Patterns of genetic connectedness between modern and medieval Estonian genomes reveal the origins of a major ancestry component of the Finnish population.

The Finnish population is a unique example of a genetic isolate affected by a recent founder event. Previous studies have suggested that the ancestors of Finnic-speaking Finns and Estonians reached the circum-Baltic region by the 1st millennium BC. However, high linguistic similarity points to a more recent split of their languages. To study genetic connectedness between Finns and Estonians directly, we first assessed the efficacy of imputation of low-coverage ancient genomes by sequencing a medieval Estonian genome to high depth (23×) and evaluated the performance of its down-sampled replicas. We find that ancient genomes imputed from >0.1× coverage can be reliably used in principal-component analyses without projection. By searching for long shared allele intervals (LSAIs; similar to identity-by-descent segments) in unphased data for >143,000 present-day Estonians, 99 Finns, and 14 imputed ancient genomes from Estonia, we find unexpectedly high levels of individual connectedness between Estonians and Finns for the last eight centuries in contrast to their clear differentiation by allele frequencies. High levels of sharing of these segments between Estonians and Finns predate the demographic expansion and late settlement process of Finland. One plausible source of this extensive sharing is the 8th-10th centuries AD migration event from North Estonia to Finland that has been proposed to explain uniquely shared linguistic features between the Finnish language and the northern dialect of Estonian and shared Christianity-related loanwords from Slavic. These results suggest that LSAI detection provides a computationally tractable way to detect fine-scale structure in large cohorts.

Hormonal contraception for female athletes presents special needs and concerns.

PURPOSE: Oral contraceptives (OCs) are commonly used by female athletes raising concerns regarding the possible adverse effects of OCs on physical performance, musculoskeletal injuries, and bone density. We aimed to review all current studies on the physiological effects of OCs in physically active women. MATERIALS AND METHODS: A review of literature in electronic search in PubMed and Google Scholar databases from December 2002 to December 2022 using relevant keywords. The reference lists of the articles found eligible were also reviewed. RESULTS: Out of 344 articles in the initial database, 54 clinical studies were eligible for inclusion in our literature review. OCs are used by about two-thirds of female athletes. Current research suggests that OCs' effects on endurance performance and muscle strength are mostly reassuring. OCs do not seem to have a major negative impact on bone health or sports injuries. In fact, new data suggests that they may even significantly reduce the risk of anterior cruciate ligament (ACL) injury. CONCLUSIONS: OCs can be safely used by young female athletes, who may also benefit from better menstrual cycle control. OCs offer newly realised protection from ACL injuries. The use of OCs must be carefully individualised according to their preferences, expectations, and experience.

Hormonal contraception can be safely prescribed to active women. The International Olympic Committee advocates a new and wider definition for the 'athlete triad', where low energy availability presents a special challenge for these athletes. New data suggests that the use of oral contraceptives may protect against ACL injury.

Rapid, Phase-free Detection of Long Identity-by-Descent Segments Enables Effective Relationship Classification.

Identity-by-descent (IBD) segments are a useful tool for applications ranging from demographic inference to relationship classification, but most detection methods rely on phasing information and therefore require substantial computation time. As genetic datasets grow, methods for inferring IBD segments that scale well will be critical. We developed IBIS, an IBD detector that locates long regions of allele sharing between unphased individuals, and benchmarked it with Refined IBD, GERMLINE, and TRUFFLE on 3,000 simulated individuals. Phasing these with Beagle 5 takes 4.3 CPU days, followed by either Refined IBD or GERMLINE segment detection in 2.9 or 1.1 h, respectively. By comparison, IBIS finishes in 6.8 min or 7.8 min with IBD2 functionality enabled: speedups of 805-946× including phasing time. TRUFFLE takes 2.6 h, corresponding to IBIS speedups of 20.2-23.3×. IBIS is also accurate, inferring ≥7 cM IBD segments at quality comparable to Refined IBD and GERMLINE. With these segments, IBIS classifies first through third degree relatives in real Mexican American samples at rates meeting or exceeding other methods tested and identifies fourth through sixth degree pairs at rates within 0.0%-2.0% of the top method. While allele frequency-based approaches that do not detect segments can infer relationship degrees faster than IBIS, the fastest are biased in admixed samples, with KING inferring 30.8% fewer fifth degree Mexican American relatives correctly compared with IBIS. Finally, we ran IBIS on chromosome 2 of the UK Biobank dataset and estimate its runtime on the autosomes to be 3.3 days parallelized across 128 cores.

