Association between pathological positivity rate of endometriosis, demographics, and concomitant gynecological conditions.

Background: To date, there remains a paucity of present-day literature on the topic of demographics and the biopsy-proven pathological positivity rate of endometriosis. Objective: The goal of this study was to explore the association between patients' demographics and other concomitant gynecological conditions or procedures and the pathological positivity rate of excision of endometriosis. Design: Retrospective cohort study. Methods: All women >18 years old who underwent laparoscopic surgery for endometriosis at a tertiary care hospital from October 2011 to October 2020. Women were classified into two groups: (1) Study group: women with >80% pathological positivity rate of endometriosis and (2) Control group: women with <80% pathological positivity rate. Results: A total of 401 women were included in the analysis. No difference was noted in the 80% pathological positivity rate based on body mass index [BMI; 68.7% in normal BMI versus 80% in underweight, versus 74.5% in overweight, and 74.1% in obese patients (p = 0.72)]. The percentage of patients reaching 80% pathological positivity of endometriosis was lower in women who had undergone previous laparoscopy for endometriosis compared to surgery naïve women (66.5% versus 76.5%, p = 0.03). In addition, a higher percentage of women who underwent concomitant hysterectomy (83.5% versus 68.8% for non-hysterectomy, p = 0.005) or bilateral oophorectomy (92.7% versus 70.0% for non-oophorectomy, p = 0.002) reached 80% pathological positivity. Women with an associated diagnosis of fibroids (79.7% versus 70.5%) or adenomyosis (76.4% versus 71.7%) were more likely to reach 80% pathological positivity compared to women without any other coexisting pathology; however, the observed differences were not statistically significant. After applying a log-binomial regression model, compared to White non-Hispanics, Hispanic patients were 30% less likely to reach 80% positivity (RR: 0.70, 95% CI: 0.49-1.02), although not statistically significant. Conclusion: No significant racial difference was found when comparing the rates of 80% pathological positivity of suspected endometriosis lesions among groups. Endometriosis pathological positivity rate was unaffected by patients' BMI and the presence of concomitant pathologies. In addition, prior laparoscopic surgery for endometriosis might cause tissue changes that result in a decrease in the observed pathological positivity rate of endometriosis lesions during subsequent surgeries.

Optimal antimüllerian hormone levels in oocyte donors: a national database analysis.

OBJECTIVE: To study the relationship between high antimüllerian hormone (AMH) levels in oocyte donors and embryo development and pregnancy outcomes among donor oocyte recipients. DESIGN: Retrospective cohort study. SETTING: Donor Egg Bank Database. PATIENTS: Patients undergoing in vitro fertilization using vitrified donor oocytes from 35 in vitro fertilization centers in the United States between 2013 and 2021. For each recipient, the first oocyte lot that was received with a planned insemination and embryo transfer (ET) was included. INTERVENTION: Oocyte donor-recipient cycles. MAIN OUTCOME MEASURES: Ongoing pregnancy rate (OPR) per ET. RESULTS: A total of 3,871 donor oocyte-recipient thaw cycles were analyzed. On the basis of donor AMH serum concentration, cycles were stratified into the high AMH group (AMH ≥5 ng/mL; n = 1,821) and the referent group (AMH <5 ng/mL; n = 2,050). Generalized estimating equation models were used to account for donors that contributed more than one lot of oocytes. The number of usable embryos per lot (median [interquartile range]) was significantly increased in the high AMH group (2 [2-4]) compared with the referent group (2 [1-3]) (relative risk [RR] 1.06; confidence interval [CI] 1.01-1.12). Among recipients with a planned ET, there was no difference in OPR between the high AMH group (45.4%) and the referent group (43.5%) (RR 1.04; 95% CI 0.94-1.15). Among preimplantation genetic testing for aneuploidy cycles, the embryo euploidy rate per biopsy was similar at 66.7% (50%-100%) in both groups (RR 1.04; CI 0.92-1.17). The OPR per euploid ET among patients who used preimplantation genetic testing for aneuploidy was also comparable, at 52% in the high AMH group and 54.1% in the referent group (RR 0.95; CI 0.74-1.23). CONCLUSION: This large national database study observed that there was no association between a high level of AMH (≥5 ng/mL) in oocyte donors and an OPR in the recipient after the first ET. On the basis of these findings, recipients and physicians can be reassured that oocyte donors with a high AMH level can be expected to produce outcomes that are at least as good as donors with an AMH level (<5 ng/mL).

