 5 cases of ACA-positive patients who underwent ICSI cycles, the two pronucleus (2PN) rate did not increase compared to c-IVF cycles (P>0.05), and there was a decrease in the number of D3 high-quality embryos and D3 suboptimal embryos (both P<0.05). After 1-2 months of immuno-suppressant treatment, 12 ACA-positive patients underwent c-IVF/ICSI again, and there were no changes in egg retrieval and fertilization before and after medication (both P>0.05), but there was an improvement in the 2PN embryo cleavage rate (P<0.05). The number of embryos transferred was similar between the ACA-positive and negative groups, but the ACA-positive group had significantly lower embryo implantation rate and clinical pregnancy rate compared to the ACA-negative group (both P<0.05), with no significant differences in the miscarriage rate between the two groups (P>0.05). Twenty-seven ACA-positive patients attempted natural conception or artificial insemination after IVF failure, resulting in a total of 7 cases of clinical pregnancy.
CONCLUSIONS: Serum ACA positivity may disrupt oocyte maturation and normal fertilization processes, with no improvement observed with ICSI and immunosuppressant use. However, ACA-positive patients may still achieve natural pregnancy.
目的: 通过观察抗着丝点抗体（ACA）阳性患者体外受精-胚胎移植和自然试孕结局，探讨此类患者的生育策略。方法: 采用病例对照研究回顾性分析2016年6月至2023年6月在浙江省人民医院接受体外受精-胚胎移植治疗且有抗核抗体（ANA）谱检查结果的3955例患者的临床资料。根据ACA结果将所纳入患者分为ACA阳性组和ACA阴性组。采用倾向评分匹配方法对两组进行1∶3配对，分别比较两组体外受精的胚胎结局；并采用自身对照分析不同授精方法和是否应用免疫抑制剂对结局的影响；对ACA阳性患者体外受精失败后的自然试孕和疾病进展进行随访。结果: ACA阳性患者34例，占总病例数的0.86%，占ANA阳性体外受精患者数的2.51%。无论是接受常规体外受精（c-IVF）还是卵胞质内单精子注射（ICSI）的患者，ACA阳性组卵母细胞成熟度和受精情况均与ACA阴性组有明显差异（均P<0.01），且ACA阳性组授精后第三日（D3）次优胚数和D3优胚数均减少（均P<0.05）。5例ACA阳性患者自身ICSI周期相比c-IVF周期双原核（2PN）率未提高（P>0.05），D3优胚数和D3次优胚数减少（均P<0.05）。12例ACA阳性患者经过免疫抑制剂治疗1~2个月后再行c-IVF/ICSI，用药前后获卵和受精情况均未改变（均P>0.05），2PN胚胎卵裂率改善（P<0.05）。ACA阳性组与ACA阴性组移植胚胎数相近，但ACA阳性组胚胎着床率、临床妊娠率显著低于ACA阴性组（均P<0.05），流产率差异无统计学意义（P>0.05）。27例ACA阳性患者体外受精失败后尝试自然试孕或人工授精，共获临床妊娠7例。结论: 血清ACA阳性会干扰卵母细胞的成熟和正常受精过程，使用ICSI和免疫抑制剂不能改善受精结局，但ACA阳性患者有可能获得自然妊娠。.

