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3.
Ultrasound Obstet Gynecol ; 63(1): 105-112, 2024 01.
Article in English | MEDLINE | ID: mdl-37926974

ABSTRACT

OBJECTIVE: Around 80% of women with endometriosis have superficial endometriosis (SE) rather than ovarian or deep endometriosis (DE). However, to date, advances in non-invasive, imaging-based diagnosis have been limited to DE or ovarian disease. The objective of this study was to determine whether we can detect SE on transvaginal ultrasound scan (TVS) by assessing the peritoneum of the pouch of Douglas (POD). METHODS: This was a retrospective diagnostic test study following a change in practice to include POD peritoneum assessment for SE during TVS at a tertiary London hospital. Eligible patients underwent TVS by a single clinician trained in endometriosis scanning and a subsequent surgical procedure (laparoscopy) between April 2018 and September 2021. Participants formed a consecutive series. The TVS findings were compared with those of laparoscopy as the gold standard. Comparison of TVS findings with intraoperative findings was performed by calculating the diagnostic test performance measures (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and positive and negative likelihood ratios). RESULTS: The study included a total of 100 patients. We found that 43/100 (43.0%) patients had no endometriosis, 33/100 (33.0%) had SE and 24/100 (24.0%) had DE on laparoscopy. SE was correctly detected on TVS in 17/33 patients, with a sensitivity of 51.5% (95% CI, 33.5-69.2%), specificity of 94.0% (95% CI, 85.4-98.4%), PPV of 81.0% (95% CI, 60.8-92.1%) and NPV of 79.7% (95% CI, 73.4-84.9%). DE was correctly diagnosed in 20/24 cases, including all ovarian cases, with a sensitivity of 83.3% (95% CI, 62.3-95.3%), specificity of 97.4% (95% CI, 90.8-99.7%), PPV of 90.9% (95% CI, 71.6-97.5%) and NPV of 94.9% (95% CI, 88.3-97.8%). The detection of SE on TVS was most accurate in the POD (sensitivity, 50.0%; specificity, 96.4%; PPV, 76.9%; NPV, 88.9%). CONCLUSIONS: This study shows that the detection of SE in the POD is possible using routine TVS. While negative TVS does not reliably confirm the absence of disease or replace diagnostic laparoscopy, positive TVS facilitates non-invasive diagnosis for a much larger group of women than was previously possible. This should help to reduce the time from the onset of symptoms to diagnosis and enable initiation of medical treatment without the risk, cost and delay associated with a surgical diagnosis. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Subject(s)
Endometriosis , Female , Humans , Endometriosis/diagnostic imaging , Endometriosis/surgery , Peritoneum/diagnostic imaging , Retrospective Studies , Sensitivity and Specificity , Douglas' Pouch/diagnostic imaging , Ultrasonography/methods
8.
J Intellect Disabil Res ; 66(5): 499-500, 2022 05.
Article in English | MEDLINE | ID: mdl-35347778
9.
Hum Reprod Open ; 2022(1): hoab046, 2022.
Article in English | MEDLINE | ID: mdl-35071800