Live birth per embryo transfer with next generation sequencing preimplantation genetic testing: an analysis of 26,107 cycles.

The technique and platform used for preimplantation genetic testing for aneuploidy (PGT-A) have undergone significant changes over time. The contemporary technique utilizes trophectoderm biopsy followed by next-generation sequencing (NGS). The goal of this study was to explore the role of PGT-A using NGS technique exclusively in contemporary in vitro fertilization (IVF) practice. For this, we performed a retrospective analysis of a large dataset collected from the Shady Grove Fertility (SGF) multicentre practice. All autologous IVF cycles which were followed by at least one single embryo transfer (ET) (fresh and/or frozen) between January 2017 to July 2020, were included. Our study group included patients who had PGT-A and the control group included patients who did not proceed with PGT-A. The primary outcome was the live birth rate (LBR) per transfer. All age-adjusted LBR was higher in the PGT-A group than the non-PGT-A group (48.9% vs. 42.7%, p < 0.001), except in women <35 years old among single embryo frozen ETs. Similarly, LBR in the PGT-A group was higher in all ages except in women <35 years old (48.7% vs. 41.7%, p < 0.001) when all single embryos fresh and frozen ETs were included. In patients of decreased ovarian reserve, transfer of euploid embryo was associated with higher LBR (46.7% vs. 26.7%, p < 0.001) whereas miscarriages were lower in patients with unexplained infertility (9.3% vs. 11.3%, p = 0.007 and endometriosis (8.9% vs. 11.6%, p < 0.001) following euploid embryo transfer. To conclude, the transfer of euploid embryos tested via NGS PGT-A was associated with improved LBR per transfer in women ≥35 years old.

The effect of trophectoderm biopsy for preimplantation genetic testing on fetal birth weight and preterm delivery.

BACKGROUND: Preimplantation genetic testing for aneuploidy (PGT-A) is used as part of in-vitro-fertilization (IVF) to assist in selection of euploid embryos, which involves performing trophectoderm biopsy. The effect of possible trauma caused by biopsy and the implication on pregnancy is unknown. Hence, the objective of the study was to determine if embryo biopsy for PGT-A affects birth weight or preterm birth rate. METHODS: Using National Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) data, we identified 6352 cycles which had single embryo transfer (SET) and a singleton live birth following frozen embryo transfer (FET) between 2014 and 2015. RESULTS: From the initial cohort of 25,121 fresh stimulation cycles, 6352 cycles were included who had a singleton live birth following FET. A total of 3482 (54.8%) had PGT-A confirmed euploid embryos and 2870 (45.2%) had embryos selected based on morphology for transfer. No difference in birthweight (g) was noted when FET was performed using PGT-A confirmed euploid embryos as compared to non-tested morphologically selected embryos (3370.7 vs. 3354.5, adjusted regression coefficient 11.4; 95% CI: -12.6; 35.3). As compared to morphologically selected embryos, performance of PGT-A did not increase the risk of small for gestation age (SGA) (3.9% vs. 4.1%, OR: 1.13; 95% CI: 0.86-1.50), low birth weight (LBW) (<2500 g but ≥1500 g) (5.8% vs. 5.5%, OR: 0.90; 95% CI: 0.66-1.21), or very low birthweight (<1500 g) (1.3% vs. 1.0%, OR: 0.44; 95% CI: 0.44 (0.18-1.10). There was no increased risk of preterm birth (PTB) associated with pregnancy resulting from PGT-A embryos vs. non PGT-A embryos (15.8% vs. 16.4%, OR: 0.94; 95% CI: 0.81-1.09). CONCLUSIONS: In our study, trophectoderm biopsy for PGT-A did not increase the risk of SGA, LBW or PTB in IVF pregnancies.

The role of preimplantation genetic testing for aneuploidy in a good prognosis IVF population across different age groups.

