Vaccination during pregnancy by race/ethnicity: a focus on American Indians/Alaska Natives.

BACKGROUND: Vaccination during pregnancy reduces the incidence of infections and their associated adverse outcomes in both mothers and infants. The American College of Obstetricians and Gynecologists has recommended influenza and Tdap vaccination during pregnancy since 2004 and 2013, respectively. Several studies have examined disparities in vaccination rates during pregnancy by race/ethnicity. However, none have included American Indians/Alaska Natives as a specific racial/ethnic group on a national level. Current literature suggests that American Indian/Alaska Native infants experience increased morbidity and mortality from both influenza and pertussis infections compared with most other groups in the United States. OBJECTIVE: This study aimed to evaluate the uptake of influenza and Tdap vaccinations during pregnancy by race/ethnicity, with a specific focus on American Indian/Alaska Native people. STUDY DESIGN: This cross-sectional study used data from the Pregnancy Risk Assessment Monitoring System. Comparisons of vaccine uptake across racial/ethnic groups (American Indian/Alaska Native, Asian, non-Hispanic Black, non-Hispanic White, Hispanic, and "None of the above") were evaluated using weighted logistic regression analyses to estimate prevalence odds ratios with 95% confidence intervals. Models were adjusted for maternal age, parity, maternal education, marital status, payment method at delivery, prenatal care in first trimester, maternal smoking status, Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) participation, and receipt of influenza vaccine reported by a health care provider. RESULTS: For both vaccines, Asian respondents had the highest uptake (influenza, 70.1%; Tdap, 68.2%), whereas Black respondents reported the lowest uptake (influenza, 44.4%; Tdap, 57.9%). For the influenza vaccine, American Indian/Alaska Native respondents demonstrated a higher uptake compared with White respondents, and the magnitude of difference increased markedly after adjusting for respondent characteristics (adjusted odds ratio, 1.74; 95% confidence interval, 1.58-1.90). In the unadjusted analyses, Black individuals reported influenza vaccination at approximately half the rate of their White counterparts during pregnancy. This effect was attenuated but remained lower after adjustment for respondent characteristics (adjusted odds ratio, 0.73; 95% confidence interval, 0.70-0.76). For the Tdap vaccine, American Indian/Alaska Native respondents reported lower uptake than White respondents; however, this difference disappeared when adjusted for respondent characteristics (adjusted odds ratio, 0.99; 95% confidence interval, 0.83-1.19). Asian and Hispanic respondents displayed a similar uptake compared with their White counterparts for both vaccines. CONCLUSION: Our findings indicate that there are racial/ethnic disparities in influenza and Tdap vaccination rates among pregnant individuals in the United States. Demonstration of increased uptake among American Indian/Alaska Native people in the crude analysis may reflect the success of various public health interventions through Tribal and Indian Health Service hospitals. Nonetheless, vaccination status during pregnancy remains seriously below national guideline recommendations. Greater measures must be taken to support preventative care in marginalized populations, with particular emphasis on community-driven solutions rooted in justice.

Association between obesity and fecundity in patients undergoing intrauterine insemination.

