A DNA methylation atlas of normal human cell types.

DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes1. Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells2-5. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hypermethylated loci are rare and are enriched for CpG islands, Polycomb targets and CTCF binding sites, suggesting a new role in shaping cell-type-specific chromatin looping. The atlas provides an essential resource for study of gene regulation and disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.

The impact of age and parity on the experience of relief and regret in women who have undergone hysterectomy for benign disease: A cross sectional survey.

OBJECTIVE: To investigate the impact of age and parity on the experience on relief and regret following elective hysterectomy for benign disease, and to explore the factors that impact relief and regret. DESIGN: Retrospective cross-sectional survey of a cohort. SETTING: Single-centre tertiary hospital in Melbourne, Australia. POPULATION: Patients who underwent elective hysterectomy for benign indications from 01 January 2008 - 31 July 2015 (inclusive) with age <51 years at time of admission. METHODS: Eligible participants completed a retrospective survey regarding their experience of relief and regret following hysterectomy. MAIN OUTCOME MEASURES: Regret was defined as a positive response to "Do you regret the decision to have a hysterectomy?". Relief was defined as responding "agree/strongly agree" to "I feel relieved I had a hysterectomy". RESULTS: 268 of 1285 (21%) eligible participants completed the study questionnaire. Of these, 29 were aged <36 years at the time of hysterectomy. Seven percent (n=18/262) reported regretting having a hysterectomy and 88% (n=230/262) reported experiencing relief. We did not observe associations between age at hysterectomy and regret (aOR 0.93; 95% CI 0.85, 1.03), age at hysterectomy and relief (aOR 1.01; 95% CI 0.93, 1.09), nulliparity and regret (aOR 0.32; 95% CI 0.06, 1.59) or nulliparity and relief (aOR 2.37; 95% CI 0.75, 7.51). Desire for future pregnancy at the time of hysterectomy was more frequently reported in those who experienced regret vs no regret (46.7% vs 12.1%, OR: 6.33; 95% CI: 2.12, 18.90; p=0.001). CONCLUSIONS: Age and parity are not associated with relief nor regret following elective hysterectomy for benign disease.

Women's attitudes towards disclosure of genetic information in pregnancy with varying levels of penetrance.

BACKGROUND: Chromosomal-microarray-analysis (CMA) may reveal susceptibility-loci (SL) of varied penetrance for autism-spectrum-disorder (ASD) and other neurodevelopmental conditions. Attitudes of women/parents to disclosure of SL during pregnancy are understudied. METHODS: A multiple-choice questionnaire was distributed to postpartum women. Data were collected on women's interest to receive prenatal genetic information with various levels of penetrance. RESULTS: Women's (n = 941) disclosure choices were dependent on the magnitude of risk: approximately 70% supported disclosure of either full or 40% penetrance, 53% supported disclosure at a 20% risk threshold, and 40% supported disclosure at 10% or less. Although most women supported, rejected or were indecisive about disclosure consistently across all risk levels, nearly one-quarter (24%) varied their responses based on penetrance, and this was associated with religiosity, education, parity and concern about fetal health (p-values <0.04). Among those who varied their choices, the risk threshold was lower among secular women (20%) than among ultraorthodox women (40%). In a multivariable analysis, ultraorthodox women were much less likely to vary their choices on ASD disclosure compared with secular women (aOR = 0.37, p < 0.001). CONCLUSION: Women's attitudes toward disclosure are influenced by the level of risk and their individual characteristics. We therefore encourage engaging women/couples in disclosure decisions regarding uncertain and probabilistic results from prenatal genomic tests.

The effect of SARS-CoV-2 BNT162b2 vaccine on the symptoms of women with endometriosis.

