Publicly available information about fertility benefits for trainees at medical schools in the US.

PURPOSE: Infertility affects one in four female physicians, yet current availability of fertility benefits within Accreditation Council for Graduate Medical Education (ACGME) accredited residency programs in the United States (US) is unknown. Our objective was to examine publicly available fertility benefits information for residents and fellows. METHODS: The top 50 medical schools in the US for research were identified using US News & World Report 2022. In April 2022, we reviewed fertility benefits available to residents and fellows at these medical schools. Websites of their associated graduate medical education (GME) websites were queried for details surrounding fertility benefits. Two investigators collected data from GME and publicly available institutional websites. The primary outcome was fertility coverage and rates are reported as percentages. RESULTS: Within the top 50 medical schools, 66% of institutional websites included publicly available medical benefits, 40% included any mention of fertility benefits, and 32% had no explicit information on fertility or medical benefits. Fertility benefit coverage included infertility diagnostic workup (40%), intrauterine insemination (32%), prescription coverage (12%), and in vitro fertilization (IVF, 30%). No information on coverage for third party reproduction or LGBT family building was available on public websites. Most programs with fertility benefits were in the South (40%) or Midwest (30%). CONCLUSION: To support the reproductive autonomy of physicians in training, it is critical to ensure access to information on fertility care coverage. Given the prevalence of infertility among physicians and the impact of medical training on family planning goals, more programs should offer and publicize coverage for fertility care.

Immediate weight loss before ovarian stimulation with intrauterine insemination is associated with a lower risk of preeclampsia in women with obesity and unexplained infertility.

Objective: To determine whether successful weight loss before ovarian stimulation with intrauterine insemination (OS-IUI) affects the risk of future pregnancy complications among women with obesity and unexplained infertility after fertility treatment. Design: Secondary analysis of the randomized controlled clinical trial Improving Reproductive Fitness Through Pretreatment With Lifestyle Modification in Obese Women With Unexplained Infertility (FIT-PLESE). Setting: Multiple academic health centers in the United States. Patients: Three hundred seventy-nine women with obesity and unexplained infertility who underwent standard infertility treatment after a lifestyle intervention. Interventions: The FIT-PLESE trial evaluated whether prepregnancy lifestyle interventions (diet with weight loss medication and exercise vs. exercise alone) before OS-IUI improved the live birth rate among women with obesity and unexplained infertility. Although the primary outcome of FIT-PLESE was live birth rate, we compared the demographics and subsequent pregnancy complications of women who successfully lost some weight with those of women who did not lose any during the interventions. Main Outcome Measures: Obstetric complications by groups were compared using χ2 and Fisher's exact tests, and continuous variables were compared using Student's t-tests. Logistic regression was used to assess the odds of preeclampsia after adjustment for the randomized treatment arm in FIT-PLESE. Results: There was a nonsignificant trend toward a lower risk of intrauterine growth restriction (4% vs. 16%, P = .124) and preterm delivery (6% vs. 15%, P = .343) among patients who lost at least some weight. The risk of preeclampsia was significantly lower (6% vs.35%, P = .002) in the weight loss group (odds ratio, 0.09; 95% confidence interval, 0.016-0.505; P = .006) after adjustment for treatment assignment. Conclusions: Among women with obesity and unexplained infertility who had live births after fertility treatment, prepregnancy weight loss due to lifestyle interventions before OS-IUI was associated with a lower risk of preeclampsia.

Altered evolution: are reproductive endocrinology and infertility specialists ready for the genetically engineered future?

Science, propelled forward by noble aspirations and, at times, human hubris, has the capacity to affect lives and alter the world in unanticipated ways. Even seemingly minor discoveries have repeatedly proven to have far reaching implications that experts within their respective fields could not have predicted. Nuclear technology is both a source of energy and a potential means of annihilation. The internet has both seamlessly connected the world but has also opened society to the misuse and manipulation of information. Both exemplify how new technologies have the potential for positive and negative outcomes that often go beyond what was initially intended. This is not a fault of science and innovation but rather an inherent occupational hazard as new discoveries exist within a gray zone between ignorance and comprehension. These gaps in our knowledge can only be filled over time as our knowledge expands. Innovations that were once seen as fringe, over time, become mainstream and that which was once revolutionary becomes a part of everyday life. Occasionally, a scientific advancement comes along that challenges societal norms and causes us to question what is feasible, acceptable, and ethical. Nowhere in the twenty-first century has this been more evident than within the fields of genetics and genetic engineering. As we gain a deeper understanding of the source code of life, from individual base pairs to epigenetic influences, the implications of new discoveries will go far beyond curing genetic diseases, and the possibilities will be endless. Reproductive endocrinology and infertility (REI) specialists utilize many tools including expanded carrier screening, preimplantation genetic testing, and embryo selection and have become some of the experts at the forefront of the ongoing genetic revolution. Now more than ever, there is a need for REIs to be trained in the fundamentals of genetics, exposed to novel gene sequencing and editing techniques, and involved in the coming ethical discussions in order to be prepared for the genetically engineered future.

