Jani R. Jensen

A potential role for colony-stimulating factor 1 in the genesis of the early endometriotic lesion

OBJECTIVE To investigate the role(s) of colony-stimulating factor 1 (CSF-1) on the development of early endometriosis in a murine model by comparing rate of lesion formation in mice [1] homozygous for a CSF-1 mutation versus syngeneic controls and [2] after treatment with imatinib, a commercially available tyrosine kinase inhibitor that alters interaction(s) between CSF-1 and its receptor, c-fms. DESIGN Prospective, placebo-controlled animal study. SETTING Academic medical center. ANIMALS Six- to 8-week old female FVB, wild-type C57BL/6, and CSF-1 op/op mice. INTERVENTION(S) Endometrial tissue from donor mice was used to induce endometriosis in murine recipients. In some experiments, mice homozygous for a CSF-1 mutation (CSF-1 op/op) were donors or recipients. In other experiments, donor and/or recipient mice received imatinib. MAIN OUTCOME MEASURE(S) Histologic confirmation of endometriosis, rate of lesion formation. RESULT(S) By 40 hours, recipient mice developed a mean of 7.2 +/- 0.9 endometriotic lesions that had invaded host surfaces, and mesothelial cells had proliferated over the entire surface of the implants. The CSF-1 op/op mice developed significantly fewer (mean 0.9 +/- 0.3) endometriotic lesions versus syngeneic controls. Imatinib treatment resulted in significantly fewer lesions when compared with sham-treated controls. CONCLUSION(S) Colony-stimulating factor 1 has a role in establishing early endometriotic lesions. Agents targeting CSF-1 or its actions have therapeutic potential for treating endometriosis.

Magnetic resonance-guided focused ultrasound surgery for leiomyoma-associated infertility.

Objective To describe magnetic resonance-guided focused ultrasound surgery (FUS) as a treatment for a case of leiomyoma-associated infertility. Design Case report from a randomized clinical trial. Setting Academic medical center. Patient(s) A 37-year-old woman with known leiomyomas and a history of 18 months of home-inseminations from a known donor. Intervention(s) Magnetic resonance-guided FUS treatment of uterine fibroids, where the dominant fibroid distorted the uterine cavity. Main Outcome Measure(s) Pregnancy. Result(s) A viable intrauterine pregnancy, with a full-term vaginal delivery, was conceived after a single clomiphene citrate and intrauterine insemination cycle. Conclusion(s) The role of FUS for enhancement of fertility in women with nonhysteroscopically resectable uterine fibroids distorting the uterine cavity should be investigated further.

Evolving spectrum: the pathogenesis of endometriosis.

Although the exact etiology of endometriosis is unknown, several hypotheses about its origin exist. Of these, Sampsons theory of retrograde menstruation is the most widely accepted. Multiple in-vitro and in vivo models have been developed to study endometriosis. Several key steps are required to establish an endometriotic implant: presence of ectopic endometrial glands and stroma, attachment of endometrial cells to the peritoneum, invasion into the mesothelium, and survival and growth of the ectopic tissue. Many of these steps are similar to those associated with neoplasia, and numerous biologic pathways are involved. It is likely that both intrinsic factors within the ectopic endometrium and permissive alterations within the host are important to the development of endometriosis.

Fertility drug use and the risk of ovarian tumors in infertile women: a case-control study

OBJECTIVE To assess the influence of infertility and fertility drugs on risk of ovarian tumors. DESIGN Case-control study (Mayo Clinic Ovarian Cancer Study). SETTING Ongoing academic study of ovarian cancer. PATIENT(S) A total of 1,900 women (1,028 with ovarian tumors and 872 controls, frequency matched on age and region of residence) who had provided complete information in a self-report questionnaire about history of infertility and fertility drug use. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Effect of infertility history, use of fertility drugs and oral contraception, and gravidity on the risk of ovarian tumor development, after controlling for potential confounders. RESULT(S) Among women who had a history of infertility, use of fertility drugs was reported by 44 (24%) of 182 controls and 38 (17%) of 226 cases. Infertile women who used fertility drugs were not at increased risk of developing ovarian tumors compared with infertile women who did not use fertility drugs; the adjusted odds ratio was 0.64 (95% CI, 0.37, 1.11). The findings were similar when stratified by gravidity and when analyzed separately for borderline versus invasive tumors. CONCLUSION(S) We found no statistically significant association between fertility drug use and risk of ovarian tumors. Further larger, prospective studies are needed to confirm this observation.

Unilateral oophorectomy results in compensatory follicular recruitment in the remaining ovary at time of ovarian stimulation for in vitro fertilization.