PURPOSE: As the use of the messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) Coronavirus disease 2019 vaccine has grown, reports on menstrual changes have arisen. We aimed to examine menstrual bleeding patterns and endometriosis-associated symptoms after receiving the mRNA BNT162b2 SARS-CoV-2 vaccine in women with endometriosis, as compared to the control group. METHODS: This is a questionnaire-based cross-sectional study including a total of 174 women. The study group included 86 women with a confirmed diagnosis of endometriosis and the control group included 88 women with no diagnosis or suspected diagnosis of endometriosis. Each woman completed a questionnaire on menstrual bleeding patterns and endometriosis-associated symptoms before and after receiving two doses of the BNT162b2 vaccine. Primary outcomes were changes in amount or length of menstrual bleeding, rates of intermenstrual bleeding and worsening in dysmenorrhea in the endometriosis patient group, as compared to the control group. Secondary outcomes included changes in all endometriosis-associated symptoms. RESULTS: In our cohort, women with endometriosis were more likely to experience changes in bleeding patterns (women with endometriosis: 39.5%, control group: 31.0%, p = 0.02), and a significant worsening in endometriosis-associated symptoms with an almost 4.3-fold worsening in dysmenorrhea [95% CI 1.9-9.9, p < 0.01] and 5.5-fold odds for any worsening in symptoms in endometriosis patients, as compared to the control group [95% CI 2.7-11.1, p < 0.01]. CONCLUSION: In our cohort, endometriosis was shown to be a significant risk factor for worsening of menstrual symptoms, after receiving the SARS-CoV-2 BNT162b2 mRNA vaccine. Further research is needed to confirm these findings.

Effect of Magnetic Resonance Imaging on Acute Surgical Treatment of Pregnant Patients: A Single Institution Study.

BACKGROUND: Abdominal pathology in pregnant patients is a frequent challenge for emergency department physicians. Ultrasound is the imaging modality of choice but is inconclusive in approximately one-third of cases. Magnetic resonance imaging (MRI) is becoming increasingly available, even in acute settings. Multiple studies have defined the sensitivity and specificity of MRI in this population. OBJECTIVES: To evaluate the use of MRI findings in pregnant patients presenting with acute abdominal complaints to the emergency department. METHODS: This retrospective cohort study was conducted at a single institution. Data were collected on pregnant patients who underwent an MRI for acute abdominal complaints between 2010 and 2019 at a university center. Patient demographics, diagnosis at admission, ultrasound and MRI findings, and discharge diagnosis were recorded and evaluated. RESULTS: In total, 203 pregnant patients underwent an MRI for acute abdominal complaints during the study period. MRI was found without pathology in 138 cases (68%). In 65 cases (32%), the MRI showed findings that could explain the patient's clinical presentation. Patients presenting with long-standing abdominal pain (> 24 hours), fever, leukocytosis, or elevated C-reactive protein values were at a significantly increased risk of having an acute pathology. In 46 patients (22.6%), MRI findings changed the primary diagnosis and management while in 45 patients (22.1%) MRI findings improved characterization of the suspected pathology. CONCLUSIONS: MRI is helpful when clinical and sonographic findings are inconclusive, leading to changes in patient management in more than one-fifth of patients.

The BNT162b2 mRNA Covid-19 vaccine does not impair sperm parameters.

RESEARCH QUESTION: Does the BNT162b2 COVID-19 vaccine affect sperm parameters of patients with a normal or an abnormal semen analysis? DESIGN: Data were collected from male patients undergoing IVF treatment after completing vaccination between February 2021 and June 2021 (post-vaccine). For comparison, records of the same patients were reviewed before the vaccination (pre-vaccine) back to January 2017. Patients with azoospermia were excluded. Sperm parameters were compared between pre- and post-vaccine groups. Each patient served as self-control. RESULTS: Seventy-two patients were included in the study (median interquartile range [IQR] age 35.7 [33.0-43.0] years), of whom 57 had a normal semen analysis. The time between the first vaccine and the post-vaccine sperm analysis was 71.0 (40.5-104.8) days. The sperm parameters before and after the vaccination were as follows: sperm volume before 3.0 (2.0-4.0) and after 3.0 (1.6-3.9) ml, P = 0.02; sperm concentration before 26.5 (14.0-64.7) and after 31.0 (14.2-80.0) 106/ml, P = 0.35; and total motile sperm count before 33.7 (9.0-66.0) and after 29 (6.0-97.5)106, P = 0.96. Sub-group analyses were conducted for patients with male infertility and patients with a normal semen analysis. Neither of the sub-groups showed significant changes after vaccination. CONCLUSION: Sperm parameters showed no significant changes after vaccination among men with a normal and abnormal semen analysis. Therefore, the BNT162b2 vaccine does not seem to affect sperm parameters. The preliminary results are reassuring for the entire global population, currently undergoing intense vaccination campaigns against COVID-19.