Objective: To determine if an association exists between body mass index (BMI) and fecundity after intrauterine insemination (IUI). Design: Retrospective cohort study. Setting: Academic-based fertility clinic. Patients: Patients undergoing IUI July 2007 to May 2012. Interventions: None. Main Outcome Measures: Primary outcome: live-birth rate (LBR) per IUI cycle; secondary outcomes: positive pregnancy test and clinical pregnancy rates (CPRs). Results: A total of 1959 cycles were performed on 661 women (mean age, 31.9 ± 4.9 years). When examined by obesity class, LBR and CPR were similar for women with class I, II, and III obesity when compared with women with normal BMI. However, class III obese women (adjusted risk ratio [aRR], 1.70; 95% confidence interval [CI], 1.12-2.59) had increased pregnancy rates compared with normal BMI, but no differences in pregnancy rates were observed for women with class I or II obesity. In addition, pregnancy rates (aRR, 1.50; 95% CI, 1.12-2.02) and CPR (aRR, 1.51; 95% CI, 1.07-2.14) were higher in overweight women relative to normal BMI. Notably, among patients with ovulatory dysfunction, CPRs after IUI were reduced by 43% in obese women (aRR, 0.57; 95% CI, 0.37-1.07), whereas women without ovulatory dysfunction were twice as likely to achieve a clinical pregnancy when they were obese (aRR, 1.96; 95% CI, 1.19-3.24). The CIs for the obesity risk ratios in each stratum of ovulatory function exhibited no overlap, suggesting evidence of potential effect modification by ovulatory function. Conclusions: LBRs after IUI were similar across BMI subgroups. This is in contrast to research of in vitro fertilization treatments showing lower LBR with increasing BMI. However, obesity may adversely affect IUI CPR in those with ovulatory dysfunction in particular. The reason for this discrepancy is unclear and warrants further study.

Meeting the demand for fertility services: the present and future of reproductive endocrinology and infertility in the United States.

The field of reproductive endocrinology and infertility (REI) is at a crossroads; there is a mismatch between demand for reproductive endocrinology, infertility and assisted reproductive technology (ART) services, and availability of care. This document's focus is to provide data justifying the critical need for increased provision of fertility services in the United States now and into the future, offer approaches to rectify the developing physician shortage problem, and suggest a framework for the discussion on how to meet that increase in demand. The Society of REI recommend the following: 1. Our field should aggressively explore and implement courses of action to increase the number of qualified, highly trained REI physicians trained annually. We recommend efforts to increase the number of REI fellowships and the size complement of existing fellowships be prioritized where possible. These courses of action include: a. Increase the number of REI fellowship training programs. b. Increase the number of fellows trained at current REI fellowship programs. c. The pros and cons of a 2-year focused clinical fellowship track for fellows interested primarily in ART practice were extensively explored. We do not recommend shortening the REI fellowship to 2 years at this time, because efforts should be focused on increasing the number of fellowship training slots (1a and b). 2. It is recommended that the field aggressively implements courses of action to increase the number of and appropriate usage of non-REI providers to increase clinical efficiency under appropriate board-certified REI physician supervision. 3. Automating processes through technologic improvements can free providers at all levels to practice at the top of their license.

The impact of the Dobbs decision on in-vitro fertilization and fertility care.

PURPOSE OF REVIEW: The 2022 Supreme Court ruling in Dobbs vs Jackson marks a frightening new reality in America. Physicians and patients have been left confused and concerned regarding the broader implications of this ruling. Now that the constitutional right to an abortion has been overturned and the power has been relinquished to individual states, there is justifiable concern regarding the impact on in-vitro fertilization (IVF). This review explores the ways IVF and fertility care are at risk in the context of our new reality. RECENT FINDINGS: The decision to overturn the right to an abortion without specifying a viability standard opens the door to interpretation of when 'life' begins. Laws that do not specifically exempt IVF, or that include language suggesting that 'life begins at fertilization' pose a real threat to IVF. The potential for personhood laws poses a threat to embryo freezing and disposition, preimplantation genetic testing and culpability among other concerns. SUMMARY: Limitations to IVF may become an unintended consequence to the Dobbs decision, making IVF less efficient, more costly and unsafe, and inevitably limiting access to care. It is therefore crucial that public health legislation be rooted in science and not dictated by religion or politics. Physicians must act alongside legislators to protect reproductive freedom and access to care.

Sperm very long-chain polyunsaturated fatty acids: relation to semen parameters and live birth outcome in a multicenter trial.