Assuring quality in assisted reproduction laboratories: assessing the performance of ART Compass - a digital art staff management platform.

PURPOSE: Staff management is the most cited ART/IVF laboratory inspection deficiency. Small ART/IVF clinics may be challenged to perform these activities by low staff volume; similarly, large ART/IVF networks may be challenged by high staff volume and large datasets. Here, we sought to investigate the performance of an automated, digital platform solution to manage this necessary task. METHODS: The ART Compass (ARTC) digital staff management platform was used to assess the clinical decision-making of ART laboratory staff. The survey modules presented standardized instructions to technologists and measured inter- and intra-technologist variability for subjective "clinical decision-making" type questions. Internal and external comparisons were achieved by providing technologists two answers: (1) a comparison to their own lab director and (2) to the most popular response collectively provided by all lab director level accounts. The platform is hosted on HIPAA compliant Amazon web servers, accessible via web browser and mobile applications for iOS (Apple) and Android mobile devices. RESULTS: Here, we investigated the performance of a digital staff management platform for single embryologist IVF practices and for three IVF lab networks (sites A, B, C) from 2020 to 2022. Embryology dish preparation survey results show variance among respondents in the following: PPE use, media volume, timing of oil overlay, and timing of moving prepared dishes to incubators. Surveying the perceived Gardner score and terms in use for early blastocysts reveals a lack of standardization of terminology and fair to poor agreement. We observed moderate inter-technologist agreement for ICM and TE grade (0.47 and 0.52, respectively). Lastly, the clinical decision of choice to freeze or discard an embryo revealed that agreement to freeze was highest for the top-quality embryos, and that some embryos can be highly contested, evenly split between choice to freeze or discard. CONCLUSIONS: We conclude that a digital platform is a novel and effective tool to automate, routinely monitor, and assure quality for staff-related parameters in ART and IVF laboratories. Use of a digital platform can increase regulatory compliance and provide actionable insight for quality assurance in both single embryologist practices and for large networks. Furthermore, clinical decision-making can be augmented with artificial intelligence integration.

PhISCS: a combinatorial approach for subperfect tumor phylogeny reconstruction via integrative use of single-cell and bulk sequencing data.

Available computational methods for tumor phylogeny inference via single-cell sequencing (SCS) data typically aim to identify the most likely perfect phylogeny tree satisfying the infinite sites assumption (ISA). However, the limitations of SCS technologies including frequent allele dropout and variable sequence coverage may prohibit a perfect phylogeny. In addition, ISA violations are commonly observed in tumor phylogenies due to the loss of heterozygosity, deletions, and convergent evolution. In order to address such limitations, we introduce the optimal subperfect phylogeny problem which asks to integrate SCS data with matching bulk sequencing data by minimizing a linear combination of potential false negatives (due to allele dropout or variance in sequence coverage), false positives (due to read errors) among mutation calls, and the number of mutations that violate ISA (real or because of incorrect copy number estimation). We then describe a combinatorial formulation to solve this problem which ensures that several lineage constraints imposed by the use of variant allele frequencies (VAFs, derived from bulk sequence data) are satisfied. We express our formulation both in the form of an integer linear program (ILP) and-as a first in tumor phylogeny reconstruction-a Boolean constraint satisfaction problem (CSP) and solve them by leveraging state-of-the-art ILP/CSP solvers. The resulting method, which we name PhISCS, is the first to integrate SCS and bulk sequencing data while accounting for ISA violating mutations. In contrast to the alternative methods, typically based on probabilistic approaches, PhISCS provides a guarantee of optimality in reported solutions. Using simulated and real data sets, we demonstrate that PhISCS is more general and accurate than all available approaches.

Crossover interference and sex-specific genetic maps shape identical by descent sharing in close relatives.