ABSTRACT

STUDY QUESTION: What is the risk of loss of a live normally sited (eutopic) pregnancy following surgical treatment of the concomitant extrauterine ectopic pregnancy? SUMMARY ANSWER: In women diagnosed with heterotopic pregnancies, minimally invasive surgery to treat the extrauterine ectopic pregnancy does not increase the risk of miscarriage of the concomitant live eutopic pregnancy. WHAT IS KNOWN ALREADY: Previous studies have indicated that surgical treatment of the concomitant ectopic pregnancy in women with live eutopic pregnancies could be associated with an increased risk of miscarriage. The findings of our study did not confirm that. STUDY DESIGN SIZE DURATION: A retrospective observational case-control study of 52 women diagnosed with live eutopic and concomitant extrauterine pregnancies matched to 156 women with live normally sited singleton pregnancies. The study was carried out in three London early pregnancy units (EPUs) covering a 20-year period between April 2000 and November 2019. PARTICIPANTS/MATERIALS SETTING METHODS: All women attended EPUs because of suspected early pregnancy complications. The diagnosis of heterotopic pregnancy was made on ultrasound scan and women were subsequently offered surgical or expectant management.There were three controls per each case who were randomly selected from our clinical database and were matched for maternal age, mode of conception and gestational age at presentation. MAIN RESULTS AND THE ROLE OF CHANCE: In the study group 49/52 (94%) women had surgery and 3/52 (6%) were managed expectantly. There were 9/52 (17%, 95% CI 8.2-30.3) miscarriages <12 weeks' gestation and 9/49 (18%, 95% CI 8.7-32) miscarriages in those treated surgically. In the control group, there were 28/156 (18%, 95% CI 12.2-24.8) miscarriages <12 weeks' gestation, which was not significantly different from heterotopic pregnancies who were treated surgically [odds ratio (OR) 1.03 95% CI 0.44-2.36]. There was a further second trimester miscarriage in the study group and one in the control group. The live birth rate in the study group was 41/51 (80%, 95% CI 66.9-90.2) and 38/48 (79%, 95% CI 65-89.5) for those who were treated surgically. These results were similar to 127/156 (81%, 95% CI 74.4-87.2) live births in the control group (OR 0.87, 95% CI 0.39-1.94). LIMITATIONS REASONS FOR CAUTION: This study is retrospective, and the number of patients is relatively small, which reflects the rarity of heterotopic pregnancies. Heterotopic pregnancies without a known outcome were excluded from analysis. WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrates that in women diagnosed with heterotopic pregnancies, minimally invasive surgery to treat the extrauterine pregnancy does not increase the risk of miscarriage of the concomitant live eutopic pregnancy. This finding will be helpful to women and their clinicians when discussing the options for treating heterotopic pregnancies. STUDY FUNDING/COMPETING INTERESTS: This work did not receive any funding. None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER: Research Registry: researchregistry6430.

10.
Facts Views Vis Obgyn ; 13(4): 395-398, 2021 12.
Article in English | MEDLINE | ID: mdl-35026101

ABSTRACT

BACKGROUND: In response to the COVID-19 pandemic, a central London tertiary referral hospital's nurse-led Early Pregnancy & Acute Gynaecology Unit (EPAGU) suspended its walk-in service in favour of a telephone triage system with scheduled appointments. OBJECTIVE: To assess if the pandemic and this adaptation to clinical services had an impact on the presentation, management and complication rate of ectopic pregnancies. MATERIALS AND METHODS: A retrospective review was performed of ectopic pregnancies diagnosed in the EPAGU between 5th of March 2020 - 15th of July 2020 (pandemic) and 5th of March 2019 - 15th of July 2019 (pre-pandemic). MAIN OUTCOME MEASURES: Ultrasound findings, patient demographics, serum hCG concentrations, operative findings and complications. RESULTS: There was a 36% reduction in attendances to the unit during the pandemic. Allowing for this, there was no significant difference in the diagnosis rate between the two periods. There was no significant difference in the gestation at diagnosis, serum hCG concentration or volume of mass at presentation. There was also no significant difference in rate of surgical intervention or complications including rupture of fallopian tube, haemoperitoneum or need for blood transfusion. CONCLUSION: This study suggests this is a safe means of caring for women with ectopic pregnancies which does not limit management options nor lead to higher complication rates. WHAT IS NEW: Other EPAGUs may choose to adopt a telephone triage system with reassurance of its safety.