Angiogenesis in folliculogenesis contributes to oocyte developmental competence in natural and in vitro fertilization (IVF) cycles. Therefore, the identification of key angiogenic factors in follicular fluid (FF) during folliculogenesis is clinically significant and important for in vitro fertilization. This study aims to identify the key angiogenic factors in FF for predicting oocyte maturity during in vitro fertilization.
Forty participants who received ovarian stimulation using a GnRH antagonist protocol in their first in vitro fertilization treatment were recruited. From each patient, two follicular samples (one preovulatory follicle, > 18 mm; one mid-antral follicle, < 14 mm) were collected without flushing during oocyte retrieval. In total, 80 FF samples were collected from 40 patients. The expression profiles of angiogenesis-related proteins in FF were analyzed via Luminex high-performance assays. Recorded patient data included antral follicle count, anti-müllerian hormone, age, and BMI. Serum samples were collected on menstrual cycle day 2, the trigger day, and the day of oocyte retrieval. Hormone concentrations including day 2 FSH/LH/E2/P4, trigger day E2/LH/P4, and retrieval day E2/LH/P4 were measured by chemiluminescence assay.
Ten angiogenic factors were highly expressed in FF: eotaxin, Gro-α, IL-8, IP-10, MCP-1, MIG, PAI-1 (Serpin), VEGF-A, CXCL-6, and HGF. The concentrations of eotaxin, IL-8, MCP1, PAI-1, and VEGF-A were significantly higher in preovulatory follicles than those in mid-antral follicles, while the Gro-α and CXCL-6 expressional levels were lower in preovulatory than in mid-antral follicles (p < 0.05). Logistic regression and receiver operating characteristic (ROC) analysis revealed that VEGF-A, eotaxin, and CXCL-6 were the three strongest predictors of oocyte maturity. The combination of VEGF-A and CXCL-6 predicted oocyte maturity with a higher sensitivity (91.7%) and specificity (72.7%) than other combinations.
Our findings suggest that VEGF-A, eotaxin, and CXCL-6 concentrations in FF strongly correlate with oocyte maturity from the mid-antral to preovulatory stage. The combination of VEGF-A and CXCL-6 exhibits a relatively good prediction rate of oocyte maturity during in vitro fertilization.

We present two separate label-free quantitative workflows based on different high-resolution mass spectrometers and LC setups, which are termed after the utilized instrument: Quad-Orbitrap (nano-LC) and Triple Quad-TOF (micro-LC) and their directed adaptation toward the analysis of human follicular fluid proteome. We identified about 1000 proteins in each distinct workflow using various sample preparation methods. With assistance of the Total Protein Approach, we were able to obtain absolute protein concentrations for each workflow. In a pilot study of twenty samples linked to diverse oocyte quality status from four donors, 455 and 215 proteins were quantified by the Quad-Orbitrap and Triple Quad-TOF workflows, respectively. The concentration values obtained from both workflows correlated to a significant degree. We found reasonable agreement of both workflows in protein fold changes between tested groups, resulting in unified lists of 20 and 22 proteins linked to oocyte maturity and blastocyst development, respectively. The Quad-Orbitrap workflow was best suited for an in-depth analysis without the need of extensive fractionation, especially of low abundant proteome, whereas the Triple Quad-TOF workflow allowed a more robust approach with a greater potential to increase in effectiveness with the growing number of analyzed samples after the initial effort of building a comprehensive spectral library.

The most common reason for in vitro fertilization (IVF) cycle cancelation is a lack of quality gametes available for intracytoplasmic sperm injection (ICSI). Here we present the successful fertility treatment of the couple affected by obstructive azoospermia combined with suboptimal response to controlled ovarian stimulation. Since the conventional approach appeared ineffective to overcome both partners\' specific problems, the targeted interventions, namely, (1) pharmacological enhancement of sperm motility and (2) polarized light microscopy (PLM)-guided optimization of ICSI time, were applied to rescue the cycle with only immature oocytes and immotile testicular sperm retrieved. The treatment with theophylline aided the selection of viable spermatozoa derived from cryopreserved testicular tissue. When the traditional stimulation protocol failed to produce mature eggs, non-invasive spindle imaging was employed to adjust the sperm injection time to the maturational stage of oocytes extruding a polar body in vitro. The fertilization of 12 late-maturing oocytes yielded 5 zygotes, which all developed into blastocysts. One embryo was transferred into the uterus on day 5 post-fertilization, and another 3 good quality blastocysts were vitrified for later use. The pregnancy resulted in a full-term delivery of a healthy child. This case demonstrates that the individualization beyond the standard IVF protocols should be considered to maximize the chance of poor-prognosis patients to achieve pregnancy with their own gametes.

UNASSIGNED: The aim is to study the effect of follicle-stimulating hormone (FSH) administration on the day of human chorionic gonadotropin (hCG) trigger on the assisted reproductive technique (ART) outcomes in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles.
UNASSIGNED: Retrospective cohort study was conducted in the ART center of our hospital.
UNASSIGNED: Two hundred and ninety IVF/ICSI cycles performed between September 2012 and August 2017 were included in the study. Patients who received 375 IU of FSH on the day of hCG trigger (149 cycles) were compared with those who did not receive FSH on the day of trigger (141 cycles).
UNASSIGNED: Chi-square test and Student\'s t-test were used.
UNASSIGNED: The FSH co-administered group had a significantly higher number of oocytes retrieved, mature oocytes, and fertilization rate compared to those who did not receive FSH on the day of trigger (p < 0.001). The total number of embryos, the number of grade 1 embryos and the number of embryos available for cryopreservation were also significantly higher in the FSH administered group (p < 0.001). Implantation rate, clinical pregnancy rate, and live birth rate were not significantly different between the two groups.
UNASSIGNED: This study has shown that FSH administration on the day of the trigger may be considered in IVF cycles receiving hCG trigger to improve the oocyte recovery and maturity if the patient is not at increased risk of ovarian hyperstimulation and serum estradiol on the day of the trigger is <4500 pg/ml. However, there is only an increase in the total number of oocytes retrieved and the number of mature oocytes but no significant change in the implantation, clinical pregnancy, and live birth rates.