Simulations of close relatives and identical by descent (IBD) segments are common in genetic studies, yet most past efforts have utilized sex averaged genetic maps and ignored crossover interference, thus omitting features known to affect the breakpoints of IBD segments. We developed Ped-sim, a method for simulating relatives that can utilize either sex-specific or sex averaged genetic maps and also either a model of crossover interference or the traditional Poisson model for inter-crossover distances. To characterize the impact of previously ignored mechanisms, we simulated data for all four combinations of these factors. We found that modeling crossover interference decreases the standard deviation of pairwise IBD proportions by 10.4% on average in full siblings through second cousins. By contrast, sex-specific maps increase this standard deviation by 4.2% on average, and also impact the number of segments relatives share. Most notably, using sex-specific maps, the number of segments half-siblings share is bimodal; and when combined with interference modeling, the probability that sixth cousins have non-zero IBD sharing ranges from 9.0 to 13.1%, depending on the sexes of the individuals through which they are related. We present new analytical results for the distributions of IBD segments under these models and show they match results from simulations. Finally, we compared IBD sharing rates between simulated and real relatives and find that the combination of sex-specific maps and interference modeling most accurately captures IBD rates in real data. Ped-sim is open source and available from https://github.com/williamslab/ped-sim.

Meltos: multi-sample tumor phylogeny reconstruction for structural variants.

MOTIVATION: We propose Meltos, a novel computational framework to address the challenging problem of building tumor phylogeny trees using somatic structural variants (SVs) among multiple samples. Meltos leverages the tumor phylogeny tree built on somatic single nucleotide variants (SNVs) to identify high confidence SVs and produce a comprehensive tumor lineage tree, using a novel optimization formulation. While we do not assume the evolutionary progression of SVs is necessarily the same as SNVs, we show that a tumor phylogeny tree using high-quality somatic SNVs can act as a guide for calling and assigning somatic SVs on a tree. Meltos utilizes multiple genomic read signals for potential SV breakpoints in whole genome sequencing data and proposes a probabilistic formulation for estimating variant allele fractions (VAFs) of SV events. RESULTS: In order to assess the ability of Meltos to correctly refine SNV trees with SV information, we tested Meltos on two simulated datasets with five genomes in both. We also assessed Meltos on two real cancer datasets. We tested Meltos on multiple samples from a liposarcoma tumor and on a multi-sample breast cancer data (Yates et al., 2015), where the authors provide validated structural variation events together with deep, targeted sequencing for a collection of somatic SNVs. We show Meltos has the ability to place high confidence validated SV calls on a refined tumor phylogeny tree. We also showed the flexibility of Meltos to either estimate VAFs directly from genomic data or to use copy number corrected estimates. AVAILABILITY AND IMPLEMENTATION: Meltos is available at https://github.com/ih-lab/Meltos. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Assessment of a double freezing approach in the management of surplus embryos in IVF.

RESEARCH QUESTION: What pregnancy rates are achieved after transfer of cryopreserved double slow-frozen embryos in IVF cycles? Patients in whom surplus thawed cleaved embryos (day 2 or 3) were grown to the blastocyst stage, re-frozen and then re-thawed for transfer (double freezing) were included. DESIGN: Data were collected on all patients who had undergone the above procedure at the IVF unit of Assuta Ramat Hachayal Hospital, Tel Aviv, during a 7-year period. For each patient in the study group, the two-consecutive, matched-by-age patients treated with frozen-thawed single blastocyst transfer were selected to form a 2:1 ratio control group. All embryos were frozen using the slow freeze protocol. RESULTS: A total of 54 patients had 70 embryos that were re-frozen at the blastocyst stage. Twenty-eight of these blastocysts were thawed and 27 underwent transfer to 25 patients. A single embryo was transferred to 23 patients and two embryos were transferred to two patients. The survival rate of the second thawing was 96.4% (27/28). Clinical pregnancy rate was 16% (4/25) and implantation rate was 14.8% (4/27). In the study group, pregnancies were achieved in 22 out of the 25 patients using IVF treatment, indicating good receptivity of the uterus. In the control group, the implantation/pregnancy rates were significantly higher (44.2% [23/52]; P < 0.01). CONCLUSION: The transfer of twice slow-frozen and thawed embryos does not seem to be a beneficial approach in the planned management of cryopreserved surplus embryos owing to the low pregnancy rate achieved after transfer of the re-frozen blastocyst embryos.

Patient-centered elective egg freezing: a binational qualitative study of best practices for women's quality of care.

