Objective-Hypothesizing that levels of 25OH-D in body fluids are reflective of vitamin repletion status, we aimed to determine if 25OH-D levels in the follicular fluid (FF) of infertile women undergoing in vitro fertilization (IVF) demonstrate a relationship with IVF cycle parameters and outcome. Design-Prospective Cohort study Setting-Academic tertiary care center Patients-84 infertile women undergoing IVFInterventions-FF from follicles ≥14mm; serum (n=10) and FF levels of 25OH-D Main outcome measures-Clinical pregnancy (CP) (defined as evidence of intrauterine gestation sac on ultrasound) following IVF; IVF cycle parameters.Results-Serum and FF levels of 25OH-D were highly correlated (r=0.94, p<0.001). In a predominantly Caucasian population (66%), significantly lower FF 25OH-D levels were noted in Black versus non-Black patients (p=0.001). Significant inverse correlations were seen between FF 25OH-D levels and BMI (r−0.25, p=0.035). Significantly higher CP and implantation rates were observed across tertiles of FF25OH-D (p=0.029 and p=0.041 respectively); patients achieving CP following IVF (n=26) exhibited significantly higher FF levels of 25OH-D (p=0.005). Multivariable logistic regression analysis confirmed FF 25OH-D levels as an independent predictor to success of an IVF cycle; adjusting for age, BMI, ethnicity and number of embryos transferred (ET) each ng/ml increase in FF 25OH-D increased the likelihood for achieving CP by 6% (p=0.030). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusion-Our findings that women with higher vitamin D level in their serum and FF are significantly more likely to achieve CP following IVF-ET are novel. A potential for benefit of vitamin D supplementation on treatment success in infertile patients undergoing IVF is suggested that merits further investigation. NIH Public Access

Lower follicular fluid IL-6 levels in IVF patients are associated with increased likelihood of clinical pregnancy. We hypothesize that endometrial receptivity is a likely target for any deleterious influences of elevated IL-6 levels.

Components of the IGF gene family are downregulated in GCs of women with DOR. These findings maybe contributory to the reproductive compromise observed in women with DOR, and merit further exploration.

Declining reproductive success with aging is attributable to qualitative and quantitative deterioration in oocytes, which are nurtured by granulosa cells (GCs). This prospective study assesses whether reproductive aging is accompanied by differential gene expression in luteinized GCs from in vitro fertilization (IVF) patients. Women with nonovarian infertility etiologies were categorized as younger (< or =30, n = 3) or older (> or =40, n = 3). During oocyte retrieval, mural GCs were isolated; messenger RNA (mRNA) was extracted and transcribed for complementary DNA (cDNA) microarray analysis. Differential gene expression was confirmed by real-time polymerase chain reaction (PCR). Analysis revealed 120 genes were differentially expressed. Three genes were upregulated and 117 were downregulated (including interleukin [IL]-1beta, IL-1R2, and IL-6R) in GCs of older versus younger patients. Our data provide evidence of downregulation in IL-1 and IL-6 gene families in luteinized GCs with advancing age. Given previously recognized roles for the IL gene family in folliculogenesis and ovulation, our findings may partly explain ovulatory and luteal dysfunctions associated with reproductive aging.

Purpose A symbiotic relationship between ovarian granulosa cells (GC) and the developing oocyte is critical. Genetic modulations in GC's can lead to reproductive insufficiency, highlighting the role of GC's in reproductive competence. Utilizing gene expression analyses in cumulus GC's, we attempt to enhance our understanding of mechanisms that may contribute to poor reproductive capacity in young women with diminished ovarian reserve (DOR). MethodsWe measured gremlin 1 (GREM1) gene expression in GC's from infertile women <38 years undergoing in vitro fertilization in the context of DOR. Results GREM1, a member of the differential screeningselected gene aberrative in neuroblastoma (DAN) family of genes known for its highly regulated expression pattern during folliculogenesis and a downstream effecter of oocytederived growth and differentiation factor 9, was downregulated 3-fold (−3.08) in women with DOR versus control; down-regulation was confirmed by qRT-PCR (−4.02). Financial Support This investigation was supported by grants from Ferring Pharmaceuticals, Inc (to SJ) and NIH grants 5K12 RR17672 (to LP) and K24 CD41978 (to NS).Capsule Gremlin 1 expression is impaired in cumulus granulosa cells of young women with diminished ovarian reserve (DOR), suggesting a possible mechanism for the ovarian dysfunction associated with DOR. Reprod Genet (2012) 29:159-162 DOI 10.1007 Conclusion This is the first demonstration linking differential expression of Gremlin with etiology of infertility in women.

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