Long-term pituitary down-regulation pretreatment for endometriosis - chronicles of guidelines and recommendations.

It was suggested in the 1980s that long-term pituitary down-regulation by a gonadotrophin-releasing hormone agonist, termed the ultra-long protocol, inducing a hypo-oestrogenic state, might improve reproductive outcomes in women with endometriosis. Subsequently, international guidelines strongly supported the long-term pituitary down-regulation protocol in women with endometriosis based on a Cochrane review from 2006. The recently published European Society for Human Reproduction and Embryology guideline, based on the updated Cochrane review from 2019 and newer evidence, has reversed this recommendation. This paper explores the past and current evidence that led to these recommendations and calls for a consideration of refinement of the international guidelines to include additional factors and evaluate whether a paradigm shift is needed in the approach to endometriosis-related infertility. We believe that this can optimize evidence-based patient-centred care and benefit women worldwide and improve the design of future studies.

Sexual Function of Women With Deep Endometriosis Before and After Surgery: A Prospective Study.

BACKGROUND: Deep endometriosis (DE) may significantly affect women's quality of life. Limited data exists on the effect of surgery on the several domains of sexual function. AIM: To prospectively compare various domains of sexual function before and after laparoscopic surgery for DE. METHODS: A prospective observational cohort study in a tertiary university-affiliated referral center. Patients with suspected DE who were planned to undergo laparoscopic surgery completed the Female Sexual Function Index questionnaire before surgery. The same questionnaire was completed by the participants 6 weeks, 6 months, and 12 months after surgery. Rate of sexual dysfunction over time was compared using multilevel logistic regression. Summary scores were then compared at each time point to the corresponding score before surgery using multilevel linear regression. Multivariable analysis was performed of potential confounders. OUTCOMES: Change in desire, arousal, orgasm, lubrication, satisfaction and pain summary scores as well as in the full-scale score between before and after surgery. RESULTS: We followed 149 patients with surgically confirmed DE. Sexual dysfunction rate as per the full-scale score was 75.5% before surgery and remained over 60% to 12 months after. The full-scale sexual function score improved at 6 (change in score = 2.8 ± 9.5, P = .004) and 12 months (change in score = 2.1 ± 9.9, P = .03). None of the summary scores improved at 6 weeks. Desire score (P < .001), arousal score (P = .02), and pain score (P = .01) improved at 6 months. Desire score (P = .03) and pain score (P = .01) also improved at 12 months, as compared to before surgery. On multivariable multilevel analysis, scores before surgery significantly contributed to the scores after surgery (P < .001). CLINICAL TRANSLATION: While sexual function improved after surgery, dysfunction rate remained substantial. Proper preoperative counseling should address sexual function measures and clinical and research attention should be given to seek ways to further reduce sexual dysfunction. STRENGTHS AND LIMITATIONS: The main strengths of our study are the prospective design, the relatively long follow-up and the use of a detailed validated questionnaire allowing assessment of a large variety of clinically relevant sexual function domains and scores as well as a full-scale score. Among our limitations are the lower response rate at 12 months and the limited generalizability as this is a single center study. CONCLUSION: Sexual function is a major and often under reported domain of quality of life. Further research is needed to identify the specific populations who may improve, not change or experience deterioration in their sexual functioning after surgery. Dior UP, Reddington C, Cheng C, et al. Sexual Function of Women With Deep Endometriosis Before and After Surgery: A Prospective Study. J Sex Med 2022;19:280-289.

Postpartum women's attitudes to disclosure of adult-onset conditions in pregnancy.

