Seizure control in women with epilepsy undergoing assisted reproductive technology.

The objective of this study was to determine seizure control in women with epilepsy (WWE) undergoing assisted reproductive technology (ART). Through retrospective chart review, WWE undergoing ART were identified. Demographics and details regarding epilepsy type, seizure control, and ART procedures were extracted. Seizure frequency prior to and during ART were compared. We identified 12 WWE, who underwent 29 embryo transfers, resulting in 16 pregnancies and 10 live births. Nine women were seizure-free at least 2 years before fertility treatment, including three with resolved epilepsy. Seven were on antiseizure medications throughout fertility treatment and pregnancy, with only one on polytherapy. Eleven (all with controlled epilepsy or epilepsy in remission) remained seizure-free throughout fertility treatment. One woman with drug-resistant epilepsy continued to have seizures throughout fertility treatment and pregnancy without an exacerbation of seizure frequency. There was no increased seizure frequency associated with fertility treatment and subsequent pregnancy in this small series of WWE. Although this study was statistically underpowered, our results provide some preliminary evidence that ART might not pose a threat to seizure control, but larger, confirmatory studies are necessary.

Normal and Abnormal Appearances of the Ovaries during Assisted Reproduction: Multimodality Imaging Review.

Infertility is a common diagnosis that prompts many couples and individuals to seek assisted reproductive technology (ART) for assistance with conception. These technologies have become increasingly used in the United States in the past several decades, with 326 468 ART cycles performed in 2020, resulting in 75 023 live births. This ubiquity of ART also increases the likelihood that radiologists will encounter both normal and abnormal imaging findings associated with these treatments. Thus, radiologists of all subspecialties should be familiar with the multimodality appearance of the ovaries and pelvis in patients undergoing ART treatments. Furthermore, it is imperative that radiologists understand the appearance expected during different stages of the ART process. During stimulated ovulatory cycles, it is normal and expected for the ovaries to appear enlarged and to contain numerous cystic follicles, often with a small to moderate volume of pelvic free fluid. After oocyte retrieval, hemorrhagic ovarian follicles and a small to moderate volume of blood products in the cul-de-sac can be expected to be seen. Multiple nonemergency and emergency complications are related to ART, many of which can be seen at imaging. The most encountered emergency complications of ART include ovarian hyperstimulation syndrome, ectopic pregnancy, heterotopic pregnancy, multiple gestations, ovarian torsion, and procedural complications related to oocyte retrieval. These complications have important clinical implications, thus necessitating accurate and timely detection by the radiologist and the clinical team. ©RSNA, 2023 Supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Fertility trends and comparisons in a historical cohort of US women with primary infertility.

BACKGROUND: There is growing interest in long-term outcomes following infertility and infertility treatment. However, there are few detailed longitudinal cohorts available for this work. This study aimed to assemble a historical cohort of women with primary infertility and age-matched controls to evaluate fertility trends, sequelae, and sociodemographic differences. Described here are cohort group characteristics and associated reproductive trends over time. METHODS: A population-based historical cohort was created using the Rochester Epidemiology Project (REP) record-linkage system (Olmsted County, MN). The cohort included women aged 18-50 with a diagnosis of primary infertility between January 1, 1980, and December 31, 1999. As part of a case-control study, we identified 1:1 age-matched female controls from the same community and era. RESULTS: A total of 1001 women with primary infertility and 1001 age-matched controls were identified. The women with primary infertility were significantly more likely to be married, college educated, use barrier contraception, and non-smokers compared to age-matched controls. The incidence of primary infertility increased from 14 to 20 per 10,000 person years from 1980-1985 to 1995-1999. Ovulatory dysfunction and unexplained infertility were the most common causes of primary infertility and clomiphene was the most widely used fertility medication. Rates of in vitro fertilization (IVF) increased from 1.8% during 1980-1985 to 26.0% during 1995-1999. CONCLUSION: Women with primary infertility were found to have unique sociodemographic characteristics compared to age-matched control women, which is consistent with previous research. The incidence of diagnosed primary infertility increased from 1980 to 1999, as did use of IVF.