The number of mature oocytes is a key factor in the success of Assisted Reproductive Techniques (ART). Exogenous gonadotropins are administered during ovarian stimulation in order to maximize the number of oocytes available for fertilization. During stimulation, monitoring is mandatory to evaluate individual response, to avoid treatment complications and assist in the determination of the optimal day for final oocyte maturation and oocyte retrieval. Routine monitoring during stimulation includes transvaginal ultrasound examinations and measurement of serum estradiol (E2). Due to multifollicular growth of follicles of varying size, serum E2 levels are commonly supraphysiological and often variable, rendering E2-measurement during ovarian stimulation unreliable as a determinant of oocyte maturity. In contrast to serum E2, serum Inhibin A levels increase once a minimum follicle size of 12-15 mm is achieved. Due to this fact, serum Inhibin A levels could present in combination with ultrasound monitoring a more reliable parameter to determine the optimal follicle size for final oocyte maturation, as only follicles with a size of 12 mm and beyond will contribute to the serum Inhibin A level. This prospective observational, cross-sectional study demonstrates, that on the day of final oocyte maturation serum Inhibin A is strongly correlated to the number of follicles ≥15 mm (0.72) and to the number of retrieved and mature oocytes (ρ 0.82/0.77, respectively), whereas serum E2 is moderately correlated to the parameters mentioned above (ρ 0.64/0.69/0.69, respectively). With an area under the curve (AUC) of 0.91 for Inhibin A, compared to an AUC of 0.84 for E2, Inhibin A can be regarded as a better predictor for the optimal timing of trigger medication with a threshold number of ≥10 mature oocytes. It can be concluded from this data that serum Inhibin A in combination with transvaginal ultrasound monitoring may be a more powerful tool in the decision making process on trigger timing as compared to E2.

