Going, gonad, gone. Gender inequalities in the management of gonadal torsion: a cohort study.

Gonadal torsion (when the gonad twists on its ligamentous supports) is a surgical emergency in both men and women. Prompt management is essential to preserve gonadal function. Our aim was to compare the timeliness with which men and women who underwent surgery for suspected gonadal torsion are managed. All adult patients who underwent surgery for suspected gonadal torsion between 1/4/16 and 31/3/18 were reviewed and the following times recorded: symptom onset; hospital presentation; gynaecological/surgical review; decision for theatre; and knife-to-skin (KTS). The surgical procedure(s) and intra-operative findings were also documented. In total, 31 women (mean age 29.4 ± 7.1yrs) and 49 men (mean age 23.2 ± 7.0yrs) were identified. Women waited significantly longer than men at every stage (p < 0.01). Time intervals between hospital presentation and review, review and decision for theatre, and decision and KTS were 1.6 (1.2-2.6 hrs), 0.3 (0.0-0.9 hrs) and 1.7 (1.5-2.5 hrs) for men and 4.3 (3.1-15.3 hrs), 10.3 hrs (2.4-20.7 hrs) and 4.7 (2.3-9.3 hrs) for women, respectively. Torsion was confirmed in 20 (64.5%) women and 25 (51.0%) men. Intraoperatively, 13(65%) ovaries were reportedly necrotic compared to only 6 (24%) testes (p = 0.0076). All necrotic gonads were removed despite conservative surgery being recommended practice during the study period. Women with suspected gonadal torsion received suboptimal care compared to their male counterparts, which has potentially catastrophic consequences for the subsequent fertility of this predominantly young population.

Hypothalamic-pituitary, ovarian and adrenal contributions to polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a prevalent heterogeneous disorder linked with disturbances of reproductive, endocrine and metabolic function. The definition and aetiological hypotheses of PCOS are continually developing to incorporate evolving evidence of the syndrome, which appears to be both multifactorial and polygenic. The pathophysiology of PCOS encompasses inherent ovarian dysfunction that is strongly influenced by external factors including the hypothalamic-pituitary axis and hyperinsulinaemia. Neuroendocrine abnormalities including increased gonadotrophin-releasing hormone (GnRH) pulse frequency with consequent hypersecretion of luteinising hormone (LH) affects ovarian androgen synthesis, folliculogenesis and oocyte development. Disturbed ovarian-pituitary and hypothalamic feedback accentuates the gonadotrophin abnormalities, and there is emerging evidence putatively implicating dysfunction of the Kiss 1 system. Within the follicle subunit itself, there are intra-ovarian paracrine modulators, cytokines and growth factors, which appear to play a role. Adrenally derived androgens may also contribute to the pathogenesis of PCOS, but their role is less defined.

Follicular-phase ovarian follicular fluid and plasma cytokine profiling of natural cycle in vitro fertilization patients.

OBJECTIVE: To characterize follicular fluid (FF) and systemic cytokine profiles at various time points during the natural-cycle follicular and periovulatory phases. DESIGN: Observational clinical study across two consecutive cycles. SETTING: Hospital-based in vitro fertilization program. PATIENT(S): Ten women undergoing modified natural-cycle in vitro fertilization (MNC-IVF). INTERVENTION(S): Plasma and follicular fluid (FF) collection. MAIN OUTCOME MEASURE(S): Forty FF cytokine concentrations from individual follicles and plasma from each patient were determined by fluid-phase multiplex immunoassay in two consecutive cycles: 1) tracking cycle-midfollicular or luteal surge; and 2) treatment cycle-periovulatory (at the time of MNC-IVF). Demographic, cycle, and cytokine data were compared with the use of chi-square, paired-scores t test, or Wilcoxon signed ranks tests. RESULT(S): Fluctuations in various FF cytokines were evident during the follicular phase: Levels of interleukin (IL) 6 and IL-8 were higher in periovulatory samples, and IL-1 receptor antagonist and vascular endothelial growth factor were elevated earlier in the cycle. Luteal surge profiles were similar to those found in periovulatory samples. Conversely, circulatory cytokine concentrations were more stable during the follicular phase. CONCLUSION(S): These findings present an extensive physiologic reference profile of FF cytokines associated with antral folliculogenesis and highlight the compartmentalization of systemic and intraovarian cytokine networks in natural cycles.

Impact of exogenous gonadotropin stimulation on circulatory and follicular fluid cytokine profiles.

Background. The natural cycle is the prototype to which we aspire to emulate in assisted reproduction techniques. Increasing evidence is emerging that controlled ovarian hyperstimulation (COH) with exogenous gonadotropins may be detrimental to oogenesis, embryo quality, and endometrial receptivity. This research aimed at assessing the impact of COH on the intrafollicular milieu by comparing follicular fluid (FF) cytokine profiles during stimulated in vitro fertilization (IVF) and modified natural cycle (MNC) IVF. Methods. Ten women undergoing COH IVF and 10 matched women undergoing MNC IVF were recruited for this pilot study. 40 FF cytokine concentrations from individual follicles and plasma were measured by fluid-phase multiplex immunoassay. Demographic/cycle/cytokine data were compared and correlations between cytokines were computed. Results. No significant differences were found between COH and MNC groups for patient and cycle demographics, including outcome. Overall mean FF cytokine levels were higher in the MNC group for 29/40 cytokines, significantly so for leukaemia inhibitory factor and stromal cell-derived factor-1α. Furthermore, FF MNC cytokine correlations were significantly stronger than for COH data. Conclusions. These findings suggest that COH perturbs intrafollicular cytokine networks, in terms of both cytokine levels and their interrelationships. This may impact oocyte maturation/fertilization and embryo developmental competence.

Metabolic profiling of follicular fluid and plasma from natural cycle in vitro fertilization patients--a pilot study.

OBJECTIVE: To investigate changes in follicular fluid (FF) and plasma composition during the follicular and periovulatory phases of the menstrual cycle in patients undergoing assisted conception, using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy-based metabolite profiling. DESIGN: A pilot prospective laboratory study. SETTING: Assisted conception clinic in a university hospital. PATIENT(S): Ten women undergoing natural-cycle (NC) in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with either male factor subfertility or unexplained subfertility. INTERVENTION(S): FF and plasma were collected during the midfollicular phase or at the LH-surge and at the time of oocyte collection. MAIN OUTCOME MEASURE(S): (1)H-NMR spectroscopy was performed on the fluids and the metabolic profiles compared across the phases with the use of principal components analysis (PCA). RESULT(S): LH-surge FF resembled periovulatory FF more than midfollicular FF, with higher levels of lactate and pyruvate and lower glucose. Periovulatory plasma contained higher levels of glucose and acetate and lower glycoprotein, trimethylamine, and glycine compared with midfollicular and LH-surge plasma. CONCLUSION(S): NMR-based metabolite profiling of FF and plasma has potential for identifying changes across menstrual stages, studying the impact of exogenous hCG administration, and in the pursuit of biomarkers to predict fertility treatment outcome.