Preimplantation genetic testing for aneuploidy is associated with increased pregnancy success and reduced miscarriage in women 35 years and older when embryos are available for transfer. In this retrospective cohort study our objective was to evaluate if this holds true in good prognosis patients and across all age groups. Data were obtained from the Society for Assisted Reproductive Technology between 2014-2015. We included only the first single frozen embryo transfer where indication for corresponding 'stimulation/freeze-all cycle' was for reducing risk of ovarian hyperstimulation syndrome and performance of PGT-A for selecting euploid embryos. Our main outcomes were live birth and miscarriage rates. Among <35 age group, no difference in LBR was observed between cycles who underwent single embryo FET using non-PGT-A tested vs. tested embryos (51.7% vs. 50.9%, aOR 1.03, 95% CI 0.87-1.21). Additionally, the miscarriage rates (8.7% vs. 8.8%, aOR 0.97, 95% CI 0.72-1.30) were not different. Among 35-37 years old, no difference was observed between non-PGT-A tested and tested groups in LBR (50.4% vs. 54.7%, aOR 1.26, 95% CI 0.96-1.67) or miscarriage rates (8.3% vs. 10%; aOR 1.11, 95% CI 0.68-1.82). Similarly, among > 37 year old, no difference was observed between non-PGT-A tested and tested groups in LBR (48.1% vs. 53.2%, aOR 1.27, 95% CI 0.8-2.02) and miscarriage rates (6.2% vs. 8.5%, aOR1.34, 95% CI 0.52-3.43). To conclude, PGT-A tested embryos did not improve LBR and miscarriage rates in a good prognosis IVF population across all age groups.Abbreviations: PGT-A: preimplantation genetic testing for aneuploidy; FET: frozen embryo transfer; LBR: live birth rate; OHSS: ovarian hyperstimulation syndrome; SART: society for assisted reproductive technology.

Use of low dose vaginal misoprostol in office hysteroscopy: a pre-post interventional study.

A pre-post interventional study of patients undergoing office hysteroscopy alone and in combination with endometrial biopsy was performed during October 2015-March 2018 to evaluate the effect of low dose vaginal misoprostol on patient's pain. Pain scores were assessed using the visual analog scale at the completion of the procedure. There were 646 patients included in the study. Of these, 462 had office hysteroscopy alone; 206 (44.6%) received 50 mcg of vaginal misoprostol the night prior to the procedure and the remaining 256 (55.4%) patients had no cervical ripening. The reported pain score following hysteroscopy was significantly lower among patients who received misoprostol [4(0-10) vs. 5(0-10); p=.001]. Most patients (78.2%) did not report any misoprostol related side effects. Of the 184 patients who underwent a combination of office hysteroscopy and endometrial biopsy, 97 (52.7%) received pre-procedure vaginal misoprostol while 87 (47.3%) did not. Post procedure pain was independent of pre-treatment with vaginal misoprostol (6.3 ± 2.7 vs. 6.6 ± 2.7; p = .54).Impact statementWhat is already known on this subject? Office hysteroscopy and endometrial biopsy is increasingly performed for evaluation of various gynaecologic conditions, however, patients' perceived pain at the time of procedure may lead to incomplete procedures. Various doses of misoprostol have been tested to reduce patients' pain, however none lower than 200 mcg vaginally, and at these doses, side effects are reported.What the results of this study add? To date, there is a scarcity of published data on the use of low dose misoprostol (50 mcg) in gynaecologic procedures. Our study found that the use of low dose vaginal misoprostol prior to office hysteroscopy is associated with lower reported pain and tenaculum utilisation during the procedure. However, vaginal misoprostol prior to successive office hysteroscopy and endometrial biopsy failed to decrease the reported pain, and the overall pain score was higher than hysteroscopy alone.What the implications are of these findings for clinical practice and/or further research? The use of low dose vaginal misoprostol (50 mcg) the evening prior to office hysteroscopy is associated with lower reported pain and tenaculum utilisation and is not associated with significant side effects. Therefore, 50 mcg of misoprostol could be used in clinical practice as a method to reduce patients' reported pain during office hysteroscopy.

Improving the fellowship interview experience for reproductive endocrinology and infertility candidates: a survey.