Is there is an association between follicle size and the quality of oocytes retrieved from them as judged by ability to achieve the blastocyst stage, blastocyst grades and blastocyst ploidy?
Although follicle size is a valuable predictor of oocyte maturity and is a significant predictor of the ability of a fertilized oocyte to become a quality blastocyst, the ploidy of each quality blastocyst is not related to the size of the follicle from which its oocyte was retrieved.
It is unclear whether the oocytes within larger follicles are the best oocytes of the cohort. Although there have been studies examining follicle size in relation to embryo quality, there has been no study relating the incidence of euploidy in embryos to follicle size.
The purpose of this study was to examine follicle sizes and the oocytes from those follicles (and the embryos that result from those oocytes) to see if there is an association between follicle size and the quality of oocytes as judged by ability to achieve the blastocyst stage, blastocyst grades and blastocyst ploidy. Follicle sizes for oocytes were assessed both as diameters (mm) and as Z values (expressed as their size relative to the mean and standard deviation of that donor\'s follicular cohort). Comparisons were made using cumulative histograms, rolling averages and receiver operator characteristic (ROC) curves and its AUC.
Twenty-two oocyte donors (ages: 24.5 ± 3.5 years) whose recipients would use ICSI for insemination were enrolled in this study. Follicles were aspirated one-at-a-time to be certain that the aspirated oocyte was from the same follicle measured. The follicle measurement (size) was noted in the embryology records. Oocytes were cultured individually throughout their time in the embryology laboratory so that follicle sizes could be uniquely associated with each oocyte. Oocytes and embryos were analyzed according to the size of the follicle from which the oocyte was retrieved.
Three hundred seventeen oocytes (96.1%) had an associated follicle size. Of the oocytes with follicle sizes, 255 (80.4%) had a polar body (MII), and 60 (18.9%) were immature: 31 (9.8%) with a visible germinal vesicle (GV stage) and 29 (9.1%) with neither a polar body nor a visible germinal vesicle (MI). The incidence of MII oocytes was significantly associated with larger follicle size using either mm (ROC\'s AUC = 0.87; P < 0.0001) or Z values (ROC\'s AUC = 0.86; P < 0.0001). Among MII oocytes there was no association with follicle size for the appearance of 228 oocytes with two pronuclei (2 PN). Among 2 PN\'s, the development of 94 quality blastocysts that underwent trophectoderm biopsy (TE Bx) exhibited a significant association with larger follicles using either mm (ROC\'s AUC = 0.59; P = 0.01) or Z values (ROC\'s AUC = 0.57; P = 0.01). The use of follicle diameter as a feature to distinguish between fertilized oocytes that would ultimately become blastocysts versus those that would not become blastocysts resulted in an enrichment for blastocyst formation from 20 to 40%. Of the 94 quality blastocysts, 51 were determined by next generation sequencing (NGS) to be euploid.Although oocyte maturity and the incidence of blastocyst formation were associated with follicle size, the incidence of euploidy among biopsied blastocysts was not. Follicles measured by two different methods (mm or Z values) led to predominantly the same conclusions.
This study investigated the relationship between follicle size and measures of oocyte/embryo quality when donors were treated similarly. Therefore, this study does not investigate the effects of triggering and retrieving oocytes when the follicle cohorts are of different sizes or lead follicles are of different sizes. Although no association was found between follicle size and euploid blastocysts, the fact that blastocyst ploidy is not entirely dependent upon oocyte ploidy (e.g. aneuploidies derived from mitotic errors or from the fertilizing sperm) makes it difficult to infer the relationship between follicle diameter and oocyte ploidy.
It is confirmed that follicle diameter is predictive of oocyte maturity. However, once oocyte maturity is known, the diameter of the follicle from which the oocyte was retrieved is not instructive. Embryos generated through fertilization and development of the mature oocytes from any observed follicle diameter were equally likely to become euploid blastocysts.
This study was funded by ReproART: Georgian American Center for Reproductive Medicine. None of the authors declare any actual conflicts of interest. D.H.M. received compensation from ReproART, Biogenetics Corporation and the Sperm and Embryo Bank of New York and honoraria and travel funding from Ferring Pharmaceuticals and from Granata Bio. S.M. received compensation from Cooper Genomics and an honorarium and travel funding from Ferring Pharmaceuticals. L.C. is the founder of LTD Ovamedi, the organization that represents Cooper Genomics in Georgia, and received travel funding from the European Society for Human Reproduction and Embryology.
N/A.

OBJECTIVE: The majority of data regarding oocyte cryopreservation (OC) outcomes focuses on healthy women. We compare trends, cycle characteristics, and outcomes between women freezing oocytes for fertility preservation due to cancer versus elective and other medical or fertility-related diagnoses.
METHODS: Retrospective cohort using national surveillance data includes all autologous OC cycles between 2012 and 2016. Cycles were divided into 4 distinct groups: cancer, elective, infertility, and medically indicated. We calculated trends and compared cycle and outcome characteristics between the 4 groups. We used multivariable log-binomial models to estimate associations between indication and gonadotropin dose, hyperstimulation, and cancelation and used Poisson regression models to estimate associations between indication and oocyte yield and maturity.
RESULTS: The study included 29,631 autologous OC cycles. Annual total (2925 to 8828) and cancer-related (177 to 504) cycles increased over the study period; the proportions remained constant. Compared to elective, cancer-related cycles were more likely to be performed among women < 35 years old, with higher BMI, living in the South, using an antagonist protocol. Compared to elective OC cycles, gonadotropin dose (aRR 0.89, 95%CI 0.80-0.99), cancelation (aRR 0.90, 95%CI 0.70-1.14), and hyperstimulation (aRR 1.46, 95%CI 0.77-2.29) were not different for cancer-related cycles. Oocyte yield and percent maturity were comparable in both groups.
CONCLUSIONS: The number of OC cycles among women with cancer has increased; however, the percentage OC cycles for cancer have remained stable. While patient demographic characteristics were different among those undergoing OC for cancer indication, cycle outcomes were comparable to elective OC. The outcomes of the subsequent oocyte thaw, fertilization, and embryo transfer cycles remain unknown.