11.
BMJ Mil Health ; 167(5): 310-315, 2021 Oct.
Article in English | MEDLINE | ID: mdl-31036748

ABSTRACT

OBJECTIVES: Health data of operational relevance from South Sudan are lacking, outdated and non-representative. This study sets out to record and analyse primary healthcare (PHC) presentations to a deployed UK Level 1 Primary Healthcare Centre (L1 PHC) facility in Bentiu, South Sudan, to inform on disease prevalence for UK Military Personnel in a sub-Saharan Operational environment. METHODS: A prospective single-centre cohort study was completed for all PHC presentations to a UK L1 PHC facility while deployed on the United Nations Mission to South Sudan from June 2017 to November 2017. RESULTS: 861 episodes of clinical care were recorded at Bentiu Camp during the 6-month period. 82% were from disease; 18% non-battle injuries and no battle injuries were seen. As per EPINATO2 categorisation, the top three presentations were acute gastrointestinal disease, dermatological disease and routine clinical care. Differences were noted for June-August and September-November, as a proportion of total cases seen. It was noted that gastrointestinal illnesses were three times more likely in the first half of the operation and bites and sting almost twice as likely. CONCLUSIONS: Gastrointestinal disease results in a significant burden on humanitarian operations where an extended Relief-in-Place is a key area of risk. The EPINATO2 reporting tool provides insufficient detail for planning purposes and an improved method of data collection is required. Targeting the diagnosis and management of infectious diseases during predeployment training should prepare L1 PHC for the most common cases encountered. Delivery of targeted Force Health Protection training for all personnel with early deployment of L1 PHC forward could improve support to commanders during the highest risk periods.


Subject(s)
Military Personnel , Cohort Studies , Humans , Primary Health Care , Prospective Studies , United Nations
12.
Case Rep Med ; 2020: 9404505, 2020.
Article in English | MEDLINE | ID: mdl-32774388

ABSTRACT

Chronic plaque psoriasis and psoriatic arthritis are common autoimmune inflammatory conditions, often existing as comorbidities that have a significant impact on a patient's quality of life. The availability of a range of novel, targeted therapies for their treatment, most notably the availability of biologic agents, has revolutionised management of these conditions and allowed for significant improvements in patient outcomes. Secukinumab (Cosentyx), a fully-human monoclonal antibody that acts by selectively binding to and neutralising the proinflammatory cytokine IL-17A, is used widely for the treatment of both chronic plaque psoriasis and psoriatic arthritis. In this report, we discuss the case of a 54-year-old female with chronic plaque psoriasis and psoriatic arthritis, who experienced the onset of symptoms and was subsequently diagnosed with Crohn's disease during treatment with secukinumab. It was determined by the gastroenterologist that this may represent secukinumab-induced inflammatory bowel disease. We will review the current understanding of the role of IL-17 in inflammatory bowel disease and the important role of novel agents that target the p19 subunit of IL-23 which have shown significant promise in the management of not only chronic plaque psoriasis and psoriatic arthritis, but also inflammatory bowel disease itself.

13.
Case Rep Obstet Gynecol ; 2020: 6283720, 2020.
Article in English | MEDLINE | ID: mdl-32566337

ABSTRACT

Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic, relapsing inflammatory skin condition characterised by the presence of painful nodules, abscesses, and sinus tracts or scarring. Affecting up to 4% of the population, it is not uncommon and is seen predominantly in females at a ratio of 3 : 1. HS carries a substantial burden for those who suffer from it, from the significant psychosocial impact, to the cost of the multitude of topical and systemic treatments which often do not successfully control its symptoms. In this case report, we discuss a 33-year-old female known to our clinic, who presented with a recurrence of her HS in a caesarean scar, with otherwise silent disease. From our review of the literature, this appears to be only the second case of recurrence of HS in a caesarean scar reported to date. With a predilection for females of reproductive ages, involvement of sensitive areas, and an average of greater than seven years from onset of symptoms until diagnosis, the ability to recognise HS and ensure referral for specialist management is essential for all who are regularly involved in the management of this patient group.

14.
BJOG ; 127(6): 757-767, 2020 05.
Article in English | MEDLINE | ID: mdl-32003141

ABSTRACT

OBJECTIVES: To assess the cost-effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding. DESIGN: Economic evaluation alongside a large multi-centre randomised placebo-controlled trial. SETTING: Forty-eight UK NHS early pregnancy units. POPULATION: Four thousand one hundred and fifty-three women aged 16-39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac. METHODS: An incremental cost-effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages. MAIN OUTCOME MEASURES: Cost per additional live birth at ≥34 weeks of gestation. RESULTS: Progesterone intervention led to an effect difference of 0.022 (95% CI -0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI -£559 to £711) more than the mean cost in the placebo group. The incremental cost-effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014-0.096) and this was associated with a cost saving of £322 (95% CI -£1318 to £673). CONCLUSIONS: The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost-effective intervention, particularly for women with previous miscarriage(s). TWEETABLE ABSTRACT: Progesterone treatment is likely to be cost-effective in women with early pregnancy bleeding and a history of miscarriage.