OBJECTIVE: To collect data on the current reproductive endocrinology and infertility (REI) fellowship interview process so that it may be improved in the future. DESIGN: Web-based cross-sectional survey. In addition, fellowship program directors and coordinators were contacted by e-mail. SETTING: Survey data were collected after completion of the 2018 REI fellowship interview season. PATIENTS: Not applicable. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Number of days used for interviews, missed opportunities to interview, frequency of travel to the same city, average money spent, recommendations for how the interview process could be improved. RESULTS: There were 44 survey respondents. The mean number of interviews attended was 12.6 (range, 1-22). On average 13.4 (0-30) days off work were used to interview. About 68.1% (n = 30) missed an opportunity to interview at a program they were interested in. The most common reasons were the interview date was the same day as another interview, could not attend due to geographic location, and cost was too high. About 72% (n = 31) traveled to the same city more than once for an interview. The average cost per interview was $478 (range, $200-$1,000) and average cost per interview season was $5,660 (range, $900-$15,000). Fellowship program data were available from 43 of 48 programs contacted. The number of dates that had conflicting interviews scheduled were 26. CONCLUSIONS: These data highlight the need to coordinate the REI fellowship recruitment process between programs to reduce conflicting interview dates and mitigate costs to applicants. Based on these results, a concrete action plan is presented.

High-dose intensity-modulated chemoradiotherapy in vulvar squamous cell carcinoma: Outcome and toxicity.

INTRODUCTION: To evaluate clinical outcomes, pattern of failure, and toxicity after high-dose intensity-modulated radiation therapy (IMRT) for advanced vulvar cancer. METHODS: In this IRB approved retrospective study, the charts of women with histologically confirmed, non-metastatic vulvar cancer consecutively treated at our institution from 2012 to 2018 were reviewed to identify patients that received high-dose IMRT with curative intent. The treatment compliance, toxicities, and patterns of failure were investigated. Actuarial local, regional and distant recurrence and survival were estimated using Kaplan-Meier method and compared using log rank test. RESULTS: Twenty-six patients were identified, 23 were unresectable, and 3 refused surgery. Fifteen patients (58%) had inguinal node metastases; 10(38%) had pelvic node metastases. Elective surgical staging of groins was performed in 9-patients. Median tumor dose was 65.4Gy. Concurrent platinum-based chemotherapy was administered in 22(84.6%) patients. Complete response (CR) was achieved in 21/26 (80.7%) patients. Five patients had persistent disease following treatment and one sustained recurrence 5-months following radiotherapy. All persistent or recurrent disease occurred inside the irradiated volume. Median follow-up was 19 months (3-52 months). Actuarial 1-year local, regional and distant controls were 72.4%, 85.4%, and 86%, respectively. One and 2-year overall survivals were 91% and 62%, respectively. Complete response at 3-months was a strong predictor for overall survival (1-yr OS 73% vs 27%, HR 7.1 (95% CI 1.2-44); p = 0.01). Lymph node metastases adversely affected overall survival (2-yr OS 49% vs. 83%, p = 0.09). Grade 3-4 late urinary and soft-tissue toxicity was seen in 5 patients. Tumor doses >66 Gy (p = 0.03) and prior pelvic radiotherapy (p = 0.002) predicted grade 3-4 toxicity. CONCLUSION: High-dose IMRT for vulvar cancer achieves high rates of local control with acceptable dose dependent long-term toxicity.

Duration of ovarian stimulation is predictive of in-vitro fertilization outcomes.