PURPOSE: How can elective egg freezing (EEF) be made patient centered? This study asked women to reflect on their experiences of EEF, which included their insights and recommendations on the optimal delivery of patient-centered care. METHODS: In this binational, qualitative study, 150 women (114 in the USA, 36 in Israel) who had completed at least one cycle of EEF were recruited from four American IVF clinics (two academic, two private) and three in Israel (one academic, two private) over a two-year period (June 2014-August 2016). Women who volunteered for the study were interviewed by two medical anthropologists. Interviews were audio recorded, transcribed, and entered into a qualitative data management program (Dedoose) for analysis. RESULTS: The majority (85%) of women were without partners at the time of EEF, and thus were undertaking EEF alone in mostly couples-oriented IVF clinics. Following the conceptual framework known as "patient-centered infertility care," we identified two broad categories and eleven specific dimensions of patient-centered EEF care, including (1) system factors: information, competence of clinic and staff, coordination and integration, accessibility, physical comfort, continuity and transition, and cost and (2) human factors: attitude and relationship with staff, communication, patient involvement and privacy, and emotional support. Cost was a unique factor of importance in both countries, despite their different healthcare delivery systems. CONCLUSIONS: Single women who are pursuing EEF alone in the mostly couples-oriented world of IVF have distinct and multifaceted needs. IVF clinics should strive to make best practices for patient-centered EEF care a high priority.

The expected cumulative incidence of live birth for patients starting IVF treatment at age 41 years or older.

RESEARCH QUESTION: What is the cumulative incidence of live birth (CILB) for high-order consecutive IVF cycles, and which factors are associated with live birth in women aged ≥41 years using autologous oocytes? DESIGN: A retrospective cohort study including 146 patients aged 41 years to <44 years who started their first IVF cycle attempt using autologous oocytes, between January 2006 and December 2013. RESULTS: After 13 IVF cycles, CILB reached up to 33.6%. After six IVF cycles, 42 (28.8%) women delivered a live infant (85.7% of the total live birth). Mean live birth rate per cycle declined with age at the initial cycle (8% at 41 years; 5.8% at 42 years; and 4.1% at 43 years). Multivariable modified Poisson regression models identified patient's age (RR for 41 years versus 43 years: 0.47; 95% CI 0.25 to 0.87; P = 0.01), smoking status (RR 0.21; 95% CI 0.05 to 0.08; P = 0.02), and mean number of fertilized oocytes (RR 1.23; 95% CI 1.08 to 1.39; P < 0.01) as factors significantly associated with the probability of a live birth. CONCLUSIONS: Multiple repeat IVF cycles in women aged 41-44 years offers a reasonable long-term success rate. After six cycles of treatment, about 29% of women of advanced reproductive age using autologous oocytes expected to achieve a live birth. This information might assist in fertility counselling and managing patients' expectations by adjusting the appropriate treatment strategy and number of IVF cycle attempts, especially in countries in which egg donation is prohibited or when multiple repeated IVF cycles attempts are financially affordable.

Ten pathways to elective egg freezing: a binational analysis.

PURPOSE: What are the specific pathways that lead women to freeze their eggs? In this binational study, women were asked directly about the life circumstances that led them on the path to elective egg freezing (EEF). METHODS: From June 2014 to August 2016, 150 women (114 in the USA, 36 in Israel) who had completed at least 1 cycle of EEF were interviewed by two medical anthropologists. Study participants were recruited through four American IVF clinics (two academic, two private) and three in Israel (one academic, two private). Interviews were audio-recorded, transcribed verbatim, and entered into a qualitative data management program (Dedoose) for analysis. RESULTS: The majority (85%) of women in the study were without partners, while 15% had partners at the time of EEF. Six pathways to EEF were found among women without partners (being single, divorced, broken up, deployed overseas, single mother, career planner), with career planning being the least common pathway to EEF. Among women with partners, four pathways to EEF were found (relationship too new or uncertain, partner not ready to have children, partner refusing to have children, or partner having multiple partners). With only one exception, the pathways and their frequencies were similar in both countries. CONCLUSIONS: Partnership problems, not career planning, lead most women on pathways to EEF. These pathways should be studied in a variety of national settings, and fertility clinics should offer patient-centered care for single women pursuing EEF in the couples-oriented world of IVF.

Reproductive Outcome Is Favorable After Laparoscopic Resection of Bladder Endometriosis.

