Guideline No. 446: Hysteroscopic Surgery in Fertility Therapy.

OBJECTIVE: To evaluate the indications, benefits, and risks of hysteroscopy in the management of patients with infertility and provide guidance to gynaecologists who manage common conditions in these patients. TARGET POPULATION: Patients with infertility (inability to conceive after 12 months of unprotected intercourse) undergoing investigation and treatment. BENEFITS, HARMS, AND COSTS: Hysteroscopic surgery can be used to diagnose the etiology of infertility and improve fertility treatment outcomes. All surgery has risks and associated complications. Hysteroscopic surgery may not always improve fertility outcomes. All procedures have costs, which are borne either by the patient or their health insurance provider. EVIDENCE: We searched English-language articles from January 2010 to May 2021 in PubMed/MEDLINE, Embase, Science Direct, Scopus, and Cochrane Library (see Appendix B for MeSH search terms). VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional recommendations). INTENDED AUDIENCE: Gynaecologists who manage common conditions in patients with infertility. TWEETABLE ABSTRACT: When offering hysteroscopic surgery to patients with infertility, ensure it improves the live birth rate. SUMMARY STATEMENTS: RECOMMENDATIONS.

Guideline No. 444: Hirsutism: Evaluation and Treatment.

OBJECTIVE: This guideline reviews the etiology, diagnosis, evaluation, and treatment of hirsutism. TARGET POPULATION: Women with hirsutism. OPTIONS: Three approaches to management include: 1) mechanical hair removal; 2) suppression of androgen production; and 3) androgen receptor blockade. OUTCOMES: The main limitations of the management options include the adverse effects, costs, and duration of treatment. BENEFITS, HARMS, AND COSTS: Implementation of the recommendations in this guideline may improve the management of hirsutism in women with this condition. Adverse effects and a potential long duration of treatment are the main drawbacks to initiating treatment, as is the possibility of significant financial costs for certain treatments. EVIDENCE: A comprehensive literature review was updated to April 2022, following the same methods as for the prior Society of Obstetricians and Gynaecologists of Canada (SOGC) Hirsutism guidelines. Results were restricted to systematic reviews, randomized controlled trials, controlled clinical trials, and observational studies. There were no date limits, but results were limited to English- or French-language materials. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, along with the option of designating a recommendation as a "good practice point." See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: Primary care providers, family medicine physicians, obstetricians and gynaecologists, reproductive endocrinologists and others who manage the care of patients with hirsutism. TWEETABLE ABSTRACT: Management of hirsutism involves a 3-pronged approach of mechanical hair removal, suppression of androgen production, and androgen receptor blockade. SUMMARY STATEMENTS: RECOMMENDATIONS.

Guideline No. 435: Minimally Invasive Surgery in Fertility Therapy.

OBJECTIVE: To evaluate the benefits and risks of minimally invasive procedures in the management of patients with infertility and provide guidance to gynaecologists who manage common conditions in these patients. TARGET POPULATION: Patients with infertility (inability to conceive after 12 months of unprotected intercourse) undergoing investigation and treatment. BENEFITS, HARMS, AND COSTS: Minimally invasive reproductive surgery can be used to treat infertility, improve fertility treatment outcomes, or preserve fertility. All surgery has risks and associated complications. Reproductive surgery may not improve fertility outcomes and may, in some instances, damage ovarian reserve. All procedures have costs, which are borne either by the patient or their health insurance provider. EVIDENCE: We searched English-language articles from January 2010 to May 2021 in PubMed/MEDLINE, Embase, Science Direct, Scopus, and Cochrane Library (see Appendix A for MeSH search terms). VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix B (Tables B1 for definitions and B2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: Gynaecologists who manage common conditions in patients with infertility. SUMMARY STATEMENTS: RECOMMENDATIONS.

Directive clinique no 435 : Chirurgie minimalement invasive dans les traitements de fertilité.

OBJECTIF: Évaluer les risques et bénéfices de la chirurgie minimalement invasive dans la prise en charge des patientes atteintes d'infertilité et fournir des conseils aux gynécologues qui prennent en charge les problèmes les plus fréquents chez ces patientes. POPULATION CIBLE: Patientes atteintes d'infertilité (incapacité à concevoir après 12 mois de rapports sexuels non protégés) en processus diagnostique ou sous traitement. BéNéFICES, RISQUES ET COûTS: On peut recourir à la chirurgie de la reproduction minimalement invasive pour traiter l'infertilité, améliorer les résultats des traitements de fertilité ou préserver la fertilité. Toutes les interventions chirurgicales comportent des risques et des complications associées. La chirurgie de la reproduction n'améliore pas toujours la fertilité et peut, dans certains cas, compromettre la réserve ovarienne. Toutes les interventions entraînent des coûts, lesquels sont assumés par la patiente ou son assureur. DONNéES PROBANTES: Des recherches ont été faites dans les bases de données PubMed-Medline, Embase, Science Direct, Scopus et Cochrane Library pour répertorier les articles publiés en anglais dans la période de janvier 2010 à mai 2021 (voir les termes de recherche MeSH à l'annexe A). MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique GRADE (Grading of Recommendations Assessment, Development and Evaluation). Voir l'annexe B en ligne (tableau B1 pour les définitions et tableau B2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]). PROFESSIONNELS CONCERNéS: Gynécologues qui prennent en charge les affections courantes chez les patientes atteintes d'infertilité. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