BACKGROUND: The aim of this study is to evaluate the effect of ovarian stimulation duration on oocyte/embryo development and pregnancy outcome in an in-vitro fertilization cycle (IVF). METHODS: Retrospective cohort study performed at University of South Florida reproductive center between January 2011 and December 2016. A total of 690 sub-fertile women who underwent autologous IVF cycle were included for analysis. The outcomes were compared between patients undergoing ovarian stimulation for ≤8 days and >8 days. Data was further categorized into accelerated stimulation group (≤8 days), normal duration stimulation group (9-12 days), and delayed stimulation group (≥13 days). Primary outcome was live birth rate. Secondary outcomes include oocyte development and embryo characteristics. RESULTS: A total of 69 (10%) and 621 (90%) patients underwent ovarian stimulation for ≤8 and >8 days, respectively. Ovarian stimulation for >8 days had 2.1 times higher odds of live birth (35.7% vs. 20.8%, 95% CI: 1.02-4.44, P=0.04), and 1.9-fold-higher odds of clinical pregnancy (42.6% vs. 27.1%, 95% CI: 1.03-3.87, P=0.05). Number of matured oocytes (P=0.002), normally fertilized embryos (P=0.008), 6-8 cell stage embryos (P=0.003) and blastocysts (P=0.014) were higher in cycles with stimulation >8 days. Further analysis showed that live birth rate was highest in the group of patients with normal duration stimulation group (37.3%) compared to patients with delayed stimulation (25%) and accelerated stimulation (20.8%). CONCLUSIONS: In an IVF cycle, optimal ovarian response and pregnancy outcome is associated with stimulation duration of at least 9 days. Both accelerated and delayed follicular recruitment are indicators for suboptimal response.

Laparoscopic Entry Technique Using a Veress Needle Insertion with and without Concomitant CO2 Insufflation: A Randomized Controlled Trial.

STUDY OBJECTIVE: To compare the time and number of attempts needed for successful Veress needle entry during laparoscopic surgery using concomitant versus subsequent CO2 insufflation approaches. DESIGN: Randomized controlled trial. SETTING: University teaching hospital. PATIENTS: One hundred consecutive patients scheduled for laparoscopic surgery by 2 high-volume laparoscopic surgeons were screened and randomized, and 95 of these were included in the final analysis. Ninety (45 in each group) was the precalculated priori number of patients needed to detect a 50% difference in the time (seconds) to obtain adequate insufflation with 90% power and alpha of 5%. INTERVENTIONS: Patients were randomized to either Veress needle entry with concomitant (Con) or subsequent (Sub) CO2 insufflation. MEASUREMENTS AND MAIN RESULTS: Forty-six patients were randomized to the Con group and 49 to the Sub group. Patient age, body mass index, prior surgical history, presence of adhesions, and type of procedure performed were similar between both groups. The median time required for adequate insufflation in the Con group was 103.5 seconds (Q1-Q3, 80.0-130.0) compared with 113.0 seconds (Q1-Q3, 102.0-144.0) in Sub group (p = .16). Approximately 89% (95% confidence interval, 80.1%-98.1%) of patients in Con group achieved successful entry in the first attempt compared with only 67% (95% confidence interval, 54.2%-80.0%) in Sub group (p = .01). The incidence of preperitoneal insufflation and failed entry was comparable between the 2 groups. No patient developed solid organ, visceral, or vascular injuries; gas embolism; or case conversion to laparotomy in relation to the Veress needle entry technique. CONCLUSION: Veress needle entry with concomitant CO2 insufflation was associated with a higher rate of successful entry during the first attempt of Veress needle insertion. The total time required for insufflation and rates of complications between the 2 techniques were similar.

Does supraphysiologic estradiol level during IVF have any effect on oocyte/embryo quality? A sibling embryo cohort analysis of fresh and subsequent frozen embryo transfer.

BACKGROUND: The aim of this paper was to determine the effect of supraphysiologic serum estradiol (E2) level on oocyte and embryo development during IVF cycles. METHODS: This is a retrospective data analysis of all autologous IVF cycles where fresh embryo transfer was performed followed by subsequent frozen embryo transfer (FET) using cryopreserved sibling embryos. Primary outcome was live birth rate (LBR). Secondary outcomes were oocyte and embryo characteristics. RESULTS: Patients with high E2 (defined as serum peak E2>50th percentile [3727 pg/mL]) recorded prior to HCG trigger had significantly higher number of matured oocytes, zygotes exhibiting two pronuclei, cleavage stage embryos, blastocysts, and vitrified embryos. Following FET, LBR was higher among patients with high than normal E2 (55% vs. 37%, odds ratio [OR] 2.02; 95% confidence interval [CI] 1.05-3.88, P=0.03). Paired analysis revealed that the likelihood of achieving live birth was higher with FET compared to fresh transfer both among high E2 (54.7% vs. 26.7%; OR 3.3; 95% CI: 1.67-6.58, P<0.001) and normal E2 (37.3% vs. 18.7%; OR 2.6; 95% CI 1.23-5.47, P=0.01) patients. CONCLUSIONS: Supraphysiologic serum E2 level prior to HCG trigger does not appear to have negative impact on oocyte and embryo quality.