OBJECTIVE: To determine whether the levels of sperm very long-chain polyunsaturated fatty acids (VLC-PUFAs) are correlated with sperm parameters and the outcome of live birth after conventional therapy for unexplained infertility. DESIGN: Cohort analysis of the Reproductive Medicine Network's Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation randomized controlled trial. SETTING: Multicenter randomized controlled trial. PATIENTS: Male partners from 185 couples with unexplained infertility who provided baseline semen samples for analysis. INTERVENTION: We determined the levels of VLC-PUFAs in total lipid isolated from sperm membranes using liquid chromatography-mass spectrometry/mass spectrometry analyses. MAIN OUTCOME MEASURES: Sperm concentration, motility, morphology, total motile count (TMC), and live birth after standard treatment for unexplained infertility. RESULTS: Total VLC-PUFA percentage was positively correlated with sperm concentration (Spearman's rank correlation (rs) 0.56, P<.0001), TMC (rs = 0.40, P<.0001), and morphology (rs = 0.26, P=.0005). After adjustment for male body mass index, age, and race, a one-standard-deviation increase in the percentage of total VLC-PUFA was associated with a 62% increase in the geometric mean (GM) of sperm concentration (GM Ratio: 1.62 [95% confidence intervals {CI}: 1.45, 1.82]) and a 43% increase in the geometric mean of TMC (GM Ratio: 1.43 [95% CI; 1.24, 1.63]). Although no evidence of association was observed for sperm motility, a positive relationship was also observed between the percentage of total VLC-PUFA and sperm morphology [adjusted incidence rate ratio (IRR) for one-standard-deviation increase in total VLC-PUFA: 1.18 (95% CI; 1.02, 1.36)]. After adjustment for female age and treatment group, the probability of a live birth outcome was 72% more likely among those in the third tertile of hydroxylated VLC-PUFA percentage than in the first tertile (RR 1.72 [95% CI; 1.01, 2.94]). CONCLUSIONS: The positive correlation between sperm VLC-PUFAs percentage and sperm parameters, as well as the significant association between hydroxylated VLC-PUFA percentage and the outcome of live birth, strongly suggest that this class of fatty liquid chromatography-mass spectrometry/mass spectrometry acids is essential for normal sperm structure and function.

Follicular phase length is not related to live birth outcome in women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination cycles in a multicenter trial.

Objective: To evaluate the effect of follicular phase length (FPL) on pregnancy outcomes and endometrial thickness (ET) among women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination (OS-IUI) with clomiphene citrate, letrozole, or gonadotropins. Design: Cohort analysis of the Reproductive Medicine Network's Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation randomized controlled trial. Setting: Multicenter randomized controlled trial. Patients: A total of 869 couples with unexplained infertility who underwent OS-IUI treatment cycles as part of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation study. Interventions: FPL was evaluated as a categorical variable defined by quintiles (q1: ≤11 days, q2: 12 days, q3: 13 days, q4: 14-15 days, and q5: ≥16 days). Main outcome measures: Clinical pregnancy, live birth rates, and ET. Results: Decreasing FPL quintiles did not reduce clinical pregnancy or live birth rates in unadjusted or adjusted models with all treatment groups combined or when stratified by the ovarian stimulation medication. All FPL categories had significantly thinner ET compared with the 5th quintile (≥16 days) among women treated with clomiphene citrate or letrozole. Similar but diminished associations were observed among women who underwent ovarian stimulation with gonadotropins, but the observed differences were limited to those with FPL of 12 days or shorter when compared with FPL ≥16 days. Conclusions: Although shorter FPL was associated with reduced ET, it was not associated with the outcomes of clinical pregnancy or live birth in women with unexplained infertility undergoing OS-IUI in all treatment groups combined. Similar patterns existed when analyses of clinical pregnancy and live birth rates were stratified by treatment. Clinical trial registration: NCT01044862.

Integration of health systems science and women's healthcare.