Subject(s)
Abortion, Spontaneous/economics , Abortion, Spontaneous/prevention & control , Progesterone/economics , Progestins/economics , Uterine Hemorrhage/drug therapy , Abortion, Spontaneous/etiology , Adolescent , Adult , Cost-Benefit Analysis , Double-Blind Method , Female , Humans , Live Birth/economics , Pregnancy , Progesterone/therapeutic use , Progestins/therapeutic use , Randomized Controlled Trials as Topic , State Medicine , Treatment Outcome , United Kingdom , Uterine Hemorrhage/complications , Uterine Hemorrhage/economics , Young Adult
16.
Clin Microbiol Infect ; 26(5): 646.e1-646.e8, 2020 May.
Article in English | MEDLINE | ID: mdl-31639470

ABSTRACT

OBJECTIVES: The significance of isolating Staphylococus epidermidis from a blood culture is highly heterogeneous, ranging from contamination to an indication of a serious infection. Herein we sought to determine whether there is a relationship between S. epidermidis genotype and clinical severity of bacteraemia. METHODS: S. epidermidis bacteraemias from a prospective, multicentre trial at 15 centres in the United States and one in Spain were classified as simple (including possible contamination), uncomplicated, and complicated. Whole-genome sequencing (WGS) was performed on 161 S. epidermidis isolates, and clinical outcomes were correlated with genotypic information. RESULTS: A total of 49 S. epidermidis sequence types (STs) were identified. Although strains of all 49 STs were isolated from patients with either simple or uncomplicated infection, all strains causing complicated infections were derived from five STs: ST2, ST5, ST7, ST16, and ST32. ST2 and ST5 isolates were significantly more likely to cause uncomplicated and complicated bloodstream infections compared to simple bacteraemia (odds ratio 2.0, 95%CI 1.1-3.9, p 0.04). By multivariate regression analysis, having an ST2 or ST5 S. epidermidis bacteraemia was an independent predictor of complicated bloodstream infection (odds ratio 3.7, 95%CI 1.2-11.0, p 0.02). ST2/ST5 strains carried larger numbers of antimicrobial resistance determinants compared to non-ST2/ST5 isolates (6.34 ± 1.5 versus 4.4 ± 2.5, p < 0.001). CONCLUSION: S. epidermidis bacteraemia was caused by a genetically heterogeneous group of organisms, but only a limited number of STs-particularly multidrug-resistant ST2 and ST5 strains-caused complicated infections.


Subject(s)
Bacteremia/microbiology , Bacteremia/pathology , Staphylococcal Infections/microbiology , Staphylococcal Infections/pathology , Staphylococcus epidermidis/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Clinical Trials as Topic , Drug Resistance, Bacterial/drug effects , Drug Resistance, Bacterial/genetics , Female , Genome, Bacterial/genetics , Genotype , Humans , Male , Microbial Sensitivity Tests , Multicenter Studies as Topic , Phenotype , Phylogeny , Staphylococcal Infections/drug therapy , Staphylococcus epidermidis/classification , Staphylococcus epidermidis/drug effects , Staphylococcus epidermidis/isolation & purification
17.
Conserv Biol ; 33(5): 1014-1022, 2019 10.
Article in English | MEDLINE | ID: mdl-30815912