Lesbian Women Undergoing Assisted Reproduction: Diverse, But Not Different.

The use of assisted reproduction among women in relationships with other women has increased in the United States over the past decade as a result of increased legal access and social acceptance. Despite this shift, limited studies currently exist to guide optimal fertility care for this growing patient population of women seeking assisted reproduction. In this Commentary, assisted reproduction will be meant to include ovulation induction, intrauterine insemination (IUI), and in vitro fertilization (IVF). Conflicting studies suggest that self-identified lesbian women may demonstrate an increased prevalence of polycystic ovarian syndrome. Most available studies find that a woman's sexual orientation does not affect the outcome of fertility treatment. Self-identified lesbian women undergoing donor sperm IUI and IVF have similar pregnancy and live-birth rates as heterosexual women. Better evidence regarding patient demographics and comorbidities, underlying etiologies of subfertility, and assisted reproductive outcomes among women building families with other women is needed to optimize care.

Mispositioned Neurokinin-1 Receptor-Expressing Neurons Underlie Heat Hyperalgesia in Disabled-1 Mutant Mice.

Reelin (Reln) and Disabled-1 (Dab1) participate in the Reln-signaling pathway and when either is deleted, mutant mice have the same spinally mediated behavioral abnormalities, increased sensitivity to noxious heat and a profound loss in mechanical sensitivity. Both Reln and Dab1 are highly expressed in dorsal horn areas that receive and convey nociceptive information, Laminae I-II, lateral Lamina V, and the lateral spinal nucleus (LSN). Lamina I contains both projection neurons and interneurons that express Neurokinin-1 receptors (NK1Rs) and they transmit information about noxious heat both within the dorsal horn and to the brain. Here, we ask whether the increased heat nociception in Reln and dab1 mutants is due to incorrectly positioned dorsal horn neurons that express NK1Rs. We found more NK1R-expressing neurons in Reln-/- and dab1-/- Laminae I-II than in their respective wild-type mice, and some NK1R neurons co-expressed Dab1 and the transcription factor Lmx1b, confirming their excitatory phenotype. Importantly, heat stimulation in dab1-/- mice induced Fos in incorrectly positioned NK1R neurons in Laminae I-II. Next, we asked whether these ectopically placed and noxious-heat responsive NK1R neurons participated in pain behavior. Ablation of the superficial NK1Rs with an intrathecal injection of a substance P analog conjugated to the toxin saporin (SSP-SAP) eliminated the thermal hypersensitivity of dab1-/- mice, without altering their mechanical insensitivity. These results suggest that ectopically positioned NK1R-expressing neurons underlie the heat hyperalgesia of Reelin-signaling pathway mutants, but do not contribute to their profound mechanical insensitivity.

Melanoma and Non-Melanoma Skin Cancer Associated with Angiotensin-Converting-Enzyme Inhibitors, Angiotensin-Receptor Blockers and Thiazides: A Matched Cohort Study.

INTRODUCTION: Controversy exists about an association between angiotensin-converting-enzyme inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), and thiazides (TZs) and the risk of malignant melanoma (MM), and non-melanoma skin cancer-basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). OBJECTIVE: The aim of this study was to determine if an association exists for ACEI, ARB, or TZ exposure and skin cancers. METHODS: This was a matched cohort study using a large electronic medical records repository, the Northwestern Medicine Enterprise Data Warehouse (NMEDW). The exposed population consisted of patients with a documented order for an ACEI, ARB, or TZ with no prior history of skin cancer. The control population consisted of matched patients without documented exposure to ACEI, ARB, or TZ and no previous skin cancer. Incident MM, BCC, or SCC diagnosis by ICD-9 codes was recorded. Odds ratios (ORs) were obtained by using logistic regression analyses. RESULTS: Among the 27,134 patients exposed to an ACEI, 87 MM, 533 BCC, and 182 SCC were detected. Among the 13,818 patients exposed to an ARB, 96 MM, 283 BCC, and 106 SCC were detected. Among the 15,166 patients exposed to a TZ, 99 MM, 262 BCC, and 130 SCC were detected. Significant associations using ORs from logistic regression were found for MM and TZs (OR 1.82; 95% confidence interval [CI] 1.01-3.82); BCC and ARBs (OR 2.86; 95% CI 2.13-3.83), ACEIs (OR 2.23; 95% CI 1.78-2.81) and TZs (OR 2.11; 95% CI 1.60-2.79); SCC and ARBs (OR 2.22; 95% CI 1.37-3.61), ACEIs (OR 1.94; 95% CI 1.37-2.76), and TZs (OR 4.11; 95% CI 2.66-6.35). CONCLUSIONS: A safety signal for ACEIs, ARBs, and TZs and BCC and SCC, as well as for TZs and MM, was detected. An increased awareness and education, especially for those who are at high risk for skin cancer, are warranted for patients and healthcare providers. Further exploration of such associations for these commonly used drug classes is warranted.

