Master’s Thesis at Al-Nahrain University College of Medicine Investigates Biomarkers for the Assessment of Primary Infertility Associated with Oxidative Stress

A Master’s thesis was discussed at the College of Medicine – Al-Nahrain University, Department of Chemistry and Biochemistry, submitted by Master’s student Alaa Mustafa Shannan, entitled:

“Evaluation of the Nuclear Factor Erythroid 2-Related Factor 2 (NRF2), Heme Oxygenase-1 (HO-1), and Vascular Endothelial Growth Factor (VEGF) in Women with Primary Infertility”

The study aimed to evaluate and compare the serum concentrations of Nuclear Factor Erythroid 2-Related Factor 2 (NRF2), Heme Oxygenase-1 (HO-1), and Vascular Endothelial Growth Factor (VEGF) in women with primary infertility compared with healthy women serving as the control group. It also sought to assess the relationships between these biomarkers and clinical variables, including age, body mass index (BMI), hormonal profile, and menstrual characteristics.

The study findings showed no significant differences in age, body weight, or BMI between the two study groups, confirming an appropriate degree of homogeneity between the groups. In contrast, serum prolactin levels were significantly lower in women with primary infertility compared with the control group, while estradiol and Anti-Müllerian Hormone (AMH) levels were also significantly lower in the primary infertility group. No significant differences were observed in FSH, LH, or TSH levels between the two groups.

The results also demonstrated that hemoglobin levels were slightly but significantly higher in the primary infertility group compared with the control group. Regarding the biomarkers investigated, NRF2 levels were significantly decreased in women with primary infertility, whereas HO-1 and VEGF levels were significantly increased compared with the control group.

Receiver Operating Characteristic (ROC) curve analysis demonstrated excellent diagnostic performance of the three biomarkers in discriminating women with primary infertility from healthy women. The area under the curve (AUC) was 1.00 for NRF2, 1.00 for HO-1, and 0.999 for VEGF, indicating a very high discriminatory capacity of these biomarkers.

Correlation analyses revealed a weak positive correlation between NRF2 and hemoglobin (r = 0.255, p = 0.049). However, NRF2, HO-1, and VEGF showed no significant correlations with age, BMI, or the hormonal variables investigated. Furthermore, no statistically significant differences in the three biomarkers were observed according to in vitro fertilization (IVF) outcomes.

The study concluded that primary infertility was associated with marked alterations in the NRF2/HO-1 axis, which is involved in antioxidant defense and oxidative stress responses, along with alterations in VEGF-related vascular signaling. NRF2, HO-1, and VEGF demonstrated excellent discriminatory performance in distinguishing women with primary infertility from healthy women, suggesting that these biomarkers may serve as promising adjunctive biomarkers for the assessment of primary infertility. However, these findings require further validation through future studies involving larger sample sizes and independent cohorts to confirm their diagnostic and clinical utility.

The thesis discussion committee consisted of:

• Prof. Dr. Raed Jassim Mohammed – Chair

• Asst. Prof. Dr. Zahraa Sabbar Imran – Member

• Asst. Prof. Dr. Inas Thamer Musa – Member

• Asst. Prof. Dr. Hind Ahmed Abbas – Member and Supervisor

• Asst. Prof. Dr. Sahar Hisham Abdul-Razzaq – Member and Supervisor

At the conclusion of the discussion, the thesis was successfully approved, and the student was awarded a grade of Excellent.

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College of Medicine – Al-Nahrain University