Health systems science addresses the complex interactions in healthcare delivery. At its core, health systems science describes the intricate details required to provide high-quality care to individual patients by assisting them in navigating the multifaceted and often complicated US healthcare delivery system. With advances in technology, informatics, and communication, the modern physician is required to have a strong working knowledge of health systems science to provide effective, low-cost, high-quality care to patients. Medical educators are poised to introduce health systems science concepts alongside the basic science and clinical science courses already being taught in medical school. Because of the common overlap of women's healthcare subject matter with health systems science topics, such as interprofessional collaboration, ethics, advocacy, and quality improvement, women's health medical educators are at the forefront of incorporating health systems science into the current medical school educational model. Here, the authors have described the concept of health systems science and discussed both why and how it should be integrated into the undergraduate medical education curriculum. Medical educators must develop physicians of the future who can not only provide excellent patient care but also actively participate in the advancement and improvement of the healthcare delivery system.

Does the ultrasound appearance of the endometrium during treatment with assisted reproductive technologies influence pregnancy outcomes?

We evaluated endometrial pattern, defined as the relative echogenicity of the endometrium on a longitudinal uterine ultrasonic section, as a surrogate for endometrial receptivity in an attempt to evaluate the association between endometrial pattern and pregnancy outcome in women who underwent ART treatment. The primary outcome was live birth and secondary outcomes were clinical intrauterine pregnancy and miscarriage. Potential associations were evaluated using cluster-weighted generalized estimating equations to account for within-couple correlation among repeated ART cycles while adjusting for potentially confounding variables. There were 1034 ART cycles with embryo transfer (778 fresh, 256 frozen) among 695 women (median age: 31.0 (6.0) years). The average number of embryos transferred per cycle was 2.1. The clinical intrauterine pregnancy rate per transfer was 56.0% for fresh and 54.3% for frozen cycles. The overall live birth rate per embryo transfer was 48.4%. Live birth rates were unchanged when the endometrium was semi-trilinear (RR:0.91 CI:0.74,1.12) or unilinear (RR:1.15 CI:0.89,1.49) in comparison to trilinear endometrium after controlling for potentially confounding variables. Results were similar when analysed separately for fresh and frozen cycles and when evaluating associations with clinical intrauterine pregnancy and miscarriage rates. It appears that endometrial pattern does not significantly affect live birth in ART and our data do not support cancelling an ART cycle if the endometrium is less than trilinear.

GnRH receptor-activating autoantibodies in polycystic ovary syndrome: identification of functional epitopes and development of epitope mimetic inhibitors.

PURPOSE: We have recently demonstrated that gonadotrophin-releasing hormone receptor-activating autoantibodies (GnRHR-AAb) are associated with polycystic ovary syndrome (PCOS). The aim of this study was to map the antigenic epitopes of GnRHR-AAb from PCOS patients, and develop retro-inverso peptide inhibitors that specifically target GnRHR-AAb. METHODS: Serum samples from ten GnRHR-AAb-positive PCOS patients and ten GnRHR-AAb-negative healthy controls were tested. Epitope mapping for GnRHR-AAb was performed using a set of 11 overlapping octapeptides spanning the second extracellular loop of GnRHR. Antibody-blocking effect of the designed retro-inverso peptide inhibitors was evaluated in a cell-based bioassay. RESULTS: Two peptide sequences, FSQCVTHC and HCSFSQWW, were found to react with all PCOS sera, but not with control sera. Two retro-inverso peptides that mimic the identified epitopes, d-CHTVCQSF and d-WWQSFSCH, significantly inhibited PCOS serum IgG-induced GnRHR activation. One of these two peptide inhibitors, d-CHTVCQSF, largely suppressed autoantibody-induced GnRHR activation, suggesting that the epitope sequence FSQCVTHC may be a major functional target of GnRHR-AAb. CONCLUSION: We have identified a dominant functional epitope for GnRHR-AAb associated with PCOS, and demonstrated effective blocking of GnRHR-AAb activity with epitope-mimicking retro-inverso peptide inhibitors. These proteolytically stable decoy peptides may have important therapeutic implications in subjects who harbor these autoantibodies.