BACKGROUND: Advanced prenatal genomic technologies can identify risks for adult-onset (AO) conditions in the fetus, challenging the traditional purpose of prenatal testing. Professional guidelines commonly support disclosure of high-penetrance AO actionable conditions, yet attitudes of women/parents to these findings and factors affecting their attitudes are understudied. METHODS: We explored 941 (77% response rate) postpartum women's attitudes towards receiving prenatal genetic information, and associations of sociodemographic, medical and psychological characteristics with their choices, focusing on AO conditions. RESULTS: Women largely support the disclosure of actionable AO findings (58.4%), in line with professional guidelines. A third of the women also supported the disclosure of non-actionable AO conditions. Stronger religious observance (p < 0.001) and higher psychological distress (p = 0.024) were associated with decreased interest in receiving actionable AO conditions, whereas higher concern for fetal health yielded increased interest (p = 0.032). Attitudes towards disclosure were strongly associated with women's perceived benefit of such information for their own, partner's, and future child's health. Termination of pregnancy based on such information received very little support. CONCLUSION: In-light of the demonstrated understanding of nuanced genetic information and the observed diversity in attitudes, a culturally competent opt-in/out policy could be considered. If full-disclosure is practiced, support should be provided to those expressing higher levels of distress.

Urinary Function after Surgery for Deep Endometriosis: A Prospective Study.

STUDY OBJECTIVE: To compare urinary function before and after surgery in patients undergoing laparoscopy for deep endometriosis and to measure the rate of postoperative deterioration in urinary function after surgery. DESIGN: Prospective questionnaire-based observational cohort study. SETTING: Tertiary university-affiliated hospital. PATIENTS: Included were 149 women who underwent surgery for deep endometriosis. INTERVENTIONS: Participants completed the international consultation on incontinence female lower urinary tract symptoms long-form questionnaire before surgery and 6 weeks, 6 months, and 12 months after surgery. MEASUREMENTS AND MAIN RESULTS: Bladder filling, voiding, and urinary incontinence summary scores were compared before and after surgery with mixed-effects linear regression analysis (correlated observations). Individual domains comprising the summary scores and their bother scores were also compared before and after surgery. Filling score at 6 weeks (3.7 ± 2.6), 6 months (3.2 ± 2.2), and 12 months (3.4 ± 2.2) improved from presurgery scores (4.2 ± 2.6) (p-value for the difference between before and after surgery: p <.001, p = .009, and p = .02 for 6 weeks, 6 months, and 12 months, respectively). No change was observed after surgery in bladder voiding score. Incontinence score improved at 6 weeks after surgery (presurgery and 6-week scores: 2.5 ± 3.3 and 1.6 ± 2.2, respectively, p <.001) but not thereafter. Patients with low preoperative summary scores had higher summary scores (worse function) after surgery, and patients with high preoperative scores had lower summary scores (improved function) after surgery. CONCLUSION: Urinary function improved after laparoscopy for deep endometriosis. Greatest improvement was found in patients with worse preoperative function, whereas postoperative deterioration in urinary function was found for patients with initially normal function. More research is needed to better identify the subpopulations in whom surgical intervention provides symptomatic benefit or deterioration.

Oophorectomy for ovarian torsion - should this be abandoned?

BACKGROUND: Management of ovarian torsion ranges from de-torsion to oophorectomy and is dependent on various factors. Oophorectomy can have significant implications for fertility and general health, thus requiring careful consideration. AIMS: We evaluate the management of ovarian torsion at a tertiary hospital over a ten-year period and identify the predictors of oophorectomy in ovarian torsion cases. MATERIALS AND METHODS: Inpatient notes of patients who underwent surgical management for acute ovarian torsion at a tertiary hospital in Victoria, Australia, were reviewed, from January 2008 to June 2018. We reported the incidence and predictors of oophorectomy and ovarian ischaemia and current practices in oophoropexy. RESULTS: Our analysis included 159 patients. The incidence of oophorectomy was 47%. After confounders were adjusted, increasing age was the only significant predictor for oophorectomy. The adjusted odds ratio of having an oophorectomy based on age alone was 1.10 for each year increase in age between the ages of 15 and 68 (P = 0.001, 95% confidence interval 1.04-1.16). Of those with oophorectomy, 57% had ischaemia confirmed histologically. There were no significant predictors for ischaemia. CONCLUSION: The incidence of oophorectomy in this audit is comparable to reported incidences in current literature. However, with increasing evidence to support ongoing ovarian function even in cases where ischaemia is histologically confirmed, this incidence could be lowered. Age was the only variable that was found to have a significant effect on the incidence of oophorectomy.