STUDY OBJECTIVE: To assess the reproductive outcome (spontaneous and assisted conception rates) in women who underwent laparoscopic resection of bladder endometriosis. DESIGN: This was a retrospective, observational study analyzing prospectively recorded data (Canadian Task Force classification II-2). SETTING: A tertiary referral center. PATIENTS: Over a 9-year period, we identified 69 consecutive women with symptomatic pelvic endometriosis who underwent laparoscopic resection of bladder endometriosis at our center. INTERVENTIONS: Group A patients (n = 21) had full-thickness endometriotic invasion of the bladder and underwent laparoscopic partial cystectomy. Group B (n = 48) patients had partial endometriotic bladder penetration and underwent partial-thickness excision of the detrusor muscle. Most patients (over 70%) had additional, nonbladder endometriotic lesions, which were also removed during surgery. MEASUREMENTS AND MAIN RESULTS: Fertility outcomes were analyzed in patients who wished to conceive (n = 42), and improvements in symptoms were assessed for all patients. The minimum follow-up after surgery was 36 months. Of the 42 patients who wished to conceive, 35 patients (83.3%) conceived: 16 patients spontaneously and 18 patients after IVF treatment. No difference was observed in fertility outcome between group A (partial cystectomy) and group B (partial-thickness excision of the detrusor muscle). For all patients, long-term follow-up revealed that 80% of the patients (55 patients) had no urinary/endometrial symptoms after surgery. CONCLUSION: Pregnancy rates after laparoscopic surgery for bladder endometriosis by either partial cystectomy or deep excision of the detrusor muscle are favorable, both for spontaneous pregnancy and conception after IVF treatment. Additionally, urinary symptoms were improved for the majority of patients. Based on our findings, it seems warranted to offer laparoscopic surgical management to symptomatic infertile patients diagnosed with bladder endometriosis, even after IVF failure.

Religion and family planning.

Religion is embedded in the culture of all societies. It influences matters of morality, ideology and decision making, which concern every human being at some point in their life. Although the different religions often lack a united view on matters such contraception and abortion, there is sometimes some dogmatic overlap when general religious principles are subject to the influence of local customs. Immigration and population flow add further complexities to societal views on reproductive issues. For example, present day Europe has recently faced a dramatic increase in refugee influx, which raises questions about the health care of immigrants and the effects of cultural and religious differences on reproductive health. Religious beliefs on family planning in, for example, Christianity, Judaism, Islam and Hinduism have grown from different backgrounds and perspectives. Understanding these differences may result in more culturally competent delivery of care by health care providers. This paper presents the teachings of the most widespread religions in Europe with regard to contraception and reproduction.

Ultrarapid Induction of Hypothermia Using Continuous Automated Peritoneal Lavage With Ice-Cold Fluids: Final Results of the Cooling for Cardiac Arrest or Acute ST-Elevation Myocardial Infarction Trial.

OBJECTIVES: Hypothermia (32-34 °C) can mitigate ischemic brain injury, and some evidence suggests that it can reduce infarct size in acute myocardial infarction and acute ischemic stroke. For some indications, speed of cooling may be crucial in determining efficacy. We performed a multicenter prospective intervention study to test an ultrarapid cooling technology, the Velomedix Automated Peritoneal Lavage System using ice-cold fluids continuously circulating through the peritoneal cavity to rapidly induce and maintain hypothermia in comatose patients after cardiac arrest and a small number of awake patients with acute myocardial infarction. DESIGN: Multicenter prospective intervention study. SETTING: Intensive care- and coronary care units of multiple tertiary referral centers. MEASUREMENTS AND MAIN RESULTS: Access to the peritoneal cavity was gained using a modified blunt dilating instrument, followed by catheter placement. Patients were cooled to a temperature of 32.5 °C, maintained for 24 hours (cardiac arrest) or 3 hours (acute myocardial infarction) followed by controlled rewarming. Forty-nine patients were enrolled, and 46 patients completed treatment. One placement was unsuccessful (abdominal wall not breached), two patients were ultimately not cooled, and only safety data are reported. Average catheter insertion time was 2.3 minutes. Mean time to temperature less than 33 °C was 10.4 minutes (average cooling rate, 14 °C/hr). Median infarct size in patients who had coronary interventions was 16% of LV. No cases of stent thrombosis occurred. Survival in cardiac arrest patients with initial rhythm of ventricular tachycardia/ventricular fibrillation was 56%, of whom 82 had a complete neurologic recovery. This compares favorably to outcomes from previous studies. CONCLUSION: Automated peritoneal lavage system is a safe and ultrarapid method to induce and maintain hypothermia, which appears feasible in cardiac arrest patients and awake patients with acute myocardial infarction. The shivering response appeared to be delayed and much reduced with this technology, diminishing metabolic disorders associated with cooling and minimizing sedation requirement. Our data suggest that ultrarapid cooling could prevent subtle neurologic damage compared with slower cooling. This will need to be confirmed in direct comparative studies.