The Association Between Hospital Surgical Volume and the Uptake of Minimally Invasive Surgical Approach and Outpatient Setting for Hysterectomy.

BACKGROUND: There are large variations in the use of minimally invasive surgery (MIS), and outpatient hysterectomy (OP) among Medicare patients according to hospital surgical volume and geographical distribution. OBJECTIVE: To explore the changing trend in OP and MIS hysterectomy in the United States. STUDY DESIGN: We used all Medicare fee-for-service claims data for 2012 and 2014 to determine the incidence of OP and MIS hysterectomy according to hospital surgical volume and geographical distribution. MIS included both laparoscopy and robotic surgery. OP procedures included only same-day discharge hysterectomies. RESULTS: A total of 55,562 and 53,054 hysterectomies were performed in the years 2012 and 2014, respectively. OP rate in 2014 in high-volume centers (16,828 [47.1%]) exceeded low-volume centers (136 [16%]) by 31.1% (p<0.001). Time trends between 2014 and 2012 show that a rise in OP rate was 17.7% and 7% for high- and low-volume hospitals (p<0.001), respectively. High-volume hospitals showed an increase of 3.1% (p=0.003) in MIS hysterectomy rate in 2014 (69%) as compared to 2012 (65.9%). There was no change in MIS rate among low-volume hospitals. CONCLUSION: In the Medicare population, the rate of OP and MIS hysterectomy for high-volume centers is significantly different form low-volume centers. Over the years, outpatient hysterectomy is being practiced widely but an increase in MIS rate is limited to high-volume centers.

Comparison of patients' reported pain following office hysteroscopy with and without endometrial biopsy: a prospective study.

BACKGROUND: When performing office based gynecologic procedures, one must provide patients with appropriate counseling on anticipated pain prior to the procedure. The goal of this study was to investigate whether there is any difference in patients' pain perception when office hysteroscopy (OH) is performed alone compared with when it is performed with endometrial biopsy (EMB) for various gynecologic indications. METHODS: A prospective study was performed of patients undergoing office hysteroscopy alone or in combination with endometrial biopsy between October 2015 and February 2017. Procedures were performed using standard gynecologic techniques. Patients described their post procedural pain using the visual analogue scale from 0-10 and data was compared between groups using SPSS version 24. RESULTS: Group 1 had OH alone (N.=243) and group 2 had OH combined with EMB (N.=80). Patients who underwent both procedures had significantly higher reported median (range) pain scores than those undergoing OH alone (7 [0-10]. vs. 5 [0-10], P=0.004). The patients in-group 2 were significantly older than those in group 1 (42.6±7.6 vs. 36.6±6.5, P<0.0001). The patients in group 2 had higher gravidity (2 vs. 1, P=0.04), were more likely to have a tenaculum used during the procedure (36.3% vs. 21.4%, P=0.01) and were more likely to be diagnosed with uterine fibroids (73% vs. 31%, P<0.0001). After controlling for patients age, gravidity, tenaculum use and diagnosis of fibroids using a multivariable regression model, patients undergoing OH with EMB had a 0.51-unit pain score greater than those that had OH alone; however, this difference was not statistically significant (95% CI: -0.32, 1.33 P=0.23). CONCLUSIONS: Patients undergoing both OH and EMB appear to report similar pain scores as those undergoing OH alone after controlling for confounding variables. The presence of fibroids was found to contribute to higher reported pain in the patients having OH in combination with EMB.

Electromechanical morcellators' black-box warning: tribulations, expectations and solutions.

Laparoscopic minimally invasive gynecologic surgery (MIGS) for benign conditions results in decreased morbidity, and faster recovery, compared with laparotomy. Tissue fragmentation by electromechanical morcellation permits the removal of large specimens through small laparoscopic incisions. Since the US Food and Drug Administration (FDA) published its safety warning about the risk of power morcellators spreading cancer during fibroid surgery in 2014, power morcellation has become rare. MIGS for fibroids and other large tissue specimens has declined. Current alternatives to preserve MIGS for large specimens include intact specimen retrieval through periumbilical mini-laparotomy incisions, vaginal removal, or in-bag manual morcellation, have limitations. Innovative intracorporeal containment tissue extraction system (ICTES) prototypes capable of enclosing, manipulating, morcellating, and removing tissue, while avoiding intraperitoneal leakage and maintaining pneumoperitoneum, are being evaluated. There is ample opportunity to optimize efficacy of ICTES by scientific study in clinical trials.

