Role of hormonal and inflammatory alterations in obesity-related reproductive dysfunction at the level of the hypothalamic-pituitary-ovarian axis.

BACKGROUND: Besides being a risk factor for multiple metabolic disorders, obesity could affect female reproduction. While increased adiposity is associated with hormonal changes that could disrupt the function of the hypothalamus and the pituitary, compelling data suggest that obesity-related hormonal and inflammatory changes could directly impact ovarian function. OBJECTIVE: To review the available data related to the mechanisms by which obesity, and its associated hormonal and inflammatory changes, could affect the female reproductive function with a focus on the hypothalamic-pituitary-ovarian (HPO) axis. METHODS: PubMed database search for publications in English language until October 2017 pertaining to obesity and female reproductive function was performed. RESULTS: The obesity-related changes in hormone levels, in particular leptin, adiponectin, ghrelin, neuropeptide Y and agouti-related protein, are associated with reproductive dysfunction at both the hypothalamic-pituitary and the ovarian levels. The pro-inflammatory molecules advanced glycation end products (AGEs) and monocyte chemotactic protein-1 (MCP-1) are emerging as relatively new players in the pathophysiology of obesity-related ovarian dysfunction. CONCLUSION: There is an intricate crosstalk between the adipose tissue and the inflammatory system with the HPO axis function. Understanding the mechanisms behind this crosstalk could lead to potential therapies for the common obesity-related reproductive dysfunction.

Blood type predicts live birth in the infertile population.

PURPOSE: To determine if blood type in infertile women relates to the likelihood for live birth (LB) following IVF, and to the etiology for infertility. METHODS: Retrospective study of patients undergoing IVF at two academic centers in the northeast US. Relationships between blood type (A, B, AB, O) and patient characteristics, IVF cycle parameters and LB were assessed utilizing multivariable logistic regression analyses. RESULTS: In the studied population (n=626), women with type O were significantly more likely to have baseline FSH > 10 IU/L after adjusting for age, BMI and race (OR 5.09, 95 % CI 1.4-18.7, p=0.01). Conversely, women with blood type A were significantly more likely to have ovulatory infertility compared to those with blood type O after adjusting for age and BMI (OR 3.2, 95 % CI 1.7-6.2). Blood type B was associated with increased likelihood of live birth (OR 1.9, 95 % CI 1.10-3.41, p=0.03) after adjusting for factors recognized to impact IVF outcome. CONCLUSION: Ovulatory infertility and baseline FSH > 10 IU/L were more prevalent in women with blood type A and O respectively. However, those of blood type B had significantly higher odds for LB compared to other blood types after adjusting for factors recognized to impact on IVF cycle outcome. While underlying mechanisms are unclear, for infertile women, patient's blood type is seemingly relevant for IVF cycle outcome.

The details matter: personalized prediction of live birth after in vitro fertilization in women with polycystic ovary syndrome.

OBJECTIVE: To derive and internally validate a clinical prediction model for live birth (LB) in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF). DESIGN: Retrospective cohort study. SETTING: Four academic reproductive endocrinology clinics. PATIENTS: A total of 207 women with PCOS confirmed using Rotterdam criteria undergoing their first fresh IVF cycle. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The primary outcome was cumulative LB per IVF cycle start. This included any LB that resulted from either fresh embryo transfer or any subsequent frozen embryo transfer from embryos obtained at the index oocyte retrieval. A prediction model was derived using multivariable logistic regression. Covariates considered for inclusion in the prediction model included demographic characteristics, medical history, and prior fertility treatment. Predicted probabilities for LB were calculated using the prediction model which included the 90% shrinkage factor for each adjusted odds ratio. RESULTS: The final model, on the basis of maximization of the area under the receiver operating characteristic curve, included age < 35 years, White race, presence of polycystic ovaries on ultrasound (polycystic ovary morphology), normal body mass index (<25 kg/m2), being metabolically healthy (no metabolic risk factors), and being a nonresponder to ovulation induction agents including letrozole and clomiphene citrate. The area under the receiver operating characteristic curve score for the model was 0.68 (95% confidence interval [CI]: 0.60, 0.77). Predicted probabilities of LB ranged from 8.1% (95% CI: 2.8, 21.5) for a woman who had no favorable predictors to 74.2% (95% CI: 59.5, 84.9) for a woman who had all favorable predictors. CONCLUSION: Our study demonstrated that, in addition to anovulation, the underlying pathophysiology and associated comorbidities alter the likelihood of a successful pregnancy in women with PCOS undergoing IVF. Further validation of this model is needed before it can serve as a tool to personalize prediction estimates for the probability of LB in women with PCOS.

Reproductive inequity and inferior intrauterine insemination outcomes in patients with limited English proficiency: a retrospective cohort study.