ABSTRACT

Leading societies toward a more sustainable, equitably shared, and environmentally just future requires elevating and strengthening conversations on the nonmaterial and perhaps unquantifiable values of nonhuman nature to humanity. Debates among conservationists relating to the appropriateness of valuing ecosystems in terms of their human utility have eclipsed the more important and impactful task of expressing conservation concerns in terms that are meaningful to diverse stakeholders. We considered the wide global diversity of perspectives on the biosocial complex-the relationships and interactions between all living species on Earth-and argue that humanity's best chance for effective conservation is to take a pluralistic approach that engages seriously with the worldviews of all stakeholders. Many worldviews-particularly those in indigenous cultures-place a higher value on the spiritual and nonmaterial aspects than what is often represented by the discourse surrounding Western conservation policy. Alternative framings of the biosocial complex that recognize nature's intrinsic value can be powerful motivators for social change and for local-scale conservation efforts. At a national and international level, changing ethical framings of human relationships with nature have started influencing conceptions of human rights relating to the environment and of the rights of nature itself. This change has led to an increased role of the judiciary in promoting environmental sustainability and promoting justice for groups who are most often affected by environmental harms. We hope our essay will motivate the scientific community to change its own perception of what a sound and sustainable relationship between humanity and other species should be and will help citizens become active environmental subjects, connected to the ecosystems around them.


Adopción de Diferentes Cosmovisiones para Compartir el Planeta Tierra Resumen Para poder llevar a las sociedades hacia un futuro sustentable, compartido equitativa y ambientalmente justo se requiere elevar y fortalecer las conversaciones sobre los valores no materiales y probablemente imposibles de cuantificar que la naturaleza no humana tiene para la humanidad. Los debates entre los conservacionistas en relación con lo apropiado que es valorar los ecosistemas en términos de utilidad para los humanos han eclipsado la labor más importante e impactante de expresar los asuntos de conservación en términos que son significativos para diferentes accionistas. Consideramos la amplia diversidad mundial de perspectivas que existen sobre el complejo biosocial - las relaciones e interacciones entre todas las especies vivientes en la Tierra - y argumentamos que la mejor oportunidad que tiene la humanidad para lograr una conservación efectiva es realizar una estrategia pluralística que se comprometa seriamente con las cosmovisiones de todos los accionistas. Muchas cosmovisiones - particularmente aquellas de las culturas indígenas - les otorgan un valor más alto a los aspectos espirituales y no materiales que lo que se suele representar en el discurso que rodea la política de conservación occidental. Los marcos alternativos del complejo biosocial que reconocen el valor intrínseco de la naturaleza pueden ser motivadores poderosos para el cambio social y para los esfuerzos de conservación a escala local. A nivel nacional e internacional, el cambio de los marcos éticos de las relaciones humanas con la naturaleza ha comenzado a influenciar las concepciones de los derechos humanos en relación con el ambiente y los derechos de la naturaleza misma. Este cambio ha resultado en un papel mucho mayor del poder judicial en la promoción de la sustentabilidad ambiental y de la justicia para grupos a los que con frecuencia les afectan los daños ambientales. Esperamos que nuestro ensayo motive a la comunidad científica a cambiar su propia percepción de lo que debe ser una relación sana y sustentable entre la humanidad y otras especies y que ayude a los ciudadanos a volverse sujetos ambientales más activos y conectados con el ecosistema.


Subject(s)
Conservation of Natural Resources , Ecosystem , Earth, Planet , Humans , Social Justice
18.
J Nutr Health Aging ; 22(10): 1211-1215, 2018.
Article in English | MEDLINE | ID: mdl-30498828

ABSTRACT

BACKGROUND: In old age, motor impairments including parkinsonian signs are common, but treatment is lacking for many older adults. In this study, we examined the association of a diet specifically developed to promote brain health, called MIND (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay), to the incidence and progression of parkinsonism in older adults. METHODS: A total of 706 Memory and Aging Project participants aged 59 -97 years and without parkinsonism at baseline were assessed annually for the presence of four parkinsonian signs using a 26-item modified version of the United Parkinson's Disease Rating Scale. Incident parkinsonism was defined as the first occurrence over 4.6 years of follow-up of two or more parkinsonian signs. The progression of parkinsonism was assessed by change in a global parkinsonian score (range: 0-100). MIND, Mediterranean, and DASH diet pattern scores were computed based on a validated food frequency questionnaire including 144 food items. We employed Cox-Proportional Hazard models and linear mixed models, to examine the associations of baseline diet scores with incident parkinsonism and the annual rate of change in global parkinsonian score, respectively. RESULTS: In models adjusted for age, sex, smoking, total energy intake, BMI and depressive symptoms, higher MIND diet scores were associated with a decreased risk of parkinsonism [(HR=0.89, 95% CI 0.83-0.96)]; and a slower rate of parkinsonism progression [(ß= -0.008; SE=0.0037; p=0.04)]. The Mediterranean diet was marginally associated with reduced parkinsonism progression (ß= -0.002; SE=0.0014; p=0.06). The DASH diet, by contrast, was not associated with either outcome. CONCLUSION: The MIND diet created for brain health may be a associated with decreased risk and slower progression of parkinsonism in older adults.