This study aimed to assemble a historic cohort of women with primary infertility and age-matched control women. The cohort included 1001 women with primary infertility diagnosed between 1980 and 1999 and 1001 age-matched controls from the same community and era. This cohort demonstrated baseline differences between the primary infertility and control groups, including differences in marital status, education, use of barrier contraception and smoking status. Additionally, the cohort showed an increased incidence in diagnosis of primary infertility from 1980 to 1999. Creation of this cohort will enable future research focused on long-term outcomes following primary infertility diagnosis and treatment.

Intrauterine insemination cycles: prediction of success and thresholds for poor prognosis and futile care.

PURPOSE: We aimed to define intrauterine insemination (IUI) cycle characteristics associated with viable birth, identify thresholds below which IUI treatments are consistent with very poor prognosis and futile care, and develop a nomogram for individualized application. METHODS: This retrospective cohort study evaluated couples using fresh partner ejaculate for IUI from January 2005 to September 2017. Variables included female age, semen characteristics, and ovarian stimulation type. Using cycle-level data, we evaluated the association of these characteristics with the probability of viable birth by fitting generalized regression models for a binary outcome with a logit link function, using generalized estimating equation methodology to account for the correlation between cycles involving the same patient. RESULTS: The cohort consisted of 1117 women with 2912 IUI cycles; viable birth was achieved in 275 (9.4%) cycles. Futile care (viable birth rate < 1%) was identified for women age > 43, regardless of stimulation type or inseminate motility (IM). Very poor prognosis (viable birth rate < 5%) was identified for women using oral medications or Clomid plus gonadotropins who were (1) age < 35 with IM < 49%, (2) age 35-37 with IM < 56%, or (3) age ≥ 38, and (4) women age ≥ 38 using gonadotropins only with IM < 60%. A clinical prediction model and nomogram was developed with an optimism-corrected c-statistic of 0.611. CONCLUSIONS: The present study highlights the impact of multiple clinical factors on IUI success, identifies criteria consistent with very poor prognosis and futile care, and provides a nomogram to individualize counseling regarding the probability of a viable birth.

Use of Genetic Testing after Abnormal Screening Ultrasound: A Descriptive Cohort Study.

BACKGROUND/AIMS: The study aimed to characterize the use of genetic testing after abnormal screening ultrasound. METHODS: We performed a retrospective review of patients undergoing genetic testing after abnormal ultrasound. Genetic evaluation consisted of noninvasive prenatal screening (NIPS) or amniocentesis. Classification of ultrasound findings, type of genetic testing, and results were collected. RESULTS: A total of 139 subjects underwent genetic evaluation after abnormal screening ultrasound. Screening via NIPS was pursued by 61 (44%) patients while 78 (56%) proceeded directly to amniocentesis. Patients electing for amniocentesis had more cardiac, neurologic, and gastrointestinal malformations while soft markers for aneuploidy prompted more NIPS screening. Results were negative in 85% of the NIPS group compared to 60% of the amniocentesis group. Only 8% of patients who underwent NIPS proceeded to diagnostic testing. CONCLUSION: Patients pursuing NIPS after abnormal ultrasound had more soft markers of aneuploidy. Patients pursuing diagnostic testing were more likely to have major structural malformations and more total abnormalities identified. Patients who proceeded directly to amniocentesis were more likely to have abnormal genetic testing.

Choosing a women's health career.

BACKGROUND: In 2005, in response to a decline in residency applications in obstetrics and gynecology (OB GYN), the American College of Obstetrics and Gynecology Presidential Task Force outlined strategies for attracting medical students to OB GYN. Application rates have increased since then, but little is known about which interventions are effective. We aimed to identify modifiable and nonmodifiable variables that may contribute to students choosing OB GYN for their careers; this information could be used to inform curriculum design, faculty development, and innovative exposures to women's health. METHODS: This qualitative study received institutional review board approval. Eligible participants were students who applied or recently matched into OB GYN residency programs from the class of 2014-2016 at our institution. Students were interviewed with open-ended questions and a Likert-type survey. Thematic analysis was performed. RESULTS: Ten qualitative interviews were completed and analyzed. Intrinsic themes such as the potential for a meaningful job in women's health, advocacy for women, or empowerment of women were identified as factors contributing to participant career choice. Extrinsic themes such as positive impressions during the clinical clerkship and welcoming teams were also identified. Most students indicated that the clerkship was the most influential experience. CONCLUSIONS: Participants identified important events, including some that even preceded medical school that guided them toward OB GYN. The data guide us to consider the importance of emphasizing the unique combination of characteristics in OB GYN and improving the learning environment in the clerkship as a way to encourage student recruitment.