Relationship between semen regurgitation and pregnancy rates with intrauterine insemination.

OBJECTIVE: To evaluate the relationship between semen regurgitation and intrauterine insemination (IUI) outcomes. We hypothesized that clinical pregnancy rates and live birth rates would be reduced when regurgitation occurred. DESIGN: Retrospective cohort study. SETTING: A university-based reproductive endocrinology and infertility clinic. PATIENT(S): Retrospective review of 1,957 IUI cycles performed on 660 patients between July 2007 and May 2012. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was live birth. Secondary outcomes were positive serum pregnancy result and clinical pregnancy. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a cluster-weighted generalized estimating equations method to estimate modified Poisson regression models with robust standard errors to account for multiple IUI cycles in the same patient. RESULT(S): Live birth rates were similar in IUI cycles with and without regurgitation (6.3% vs. 6.8%, respectively, RR = 0.82, 95% CI [0.53-1.26]). Clinical pregnancy rates in the presence or absence of regurgitation were 10.5% vs. 10.0% (RR = 0.99, 95% CI [0.73-1.35]). Positive serum pregnancy tests after IUI did not differ by regurgitation status (15.0% vs. 15.4%, RR = 0.97, 95% CI [0.75-1.24]). Results were unchanged when adjusted for covariates (age, race and ethnicity, body mass index, duration of infertility, medication, infertility diagnosis, total motile count, and method of sperm preparation). CONCLUSION(S): The presence of regurgitation during the IUI procedure is not related to pregnancy outcome.

Increased testosterone and proinflammatory cytokines in patients with polycystic ovary syndrome correlate with elevated GnRH receptor autoantibody activity assessed by a fluorescence resonance energy transfer-based bioassay.

PURPOSE: The recently identified agonistic autoantibodies (AAb) to the gonadotropin-releasing hormone receptor (GnRHR) are a novel investigative and therapeutic target for polycystic ovary syndrome (PCOS). In this study, we used a new cell-based fluorescence resonance energy transfer (FRET) bioassay to analyze serum GnRHR-AAb activity and examine its relationship with testosterone and proinflammatory cytokines in patients with PCOS. METHODS: Serum samples from 33 PCOS patients, 39 non-PCOS ovulatory infertile controls and 30 normal controls were tested for GnRHR-AAb activity and proinflammatory cytokines in a FRET-based bioassay and multiplex bead-based immunoassay, respectively. Correlation was analyzed using the Spearman's correlation test. RESULTS: Serum GnRHR-AAb activity was significantly higher in the PCOS patients than for the ovulatory infertile (p < 0.05) and normal (p < 0.01) controls. GnRHR-AAb were positive in 39% of PCOS patients, 10% of ovulatory infertile controls, and 0% of normal controls. PCOS IgG-induced GnRHR activation was specifically blocked by the GnRHR antagonist cetrorelix. Serum levels of proinflammatory cytokines interleukin-2, interleukin-6, interferon-γ, and tumor necrosis factor-α were significantly increased in PCOS patients compared with ovulatory infertile and normal controls (p < 0.01). Correlation analysis demonstrated positive correlations of GnRHR-AAb activity with testosterone and proinflammatory cytokine levels in the PCOS group. CONCLUSIONS: Elevated GnRHR-AAb activity, as assessed by a new FRET assay, is associated with increased testosterone and proinflammatory cytokines in PCOS, suggesting autoimmune activation of GnRHR may contribute to the pathogenesis of this common disorder.

Gonadotrophin-releasing hormone receptor autoantibodies induce polycystic ovary syndrome-like features in a rat model.

