Eden R. Cardozo

Reproductive outcomes in oocyte donation cycles are associated with donor BMI

STUDY QUESTION When adjusting for recipient BMI, is donor body mass index (BMI) associated with IVF outcomes in donor oocyte IVF cycles? SUMMARY ANSWER Increasing oocyte donor BMI is associated with a reduction in clinical pregnancy and live birth rates. WHAT IS KNOWN ALREADY Increased BMI has been associated with suboptimal reproductive outcomes, particularly in assisted reproductive technology (ART) cycles. However, it remains unclear if this association implies an effect of BMI on oocyte quality and/or endometrial receptivity. STUDY DESIGN, SIZE, DURATION A retrospective cohort study of two hundred and thirty five consecutive fresh donor oocyte IVF cycles from 1 January 2007 through 31 December 2013 at the Massachusetts General Hospital (MGH) Fertility Center. PARTICIPANTS/MATERIALS, SETTING, METHODS Analyses included a total of 202 oocyte donors and 235 total cycles. Following adjustments for recipient BMI, the relationship between donor BMI (categorized into quartiles) and IVF outcomes was assessed. MAIN RESULTS AND THE ROLE OF CHANCE In the entire (anonymous and known) donor population, a reduced odds of clinical pregnancy (P-trend = 0.046) and live birth (P-trend = 0.06) was observed with increasing BMI quartile. Compared with quartile 1 (BMI 17.8-21.1), odds ratio (OR) (95% CI) of clinical pregnancy was 0.9 (0.4-2.0), 0.5 (0.2-1.1) and 0.5 (0.2-1.1), and OR of live birth was 1.1 (0.5-2.6), 0.6 (0.3-1.2) and 0.6 (0.3-1.2) for quartiles 2 through 4 respectively. In anonymous donors only, the odds of clinical pregnancy (P-trend = 0.02) and live birth (P-trend = 0.03) also declined as BMI quartile increased. Compared with quartile 1 (BMI 17.8-21.1), odds ratio (OR) (95% CI) of clinical pregnancy was 0.7 (0.3-1.7), 0.5 (0.2-1.1) and 0.4 (0.1-0.9), and OR of live birth was 0.9 (0.4-2.2), 0.5 (0.3-1.2) and 0.4 (0.2-1.1) for quartiles 2 through 4 respectively. LIMITATIONS, REASONS FOR CAUTION Limitations include the retrospective design, sample size and data from a single institution. Clinical application may not be limited to oocyte donors, though caution should be used prior to applying these principles to the general population. Data should not be interpreted to mean that all oocyte donors should be restricted to a BMI of less than 21.2 kg/m(2). WIDER IMPLICATIONS OF THE FINDINGS Following adjustments for the respective BMI of the oocyte donor and recipient, this study demonstrates an association of preconception BMI with subsequent IVF outcomes. The observations of this study are consistent with prior animal studies, suggest a possible effect of BMI at the oocyte level prior to fertilization and implantation, and warrant further investigation. STUDY FUNDING/COMPETING INTERESTS None.

MicroRNAs in the development and pathobiology of uterine leiomyomata: does evidence support future strategies for clinical intervention?

BACKGROUND Human leiomyomata (fibroids) are benign tumors of the uterus, represent the most common neoplasms of reproductive-aged women and have a prevalence of ∼70% in the general population. This disorder conveys a significant degree of morbidity and remains the leading indication for hysterectomy in the USA. Prior investigations of aberrant microRNA (miRNA) expression in various malignancies have provided invaluable insight into the role of this class of small non-coding RNAs in tumor growth. Evidence of irregular miRNA expression in uterine fibroids has garnered recent interest for diagnostic and therapeutic applications. Since miRNA gene targets modulate several processes implicated in the genesis of uterine fibroids, more focused investigation has the potential to elucidate the functional significance of miRNA in the genesis and pathology of the disease. METHODS Comprehensive electronic searches of peer reviewed published literature in PubMed (US National Library of Medicine, National Institute of Health; http://www.ncbi.nlm.nih.gov/pubmed/) were performed for content related to the biologic functions of miRNA, the roles of miRNA in human disease and studies investigating miRNA in the context of uterine leiomyomata. Herein, this article will review the current evidence supporting the use of miRNA expression profiling as an investigative tool to assess the pathobiology of uterine fibroids and will discuss potential future applications of miRNAs as biomarkers and therapeutic targets. RESULTS Mounting evidence supports a functional role for miRNA as either indirect or direct regulators of gene expression which impacts the pathobiology of uterine fibroids. Specifically, miRNAs let-7, 200a, 200c, 93, 106b and 21 have been implicated in cellular proliferation, apoptosis, extracellular matrix turnover, angiogenesis and inflammation. Preliminary data provide evidence to suggest that respective in vitro miRNA expression in leiomyomata and myometrium is regulated by sex steroids. CONCLUSIONS Collectively, the identification of aberrantly expressed miRNAs in uterine leiomyomata and accumulating data derived from mining of gene target prediction models and recent functional studies support the concept that miRNAs might impact the genesis and progression of disease. However, the specific biologic functions of differential miRNA expression have yet to be confirmed in vivo. Further functional studies and developing miRNA technology may provide the basis for future applications of miRNAs in clinical medicine as biomarkers and therapeutic targets.