Development and evaluation of a service-learning model for preclinical student education in cardiovascular disease prevention.

BACKGROUND: Cardiovascular diseases are the leading cause of preventable morbidity and mortality in the USA. Medical schools must prepare trainees to address prevention, including improving ability in counseling patients to modify lifestyle risk factors. Most medical students do not receive significant training or clinical experience in preventive medicine until the clinical years of medical school. To enhance student education in disease prevention and lifestyle counseling, and simultaneously target cardiovascular disease prevention in high-risk Chicago neighborhoods, the Northwestern University Feinberg School of Medicine and Chicago Department of Public Health with support from the GE Foundation, developed the Keep Your Heart Healthy program. METHODS: Medical students participated in intensive faculty-led training. They subsequently screened local residents to identify and counsel for cardiovascular disease risk factors. Fifty-one predominantly preclinical medical students screened residents of the Humboldt Park and North Lawndale neighborhoods in Chicago, IL, at 31 screening events from August to December 2013. Fifty students (98% response rate) completed a survey assessing the educational value of various program components following the pilot. RESULTS: Of all respondents, 92% of students reported improved knowledge of cardiovascular disease prevention and 94% reported improved knowledge of vulnerable populations and health equity. The majority (88%) reported that their participation supplemented material they learned in the classroom. Eighty-six percent of students reported that their encounters with community participants were of educational value. Integration of this program into the medical school curriculum was supported by 68% of students. CONCLUSION: Keep Your Heart Healthy educates primarily preclinical medical students in cardiovascular disease prevention and prepares them to apply this knowledge for patient counseling. Results from student surveys demonstrate that this service-learning initiative enhances medical student knowledge in cardiovascular disease prevention, supplements classroom material, and provides students a valuable opportunity to apply interviewing and counseling skills in a real patient encounter.

WDR34 mutations that cause short-rib polydactyly syndrome type III/severe asphyxiating thoracic dysplasia reveal a role for the NF-κB pathway in cilia.

Short-rib polydactyly (SRP) syndrome type III, or Verma-Naumoff syndrome, is an autosomal-recessive chondrodysplasia characterized by short ribs, a narrow thorax, short long bones, an abnormal acetabulum, and numerous extraskeletal malformations and is lethal in the perinatal period. Presently, mutations in two genes, IFT80 and DYNC2H1, have been identified as being responsible for SRP type III. Via homozygosity mapping in three affected siblings, a locus for the disease was identified on chromosome 9q34.11, and homozygosity for three missense mutations in WDR34 were found in three independent families, as well as compound heterozygosity for mutations in one family. WDR34 encodes a member of the WD repeat protein family with five WD40 domains, which acts as a TAK1-associated suppressor of the IL-1R/TLR3/TLR4-induced NF-κB activation pathway. We showed, through structural modeling, that two of the three mutations altered specific structural domains of WDR34. We found that primary cilia in WDR34 mutant fibroblasts were significantly shorter than normal and had a bulbous tip. This report expands on the pathogenesis of SRP type III and demonstrates that a regulator of the NF-κB activation pathway is involved in the pathogenesis of the skeletal ciliopathies.

The neuroprotective effects of GLP-1: possible treatments for cognitive deficits in individuals with mood disorders.

Incretins are a group of gastrointestinal hormones detected both peripherally and in the central nervous system (CNS). Recent studies have documented multiple effects of incretins on brain structure and function. Research into the neurological effects of incretins has primarily focused on animal models of neurodegenerative disorders (e.g., Alzheimer's Disease, Huntington's and Parkinson's diseases). Mood disorders (e.g. bipolar disorder (BD), major depressive disorder (MDD)) are associated with similar alterations in brain structure and function, as well as a range of cognitive deficits (e.g. memory, learning, executive function). Brain abnormalities and cognitive deficits are also found in populations with metabolic disorders (e.g., diabetes mellitus Type 2). In addition, individuals with mood disorders often have co-morbid metabolic conditions, thus treatment strategies which can effectively treat both cognitive deficits and metabolic abnormalities represent a possible integrated treatment avenue. In particular, glucagon-like peptide-1 (GLP-1) and its more stable, longer-lasting analogues have been demonstrated to exert neuroprotective and anti-apoptotic effects, reduce beta-amyloid (Aß) plaque accumulation, modulate long-term potentiation and synaptic plasticity, and promote differentiation of neuronal progenitor cells. In animal models of behaviour, treatment with GLP-1 receptor agonists has been demonstrated to improve measures of cognitive function including learning and memory, as well as reduce depressive behaviour. Available GLP-1 treatments also have a favourable metabolic profile which includes weight loss and reduced risk for hypoglycemia. Systematic evaluation of the effects of GLP-1 treatment in psychiatric populations who evince cognitive deficits represents a promising treatment avenue.