Improved detection of mineral oil toxicity using an extended mouse embryo assay.

PURPOSE: Successful in vitro fertilization (IVF) relies on sound laboratory methods and culture conditions which depend on sensitive quality control (QC) testing. This study aimed to improve the sensitivity of mouse embryo assays (MEA) for detection of mineral oil toxicity. METHODS: Five experiments were conducted to study modifications of the standard mouse embryo assay (MEA) in order to improve sensitivity using clinical grade mineral oil with known peroxide concentrations. Assessment of blastocyst development at either 96 h or in an extended MEA (eMEA) to 144 h was tested in each experiment. In experiment 1, ability to detect peroxides in oil was compared in the MEA, eMEA, and cell number at 96 h. In experiment 2, serial dilutions of peroxide in oil were used along with time-lapse imaging to compare sensitivity of the morphokinetic MEA to the eMEA. Culture conditions that may affect assay sensitivity were assessed in experiments 3-5, which examined the effect of group versus individual culture, oxygen concentration, and protein supplementation. RESULTS: Extended MEA and cell counts identified toxicity not detected by the routine endpoint of blastocyst rate at 96 h. The eMEA was fourfold more sensitive than the standard MEA, and this sensitivity was similar to the morphokinetic MEA. Group culture had a protective effect against toxicity, while oxygen concentration did not affect blastocyst development. Protein supplementation with HSA had a protective effect on blastocyst development in eMEA. CONCLUSIONS: The standard MEA used by manufacturers does not detect potentially lethal toxicity of peroxides in mineral oil. While group culture may mask toxicity, protein supplementation and oxygen concentration have minimal effect on assay sensitivity. The eMEA and time-lapse morphokinetic assessment are equally effective in detection of peroxide toxicity and thus provide manufacturers and end-users a simple process modification that can be readily adopted into an existing QC program.

Evaluation of the maternal systemic immune system during frozen euploid embryo transfer according to cycle outcome.

Infertility affects 15 % of couples in the US, and many turn to assisted reproductive technologies, including in vitro fertilization and subsequent frozen embryo transfer (FET) to become pregnant. This study aimed to perform a broad assessment of the maternal immune system to determine if there are systemic differences on the day of FET in cycles that result in a live birth compared to those that do not. Women undergoing FET of euploid embryos were recruited and blood was collected on the day of FET as well as at early timepoints in pregnancy. Sixty immune and angiogenic proteins were measured in plasma, and gene expression of 92 immune-response related genes were evaluated in peripheral blood mononuclear cells (PBMCs). We found plasma concentrations of interleukin-13 (IL-13) and macrophage derived chemokine (MDC) were significantly lower on the day of FET in cycles that resulted in a live birth. We also found genes encoding C-C chemokine receptor type 5 (CCR5), CD8 subunit alpha (CD8A) and SMAD family member 3 (SMAD3) were upregulated in PBMCs on the day of FET in cycles that resulted in live birth. Measurements of immune mediators from maternal blood could serve as prognostic markers during FET to guide clinical decision making and further our understanding of implantation failure.

Women With a History of Primary Infertility and Increased Rates of Bilateral Oophorectomy.