The Role of Oncofertility Clinics in Facilitating Access to Reproductive Specialists

Purpose: To determine the impact of the establishment of a dedicated oncofertility clinic on the frequency of patient referrals for fertility preservation (FP) consultation and the time from patient referral to consultation. Methods: A retrospective chart review of all women aged 21 to 44 years with an active cancer diagnosis who were referred for FP consultation from 2011 to 2015. Results: A total of 6895 female patients eligible for FP were seen at the Massachusetts General Hospital (MGH) Cancer Center. Of those eligible, a total of 209 patients were referred for FP consultation with 150 included in the final analysis. Since the establishment of the oncofertility clinic, the mean time to nonemergent consultation with a reproductive endocrinologist decreased by 27%, from 10.4 to 7.6 days (P = .03). Furthermore, the proportion of reproductive-aged females seen at the MGH Cancer Center referred for FP consultation increased from 1.7% to 3.0% (P < .01). Conclusion: A dedicated oncofertility clinic increases physician referrals for FP and decreases the mean time to consultation, improving access to FP consultation for reproductive-aged women with cancer.

Nutrition in Human Fertility

Increasing evidence suggests that diet plays an important role in human fertility independently of its effects on body weight. This chapter summarizes the current evidence linking nutritional factors to human fertility and their potential role in the primary prevention of infertility and as adjuvants to infertility treatments. The chapter first discusses the role of diet on female fertility focusing on factors that may be relevant to the primary prevention of female causes of infertility. Next, the growing literature on the potential role of dietary factors on male fertility, as reflected on semen quality, is summarized. Last, we review the emerging literature on the relation between nutritional factors and treatment outcomes of couples undergoing infertility treatment (primarily of couples undergoing assisted reproduction). Throughout the chapter, greater focus is placed on novel nutritional factors and emerging literature at the expense of factors that have historically received greater attention in the literature (e.g., alcohol and caffeine). In addition, throughout the chapter we point to important methodological considerations influencing the interpretation of the existing literature and point at current knowledge gaps in this area.

MicroRNA 21a-5p overexpression impacts mediators of extracellular matrix formation in uterine leiomyoma

BackgroundMicroRNAs (MiR) may promote fibroid development via altered expression of genes involved in cell proliferation and ECM formation, and evidence supports aberrant expression of MicroRNA (MiR) 21a-5p in fibroids. The purpose of this study was to investigate the functional significance of MiR 21a-5p overexpression in the pathobiology of leiomyomata (fibroids).MethodsA basic science experimental design using immortalized fibroid and myometrial cell lines derived from patient-matched specimens was used. Stable overexpression of MiR-21a-5p in an immortalized fibroid and patient matched myometrial cell line was achieved through lentiviral vector infection. Main outcome measures were MiR-21-5p overexpression, target gene and protein expression, collagen (COL1A1) production, cell proliferation, cell migration, and cell cycle stages of fibroid and myometrial immortalized cell lines.ResultsMiR-21a-5p was overexpressed to similar levels in fibroid and myometrial cell lines after lentiviral infection. Increased expression of miR-21 resulted in increased gene and protein expression of TGF-β3 in both fibroid and myometrial cells. Changes in expression of the ECM genes Fibronectin, Collagen 1A1, CTGF, Versican and DPT were seen in both fibroid and myometrial cells. Changes were also seen in Matrix Metalloproteinase (MMP) related genes including MMP 2, MMP 9, MMP 11 and Serpine 1 in both fibroid and myometrial cells. MiR-21 upregulation resulted in increased proliferation and migration in fibroid cells compared to myometrial cells.ConclusionsMiR-21a-5p overexpression results in changes in the expression of ECM mediators in both fibroid and myometrial cells, and increased cell proliferation in fibroid cells. These finding suggest a potential functional role of MiR-21a-5p in the development of uterine fibroids and warrant further investigation.

Clomid Compared With Follicle-Stimulating Hormone Treatment: Similar Follicle Number Means Different Success Rates [178]

INTRODUCTION: Clomiphene citrate and gonadotropins are used during intrauterine insemination cycles to help recruit one or more follicles. The objective of this study is to evaluate whether one treatment confers a higher pregnancy rate over the other, even when number of preovulatory follicles are held constant. METHODS: Data from 1,463 women who underwent 3,960 clomiphene or gonadotropin intrauterine insemination cycles were reviewed. Cycles occurred at Massachusetts General Hospital between 2004 and 2012. Regression models using generalized estimating equations were fit to investigate the relationship between cycle type and clinical pregnancy. Results were adjusted for age, body mass index, infertility diagnosis, day 3 follicle-stimulating hormone, and number of follicles greater than 14 mm. A final model was fit adjusting for endometrial thickness in addition to other covariates. RESULTS: Mean endometrial thickness was 7.0 mm and 8.5 mm among women who underwent clomiphene and gonadotropin cycles, respectively (P<.01). Crude clinical pregnancy rate per intrauterine insemination was 11% and 13% among clomiphene and gonadotropin cycles, respectively. After adjusting for potential confounders including number of follicles, odds of clinical pregnancy was higher among gonadotropin cycles as compared with clomiphene cycles (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.1–1.7). When endometrial thickness was also controlled for, odds of clinical pregnancy remained higher among gonadotropin cycles although the strength of the relationship decreased (OR 1.3, 95% CI 1.0–1.6). CONCLUSION: Even when number of follicles is held constant, gonadotropin cycles are more likely to result in clinical pregnancy compared with clomiphene cycles. Differential effects on the endometrium may play a role.