NEW FINDINGS: What is the central question of this study? Is there a causal relationship between gonadotrophin-releasing hormone (GnRH) receptor-activating autoantibodies and polycystic ovary syndrome (PCOS)? What is the main finding and its importance? Induction of GnRH receptor-activating autoantibodies in rats resulted in increased luteinizing hormone pulsatility and testosterone concentrations, disrupted oestrous cycles, increased atretic follicles, and activation of insulin signalling in the pituitary and ovary. These changes replicate those seen in humans with PCOS, suggesting that GnRH receptor-activating autoantibodies might be involved in the pathogenesis of PCOS. ABSTRACT: Gonadotrophin-releasing hormone receptor-activating autoantibodies (GnRHR-AAb) are associated with polycystic ovary syndrome (PCOS). In the present study, we examined the impact of GnRHR-AAb on reproductive function in GnRHR-immunized female rats. All immunized rats produced high titres of GnRHR-AAb targeting a dominant epitope located in the central region of the second extracellular loop of the GnRHR. Increased pulsatile luteinizing hormone secretion and testosterone concentrations were found in immunized rats. These rats exhibited disrupted oestrous cycles, increased ovarian follicular atresia, and activation of insulin signalling in the pituitary and ovary, as indicated by increased mRNA expressions of insulin receptor substrate, phosphatidylinositol 3-kinase and glucose transporter 1. No significant changes in inflammatory cytokines were detected in the ovarian tissue. These features mimic those observed in humans with PCOS. Our findings support the concept that chronic stimulation of the GnRHR by GnRHR-AAb, with an associated increase in pituitary luteinizing hormone secretion and ovarian androgen overproduction, might represent a new aetiological mechanism for PCOS.

To the Point: advising students applying to Obstetrics and Gynecology residency in 2020 and beyond.

This article, from the "To the Point" series by the Undergraduate Medical Education Committee of the Association of Professors of Gynecology and Obstetrics, is a guide for advising medical students applying to Obstetrics and Gynecology residency programs. The residency application process is changing rapidly in response to an increasingly complex and competitive atmosphere, with a wider recognition of the stress, expense, and difficulty of matching into graduate training programs. The coronavirus disease 2019 pandemic and societal upheaval make this application cycle more challenging than ever before. Medical students need reliable, accurate, and honest advising from the faculty in their field of choice to apply successfully to residency. The authors outline a model for faculty career advisors, distinct from mentors or general academic advisors. The faculty career advisor has detailed knowledge about the field, an in-depth understanding of the application process, and what constitutes a strong application. The faculty career advisor provides accurate information regarding residency programs within the specialty, helping students to strategically apply to programs where the student is likely to match, decreasing anxiety, expense, and overapplication. Faculty career advisor teams advise students throughout the application process with periodic review of student portfolios and are available for support and advice throughout the process. The authors provide a guide for the faculty career advisor in Obstetrics and Gynecology, including faculty development and quality improvement.

Autoimmune activation of the GnRH receptor induces insulin resistance independent of obesity in a female rat model.

Polycystic ovary syndrome (PCOS), a metabolic and reproductive disease, is frequently associated with type 2 diabetes. We have demonstrated activating autoantibodies (AAb) directed toward the second extracellular loop (ECL2) of the gonadotropin-releasing hormone receptor (GnRHR) are present in a significant subgroup of PCOS patients. It is unclear whether GnRHR-AAb can induce peripheral tissue insulin resistance (IR) in animal models. Sixteen rats were divided equally into a GnRHR ECL2 peptide-immunized group (IMM group) and a control group (CON group). Sera GnRHR-AAb titer, luteinizing hormone (LH), and testosterone (T) were higher in IMM rats compared with CON rats. No significant difference in fasting blood glucose was observed between the two groups. However, the plasma glucose level at other time points of the IMM group was higher than that of the CON group during an intraperitoneal glucose tolerance test (IPGTT) and an insulin tolerance test (ITT) (p < 0.01). These data support the likelihood of the GnRHR-AAb induction of glucose intolerance and IR. Compared with the CON group, the IMM group showed a significant increase in insulin-stimulated phosphorylation of IRS-1 (p-IRS-1 S636/639) and a decrease in insulin-stimulated phosphorylation of Akt (p-AKT S473). Expression of the glucose transport genes including GLUT-2 in liver and GLUT-4 in white adipose tissue and skeletal muscle was significantly decreased in IMM rats compared with the CON rats. Serum levels of proinflammatory cytokines (TNF-α, IL-1α, and IL-18) were increased, while anti-inflammatory cytokines (IL-4 and IL-10) were decreased in the IMM group. Taken together, elevated GnRHR-AAb enhanced LH, hyperandrogenism, and inflammation. These changes are likely related to the observed peripheral tissue IR through the downregulation of the insulin-stimulated IRS/PI3K/Akt/Glut signaling pathway.