OBJECTIVE: To evaluate the association of primary infertility with subsequent bilateral oophorectomy and hysterectomy, using a population-based cohort of women with primary infertility and age-matched women in a referent group. METHODS: The Rochester Epidemiology Project record-linkage system was used to assemble a population-based cohort of women with primary infertility diagnosed between 1980 and 1999 (index date). Women were age-matched (±1 year) 1:1 to women without a history of infertility or hysterectomy at the index date (referent group). Cox proportional hazards models were fit to compare long-term risks of bilateral oophorectomy and hysterectomy, respectively, between women with infertility and women in the referent group. RESULTS: Among both groups of 1,001 women, the mean age at the index date was 29.2±4.4 years. Median duration of follow-up was 23.7 years for both groups. Women with primary infertility were 1.7 times (adjusted hazard ratio [aHR] 1.69, 95% CI 1.22-2.33) more likely to undergo bilateral oophorectomy compared with women in the referent group. In a sensitivity analysis that excluded women with a diagnosis of infertility related to endometriosis and their matched referent group participants, this association persisted (aHR 1.50, 95% CI 1.06-2.14). Women with primary infertility did not have a significant increased risk of hysterectomy (aHR 0.98, 95% CI 0.79-1.23). However, risk of hysterectomy was increased in those with primary infertility related to endometriosis (aHR 1.94, 95% CI 1.12-3.34). We observed that women with primary infertility were more likely to undergo hysterectomy with bilateral oophorectomy. Women in the referent group were more likely to undergo hysterectomy with ovarian conservation. Few women in either group had isolated bilateral oophorectomy. CONCLUSION: Primary infertility, with and without a diagnosis of endometriosis, is associated with an increased risk of bilateral oophorectomy. In women with endometriosis-related infertility, there is an association with future hysterectomy. These findings represent important confounders in the evaluation of long-term health outcomes related to primary infertility.

Impact of the COVID-19 Pandemic on Patient Fertility Care.

The effects of the COVID-19 pandemic on the healthcare system have been widespread, with many institutions in the United States pausing elective procedures to redirect resources to critical care. Fertility care and assisted reproductive procedures were classified as elective procedures and similarly paused. We conducted qualitative interviews with patients and/or their partners (n = 25 female patients; n = 3 male partners) receiving care at a fertility clinic in the Midwest to understand patient appraisal of COVID-19 risk on the resumption of care following a month-long closure of an infertility clinic, and patient agreement with the clinic closure. Interview transcripts were thematically analyzed from a grounded theory approach. Study participants reported an increased sense of urgency due to the delay in fertility procedures. This urgency often superseded concerns of potential COVID-19 infection, motivating patients to continue fertility treatment during a pandemic. In hindsight, some participants did not agree with the clinic's closure and treatment cessation, feeling that these steps negatively interrupted time-sensitive reproductive goals. Patient responses highlight the need for additional resources to support decision-making during times of crisis. Triaging patients based on time-sensitivity of treatment instead of a total shutdown respects patient autonomy for continuing treatment amidst uncertain COVID-19-impact.

Abnormal rate of human chorionic gonadotropin rise: a case series of patients with viable intrauterine pregnancies after embryo transfer.

OBJECTIVE: To report three cases of viable intrauterine pregnancies after embryo transfer with lower quantitative human chorionic gonadotropin (hCG) rates of rise than that expected in 99% of normal intrauterine pregnancies, based on current guidelines. DESIGN: Case series. SETTING: Tertiary care center. PATIENTS: Three patients underwent in vitro fertilization for ovulatory dysfunction or male factor infertility and had successful live births after an unusually low rate of hCG rise following embryo transfer. INTERVENTIONS: In vitro fertilization was utilized for all three patients. MAIN OUTCOME MEASURES: Serial hCG levels. RESULTS: Three cases of abnormally rising hCG levels were described. All cases presented achieved pregnancy through assisted reproductive technologies. The lowest documented rate of rise for each case, over 48 hours, was 22.1%, 23.3%, and 26.9%. All three cases resulted in live births. Literature on this topic was reviewed. CONCLUSIONS: Based on the cases presented, we recommend conservative management for patients found to have abnormally low rise hCG levels after embryo transfer; a high clinical suspicion for ectopic pregnancy should be maintained.

Lavender Aromatherapy to Reduce Anxiety During Intrauterine Insemination: A Randomized Controlled Trial.