Assisted human reproduction and pregnancy outcomes in Alberta, 2009-2018: a population-based study.

BACKGROUND: Assisted human reproduction (AHR) can be used to help individuals and couples overcome infertility issues. We sought to describe trends in pregnancies using AHR and to evaluate the impact of AHR on perinatal outcomes in a large population-based cohort in Alberta, Canada. METHODS: We linked maternal and child administrative data for all live births occurring July 1, 2009, to Dec. 31, 2018, in Alberta, Canada, for this retrospective study. We identified AHR pregnancies from pharmaceutical claims or codes from the International Classification of Diseases and Related Health Problems (9th or 10th revision). Our main outcome measures were the incidence and temporal trends of live births in AHR pregnancies. We also compared maternal characteristics and perinatal outcomes of AHR and non-AHR pregnancies, and by maternal age group. RESULTS: Of 518 293 live births during the study period, 26 270 (5.1%) were conceived with AHR. The incidence of AHR pregnancies increased from 30.8 per 1000 pregnancies in 2009 to 54.7 per 1000 pregnancies in 2018. Females who used AHR were older (33.9 yr v. 30.1 yr, p < 0.001) and the number of females aged 30-35 years and older than 35 years who delivered following AHR increased over the study period (30-35 yr: 36.9 to 55.3 per 1000 pregnancies; > 35 yr: 79.1 to 95.2 per 1000 pregnancies). The proportion of live births with cesarean delivery (40.5% v. 23.3%, p < 0.001), low birth weight (26.9% v. 7.6%, p < 0.001), congenital malformation (0.5% v. 0.3%, p = 0.002) and admission to the neonatal intensive care unit (25.3% v. 9.7%, p < 0.001) was higher in the AHR group than the non-AHR group. INTERPRETATION: The incidence of live births following AHR pregnancies in Alberta was 5.1% between 2009 and 2018, and increased by 0.26% per year; newborns in the AHR group appeared smaller and showed signs of poorer health. This study provides insights on potential perinatal complications following AHR that may be important when caring for the newborn child.

Predicting acute ovarian failure in female survivors of childhood cancer: a cohort study in the Childhood Cancer Survivor Study (CCSS) and the St Jude Lifetime Cohort (SJLIFE).

BACKGROUND: Cancer treatment can cause gonadal impairment. Acute ovarian failure is defined as the permanent loss of ovarian function within 5 years of cancer diagnosis. We aimed to develop and validate risk prediction tools to provide accurate clinical guidance for paediatric patients with cancer. METHODS: In this cohort study, prediction models of acute ovarian failure risk were developed using eligible female US and Canadian participants in the Childhood Cancer Survivor Study (CCSS) cohort and validated in the St Jude Lifetime Cohort (SJLIFE) Study. 5-year survivors from the CCSS cohort were included if they were at least 18 years old at their most recent follow-up and had complete treatment exposure and adequate menstrual history (including age at menarche, current menstrual status, age at last menstruation, and menopausal aetiology) information available. Participants in the SJLIFE cohort were at least 10-year survivors. Participants were excluded from the prediction analysis if they had an ovarian hormone deficiency, had missing exposure information, or had indeterminate ovarian status. The outcome of acute ovarian failure was defined as permanent loss of ovarian function within 5 years of cancer diagnosis or no menarche after cancer treatment by the age of 18 years. Logistic regression, random forest, and support vector machines were used as candidate methods to develop the risk prediction models in the CCSS cohort. Prediction performance was evaluated internally (in the CCSS cohort) and externally (in the SJLIFE cohort) using the areas under the receiver operating characteristic curve (AUC) and the precision-recall curve (average precision [AP; average positive predictive value]). FINDINGS: Data from the CCSS cohort were collected for participants followed up between Nov 3, 1992, and Nov 25, 2016, and from the SJLIFE cohort for participants followed up between Oct 17, 2007, and April 16, 2012. Of 11 336 female CCSS participants, 5886 (51·9%) met all inclusion criteria for analysis. 1644 participants were identified from the SJLIFE cohort, of whom 875 (53·2%) were eligible for analysis. 353 (6·0%) of analysed CCSS participants and 50 (5·7%) of analysed SJLIFE participants had acute ovarian failure. The overall median follow-up for the CCSS cohort was 23·9 years (IQR 20·4-27·9), and for SJLIFE it was 23·9 years (19·0-30·0). The three candidate methods (logistic regression, random forest, and support vector machines) yielded similar results, and a prescribed dose model with abdominal and pelvic radiation doses and an ovarian dose model with ovarian radiation dosimetry using logistic regression were selected. Common predictors in both models were history of haematopoietic stem-cell transplantation, cumulative alkylating drug dose, and an interaction between age at cancer diagnosis and haematopoietic stem-cell transplant. External validation of the model in the SJLIFE cohort produced an estimated AUC of 0·94 (95% CI 0·90-0·98) and AP of 0·68 (95% CI 0·53-0·81) for the ovarian dose model, and AUC of 0·96 (0·94-0·97) and AP of 0·46 (0·34-0·61) for the prescribed dose model. Based on these models, an online risk calculator has been developed for clinical use. INTERPRETATION: Both acute ovarian failure risk prediction models performed well. The ovarian dose model is preferred if ovarian radiation dosimetry is available. The models, along with the online risk calculator, could help clinical discussions regarding the need for fertility preservation interventions in girls and young women newly diagnosed with cancer. FUNDING: Canadian Institutes of Health Research, Women and Children's Health Research Institute, National Cancer Institute, and American Lebanese Syrian Associated Charities.

