GH4 -- Predicting In Vitro Fertilization (IVF) Success: Utilization of Ovarian Cytokine Expression as Biomarkers for Endometriosis
Document Type
Event
Abstract
Endometriosis, a disease of inflammation, is a leading cause of female infertility. The diagnosis of endometriosis is often delayed, or undiagnosed, because it requires confirmation through surgery. Many couples with unexplained infertility are believed to have undiagnosed female infertility due to endometriosis. Endometriosis is known to negatively affect the quality of the endometrium and it also reduces oocyte quality. Recent studies have identified elevated markers of inflammation within the endometrium of women with a diagnosis of endometriosis. Women with endometriosis or evidence of endometrial inflammation are more likely to conceive with the addition of GnRH agonists to their embryo transfer protocol. The purpose of this study is to determine if differences in cytokine expression can be found within the follicular fluid of women with endometriosis. This could help to identify subjects who may benefit from GnRH agonist treatment prior to embryo transfer. In this prospective case control study, we divided subjects undergoing in vitro fertilization (IVF) into two groups, those with and without a diagnosis of endometriosis. All women undergoing IVF oocyte retrieval were recruited to participate in this study. Subjects with a diagnosis of Polycystic Ovarian Syndrome were excluded from the analysis. Follicular fluid was collected from all subjects during oocyte retrieval and a Bio-Plex Pro Human Cytokine 8 plex was ran on all samples: IFN-gamma, IL-2, IL-4, IL-6, IL-8 IL-10, TNF alpha, all of which are pro-inflammatory biomarkers, excluding IL-10 which is anti-inflammatory. Comparison analysis was then performed using Wilcoxon rank sum test and Fisher’s exact test to determine statistical difference between cytokine expression and proportion of OOR (out of range), or undetectable, cytokine levels among the two groups of subjects, respectively. The results demonstrate that levels of IFN-g in follicular fluid of subjects with endometriosis were statistically higher compared to controls (p=0.045). The proportion of OOR IL-2 was statistically higher in subjects without endometriosis (p=0.007) as well. These findings suggest that subjects with a diagnosis of endometriosis have increased cytokine expression within the follicular fluid of the ovary. Identified subjects with higher IFN-g and detectable IL-2 may benefit from further evaluation or uterine preparation with GnRH agonists prior to embryo transfer. In conclusion, this pilot study suggests the potential for cytokine analysis to identify women with undiagnosed inflammatory disorder, thereby reducing the number of failed embryo transfers due to inappropriate uterine preparation.
Keywords
Graduate Health Sciences, Physiology
GH4 -- Predicting In Vitro Fertilization (IVF) Success: Utilization of Ovarian Cytokine Expression as Biomarkers for Endometriosis
URC Greatroom
Endometriosis, a disease of inflammation, is a leading cause of female infertility. The diagnosis of endometriosis is often delayed, or undiagnosed, because it requires confirmation through surgery. Many couples with unexplained infertility are believed to have undiagnosed female infertility due to endometriosis. Endometriosis is known to negatively affect the quality of the endometrium and it also reduces oocyte quality. Recent studies have identified elevated markers of inflammation within the endometrium of women with a diagnosis of endometriosis. Women with endometriosis or evidence of endometrial inflammation are more likely to conceive with the addition of GnRH agonists to their embryo transfer protocol. The purpose of this study is to determine if differences in cytokine expression can be found within the follicular fluid of women with endometriosis. This could help to identify subjects who may benefit from GnRH agonist treatment prior to embryo transfer. In this prospective case control study, we divided subjects undergoing in vitro fertilization (IVF) into two groups, those with and without a diagnosis of endometriosis. All women undergoing IVF oocyte retrieval were recruited to participate in this study. Subjects with a diagnosis of Polycystic Ovarian Syndrome were excluded from the analysis. Follicular fluid was collected from all subjects during oocyte retrieval and a Bio-Plex Pro Human Cytokine 8 plex was ran on all samples: IFN-gamma, IL-2, IL-4, IL-6, IL-8 IL-10, TNF alpha, all of which are pro-inflammatory biomarkers, excluding IL-10 which is anti-inflammatory. Comparison analysis was then performed using Wilcoxon rank sum test and Fisher’s exact test to determine statistical difference between cytokine expression and proportion of OOR (out of range), or undetectable, cytokine levels among the two groups of subjects, respectively. The results demonstrate that levels of IFN-g in follicular fluid of subjects with endometriosis were statistically higher compared to controls (p=0.045). The proportion of OOR IL-2 was statistically higher in subjects without endometriosis (p=0.007) as well. These findings suggest that subjects with a diagnosis of endometriosis have increased cytokine expression within the follicular fluid of the ovary. Identified subjects with higher IFN-g and detectable IL-2 may benefit from further evaluation or uterine preparation with GnRH agonists prior to embryo transfer. In conclusion, this pilot study suggests the potential for cytokine analysis to identify women with undiagnosed inflammatory disorder, thereby reducing the number of failed embryo transfers due to inappropriate uterine preparation.