The Role of GnRH Receptor Autoantibodies in Polycystic Ovary Syndrome.

OBJECTIVE: Is polycystic ovary syndrome (PCOS) associated with activating autoantibodies (AAb) to the second extracellular loop (ECL2) of gonadotropin-releasing hormone receptor (GnRHR)? DESIGN AND METHODS: We retrospectively screened sera from 40 patients with PCOS and 14 normal controls (NCs) with regular menses using enzyme-linked immunosorbent assay (ELISA) for the presence of GnRHR-ECL2-AAb. We obtained similar data from 40 non-PCOS ovulatory but infertile patients as a control group (OIC) of interest. We analyzed GnRHR-ECL2-AAb activity in purified immunoglobulin (Ig)G using a cell-based GnRHR bioassay. RESULTS: The mean ELISA value in the PCOS group was markedly higher than the NC (P = .000036) and the OIC (P = .0028) groups. IgG from a sample of 5 PCOS subjects, in contrast to a sample of 5 OIC subjects, demonstrated a dose-dependent increase in GnRHR-stimulating activity qualitatively similar to the acute action of the natural ligand GnRH and the synthetic agonist leuprolide. The GnRHR antagonist cetrorelix significantly suppressed (P < .01) the elevated GnRHR activity induced by IgG from 7 PCOS patients while the IgG activity level from 7 OIC subjects was unchanged. Five other OIC subjects had relatively high ELISA values at or above the 95% confidence limits. On further study, 3 had normal or low activity while 2 had elevated IgG-induced GnRHR activity. One suppressed with cetrorelix while the other did not. The copresence of PCOS IgG increased the responsiveness to GnRH and shifted the dosage response curve to the left (P < .01). CONCLUSIONS: GnRHR-ECL2-AAb are significantly elevated in patients with PCOS compared with NCs. Their presence raises important etiological, diagnostic, and therapeutic implications.

Elevated activity levels of activating autoantibodies to the GnRH receptor in patients with polycystic ovary syndrome.

OBJECTIVES: 1) To confirm the correlation of GnRH receptor (GnRHR) activating autoantibody (AAb) activity with polycystic ovary syndrome (PCOS) diagnosis in large well defined cohorts; and 2) to evaluate suppression of AAb activity with GnRH antagonist medication in transfected GnRHR cells exposed to serum of PCOS patients. DESIGN: Cross-sectional matched case-control study. SETTING: University-based research facility. PATIENTS: Sera from 200 patients with PCOS from the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial and from 200 race, parity-, age-, and body mass index (BMI)-matched ovulatory unexplained infertile control patients from the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) trial were obtained and used for this study. INTERVENTIONS: GnRHR AAb activity was determined with the use of the GeneBlazer cell-based fluorescence resonance energy transfer assay with and without cetrorelix, a GnRH antagonist. MAIN OUTCOME MEASURES: 1) GnRHR AAb activity in PCOS patients compared with control subjects; and 2) effectiveness of GnRH antagonist in suppressing GnRHR AAb activity. RESULTS: GnRHR AAb activity levels in the PCOS group were significantly higher than in the control group. With cetrorelix, GnRHR AAb activity was largely suppressed in the PCOS group but not in the control group. These differences remained significant after adjusting for within-pair differences in age, BMI, and antimüllerian hormone (AMH) levels. CONCLUSIONS: We confirmed higher GnRHR AAb activity levels in the sera of a large cohort of PCOS patients compared with unexplained infertile control subjects. Addition of cetrorelix resulted in significant suppression of AAb activity levels in PCOS patients as a group whereas control subjects were unaffected. GnRHR AAb, along with patient age and AMH level, may provide a promising future diagnostic test for PCOS.