Evolution of the fetal atrioventricular interval from 6 to 40 weeks of gestation

Doppler-based methods of estimating the atrioventricular interval are commonly used as a surrogate for the electrical PR in fetuses at risk of conduction abnormalities; however, to date, normal values for the fetal atrioventricular interval and an understanding of the evolution of its components in the late first trimester are lacking. We sought to investigate changes in the fetal atrioventricular interval from the first trimester to 40 weeks gestational age, and to explore functional and electrophysiological events that potentially impact its evolution. We prospectively examined healthy pregnancies by fetal echocardiography from 6 to 40 weeks' gestational age. The atrioventricular interval, heart rate, isovolumic contraction time, and A-wave duration were measured from simultaneous ventricular inflow-outflow Doppler tracings. Regression analysis was used to examine relations with gestational age, and linear relations with heart rate were assessed by Pearson's correlation coefficient. Data were collected in 305 fetuses from 279 pregnancies. Atrioventricular interval demonstrated an inverse relation with heart rate (r = -0.45, p <0.0001), dramatically decreasing before 10 weeks and slowly increasing thereafter. Between 6 and 9 weeks, isovolumic contraction time acutely decreasedapproaching 0, thereafter minimally increasing to term. In contrast, from 6 weeks, the A-wave duration linearly increased through gestation, and negatively correlated with heart rate (r = -0.62, p <0.0001). In conclusion, we have established normal measures of the atrioventricular interval from 6 to 40 weeks' gestational age. Before 10 weeks, a prolonged atrioventricular interval in healthy fetuses largely reflects the lengthened isovolumic contraction time which is likely influenced by the evolution of ventricular function and afterload. (AU)

Evolution of the Fetal Atrioventricular Interval from 6 to 40 Weeks of Gestation.

Doppler-based methods of estimating the atrioventricular interval are commonly used as a surrogate for the electrical PR in fetuses at risk of conduction abnormalities; however, to date, normal values for the fetal atrioventricular interval and an understanding of the evolution of its components in the late first trimester are lacking. We sought to investigate changes in the fetal atrioventricular interval from the first trimester to 40 weeks gestational age, and to explore functional and electrophysiological events that potentially impact its evolution. We prospectively examined healthy pregnancies by fetal echocardiography from 6 to 40 weeks' gestational age. The atrioventricular interval, heart rate, isovolumic contraction time, and A-wave duration were measured from simultaneous ventricular inflow-outflow Doppler tracings. Regression analysis was used to examine relations with gestational age, and linear relations with heart rate were assessed by Pearson's correlation coefficient. Data were collected in 305 fetuses from 279 pregnancies. Atrioventricular interval demonstrated an inverse relation with heart rate (r = -0.45, p <0.0001), dramatically decreasing before 10 weeks and slowly increasing thereafter. Between 6 and 9 weeks, isovolumic contraction time acutely decreased approaching 0, thereafter minimally increasing to term. In contrast, from 6 weeks, the A-wave duration linearly increased through gestation, and negatively correlated with heart rate (r = -0.62, p <0.0001). In conclusion, we have established normal measures of the atrioventricular interval from 6 to 40 weeks' gestational age. Before 10 weeks, a prolonged atrioventricular interval in healthy fetuses largely reflects the lengthened isovolumic contraction time which is likely influenced by the evolution of ventricular function and afterload.