Central sensitisation in pelvic pain: A cohort study.

BACKGROUND: Central sensitisation (CS) leads to pain amplification and impacts on the management of pelvic pain (PP). Identification of CS in patients with PP may provide additional treatment pathways and improve patient outcomes. AIMS: The aims are to quantify the prevalence of questionnaire-predicted CS (QPCS) in patients presenting with PP and investigate associations between QPCS and clinical variables. MATERIALS AND METHODS: This was an observational, cross-sectional study. Subjects with PP completed a questionnaire comprising four validated tools: the Central Sensitisation Inventory (CSI) for QPCS, Pain Catastrophising Scale for Catastrophising Trait, Bladder Pain/Interstitial Cystitis Symptom Score for bladder pain syndrome (BPS) and the Rome IV criteria for irritable bowel syndrome (IBS). RESULTS: One hundred and eleven women were enrolled in the study; 74.8% (n = 83) had a CSI score of >40, indicating the presence of QPCS. Subjects with QPCS were more likely to screen positive for catastrophising trait (odds ratio (OR) 3.57, 95% CI 1.19-10.76, P = 0.02), BPS (OR 11.77, 95% CI 2.13-64.89, P = 0.005) and IBS (OR 2.6, 95% CI 1.05-6.43, P = 0.04). They were more likely to experience pain for more than two years (OR 4.98, 95% CI 1.94-12.82, P = 0.001) and other pain symptoms involving bladder (OR 9.87, 95% CI 2.52-38.67, P = 0.001), bowel (OR 3.13, 95% CI 1.31-7.48, P = 0.01), back (OR 4.17, 95% CI 1.66-10.51, P = 0.002) and vulva (OR 3.61, 95% CI 1.21-10.82, P = 0.02). They also had higher previous diagnoses of mental health disorder (OR 3.5, 95% CI 1.5-8.4, P = 0.005) or IBS (OR 8.9, 95% CI 1.6-49.1, P = 0.01). CONCLUSIONS: QPCS occurs frequently in patients with PP, and subjects with QPCS experience more prolonged and complex pain.

The role of social media in management of individuals with endometriosis: A cross-sectional study.

BACKGROUND: To better understand the potential role of social media (SM) as a self-management tool for individuals with endometriosis and to assess its current use by endometriosis patients. AIMS: The primary outcome was use of SM for health in patients with endometriosis. Secondary outcomes included preferred SM platforms for health information sharing and factors that influenced use, positive and negative experiences and reported impacts on health. MATERIALS AND METHODS: A single-centre, cross-sectional study performed within benign gynaecology units at a tertiary hospital in Melbourne, Australia. One hundred patients with a confirmed diagnosis of endometriosis participated. Individuals did not have to be users of SM. Data were collected through an electronic third-party survey tool (SurveyMonkey® ). Analysis methods included descriptive statistical analysis, frequency counts, as well as cross-tabulation to examine statistical association between variables. Free-text responses were qualitatively analysed using deductive-inductive semantic thematic analysis. RESULTS: Social media was used for health by 76% of patients with endometriosis in this study. SM users were younger, had pelvic pain for more than six months and reported higher rates of psychosocial impact and symptoms from endometriosis. Respondents reported overall positive impacts on psychological, social and cognitive health outcomes (76%) from SM use. CONCLUSION: In our cohort, a high number of people with endometriosis are using SM for health. These individuals are more likely to suffer both physical and psychosocial impacts from endometriosis. Hospitals and health organisations may consider support of the endometriosis community through SM.

Self-reported elevated pain levels: A coping strategy used by women undergoing medical abortion procedures.