BACKGROUND: Infertility is a global public health issue. Therapies such as intrauterine insemination (IUI) are effective but may be associated with considerable anxiety. Preliminary data suggest that decreasing this anxiety might lead to improved outcomes. OBJECTIVE: To determine whether lavender aromatherapy (LA) reduces anxiety during an IUI procedure. METHODS: A randomized controlled trial of women undergoing IUI at a hospital-based fertility clinic. The intervention and comparison were the use of LA vs water. Measurements were the change in anxiety level during an IUI procedure, with secondary assessment of pain scores, patient satisfaction, and pregnancy rates. RESULTS: In total, 67 women were screened, and 62 women randomly assigned to either placebo (n = 31) or LA (n = 31). No differences were observed in baseline demographic characteristics or visual analog scores for anxiety before IUI (mean [95% CI], 33.9 [25.2 to 45.6] mm vs 41.0 [33.0 to 49.0] mm) in the LA and placebo groups. However, a statistically significant change in anxiety was observed after LA inhalation during the procedure (mean [95% CI], -11.2 [-19.1 to -3.2]) compared with placebo (mean [95% CI], 1.3 [-5.6 to 8.2]; P = .02). No significant difference was observed in pain during IUI in the LA group vs placebo group. Patient satisfaction was high, with 93% of respondents in the LA group satisfied with the aromatherapy during their procedure. Additionally, 76% of participants who received placebo reported that they would prefer to use LA during their IUI. No statistically significant difference was detected in pregnancy rates between the 2 groups: 19.4% with LA vs 9.7% with placebo (P = .47). CONCLUSION: LA reduced anxiety and was preferred by women during IUI fertility treatments.

Fertility Preservation for Transgender Individuals: A Review.

Transgender individuals represent a small, albeit growing, patient population that is encountered more frequently in clinical care due to improved insurance coverage and increasing awareness. Gender-affirming treatments, including both gender-affirming hormone therapy and gender-affirming surgery, pose significant risks to fertility potential and outcomes, ranging from potentially impaired fertility rates to full elimination of reproductive potential depending on the type of treatment pursued. However, there are relatively limited data specific to fertility preservation for transgender individuals. Current approaches to treatment are extrapolated from options for fertility preservation after oncologic diagnoses. In this review, we aim to summarize current clinical approaches, fertility preservation options, and patient experiences in fertility preservation for transgender individuals. Several forms of fertility preservation options are available depending on the pubertal status of a transgender individual. Despite the multiple options for fertility preservation, major barriers exist to patient care and there are reports of mixed patient experiences. Further awareness of this clinical situation and understanding of these processes will allow for comprehensive and specialized care for transgender individuals who may otherwise miss opportunities for adequate counseling or treatment options regarding fertility preservation.

Current and Future Medical Therapies for Adenomyosis.

There is no approved medical therapy for adenomyosis and limited evidence to guide treatments in part due to the complexity of nonhistologic diagnosis and the prevalence of concomitant gynecologic conditions. Most available evidence focuses on the treatment of heavy menstrual bleeding, painful menses, and pelvic pain. Data evaluating fertility outcomes, sexual function, and quality of life following treatment are lacking. Additionally, there is no disease-specific measure of quality of life for adenomyosis. The levonorgestrel-releasing intrauterine system appears to be the most effective first-line therapy based on efficacy compared with oral agents, maintenance of steady-state hormonal levels, and contraceptive benefit. In areas where it is marketed, the progestin dienogest appears superior to combined oral contraceptives. Long-acting gonadotropin-releasing hormone agonists are effective and should be considered second-line therapy but are limited by hypogonadal effects. Additional data regarding oral gonadotropin-releasing hormone antagonists are required. While aromatase inhibitors demonstrate improvement in heavy menstrual bleeding and pelvic pain, further research is needed to determine their role in the management of adenomyosis. Progesterone receptor modulators may have a role for this disease if released again to market with appropriate safety parameters. Finally, modulation of prolactin and/or oxytocin may provide novel nonsteroidal treatment options.