Fostering Inclusive Approaches to Lesbian, Gay, Bisexual, and Transgender (LGBT) Healthcare on the Obstetrics and Gynecology Clerkship.

This article from the "To the Point" series prepared by the Association of Professors in Gynecology and Obstetrics (APGO) Undergraduate Medical Education Committee (UMEC) provides educators with strategies for inclusion of Lesbian, Gay, Bisexual, Transgender (LGBT)-related content into the medical school curriculum. With a focus on the Obstetrics and Gynecology (OB/GYN) clerkship, we also address ways to enhance visibility of these curricula within existing clinical and teaching experiences.

A National Survey of Profiles of Clerkship Directors in Obstetrics and Gynecology.

OBJECTIVE: To monitor demographics and factors associated with quality of life among obstetrics and gynecology clerkship directors. A secondary goal was to compare current demographics and survey responses to a 1994 survey of clerkship directors. METHODS: A 36-item electronic survey was developed and distributed to the 182 U.S. clerkship directors with active memberships with the Association of Professors of Gynecology and Obstetrics. Items queried respondents on demographics, attitudes about being a clerkship director, quality of life, and burnout. RESULTS: A total of 113 of the 182 (62%) clerkship directors responded to the survey. The mean full-time time equivalent allocated for clerkship director responsibilities was 25%. When compared with clerkship directors from 1994, current clerkship directors are younger, work fewer total hours per week, spend more time on patient care, and less time on research. Notably, 78% (87) of respondents were female compared with 21% (31) of respondents in 1994. Overall, most current clerkship directors responded optimistically to quality of life and burnout measures, with 25% (28) reporting symptoms of high emotional exhaustion and 17% (19) reporting symptoms of depersonalization. Clerkship directors' perception of support from their medical school was significantly correlated with increased personal fulfilment and positive quality of life, as well as decreased burnout and emotional exhaustion measures. CONCLUSION: The gender demographics of obstetrics and gynecology undergraduate medical education leadership have dramatically shifted over the past 25 years; however, many of the changes are not correlated with quality of life and burnout. The association between perceived support from the medical school and multiple quality of life measures point to the vital importance of support for our medical educators.

Developing as an Academic Medical Educator in Obstetrics and Gynecology.

The lack of a defined framework for advancement and development of professional identity as a medical educator may discourage faculty from pursuing or progressing through a career in academic medical education. Although career advancement has historically been linked to clinical work and research, promotion for teaching has not been supported at the same level. Despite potential challenges, a career in academic medicine has its share of rewards. This article by the Association of Professors of Gynecology and Obstetrics Undergraduate Medical Education Committee will describe how to develop as an academic medical educator in obstetrics and gynecology, providing tips on how to start, advance, and succeed in an academic career, and provide an overview of available resources and opportunities.

To the Point: a prescription for well-being in medical education.

This article is from the "To The Point" series prepared by the Association of Professors of Gynecology and Obstetrics Undergraduate Medical Education Committee. The purpose of this review was to provide an overview of the importance of well-being in medical education. A literature search was performed by a Reference Librarian who used Ovid/MEDLINE to identify scholarly articles published in English on learner well-being, using the search terms "burnout," "resilience," "wellness," and "physicians" between 1946 and January 11, 2019. The accreditation expectations and standards, available assessment tools for learner well-being, existing programs to teach well-being, and some key elements for curriculum development are presented. This is a resource for medical educators, learners, and practicing clinicians from any field of medicine.