PURPOSE: Epidural analgesia alleviates pain during normal labour but women who undergo medical abortion procedures using epidural analgesia continue to express high pain levels. To understand this we assessed if patients undergoing medical abortions, treated with epidural analgesia, use their pain for psychological benefits. METHODS: This study comprised 105 patients over 13 weeks of gestational age diagnosed with foetal abnormalities after selecting a medical abortion procedure using epidural analgesia. Three questionnaires were handed-out: 1) 'Need for Affect', assessed the motivation to react to emotions; 2) 'Pain-Levels' 3) PANA- 'Positive Affect' (PA), 'Negative Affect' (NA) assessed emotions pre-abortion and post-abortion. RESULTS: Patients with a strong Need for Affect and high Pain-Levels expressed a stronger PA post-abortion (b = .69, se = .11, ß = .68, p < .001, 95%CI [.48,.90]). Patients with a strong NA pre-abortion and high Pain-Levels expressed a higher NA post-abortion (b = .48, se = .11, ß = .53, p < .001, 95%CI [.26, .70]). CONCLUSION: Patients with a strong Need for Affect who express a strong PA pre-abortion intensify their pain to fulfill their Need for Affect, which then helps recovery. Patients with a strong NA pre-abortion and high Pain-Levels indicate a less favourable outcome.

Endometrial thickness following early miscarriage in IVF patients - is there a preferred management approach?

BACKGROUND: Endometrial thickness (ET) has previously been shown to positively correlate with implantation and clinical pregnancy rates. Pregnancies achieved using in-vitro fertilization (IVF) technique are prone to higher rates of early miscarriage. The aim of this study was to compare the effects of expectant management, medical treatment (Misoprostol) and dilation and curettage (D&C) for early miscarriage following IVF cycles on the subsequent cycle outcomes - endometrial thickness and reproductive outcomes. METHODS: A retrospective cohort study of women who underwent embryo transfer, conceived and had first trimester miscarriage with at least one subsequent embryo transfer. ET measurements during fresh or frozen-thawed IVF cycles were assessed for each patient. Comparisons of ET differences between the miscarriage and the subsequent cycles, as well as reproductive outcomes, were performed according to the initial miscarriage management approach. RESULTS: A total of 223 women were included in the study. Seventy-eight women were managed conservatively, 61 were treated with Misoprostol and 84 women underwent D&C. Management by D&C, compared to conservative management and Misoprostol treatment was associated with higher prevalence of a significant (> 2 mm) ET decrease (29.8%% vs. 14.1and 6.6%, respectively; p < .001) and was the only approach associated with a significant increase in the rates of ET under 7 and 8 mm in the following cycle (p = 0.006 and 0.035; respectively). Clinical pregnancy rates were significantly lower following D&C compared with conservative management and Misoprostol (16.7% vs. 38.5 and 27.9%, respectively; p = 0.008) as well as implantation rate (11.1% vs. 30.5.% and 17.7, respectively; p < 0.001). CONCLUSION: Our data suggest that D&C management of a miscarriage is associated with decreased ET and higher rates of thin endometrium in the subsequent IVF cycle, compared with conservative management and Misoprostol treatment. In addition, implantation and pregnancy rates were significantly lower after D&C.

Associations between body mass index and the surgical phenotype and location of endometriotic lesions.

RESEARCH QUESTION: Is there a relationship between body mass index (BMI) and endometriotic lesions, specifically surgical phenotype and lesion location? DESIGN: An observational retrospective cohort study at the Royal Women's Hospital, Melbourne, Australia, including 471 histologically confirmed endometriosis patients. Statistical analyses included multivariate logistic regression and multivariate modelling, correcting for multiple testing. Outcomes were the presence or absence of surgically classified lesion phenotypes, as per revised American Society for Reproductive Medicine criteria including superficial or deep, peritoneal or ovarian, and adhesions (Study I); and lesions at specific anatomical locations (including pelvic side wall, uterosacral ligament, pouch of Douglas, ovarian, uterovesical fold, bladder, and pararectal endometriosis) (Study II). RESULTS: In Study I, patients with higher BMI were more likely to have superficial peritoneal lesions (odds ratio [OR] 1.070, 95% confidence interval [CI] 1.004-1.144; P = 0.044), and less likely to have deep ovarian lesions (OR 0.928, 95% CI 0.864-0.993; P = 0.034). In Study II, patients with higher BMI were less likely to have uterovesical fold lesions (OR 0.927, 95% CI 0.867-0.985; P = 0.021) or anterior compartment lesions (OR 0.940, 95% CI 0.888-0.989; P = 0.023). After correcting for multiple testing, the relationship between BMI and lesion phenotypes did not persist (P > 0.01). CONCLUSIONS: This analysis does not conclusively support an influence of BMI on endometriotic lesion phenotype based on surgical classification or location. Further investigation of the physiological disturbances underlying BMI and the promotion of endometriotic lesion phenotypes and their location is warranted, but any effect is likely to be small.