Fresh versus frozen embryo transfer has no effect on childhood weight.

OBJECTIVE: To evaluate the effect of frozen, compared with fresh, embryo transfer on neonatal and pediatric weight and weight gain trajectory. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): Women who underwent fresh or frozen embryo transfer at the Mayo Clinic from 2010 to 2014. All included embryo transfers resulted in a singleton live birth. Children were followed from birth to at least 18 months. When possible, growth was evaluated to 5 years of age. INTERVENTIONS(S): Fresh versus frozen embryo transfer. MAIN OUTCOME MEASURE(S): Propensity score methodology was used to balance the two groups by maternal characteristics and gestational age before evaluating outcomes. Each infant and childhood growth measurement was compared between the two groups. RESULT(S): Of the 136 women, 87 underwent a fresh embryo transfer and 49 underwent a frozen embryo transfer. Birth length and head circumference were significantly different in infants delivered after fresh versus frozen embryo transfer. There was a statistically significant difference in birth weight between infants born after fresh versus frozen embryo transfer. However, this difference did not persist when adjusted for gestational age, sex, and maternal factors. Childhood growth measurements including age- and sex-specific weight, and body mass index percentiles were not significantly different between groups. CONCLUSION(S): This study confirmed an association of frozen embryo transfer and increased birth weight, but the association did not persist when controlling for confounding maternal factors. We found no effect of fresh versus frozen embryo transfer on neonatal weight and childhood weight gain trajectory.

Tubal Ligation and Age at Natural Menopause.

OBJECTIVE: To determine the effect of tubal ligation on age at natural menopause, as a marker of long-term ovarian function. METHODS: Three preexisting population-based cohorts were included in this cross-sectional study. Data from each cohort was analyzed separately. The cohorts were restricted to women who never smoked and had reached natural menopause, without prior hysterectomy or oophorectomy. The following variables were collected: race, age at menarche, age at menopause, history of hysterectomy or oophorectomy, gravidity and parity, tobacco use, and ever use of hormonal contraception. The type of tubal ligation and age at tubal ligation were manually abstracted in cohort 1. For cohorts 2 and 3, history of tubal ligation was obtained from an institutional form, completed by patient report. The primary outcome, age at natural menopause, was compared between the two groups (those with and without a history of tubal ligation). RESULTS: Inclusion criteria was met by 555 women from cohort 1, 1,816 women from cohort 2, and 1,534 women from cohort 3. Baseline characteristics did not differ between cohorts. The percentage with tubal ligation was the same in all cohorts: 26.0%, 25.5%, and 25.0%, respectively. Women with a tubal ligation were more likely to have had at least one pregnancy and to have used hormonal contraception compared with women without a tubal ligation. There was no significant difference in age at natural menopause in women who underwent tubal ligation (50.1, 49.9, 50.0 years, respectively) compared with those who did not (50.7, 49.6, 50.0 years, respectively). The type of tubal ligation (cohort 1 only) had no effect on age at menopause. CONCLUSIONS: Tubal ligation did not affect age at natural menopause in the three large cohorts included in this study.

Leiomyoma with KAT6B-KANSL1 fusion: case report of a rapidly enlarging uterine mass in a postmenopausal woman.

BACKGROUND: Uterine leiomyomas, in contrast to sarcomas, tend to cease growth following menopause. In the setting of a rapidly enlarging uterine mass in a postmenopausal patient, clinical distinction of uterine leiomyoma from sarcoma is difficult and requires pathologic examination. CASE PRESENTATION: A 74-year-old woman presented with postmenopausal bleeding and acute blood loss requiring transfusion. She was found to have a rapidly enlarging uterine mass clinically suspicious for sarcoma. An abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. A 15.5 cm partially necrotic intramural mass was identified in the uterine corpus. The tumor was classified as a cellular leiomyoma. RNA sequencing identified a KAT6B-KANSL1 fusion that was confirmed by RT-PCR and Sanger sequencing. After 6 months of follow-up, the patient remains asymptomatic without evidence of disease. CONCLUSION: Prior studies of uterine leiomyomas have identified KAT6B (previously MORF) rearrangements in uterine leiomyomas, but this case is the first to identify a KAT6B-KANSL1 gene fusion in a uterine leiomyoma. While alterations of MED12 and HMGA2 are most common in uterine leiomyomas, a range of other genetic pathways have been described. Our case contributes to the evolving molecular landscape of uterine leiomyomas.