OBJECTIVE: To evaluate if language preference influences intrauterine insemination outcomes. DESIGN: Retrospective cohort. SETTING: The study was conducted at an urban medical center in New York from January 2016 to August 2021. PATIENT(S): All women older than 18 years undergoing their first IUI cycle with an infertility diagnosis were included. INTERVENTION(S): Intrauterine insemination after ovarian stimulation. MAIN OUTCOME MEASURE(S): Primary outcomes were intrauterine insemination success rate and duration of infertility before seeking infertility care. The primary outcomes used the Kaplan-Meier estimator to investigate the difference in duration of infertility before specialty consultation and logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) of clinical pregnancy among English speakers vs. those with limited English proficiency (LEP) undergoing initial IUI. Secondary outcomes included final IUI outcomes compared by language preference. Adjusted analyses controlled for race/ethnicity. RESULTS: A total of 406 patients were included in this study, of which 86% preferred English, 7.6% preferred Spanish, and 5.2% preferred other. Patients with LEP have longer duration of infertility before seeking infertility care than English-proficient women (mean 4.53 ± 3.65 years vs. 2.01 ± 1.58 years). Although clinical pregnancy rate of initial IUI did not significantly vary (OR, 2.92; 95% CI, 0.68-12.47 unadjusted and OR, 2.88; 95% CI, 0.67-12.35 adjusted), the cumulative pregnancy rate was significantly higher in English-proficient patients than in LEP patients at the time of final IUI (22.32% vs. 15.38%). This is despite a similar number of total IUIs (2.40 English vs. 2.70 LEP). Additionally, LEP patients were significantly more likely to discontinue care after unsuccessful IUI, instead of proceeding to further fertility treatments such as in vitro fertilization. CONCLUSIONS: Limited English proficiency is associated with longer duration of infertility before initiating care as well as poorer IUI outcomes, including lower cumulative pregnancy rate. Further research is needed to assess what clinical and socioeconomic factors are contributing to lower IUI success rates and lower continuation in infertility care in LEP patients.

Dietary Advanced Glycation End Products (AGEs) could alter ovarian function in mice.

Nutrition is an important source of exogenous AGEs and thermally processed foods present in western-style diets contain a large amount of these pro-inflammatory AGEs. Additionally, the intake of dietary AGEs could upregulate ovarian gene expression of inflammatory macrophage markers. The objective of this study was to investigate the effect of diet rich in AGEs on estrous cyclicity and ovarian function in a mouse model. Six-week old C57BL/6 J female mice were randomly subjected to either a diet low in AGEs (L-AGE) or a diet high in AGEs (H-AGE) for a total of 13 weeks. Experiments performed included daily vaginal smears to assess estrous cyclicity, ovarian superovulation with gonadotropins to assess the number of oocytes released, whole ovarian tissue mRNA quantification by RT-PCR to quantify genes involved in folliculogenesis, steroidogenesis, and macrophage markers, and ovarian morphology for follicle count. Outcome measures included estrous cyclicity, number of oocytes following superovulation, expression of genes involved in folliculogenesis, steroidogenesis, and macrophage infiltration as well as the number of primordial, primary, secondary, antral follicles and corpora lutea. Compared to mice on L-AGE diet, mice on H-AGE spent significantly longer time in the diestrus phase, had similar number of oocytes released following ovarian superovulation, and showed significant alterations in genes involved in steroidogenesis (increase in Star mRNA expression levels) and folliculogenesis (increase in Gdf-9 and Fshr mRNA expression levels). Mouse macrophage marker F4/80 mRNA expression was upregulated in mice on H-AGE diet compared to mice on L-AGE diet. Finally, mice on H-AGE diet had significantly fewer corpora lutea in their ovaries. These results indicate that the ingestion of high amounts of dietary AGEs could disrupt folliculogenesis and steroidogenesis that might lead to abnormal estrous cyclicity. Intake of dietary AGEs could also upregulate ovarian gene expression of inflammatory macrophage markers.

Physician shadowing: a review of the literature and proposal for guidelines.

PURPOSE: Premedical students commonly shadow physicians to gain an understanding of what careers in medicine entail. The authors reviewed the literature to explore (1) whether shadowing achieves this goal consistently and effectively, (2) the ethical issues involved, and (3) other reasons that individuals shadow physicians. METHOD: The authors searched the MEDLINE database via Ovid for English-language articles published from 1948 to March 2011. Eligible articles described physician shadowing programs and/or assessed the value of physician shadowing independently or in comparison with other educational methods. RESULTS: Of 770 articles identified, 13 articles about physician shadowing programs met inclusion criteria. Two of the 13 programs involved shadowing only, whereas 11 included other educational initiatives. Participants varied; shadowers included students (high school, college, medical school), recent medical school graduates, or international medical graduates. Few studies addressed shadowing by premedical students. Most studies involved programs outside the United States. Shadowing program objectives and characteristics differed. Data reported from focus groups, interviews, and surveys suggest that shadowing experiences generally increased participants' interest in medicine (or a specialty) or improved participants' confidence in transitioning to a new position. Some articles raised ethical and practical concerns related to shadowing. CONCLUSIONS: The few shadowing programs described in the literature were heterogeneous and often involved other activities. Further research is warranted; objective outcomes measures would be useful. The authors propose developing guidelines and introducing a code of conduct for premedical students, to enhance the consistency of shadowing experiences and address ethical and practical considerations.