New Diagnosis of Endometriosis is Less Common in Women over Age Forty Presenting with Pelvic Pain.

STUDY OBJECTIVE: To investigate the incidence of new diagnosis of endometriosis in women at or above the age of 40 who present with previously undiagnosed pelvic pain and no previous surgical or sonographic evidence of endometriosis to a tertiary care clinic specializing in pelvic pain and endometriosis. DESIGN: Retrospective cohort study (on the basis of the Strengthening the Reporting of Observational Studies in Epidemiology guidelines) of the incidence of laparoscopically proven endometriosis in women presenting with previously undiagnosed pelvic pain on the basis of age category (age <40 years or ≥40 years). Adjusted odds ratios and 95% confidence intervals were calculated using a multivariable logistic regression model. SETTING: Pelvic pain focused gynecology clinic at a tertiary care hospital. PATIENTS: Premenopausal women between 18 to 51 years who presented with pelvic pain and were booked for laparoscopy for the diagnosis and the possible treatment of endometriosis between the years 2012 to 2016. Patients who had had previous laparoscopy and those who had sonographic evidence of endometriosis were excluded from the study. INTERVENTIONS: Laparoscopic visual evaluation and treatment was carried out in all patients by specialized gynecologists focusing on endometriosis surgery. MEASUREMENTS AND MAIN RESULTS: Presence or absence of visualized endometriosis at laparoscopy. We evaluated 174 women who met the inclusion criteria. Endometriosis was diagnosed in 35% (19/55) of patients aged 40 years and above and in 67% (80/119) of patients below the age of 40 years. Odds ratio adjusted for body mass index and parity was 2.38 (1.09-5.00; p = .03). When assessed as a continuous curvilinear variable without division to age categories, age was significant even in the more comprehensive model including more potential confounders. Secondary outcome analysis demonstrated that deep infiltrating endometriosis was diagnosed in 5% (3/55) of the women at or above 40 years and in 8% (10/119) of women below 40 years (p = .76). In addition, a curvilinear relationship was found with age, and there was also a lower incidence of endometriosis of 50% (19/38) in the youngest cohort of women aged 18 to 25 years. CONCLUSION: The likelihood of a new diagnosis of endometriosis in women with pelvic pain, no previous laparoscopy and a normal sonogram in our referral center was lower in women aged 40 and above. Careful counseling and consideration of the risks and yield of surgery is recommended before performing a laparoscopy for investigation of pelvic pain in this age group.

Risk Factors and Outcomes of Conversion to Open Surgery in Benign Gynecologic Laparoscopies: A Case-Control Study.

STUDY OBJECTIVE: To describe cases of conversion from gynecologic laparoscopy to open surgery and to assess risk factors for conversion and conversion outcomes. DESIGN: A retrospective case-control study. SETTING: Tertiary referral hospital in Melbourne, Australia. PATIENTS: Eighty-five cases of conversion from laparoscopy to laparotomy and 170 controls matched by age, surgical date, and gynecologic unit from 2006 to 2017. INTERVENTIONS: Demographic, clinical, and surgical data were collected and compared between the study groups. Logistic regression was performed to identify preoperative and intraoperative risk factors for conversion. MEASUREMENTS AND MAIN RESULTS: Rate of conversion during the study period was 0.7%. The most common indication for conversion was unexpected surgical complexity (67% of cases), which included severe adhesive disease, specimen size, severe pathology, and inadequate views. Factors that were significantly associated with risk of conversion in multivariate analysis were previous pelvic inflammatory disease (adjusted odds ratio [aOR] 5.16; 95% confidence interval [CI], 1.35-19.71; p = .02), previous open surgery (aOR 3.62; 95% CI, 1.52-8.58; p <.01), history of endometriosis (aOR 2.96; 95% CI, 1.17-7.50; p = .02), and elevated body mass index (aOR 1.07; 95% CI, 1.01-1.13; p = .02). As compared with current surgery for endometriosis, odds of conversion were higher in surgeries for emergency indications (aOR 5.40; 95% CI, 1.53-18.98; p <.01), uterine pathologies (aOR 3.34; 95% CI, 1.10-10.12; p = .03), and adnexal pathologies (aOR 2.76; 95% CI, 1.19-6.40; p = .02). With the inclusion of intraoperative factors, surgical adhesions were also found to be associated with conversion (aOR 3.19; 95% CI, 1.30-7.85; p = .01). Most skilled laparoscopic surgeon level as defined by the Australasian Gynaecological Endoscopy and Surgery Society was not associated with conversion risk. Conversion to laparotomy was associated with a higher rate of intraoperative and postoperative complications and prolonged length of stay. CONCLUSION: Conversion to laparotomy is a rare but very important clinical outcome measure of laparoscopic surgery. Understanding the factors contributing to conversion and perioperative outcomes may help clinicians to identify and counsel patients before surgery and to reduce surgical morbidity.

