A Study of Follicular Development and Oocyte Maturity Predicted by Transvaginal Ultrasound on the Day of Human Chorionic Gonadotropin Injection
Introduction
The quality of oocytes plays a pivotal role in determining the success of in vitro fertilization (IVF) outcomes. Human chorionic gonadotropin (hCG) is administered during controlled ovarian hyperstimulation (COH) to mimic the luteinizing hormone (LH) surge, triggering final follicular maturation and ovulation. The timing of hCG injection is critical, as it directly influences oocyte retrieval quality. Traditionally, follicular diameter measured via transvaginal ultrasound has been the primary criterion for determining the optimal time for hCG administration. However, the reliability of diameter-based thresholds becomes questionable in COH cycles, where multiple follicles of varying sizes and irregular shapes develop. Recent studies highlight the importance of peri-follicular blood flow (PFBF) as a marker of follicular health and oocyte maturity. This study investigates the combined role of follicular morphology (diameter) and PFBF parameters in predicting oocyte maturity, fertilization potential, and embryo quality on the day of hCG injection.
Methods
Study Population and Design
Thirty-two infertile women undergoing IVF-embryo transfer (IVF-ET) were prospectively enrolled, and 211 follicles were analyzed. Follicles were categorized into four groups based on average diameter measured on the day of hCG injection:
- Group A: Small follicles (≥12 mm, <15 mm; potential mature follicles).
- Group B: Medium follicles (≥15 mm, <18 mm; premature follicles).
- Group C: Large follicles (≥18 mm, <23 mm; mature follicles).
- Group D: Ultra-large follicles (≥23 mm; postmature follicles).
Ultrasound and PFBF Assessment
Transvaginal ultrasound was performed using a Philips IU22 system. PFBF parameters, including peak systolic velocity (PSV), resistance index (RI), and a semi-quantitative PFBF grading system, were evaluated. The PFBF grading, adapted from Bhal et al., classified blood flow around follicles as follows:
- Grade 0: No blood flow.
- Grade I: <25% of follicular circumference.
- Grade II: 25–49%.
- Grade III: 50–75%.
- Grade IV: >75%.
Oocyte and Embryo Evaluation
Oocyte maturity was classified into metaphase II (MII), metaphase I (MI), and germinal vesicle (GV) stages, with scores of 2, 1, and 0, respectively. Degenerated oocytes scored 0. Fertilization status was assessed by pronuclei count: 0PN (0), 1PN (1), 2PN (2), or polynucleated (PPN; 1). Cleavage and embryo quality were graded based on blastomere morphology and cytoplasmic debris: Grade I (≤5% debris) to Grade IV (>50% debris). High-quality embryos were defined as Grades I or II.
Statistical Analysis
Non-normally distributed data were presented as median (Q1, Q3). Group comparisons used Kruskal-Wallis and Dunn-Bonferroni tests. Spearman correlation analyzed relationships between follicular parameters and laboratory outcomes. Receiver operating characteristic (ROC) curves evaluated diagnostic accuracy.
Results
Follicular Diameter and PFBF Characteristics
As follicular diameter increased, PSV of PFBF (PSVF) rose significantly, while RI decreased. PFBF scores differed markedly between groups:
- Group A vs. B: 0.53 [0, 1.06] vs. 1.86 [1.34, 2.38], P <0.001.
- Group A vs. C: 0.53 vs. 2.47 [1.82, 3.12], P <0.001.
- Group A vs. D: 0.53 vs. 2.51 [1.66, 3.36], P =0.001.
- Group B vs. C: 1.86 vs. 2.47, P <0.001.
Oocyte Maturity and Fertilization Outcomes
Oocyte maturation rates increased with follicular diameter:
- Group A: 59.6%.
- Group B: 86.1%.
- Group C: 97.1%.
- Group D: 100%.
Normal fertilization rates followed a similar trend but declined in ultra-large follicles:
- Group C: 91.3%.
- Group D: 80.0% (χ²=57.167, P=0.007).
Cleavage rates were highest in Groups C and D (98.5% and 100%, respectively). However, high-quality embryo rates dropped in Group D (70.0% vs. 89.6% in Group C; χ²=12.550, P=0.022).
Correlation Analysis
Follicular diameter correlated positively with PFBF grade (r=0.680, P=0.001), PSVF (r=0.709, P=0.010), oocyte maturation (r=0.394, P=0.001), cleavage scores (r=0.523, P=0.003), and high-quality embryos (r=0.411, P=0.008). RI inversely correlated with diameter (r=−0.723, P=0.005).
PFBF grade and PSVF showed strong correlations with oocyte maturity (r=0.485 and 0.346), fertilization (r=0.629 and 0.405), cleavage (r=0.650 and 0.529), and embryo quality (r=0.567 and 0.419). RI negatively correlated with these outcomes (r=−0.319 to −0.723).
Diagnostic Accuracy of Parameters
ROC analysis revealed robust predictive value for follicular diameter (AUC=0.832), PFBF grade (AUC=0.837), and PSVF (AUC=0.800). Optimal diagnostic thresholds were:
- Diameter: 15.65 mm.
- PFBF Grade: 1.5 (37.5% of circumference).
- PSVF: 8.45 cm/s.
Discussion
This study demonstrates that combining follicular diameter with PFBF parameters enhances the prediction of oocyte maturity and IVF outcomes. Larger follicles (≥18 mm, <23 mm) exhibited optimal maturation (97.1%), fertilization (91.3%), and embryo quality (89.6%). However, ultra-large follicles (≥23 mm) showed reduced fertilization rates and lower high-quality embryo yields, likely due to oocyte degeneration or overmaturity.
PFBF metrics, particularly PSVF and vascular grading, provided additional prognostic value. Elevated PSVF and PFBF grades reflect robust angiogenesis, essential for follicular rupture and oocyte release. Conversely, declining RI indicates reduced vascular resistance, facilitating nutrient delivery to developing oocytes. The ROC-derived thresholds (15.65 mm diameter, 37.5% PFBF circumference, 8.45 cm/s PSVF) offer actionable benchmarks for timing hCG administration.
Clinical Implications
These findings advocate for a multimodal ultrasound approach during COH cycles. While follicular diameter remains a practical metric, integrating PFBF parameters mitigates limitations posed by heterogeneous follicular sizes and shapes. Clinicians should avoid delaying hCG injection until follicles exceed 23 mm, as postmaturity compromises oocyte viability. Future studies should explore three-dimensional Doppler techniques and age-specific thresholds to refine ovarian response assessments.
Conclusion
Transvaginal ultrasound parameters, including follicular diameter, PFBF grade, and PSVF, are critical predictors of oocyte maturity and IVF success. Ultra-large follicles, despite high maturation rates, exhibit diminished fertilization potential and embryo quality, underscoring the importance of timely hCG administration. Integrating morphological and hemodynamic assessments optimizes follicular selection, improving reproductive outcomes in IVF-ET cycles.
doi.org/10.1097/CM9.0000000000001341
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