Optimal Order of Successive Office Hysteroscopy and Endometrial Biopsy for the Evaluation of Abnormal Uterine Bleeding: A Randomized Controlled Trial.

OBJECTIVE: To estimate the optimal order of office hysteroscopy and endometrial biopsy when performed successively for evaluation of abnormal uterine bleeding. METHODS: Patients undergoing successive office hysteroscopy and endometrial biopsy were included in a single-blind, prospective, randomized trial. The primary outcome was to evaluate the effect of order of procedures on patients' pain score. Prespecified secondary outcomes include procedure duration, hysteroscopic visualization of the uterine cavity, endometrial sample adequacy, and number of attempts at biopsy. Pain scores were assessed using a visual analog scale from 0 to 10 and endometrial sample adequacy was determined from the histopathology report. Hysteroscopy images were recorded. Sample size of 34 per group (n=68) was determined to be adequate to detect a difference of 20% in visual analog scale score between hysteroscopy first (group A) and biopsy first (group B) at α of 0.05 and 80% power. RESULTS: Between October 2015 and January 2017, 78 women were randomized to group A (n=40) and group B (n=38). There was no difference in global pain perception [7 (0-10) vs 7 (0-10); P=.57, 95% CI 5.8-7.1]. Procedure duration [3 (1-9) vs 3 (2-10), P=.32, 95% CI 3.3-4.1] and endometrial sample adequacy (78.9% vs 75.7%, P=.74) were similar in both groups. Group A patients had better endometrial visualization (P<.001) than group B based on the hysteroscopic images: excellent (50% vs 7.9%), good (20% vs 34.2%), and fair (22.5% vs 44.7%); group B participants required fewer endometrial biopsy attempts at obtaining adequate tissue sample (two vs one; P<.001, 1.6-1.9). CONCLUSION: Patients having successive office hysteroscopy and endometrial biopsy for evaluation of abnormal uterine bleeding, the global pain perception, and time required are independent of the order in which procedures are performed. Performing hysteroscopy first ensures better image, whereas biopsy first yields adequate tissue sample with fewer attempts. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02472184.

Primary cutaneous adenoid cystic carcinoma.

Primary cutaneous adenoid cystic carcinoma is a rare, slow-growing malignancy first described by Boggio in 1975. This tumor characteristically consists of basophilic cells with a distinct adenoid or cribriform pattern in the mid to deep reticular dermis. Modified myoepithelial cells with prominent basement membrane material often surround true lumina. Definitive diagnosis relies on the characteristic histologic features and the exclusion of metastatic disease. We describe two patients who presented with painful papules of the scalp and were successfully treated with wide local excision.

How disruption of cell cycle regulating genes might predispose to sun-induced skin cancer.

The Ink4a/Arf (CDKN2a) locus encodes two proteins that regulate two of the most important tumor suppressor pathways represented by p53 and Rb.(1) Loss of either p16(INK4a) or p19(ARF) was recently reported to reduce the ability of mouse cells to repair UV-induced DNA damage and to induce a UV-mutator phenotype. This observation was independent of cell cycle effects incurred by either p16(INK4a) and/or p19(ARF) loss, as it was demonstrable in unirradiated cells using UV-treated DNA. We suggest that this might explain why germ line mutations of INK4a/ARF predispose mainly to malignant melanoma, a UV-induced skin cancer, and provides a molecular explanation for the link between melanomagenesis and impaired DNA repair. It also further demonstrates that regulation of cell cycle check points and DNA repair in response to genomic insults, such as ultraviolet irradiation are intricately interwoven processes. Differences in the apoptotic response to ultraviolet light between melanocytes and keratinocytes might explain why INK4a/ARF mutations predispose to malignant melanoma, but not to keratinocyte-derived skin cancers.