Recurrent Tubal Ectopic Pregnancy Management and the Risk of a Third Ectopic Pregnancy.

STUDY OBJECTIVE: To evaluate the rate of a third ectopic pregnancy according to the modality of treatment of the second ectopic pregnancy. DESIGN: Retrospective cohort study. SETTING: University-affiliated tertiary medical center. PATIENTS: One hundred eleven women who had 2 ectopic pregnancies and a third consecutive pregnancy between 2003 and 2018. INTERVENTIONS: Surgery or medical treatment as required. MEASUREMENTS AND MAIN RESULTS: With regard to the modality of treatment of the second ectopic pregnancy, the patients were divided into 3 groups: expectant management, medical treatment with methotrexate, and laparoscopic salpingectomy. Univariate and multivariate analyses were conducted to assess the association of various parameters of the second ectopic pregnancy with the occurrence of a third ectopic pregnancy in the consecutive pregnancy. Twenty women (18.0%) were managed expectantly, 55 (49.6%) were treated with methotrexate, and 36 (32.4%) underwent surgery. Expectant management resulted in significantly higher rates of a third ectopic pregnancy compared with treatment with methotrexate or surgical intervention (50.0% vs 18.2% and 13.8%, respectively; p = .005). In the cases of 2 ipsilateral ectopic pregnancies, the interventional approach (medical or surgical treatment) resulted in lower recurrence rates compared with expectant management (25.7% vs 60.0%, respectively; p = .043). CONCLUSION: The risk of a third episode of an ectopic pregnancy after expectant management of a second ectopic pregnancy is extremely high. An interventional approach by treatment with methotrexate or salpingectomy is therefore preferred for recurrent ectopic pregnancy management, especially in ipsilateral recurrences.

Birth Weight and Maternal Body Size as Determinants of Blood Pressure at Age 17: Results from the Jerusalem Perinatal Study Cohort.

OBJECTIVES: To investigate the effect of birth weight (BW) and maternal pre-pregnancy BMI (mBMI) on blood pressure (BP) in adolescence. METHODS: A Population-based cohort of 11,729 births in Jerusalem during 1974-1976, with archival data on maternal and birth characteristics was performed. Measurements at age 17 were assessed and linear regression models were used to evaluate the associations of birth characteristics with BP outcomes. RESULTS: BW was inversely associated with both systolic (SBP) and diastolic (DBP) BP at age 17 (SBP: B = - 0.829, p = 0.002; DBP: B = - 0.397, p = 0.033). The interaction term between BW and weight at age 17 was significant for DBP (p = 0.017) and pulse pressure (p = 0.005). mBMI yielded significant positive associations with BP, independent of BW. CONCLUSIONS FOR PRACTICE: Our findings indicate that there are at least two distinct pathways linking early life characteristics with subsequent BP: Intrauterine growth, as reflected by BW and other genetic or environmental factors, reflected by mBMI and maternal education, contribute to offspring adolescent BP. These results warrant replication in other birth cohorts and underline the need to explore specific mechanisms that account for these associations.