Implementation of the "Pregnancy Reasonably Excluded Guide" for Pregnancy Assessment: A Quality Initiative in Outpatient Gynecologic Surgery.

OBJECTIVE: Preoperative evaluation for pregnancy at our institution lacked standardization among individual health care providers and surgical services. This pilot project aimed to improve assessment for pregnancy before scheduled outpatient gynecologic surgical procedures. The Pregnancy Reasonably Excluded Guide incorporates historic, evidence-based criteria to facilitate identification of patients with a higher chance of pregnancy. METHODS: We retrospectively reviewed documentation for women undergoing gynecologic surgery at an outpatient surgical center from March through September 2016, before and after implementation of the pregnancy assessment protocol. After implementation, all eligible women (aged 18-50 years, not undergoing an emergent or pregnancy-related procedure) were assessed using the Pregnancy Reasonably Excluded Guide on arrival to the preoperative area. The Pregnancy Reasonably Excluded Guide checklist uses traditional and World Health Organization criteria for reasonable exclusion of pregnancy. Nursing staff reviewed responses with patients and pregnancy tests were completed as indicated by patient responses. Women who were unable to read, understand, or freely respond to the checklist received pregnancy testing. Pregnancy assessment, testing, results, and delays were recorded. This project was deemed exempt by the institutional review board. RESULTS: Two hundred thirteen eligible patients underwent outpatient gynecologic procedures during the study period (excluding a 2-week washout period at implementation). In the preimplementation period, 93 of 136 patients (68%) had pregnancy risk documented; 73 of 77 (95%) had documentation in the postimplementation period (P≤.01). Pregnancy tests were completed in 45 preimplementation patients (33%) and 16 postimplementation patients (21%) (P=.06). No pregnancy test results were positive. No procedural delays were associated with pregnancy assessment. CONCLUSION: Patient-centered assessment using the Pregnancy Reasonably Excluded Guide at presentation for outpatient gynecologic surgery significantly improved evaluation and documentation of pregnancy status before scheduled procedures without increasing the number of pregnancy tests or causing procedural delays.

KLF11 is an Epigenetic Mediator of DRD2/Dopaminergic Signaling in Endometriosis.

Endometriosis is a heterogeneous, recalcitrant disease that affects 10% of reproductive-age women. Resistance to conventional therapy critically raises the need for novel treatment options that target specific, dysregulated underlying molecular mechanisms. Dopamine receptor 2 (DRD2) has been shown to be associated with vascularity and fibrosis in endometriosis. Transcription factor KLF11 has been implicated in the pathogenesis of several human endocrine and reproductive tract diseases including endometriosis. KLF11 recruits epigenetic cofactors for regulation of target genes; dysregulation of critical target genes and associated signaling pathways results in diverse disease phenotypes. KLF11 regulates the expression of DRD2 in neurons. We investigated the regulation of DRD2 by KLF11 in the established eutopic and ectopic endometrial cell lines as well as in an animal model of endometriosis. KLF11 binding and activation of the DRD2 promoter was conserved across species. Promoter activation was reflected in correspondingly increased gene expression in an endometrial cell line and in primary endometriotic cells. In vivo, disease relevance was further evaluated in a surgically induced murine endometriotic model using Klf11-/- and wild-type mice. Consistent with loss of Klf11-mediated activation, lesions in Klf11-/- animals were associated with progressive fibrosis and decreased Drd2 expression. KLF11 binds specific epigenetic corepressors to repress several target genes. Activation of DRD2 by KLF11 could not be explained simply by loss of corepressor binding and is thus likely due to selective coactivator recruitment; identification of the precise pathway is the focus of ongoing investigation. Characterization of pharmacologically reversible epigenetic regulatory mechanisms has translational relevance in health and disease.