Endometrium development patterns and BMI groups among in vitro fertilization patients; prognostic aspects

Abstract

Introduction: The impact of the obesity pandemic on female reproductive capability is a factor that needs to be investigated. In addition, the link between endometrial thickness and in vitro fertilization (IVF) outcomes is contentious.

Goal: Our goal was to analyze the association among endometrium development, hormone levels, embryo quality, clinical pregnancy, anamnestic parameters, and body mass index (BMI) in women receiving IVF treatment.

Patients and methods: 537 participants undergoing IVF/ICSI cycles with successful oocyte retrieval were enrolled. Subjects were divided into four BMI based groups: underweight (UW; n=32), normal weight (NW; n=324), overweight (OW; n= 115), obesity (OB; n=66). Anthropometric and anamnestic parameters, characteristics of stimulation, endometrial thickness on the day of hCG injection, at puncture, at embryo transfer, FSH, LH, AMH, partner's age and the semen analysis indicators, embryo quality, clinical pregnancy, were recorded and analyzed. Support Vector Machine (SVM) was built to predict potential pregnancies based on medical data using 22 dimensions.

Results: In accordance with BMI categories, when examining pregnant/non-pregnant division, the average age of pregnant women was significantly lower in the UW (30.9 ± 4.48 vs. 35.3 ± 5.49 years, p=0.022), NW (34.2 ± 4.25 vs. 36.3 ± 4.84 years, p<0.001), and OW (33.8 ± 4.89 vs. 36.3 ± 5.31 years, p=0.009) groups. Considering FSH, LH, and AMH levels in each BMI category, a statistically significant difference was observed only in the NW category FSH was significantly lower (7.8 ± 2.99 vs. 8.6 ± 3.50 IU/L, p=0.032) and AMH (2.87 ± 2.40 vs. 2.28 ± 2.01 pmol/L, p=0.021) was higher in pregnant women. There were no further statistically significant differences observed between the pregnant and non-pregnant groups across any BMI categories, especially concerning endometrial development. Surprisingly, BMI and weight correlated negatively with FSH (r=-0.252, p<0.001; r=-0.206, p<0.001, respectively) and LH (r= -0.213, p<0.001; r= -0.195, p<0.001) in the whole population. SVM model average accuracy on predictions was 61.71%.

Discussion: A convincing correlation between endometrial thickness development and patients' BMI could not be substantiated. However, FSH and LH levels exhibited a surprising decreasing trend with increasing BMI, supporting the evolutionary selective role of nutritional status. Our SVM model outperforms previous models; however, to confidently predict the outcome of embryo transfer, further optimization is necessary.

Keywords: body mass index; clinical pregnancy rate; endometrium thickness; in vitro fertilization; obesity.

Figure 1

Significant differences between four BMI categories. Significant differences between four BMI categories: UW, NW, OW, OB. (A) Boxplot represents the duration of infertility. (B) Boxplot represents the duration of stimulation. (C) Bar plot represents the total number of transferred embryos. (D) Boxplot represents FSH levels. (E) Boxplot represents LH levels. (F) Boxplot represents AMH levels. (G) Boxplot represents endometrial thickness on the day of triggering hCG injection. (H) Boxplot represents endometrial thickness on the day of puncture. (I) Bar plot represents the number of unsuccessful IUI. Bar plot error bars indicate 95% confidence intervals. Significance boundaries and sample numbers are available at the bottom right corner.

Figure 2

Significant differences between pregnant and non-pregnant subgroups within the four BMI categories. Significant differences between pregnant and non-pregnant subgroups within the four BMI categories: UW, NW, OW, OB. (A) Boxplot represents age. (B) Boxplot represents FSH levels. (C) Boxplot represents LH levels. (D) Boxplot represents AMH levels. (E) Boxplot represents the number of follicles. (F) Boxplot represents paternal age. (G) Bar plot represents the embryo score of the best embryo transferred. Bar plot error bars indicate 95% confidence intervals. Significance boundaries and sample numbers are available at the bottom right corner.

Figure 3

AMH, FSH and LH hormone levels in age and BMI groups. AMH, FSH and LH hormone levels in age and BMI groups. (A) Age categories and the number of measurements. (B) BMI categories and the number of measurements. (C) Boxplot represents the distribution of BMI in age categories. (D) Boxplot represents the distribution of age in BMI categories. (E) Boxplot represents the AMH levels in age groups. (F) Boxplot represents the AMH levels in BMI groups. (G) Boxplot represents the FSH levels in age groups. (H) Boxplot represents the FSH levels in BMI groups. (I) Boxplot represents the LH levels in age groups. (J) Boxplot represents the LH levels in BMI groups.

Figure 4

Correlations. (A) heatmap represents the correlations within the entire dataset, with rho values rounded to three decimals. (B) heatmap illustrates the correlation between BMI groups correlations.

Figure 5

Results of endometrial thickness measurement. Sample numbers and significance boundaries are available in the top right corner. (A) The boxplot represents alterations in endometrial thickness at three measurement times (ENDOV, ENDPU, ENDET). Significance is highlighted in the relation of ENDOV and the corresponding BMI categories in ENDPU and ENDET. (B) The boxplot represents the difference in endometrial thickness between the ENDOV and ENDET measurements in non-pregnant and pregnant categories. (C, D) Boxplots illustrate alterations in endometrial thickness across three measurement times (ENDOV, ENDPU, ENDET) for both non-pregnant and pregnant groups. Significance is emphasized in the relationship between ENDOV and the corresponding BMI categories in ENDPU and ENDET. (E, F) Boxplots illustrate the difference in endometrial thickness between ENDOV and ENDET measurements across BMI categories for non-pregnant and pregnant groups. Only significant differences are indicated. Additional statistical information is available in the *.xlsx file.

Figure 6

Endometrial thickness in k-means clusters. (A) Line graphs represent endometrial thickness in nine categories, using the 3 measurement times. (B) Line graphs represent the changes in endometrial thickness between the measurements, in the nine groups. (C) Table describing the nine categories, including the percentage and the enrichment of pregnant outcomes (higher values represented with a red, lower values a blue background), the mean overall thickness measured in each category (higher values represented with a red, lower values with a green background), and the number of the members of the group.

Figure 7

Endometrial thickness categorized based on thickness at different measurement time points. (A) line graphs depict endometrial thickness in five categories (I, II, III, IV, V), across three measurement times (OV, PU, ET). (B) table describing the categories, including the percentage and enrichment of pregnant outcomes (higher values represented with a red, lower value with a blue background), the mean overall thickness measured in each category (higher values represented with a red, lower value with a green background), and the number of members in each group.

Figure 8

The effect of omitting dimensions on SVM models accuracy. The boxplot illustrates the accuracy of optimized Support Vector Machine (SVM) models using 100 different random states. The unused data for model training is listed on the x-axis. Significant differences in performance compared to the full dataset (All) are marked by *** p<0.001.

Figure 9

SVM models accuracy. Boxplot represents the mean accuracy of optimized Support Vector Machine (SVM) models through 100 different random state iterations. ‘All’ group SVM calculations contain all 22 dimensions, ‘Selection’ group contains age, total number of transferred embryos, endometrial thickness on the day of puncture and embryo quality, The Best two group contains age and embryo quality scores. Significant differences in performance compared to the full dataset (All) are marked by *** p<0.001.