OBJECTIVE To assess the effect of unilateral oophorectomy (UO) by assessing ovarian reserve (OVR) and the response to gonadotropin stimulation in women with UO undergoing in vitro fertilization (IVF) compared with the response of the ipsilateral ovary of women without UO. DESIGN Historical cohort study. SETTING Academic fertility clinic. PATIENT(S) Fifty-one women with single ovary compared with a referent group with both ovaries in a 1:2 fashion. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Day-3 follicle-stimulating hormone (FSH), estradiol, and antral follicle counts as measures of OVR, and IVF outcomes including number of follicles aspirated and oocytes retrieved. RESULT(S) The baseline demographics and serum markers of OVR were not different. Referent women had greater follicular yield and oocyte numbers when compared with women with UO; however, when compared with the ipsilateral ovary of the referents, women with UO had a higher antral follicle count and greater follicle and oocyte numbers. In multivariate analyses, the ovary from women with UO was more likely to yield more than the median number of follicles and oocytes than the ipsilateral ovary in referent women. Live-birth rates in both groups were similar. CONCLUSION(S) Our results suggest that the remaining ovary appears to compensate in follicular yield after UO in women, confirming the animal data. Women with UO can be reassured and appropriately counseled regarding IVF.

Challenges in the Gynecologic Care of Premenopausal Women With Breast Cancer

Premenopausal women with a new diagnosis of breast cancer are faced with many challenges. Providing health care for issues such as gynecologic comorbidities, reproductive health concerns, and vasomotor symptom control can be complicated because of the risks of hormone treatments and the adverse effects of adjuvant therapies. It is paramount that health care professionals understand and be knowledgeable about hormonal and nonhormonal treatments and their pharmacological parameters so they can offer appropriate care to women who have breast cancer, with the goal of improving quality of life. Articles for this review were identified by searching the PubMed database with no date limitations. The following search terms were used: abnormal uterine bleeding, physiologic sex steroids, endometrial ablation, hysteroscopic sterilization, fertility preservation in endometrial cancer, tranexamic acid and breast cancer, menorrhagia treatment and breast cancer, abnormal uterine bleeding and premenopausal breast cancer, levonorgestrel IUD and breast cancer, tamoxifen and gynecologic abnormalities, tamoxifen metabolism, hormones and breast cancer risk, contraception and breast cancer, pregnancy and breast cancer, and breast cancer and infertility treatment.

Maternal and Neonatal Complications of Elective Early-Term Deliveries

Approximately 10% to 15% of all deliveries in the United States are performed before 39 completed weeks of gestation without a true medical indication for early delivery, despite long-standing recommendations against this practice. Early-term deliveries are those that occur between 3707 and 3867 weeks. It is now recognized that maternal and neonatal complications have increased for deliveries that occur at early- vs late-term gestation. The reasons for the increase in the rate of elective early-term deliveries are unclear but likely involve both patient and physician factors. Various strategies have been used to increase awareness of the morbidities associated with the practice of elective early-term delivery and to reduce its frequency. Insurers and quality accrediting agencies are increasingly holding hospitals accountable for their rates of elective early-term deliveries, and this pressure will likely continue to lead to widespread change in the practice of obstetrics. The interventions to increase adherence to evidence-based medicine guidelines that are described within this review may also be applicable to other areas of medicine.

Predictors of medical school clerkship performance: a multispecialty longitudinal analysis of standardized examination scores and clinical assessments

BackgroundEvidence suggests that poor performance on standardized tests before and early in medical school is associated with poor performance on standardized tests later in medical school and beyond. This study aimed to explore relationships between standardized examination scores (before and during medical school) with test and clinical performance across all core clinical clerkships.MethodsWe evaluated characteristics of 435 students at Mayo Medical School (MMS) who matriculated 2000–2009 and for whom undergraduate grade point average, medical college aptitude test (MCAT), medical school standardized tests (United States Medical Licensing Examination [USMLE] 1 and 2; National Board of Medical Examiners [NBME] subject examination), and faculty assessments were available. We assessed the correlation between scores and assessments and determined USMLE 1 cutoffs predictive of poor performance (≤10th percentile) on the NBME examinations. We also compared the mean faculty assessment scores of MMS students vs visiting students, and for the NBME, we determined the percentage of MMS students who scored at or below the tenth percentile of first-time national examinees.ResultsMCAT scores correlated robustly with USMLE 1 and 2, and USMLE 1 and 2 independently predicted NBME scores in all clerkships. USMLE 1 cutoffs corresponding to poor NBME performance ranged from 220 to 223. USMLE 1 scores were similar among MMS and visiting students. For most academic years and clerkships, NBME scores were similar for MMS students vs all first-time examinees.ConclusionsMCAT, USMLE 1 and 2, and subsequent clinical performance parameters were correlated with NBME scores across all core clerkships. Even more interestingly, faculty assessments correlated with NBME scores, affirming patient care as examination preparation. USMLE 1 scores identified students at risk of poor performance on NBME subject examinations, facilitating and supporting implementation of remediation before the clinical years. MMS students were representative of medical students across the nation.

