Association between Serum Estradiol Level on the Human Chorionic Gonadotrophin Administration Day and Clinical Outcome

Association between Serum Estradiol Level on the Human Chorionic Gonadotrophin Administration Day and Clinical Outcome

Introduction
In vitro fertilization-embryo transfer (IVF-ET) is a cornerstone of assisted reproductive technology (ART), offering hope to infertile couples. A critical factor in IVF success is the controlled ovarian hyperstimulation (COH) process, which significantly elevates serum estradiol (E2) levels compared to natural cycles. Estradiol plays a pivotal role in follicular development and endometrial receptivity, making it a key determinant of IVF outcomes. However, the relationship between elevated serum E2 levels on the day of human chorionic gonadotrophin (hCG) administration and clinical outcomes remains controversial. Some studies suggest a positive correlation between high E2 levels and pregnancy rates, while others report no significant impact. This study aims to evaluate the association between serum E2 levels on hCG administration day and IVF-ET outcomes, including pregnancy rates and perinatal complications, to identify an optimal E2 range for successful IVF treatment.

Methods
This retrospective study analyzed data from 1771 infertile patients undergoing their first fresh IVF-ET cycles at Peking University First Hospital between January 2011 and January 2016. Patients were categorized into six groups based on serum E2 levels on the day of hCG administration: group 1 (E2 ≤ 1000 pg/mL, n = 205), group 2 (E2 1001–2000 pg/mL, n = 457), group 3 (E2 2001–3000 pg/mL, n = 425), group 4 (E2 3001–4000 pg/mL, n = 310), group 5 (E2 4001–5000 pg/mL, n = 237), and group 6 (E2 > 5000 pg/mL, n = 137). The primary outcomes assessed were the number of retrieved oocytes, mature (MII) oocytes, implantation rates, and clinical pregnancy rates. Secondary outcomes included perinatal complications such as preterm delivery (PT), low birth weight (LBW), and preeclampsia (PreE) in singleton pregnancies.

Results
The study revealed a concentration-dependent relationship between serum E2 levels and IVF outcomes. The number of retrieved oocytes, MII oocytes, implantation rates, and clinical pregnancy rates increased progressively from group 1 to group 5 but declined in group 6. Specifically, the number of retrieved oocytes was 4.1 ± 2.4 in group 1, 7.0 ± 3.1 in group 2, 10.0 ± 3.9 in group 3, 11.1 ± 4.3 in group 4, 12.9 ± 4.4 in group 5, and 12.5 ± 4.6 in group 6. Similarly, the number of MII oocytes increased from 3.5 ± 1.9 in group 1 to 11.0 ± 4.5 in group 5 before decreasing to 10.5 ± 4.0 in group 6. Implantation rates and clinical pregnancy rates followed a similar trend, peaking in group 5 at 41.1% ± 3.8% and 56.1% ± 4.8%, respectively, before declining in group 6.

In singleton pregnancies, higher peak serum E2 levels were associated with an increased risk of LBW. The odds of delivering LBW infants were 16.8 times higher in group 6 (E2 > 5000 pg/mL) compared to group 1 (E2 ≤ 1000 pg/mL). Receiver operating characteristic (ROC) curve analysis identified a peak serum E2 level of 3148 pg/mL as a threshold for predicting LBW, with a sensitivity of 71.4% and specificity of 68.3%. However, no significant differences were observed in the rates of PT or PreE across the E2 groups.

Discussion
The findings of this study underscore the importance of optimizing serum E2 levels during IVF treatment. While higher E2 levels are associated with improved IVF outcomes up to a certain threshold, excessively high levels can have detrimental effects. The data suggest that serum E2 levels between 1000 and 3148 pg/mL are optimal for achieving favorable IVF outcomes and minimizing perinatal complications.

The concentration-dependent effect of E2 on IVF outcomes aligns with previous research. Studies have shown that E2 levels within a specific range enhance endometrial receptivity and improve implantation rates. However, excessively high E2 levels can disrupt endometrial receptivity and negatively impact embryo implantation. This biphasic response highlights the need for careful monitoring and adjustment of E2 levels during COH.

The association between elevated E2 levels and LBW is particularly noteworthy. High E2 concentrations during COH may impair placental development, leading to inadequate nutrient and oxygen supply to the fetus. This finding is consistent with earlier studies that linked supraphysiologic E2 levels to adverse perinatal outcomes, including LBW and PreE. However, the lack of a significant association between E2 levels and PT or PreE in this study warrants further investigation.

Limitations of this study include its retrospective design and the potential for unmeasured confounding variables. Additionally, the single-center nature of the study limits the generalizability of the findings. Future multicenter prospective studies are needed to confirm these results and explore the underlying mechanisms linking E2 levels to IVF outcomes and perinatal complications.

Conclusion
This study demonstrates that serum E2 levels on the day of hCG administration significantly influence IVF outcomes and perinatal complications. An optimal E2 range of 1000 to 3148 pg/mL is associated with improved IVF success rates and reduced risk of LBW. These findings emphasize the importance of individualized COH protocols to achieve optimal E2 levels and enhance the likelihood of successful IVF treatment.

doi.org/10.1097/CM9.0000000000000251

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