Longitudinal Correlates of Health Risk Behaviors in Children and Adolescents with Type 2 Diabetes.

OBJECTIVES: To characterize, during a 2-year period, the proportion of youth with type 2 diabetes (T2D) enrolled in the Treatment Options for Type 2 Diabetes in Adolescents and Youth study that reported ever at least trying smoking cigarettes and/or drinking alcohol. STUDY DESIGN: Longitudinal data were examined for participants with T2D ages 10-18 years at baseline. Youth psychosocial, parent/family, environmental, and biological correlates of trying health risk behaviors were tested via cross-sectional multivariate models at each time point. Longitudinal models were explored for selected factors. RESULTS: Data were obtained from the Treatment Options for Type 2 Diabetes in Adolescents and Youth study's ethnically diverse participants at baseline (N=644), 6-month (N=616), and 24-month (N=543) assessments. The percentage of youth ever trying only smoking remained stable at 4%; only drinking alcohol increased from 17% to 26%, and both smoking and drinking increased from 10% to 18% during the 2-year period. Factors related to trying health risk behaviors were older age, male sex, non-Hispanic white race-ethnicity, lower grades, more depressive symptoms, and stressful life events. Depressive symptoms, stressful life events, and body mass index Z-score (the latter with smoking only) were related to engagement in health risk behaviors over time. CONCLUSIONS: Youth with T2D who are already at risk for health complications and who reported engaging in activities that further increase the likelihood of life-threatening morbidities were characterized. Although most correlates of trying these risk behaviors are nonmodifiable, intervention efforts may need to focus on potentially modifiable factors, such as depressive symptoms and lower grades.

Why do couples discontinue unlimited free IVF treatments?

Worldwide, IVF is often discontinued before a live birth is achieved due to high costs. Even when partial financial coverage is provided, often medical providers advise treatment discontinuation. In Israel, unlimited IVF is offered free of charge for a couples' first two children. Our objective was to assess the reasons couples discontinue IVF treatments before achieving two children in a completely unlimited cost-free environment. This cohort study included all primary infertile women, <35 years, referred for their first IVF cycle to Sheba IVF unit between 2001 and 2002. Patients were followed until February 2012. Those who ceased treatments for 12 months were interviewed to assess the main reason they ceased treatments. Of the 134 couples included, only 46 ceased IVF treatments without achieving two children, after performing an average of 6.2 IVF cycles to achieve their first birth. The reasons given were: lost hope of success (13), psychological burden (18), divorce (6), medical staff recommendation (5), bureaucratic difficulties (3) and general medical condition (1). The main reasons for "drop out" in our cost-free environment were as follows: psychological burden and lost hope of success. Due to high availability of treatments, medical staff recommendation was a less significant factor in our study.

Pelvic inflammatory disease in women with endometriosis is more severe than in those without.

AIMS: To determine the incidence and severity of acute pelvic inflammatory disease (PID) or tubo-ovarian abscess (TOA) in hospitalised women with and without a history of endometriosis. METHODS: Retrospective analysis of hospital records retrieved for all women hospitalised with PID or TOA between January 2008 and December 2011 in a tertiary referral centre. Women were compared with regard to a history of endometriosis for demographic, clinical and fertility data. RESULTS: 26 (15%) of the 174 women hospitalised due to PID or TOA were excluded because of age older than 45 years, leaving 148 for analysis. The mean age was 35.7 ± 9.3 years and mean duration of hospitalisation was 5.9 ± 3.7 days. The women were divided into two groups: Group 1 with endometriosis (n = 21) and Group 2 without endometriosis (n = 127). Women in Group 1 as compared with Group 2 were significantly more likely to have undergone a fertility procedure prior to being admitted to the hospital with PID (9/27 (45%) vs 22/121 (17%), P < 0.001); particularly in vitro fertilisation (IVF) (7/ 27 (33%) vs 12/121 (9%), P < 0.006); Women in Group 1 more frequently experienced a severe and complicated course involving longer duration of hospitalisation (8.8 ± 4.7 vs 4.4 ± 2.3 days, P < 0.0001) and antibiotic treatment failure (10/27 (48%) vs 8/121 (6%), P < 0.0001). CONCLUSIONS: Pelvic inflammatory disease in women with endometriosis is more severe and refractory to antibiotic treatment, often requiring surgical intervention. It is likely that endometriosis is a risk factor for the development of severe PID, particularly after IVF treatment.