Multiple pregnancy: changing expectations for patients and patterns for physicians

When asked about the optimal outcome of assisted reproductive technology (ART), most ART providers would reflexively respond in the same way: the birth of a healthy singleton. But do we really practice what we preach? And what happens even if we do? In this issue, Kissin et al. (1) evaluate ET practices in the United States and assess their impact onmultiple births. Using 2012 data from the National ART Surveillance System, they report that nearly half of ART-related multiple births resulted from transfer of two fresh blastocysts to favorableor average-prognosis patients aged <35 years or to donor oocyte recipients, or from the transfer of two frozen–thawed embryos to women aged <35 years. Recommended criteria for the number of embryos to transfer were first published by the Practice Committees of the American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technologies (SART) more than 15 years ago (2). Although guidelines were updated for a sixth time in 2013, there was no difference in the recommended number of embryos to transfer between the prior version (published in 2009 and used by the authors to analyze 2012 ART Surveillance data) and the current iteration (3). According to ASRM/SART guidelines, favorableprognosis patients aged <35 years and those receiving embryos created from oocyte donors aged <35 years should undergo single embryo transfer (SET) of a fresh blastocyst, but guidelines allow for up to two blastocysts (double embryo transfer, DET) to be transferred provided that justification is documented in the medical record. For frozen embryo transfer cycles, the number of good-quality embryos transferred is recommended to not exceed the limit for fresh embryos. One major observation is that, collectively, ART providers seem to follow ASRM/SART guidelines for the number of embryos transferred: nearly all (94.5%) ETs were performed in accordance with the guidelines current at the time of data reporting. The compliance rate was higher for SART-member clinics than for non–SART-member practices (94.7% vs. 89.7%, respectively). Thus, despite what seem to be good faith practices among the vast majority of ART providers, this still raises the question: is two too many? Data supporting the goal of a healthy singleton are overwhelmingly clear. Compared with ART singletons, ART twins are approximately five times more likely to be born preterm and have a nearly six-fold increased risk of having low birth weight (4). A recent Cochrane review also showed that SET performed sequentially for two transfers yielded pregnancy rates equivalent to those with single DET, with a marked reduction of twins (5). This evidence makes the argument for SET difficult to ignore. Despite this, the authors report that for favorable-prognosis patients younger than 35 years using autologous oocytes, SET was performed in approximately one-third of transfers, with DET in the remaining two-thirds. It is hoped that appropriate justification was documented in the medical

Curbside consultations in the era of social media connectivity and the creation of the Society for Reproductive Endocrinology and Infertility Forum

Social media, as defined by Wikipedia, the social encyclopedia, is a computer-mediated tool that allows people to create, share, or exchange information, career interests, ideas, and pictures/videos in virtual communities and networks. A Google search for the term yields 1.2 billion hits and you are hard pressed to get through your morning coffee without being asked to give or receive information through one of the many outlets that fall under this umbrella. Given its meteoric rise, it was only a matter of time before electronic connectivitys impact on the medical field was felt. A Pubmed search for ‘‘social media’’ as the keyword in 2007 would have yielded zero search results, although ‘‘social networks’’ were noted to have ‘‘considerable opportunity to advance the public health’’ (1). The first four results for ‘‘social media’’ were listed the ensuing year in 2008 followed by an exponential rise culminating in nearly 4,000 results in the medical literature as of January 2016. Not only is it being studied in terms of patient and physician interaction, it has also become a ‘‘hallway forum’’ for the old curbside consultation. There is little doubt that the way the world electronically communicates is changing, and the medical field is no exception. This evolution in medical communication brings along with it some significant concerns. Many question the validity or trustworthiness of information dispersed on social media given the lack of requirements or disclosure of user qualifications. Most platforms require only an internet connection, circumventing the traditional gatekeepers previously in place in the media. A second concern is the existence of disparities in social media, less having to do with access in modern society, and more having to do with the desire to learn the new skills required to function in this quickly evolving environment— the so called ‘‘digital divide.’’ These issues take a backseat to privacy which is of paramount concern when discussing social media in the medical community. In the era of big datamining, electronicfingerprints are constantly being captured, processed, and analyzed. Indeed, electronic tracking via third party applications allow data miningwithout user consent or knowledge. Socialmedia integration in the work environment can lead to conflicts with employees and employers as popular platforms, such as Facebook, Twitter, Instagram, and others, are used to fulfill professional roles when they are better suited for social communication. These concerns over both patient and personal confidentiality, reputation, and risk management need to be acknowledged and squarely addressed. In a study of 57 general surgery residency programs in 2014, 32% of residents had publically identifiable Facebook profiles that contained unprofessional content ranging from binge drinking and sexually suggestive photographs to clear violations of the Health Insurance Portability and Accountability Act (HIPAA) in 26% of cases (2). In response to this growth and in an attempt to establish guidelines for its membership, the American Congress of Obstetricians and Gynecologists issued Committee Opinion 622 in February 2015, which addressed the use of