Subject(s)
Diet, Mediterranean/psychology , Parkinsonian Disorders/diet therapy , Aged, 80 and over , Disease Progression , Female , Humans , Incidence , Longitudinal Studies , Male , Prospective Studies
19.
Ultrasound Obstet Gynecol ; 48(3): 318-32, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27349699

ABSTRACT

The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the sonographic features of the different phenotypes of endometriosis. Currently, it is difficult to compare results between published studies because authors use different terms when describing the same structures and anatomical locations. We hope that the terms and definitions suggested herein will be adopted in centers around the world. This would result in consistent use of nomenclature when describing the ultrasound location and extent of endometriosis. We believe that the standardization of terminology will allow meaningful comparisons between future studies in women with an ultrasound diagnosis of endometriosis and should facilitate multicenter research. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.


Subject(s)
Consensus , Endometriosis/diagnostic imaging , Peritoneal Diseases/diagnostic imaging , Ultrasonography , Endometriosis/pathology , Female , Humans , Pelvis/pathology , Peritoneal Diseases/pathology , Practice Guidelines as Topic
20.
Hum Reprod ; 31(6): 1253-64, 2016 06.
Article in English | MEDLINE | ID: mdl-27060174

ABSTRACT

STUDY QUESTION: Is the risk of severe ovarian hyperstimulation syndrome (OHSS) similar in a short GnRH antagonist and long GnRH agonist protocol in first cycle IVF/ICSI patients less than 40 years of age?. SUMMARY ANSWER: There is an increased risk of severe OHSS in the long GnRH agonist group compared with the short GnRH antagonist protocol. WHAT IS KNOWN ALREADY?: In the most recent Cochrane review, the GnRH antagonist protocol was associated with a similar live birth rate (LBR), a similar on-going pregnancy rate (OPR), and a lower incidence of OHSS (odds ratio (OR) = 0.43 95% confidence interval (CI): 0.33-0.57) compared with the traditional GnRH agonist protocol. Previous trials comparing the two protocols mainly included selected patient populations, a limited number of patients and the applied OHSS criteria differed, making direct comparisons difficult. In two recent large meta-analyses, no significant differences in LBR (OR = 0.86; 95% CI: 0.72-1.02) or in the incidence of severe OHSS were reported, while others found a lower LBR (OR = 0.82; 95% CI: 0.68-0.97) and a reduced risk of severe OHSS using the GnRH antagonist protocol (OR = 0.60; 95% CI: 0.40-0.88). STUDY DESIGN, SIZE, DURATION: Phase IV, dual-centre, open-label, RCT including 1050 women allocated to either short GnRH antagonist or long GnRH agonist protocol in a 1:1 ratio and enrolled over a 5-year period using a web-based concealed randomization code. This is a superiority study designed to detect a difference in severe OHSS, the primary outcome, between the two groups with a power of 80% and stratified for age, assisted reproductive technology (ART) clinic and planned fertilization procedure (IVF/ICSI). The secondary aims were to compare rates of mild and moderate OHSS, positive plasma (p)-hCG, on-going pregnancy and live birth between the two arms. None of the women had undergone previous ART treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: All infertile women referred for their first IVF/ICSI at two public fertility clinics, less than 40 years of age and with no uterine malformations were asked to participate. A total of 1099 subjects were randomized, including women with poor ovarian reserve, polycystic ovary syndrome and irregular cycles. A total of 49 women withdrew their consent, thus 1050 subjects were allocated to the GnRH antagonist (n = 534) and agonist protocol (n = 516), respectively. In total 1023 women started recombinant human