Farrah Khoyloo

Background/Objectives: Endometriosis is a chronic, inflammatory, estrogen-dependent disease that has historically been underdiagnosed, especially in patients with unexplained infertility. On average, diagnosis is delayed by 11 years, underscoring the need for precision medicine to improve outcomes. To compare disease severity and anatomical distribution of endometriosis between patients with unexplained infertility who underwent noninvasive Receptiva BCL6 testing before surgery and those who did not. Methods: A cross-sectional analysis was conducted on 195 women with unexplained infertility and histologically confirmed endometriosis following diagnostic video laparoscopy, with or without robotic assistance. Disease severity was staged using updated guidelines. Anatomical sites of endometriosis were documented. Patients were grouped based on whether they had undergone the Receptiva BCL6 overexpression test prior to surgery. Results: Of the 195 patients, 43 underwent Receptiva testing; 41 of them tested positive and were confirmed to have endometriosis during surgery. These patients had fewer affected anatomical regions (3.14 ± 2.09) compared to those without testing (3.93 ± 2.26; p = 0.04). The No Receptiva group also had more high-stage cases (70.39% vs. 65.12%, p-value: 0.038). In both groups, endometriosis most frequently involved the periureteral region, rectovaginal septum, and ovaries, though ovarian tissue was rarely excised to preserve fertility. Conclusions: Among patients with unexplained infertility and confirmed endometriosis, those who had preoperative Receptiva testing showed lower disease burden and severity. These findings support the potential utility of noninvasive testing to enrich diagnostic accuracy and guide earlier, more targeted intervention.

Endometriosis, a systemic ailment, profoundly affects various aspects of life, often eluding detection for over a decade. This leads to enduring issues such as chronic pain, infertility, emotional strain, and potential organ dysfunction. The prolonged absence of diagnosis can contribute to unexplained obstetric challenges and fertility issues, necessitating costly and emotionally taxing treatments. While biopsy remains the gold standard for diagnosis, emerging noninvasive screening methods are gaining prominence. These tests can indicate endometriosis in cases of unexplained infertility, offering valuable insights to patients and physicians managing both obstetric and non-obstetric conditions. In a retrospective cross-sectional study involving 215 patients aged 25 to 45 with unexplained infertility, diagnostic laparoscopy was performed after unsuccessful reproductive technology attempts. Pathology results revealed tissue abnormalities in 98.6% of patients, with 90.7% showing endometriosis, confirmed by the presence of endometrial-like glands and stroma. The study underscores the potential role of endometriosis in unexplained infertility cases. Although the study acknowledges selection bias, a higher than previously reported prevalence suggests evaluating endometriosis in patients who have not responded to previous reproductive interventions may be justified. Early detection holds significance due to associations with ovarian cancer, prolonged fertility drug use, pregnancy complications, and elevated post-delivery stroke risk.

Rationale Anxiety, a negative state of high arousal and vigilance, is especially prevalent in women, making identification of underlying mechanisms critical for developing effective therapies. With the challenge of disentangling biological and social factors in humans, animal tests can provide valuable insights, although such tests, developed in males, have unclear validity for females. Objective To better understand patterns of sex differences across multiple measures within two classical rodent anxiety tests. Methods We examined female and male adult Wistar rats (n = 15–18/group) that were single-housed in the novelty suppression of feeding test (NSFT) that involves food under a bright light in food-restricted animals, and light–dark test (LDT), which reflects innate aversion to bright light. To further validate these tests in females, we also examined the impact of 1 mg/kg diazepam. Results NSFT measures of the most direct interaction with food, latency to grab food and food consumed, indicated increased anxiety-like behavior in females versus males, with diazepam altering these behaviors in females but not males. Most other measures showed more similar effects of diazepam across the sexes, with some evidence of reduced anxiety-like behavior in LDT for females. Principal component analyses indicated limited relationships across behavioral factors, underscoring previous suggestions of the importance of assessing multiple measures to maximize information and ethological relevance. Conclusions Combining our findings and previous studies, we speculate that increased anxiety-like behavior in females manifests especially when there is a specific, life-relevant condition (e.g., food in the NSFT). Our findings also validate NSFT and LDT use in females.