Intradermal sex hormone desensitization for relief of premenstrual symptoms may improve the obstetric outcome of women with recurrent pregnancy loss.

The aim of this study was to determine whether women with recurrent pregnancy loss (RPL) and concurrent premenstrual syndrome (PMS) who underwent desensitization with sex hormones had an improved obstetric outcome. This manuscript summarizes a 10 year open label prospective follow up study of 26 women with RPL, aged 25-42 with 3-8 previous miscarriages and PMS, who had hormone hypersensitivity on skin testing. Skin testing was positive to estradiol in 23 women, progesterone in 20 women and to both estrogen and progesterone in 17 women. Amelioration of the symptoms of PMS (according to the VAS) was seen in 21 of 26 patients after desensitization with small doses of sex hormones intradermally. There was long term and stable reduction of severe PMS in 21 of 26 patients after desensitization. Five women conceived after skin testing, prior to desensitization. Sixteen of 26 women (61%) had subsequent live births. Five women had two subsequent live births in the subsequent pregnancy. There were no obstetric complications. Five women had two subsequent pregnancies with live births. It seems that correction of sex hormone hypersensitivity was accompanied by relief of persistent PMS, may have a positive effect on the chances of a successful pregnancy.

Deep endometriosis inflicting the bladder: long-term outcomes of surgical management.

OBJECTIVE: To assess the efficacy and safety of laparoscopic treatment of bladder endometriosis, especially in cases of full thickness endometriotic nodules. DESIGN: Retrospective review of medical records. SETTING: Tertiary medical center and a referral center for endometriosis. POPULATION: Sixty-nine patients with bladder endometriosis that underwent surgery between January 2005 and December 2011. METHODS: The records of all patients with bladder endometriosis were reviewed and the pre-, intra- and postoperative information of patients who underwent surgery was collected. MAIN OUTCOME MEASURES: Efficacy, safety and long-term outcome of laparoscopic treatment of bladder endometriosis. RESULTS: The mean age of 69 patients with bladder endometriosis was 31.3 ± 4.6 years. Preoperative urinary symptoms (such as frequency, urgency, dysuria and others) were present in 28 (40.0%) patients. Laparoscopy was performed in all patients. Deep detrusor involvement was found in 45 (65.2%) patients. Of these, 21 patients underwent partial cystectomy due to a full thickness lesion. Deep nodule resection without bladder invasion was performed in 24 (34.8%) patients and bladder nodule coagulation and ablation in the remaining 24 (34.8%) patients with superficial involvement. No intraoperative complications were noted. Postoperative follow-up results were available for all patients. After a median (range) follow-up period of 60 (4-92) months, 92.7% of the patients were asymptomatic or reported improvement in symptoms. CONCLUSIONS: After a long-term follow-up surgical management of bladder endometriosis is strongly recommended. During surgery, careful inspection and full excision of bladder lesions should be performed. Laparoscopic excision is a safe and efficacies approach.

Failure to insert a levonorgestrel-releasing intrauterine system: a survey based on self-reports by Israeli gynecologists.

BACKGROUND: The insertion of a levonorgestrel-releasing intrauterine system (LNG-IUS) requires experience and is associated with a low failure rate. OBJECTIVES: To assess the reasons given by gynecologists why they failed to insert a LNG-IUS. METHODS: We obtained data from the sole distributor in Israel that prospectively recorded these cases when contacted by gynecologists following an insertion failure. RESULTS: The mean rate of failed insertions was 0.95% (range 0.77-1.03%) for the 5 year study period 2006-2010. The most common reasons reported by gynecologists for LNG-IUS insertion failure were loss of sterility of the device, inability to insert the device due to a stenotic cervical canal, accidental removal of the device following a successful insertion due to hasty removal of the inserter or the use of blunt scissors, and removal of the newly inserted LNG-IUS following ultrasound evidence that it was misplaced. CONCLUSIONS: Gynecologists should be aware of the common pitfalls associated with insertion of an LNG-IUS. Several techniques that may aid in avoiding these mishaps are described.