follitropin-ß (rFSH) stimulation, 528 in the GnRH antagonist group and 495 in the GnRH agonist group. All subjects were given a fixed rFSH dose of 150 IU or 225 IU according to age ≤36 years or >36 years, with the option to adjust dose at stimulation day 6. Clinical OHSS parameters were collected at oocyte retrieval, and Days 3 and 14 post-transfer. On-going pregnancy was determined by transvaginal ultrasonography at gestational weeks 7-9. In the intention-to-treat (ITT) analysis for reproductive outcomes, 1050 subjects were included. For the ITT analyses on OHSS 1023 subjects who started gonadotrophin stimulation were included. MAIN RESULTS AND THE ROLE OF CHANCE: The incidence of severe OHSS [5.1% (27/528) versus 8.9% (44/495) (difference in proportion percentage point (Δpp) = -3.8pp; 95% CI: -7.1 to -0.4; P = 0.02)] and moderate OHSS [10.2% (54/528) versus 15.6% (77/495) (Δpp = -5.3pp; 95% CI: -9.6 to -1.0; P = 0.01) ] was significantly lower in the GnRH antagonist group compared with the agonist group, respectively. In the GnRH antagonist and agonist group, respectively, 4.7% (25/528) versus 8.5% (42/495) women were seen by a physician due to OHSS (P = 0.01), and 1.7% (9/528) versus 3.6% (18/495) were admitted to hospital due to OHSS (P = 0.06). No women had ascites-puncture in the GnRH antagonist group versus 2.0% (10/495) in the GnRH agonist group (P < 0.01). LBRs were 22.8% (122/534) versus 23.8% (123/516) (Δpp = -1.0pp; 95% CI: -6.3 to 4.3; P = 0.70) and OPRs were 24.9% (133/528) versus 26.2% (135/516) (Δpp = -1.3pp; 95% CI: -6.7 to 4.2; P = 0.64) per randomized subject in the GnRH antagonist versus agonist group, with a mean number of 1.1 versus 1.2 embryos transferred in the two groups. Pregnancy rates (PR) per randomized subject, per started gonadotrophin stimulation and per embryo transfer were all similar in the two groups. LIMITATIONS, REASONS FOR CAUTION: A possible limitation is the duration of the trial, with new methods, such as 'freeze all' and 'GnRH agonist triggering', being developed during the trial, the new methods were sought avoided, however a total number of 32 women had 'freeze all' and 'GnRH agonist triggering' was performed in three cases. Ultrasonic measurements were performed by different physicians and inter-observer bias may be present. Measures of anti-Mullerian hormone and antral follicle count, to estimate ovarian reserve and thus predict risk of OHSS, were not performed. Finally, the physicians were not blinded to GnRH treatment group after randomization. WIDER IMPLICATIONS OF THE FINDINGS: The short GnRH antagonist protocol should be the protocol of choice for patients undergoing their first ART cycle in females <40 years of age including both low and high responders when an age-dependent initially fixed gonadotrophin dose is used, as an increased risk of severe OHSS and the associated complications is seen in the long GnRH agonist group and as PRs and LBRs are similar in the two groups. Patients at risk of OHSS particularly benefit from the short GnRH antagonist treatment as GnRH agonist triggering can be used. STUDY FUNDING/COMPETING INTERESTS: An unrestricted research grant is funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD). The funders had no influence on the data collection, analyses or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER: EudraCT #: 2008-005452-24. ClinicalTrial.gov: NCT00756028. Trial registration date: 18 September 2008. Date of first patient's enrolment: 14 January 2009.


Subject(s)
Fertilization in Vitro/methods , Gonadotropin-Releasing Hormone/agonists , Ovarian Hyperstimulation Syndrome/epidemiology , Chorionic Gonadotropin/blood , Clinical Protocols , Female , Gonadotropin-Releasing Hormone/administration & dosage , Humans , Incidence , Live Birth , Pregnancy , Pregnancy Rate , Risk Assessment , Time Factors
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