No. 350-Hirsutism: Evaluation and Treatment.

OBJECTIVES: To review the etiology, evaluation, and treatment of hirsutism. EVALUATION: A thorough history and physical examination plus selected laboratory evaluations will confirm the diagnosis and direct treatment. TREATMENT: Pharmacologic interventions can suppress ovarian or adrenal androgen production and block androgen receptors in the hair follicle. Hair removal methods and lifestyle modifications may improve or hasten the therapeutic response. OUTCOMES: At least 6 to 9 months of therapy are required to produce improvement in hirsutism. EVIDENCE: The quality of evidence reported in this guideline has been determined using the criteria described by the Canadian Task Force on the Periodic Health Examination. RECOMMENDATIONS: Hirsutism can be slowly but dramatically improved with a 3-pronged approach to treatment: mechanical hair removal, suppression of androgen production, and androgen receptor blockade. Lifestyle changes, including weight loss and exercise, will lower serum androgen levels and improve self-esteem in patients with polycystic ovary syndrome. The patient should be educated regarding the associated health problems or long-term medical consequences of hyperandrogenism, particularly in the context of polycystic ovary syndrome, including obesity, irregular menses, anovulation, infertility, pregnancy-induced hypertension, diabetes, hyperlipidemia, hypertension, and heart disease. SUMMARY STATEMENTS: RECOMMENDATIONS.

First-Trimester Fetal Echocardiography: Identification of Cardiac Structures for Screening from 6 to 13 Weeks' Gestational Age.

BACKGROUND: Early fetal echocardiography (FE), performed at 12 to 16 weeks' gestational age (GA), can be used to screen for fetal heart disease akin to that routinely performed in the second trimester. The efficacy of FE at earlier GAs has not been as well explored, particularly with recent advances in ultrasound technology. The aim of this study was to evaluate the efficacy of early FE in assessing fetal heart structure, and the added benefit of color Doppler (CD), from as early as 6 weeks through to 13+6 weeks' GA. METHODS: Pregnant women were prospectively recruited for first-trimester FE. All underwent two-dimensional (2D) cardiac imaging combined with CD assessment, and all were offered second-trimester fetal echocardiographic evaluations. Fetal cardiac anatomy was assessed both in real time during FE and additionally offline by two separate reviewers. RESULTS: Very early FE was performed in 202 pregnancies including a total of 261 fetuses, with 92% (n = 241) being reassessed at ≥18 weeks' GA. Mean GA at FE was 10+6 weeks (range, 6+1 to 13+6 weeks). Transabdominal scanning was used in all cases, and transvaginal scanning was used additionally in most at <11 weeks' GA (n = 103 of 117 [88%]). There was stepwise improvement in image resolution of the fetal heart in those pregnancies that presented at later gestation for assessment. CD assisted with definition of cardiac anatomy at all GAs. A four-chambered heart could be identified in 52% of patients in the eighth week (n = 12 of 23), improving to 80% (n = 36 of 45) in the 10th week and 98% (n = 57 of 58) by the 11th week. The inferior vena cava was visualized by 2D imaging in only 4% (n = 1 of 23) in the eighth week, increasing to 13% (n = 6 of 45) by the 10th week and 80% (n = 25 of 31) by the 13th week. CD improved visualization of the inferior vena cava at earlier GAs to >80% (n = 37 of 45) from 10 weeks. Pulmonary veins were not visualized by either 2D imaging or CD until after the 11th week. Both cardiac outflow tracts could be visualized by 2D imaging in the minority from 8+0 to 10+6 weeks (n = 18 of 109 [16%]) but were imaged in most from 11+0 to 13+6 weeks (n = 114 of 144 [79%]). CD imaging improved visualization of both outflow tracts to 64% (n = 29 of 45) in the 10th week. On 2D imaging alone, both the aortic and ductal arches were seen in only 29% of patients in the 10th week (n = 13 of 45), increasing to 58% when CD was used (58% [n = 26 of 45]) and to >80% (n = 47 of 58) using CD in the 11th week. CONCLUSIONS: Very early FE, from as early as 8 weeks, can be used to assess cardiac structures. The ability to image fetal heart structures between 6 and 8 weeks is currently nondiagnostic. The use of CD significantly increases the detection of cardiac structures on early FE. The ideal timing of complete early FE, excluding pulmonary vein assessment, appears to be after 11 weeks' GA.

Mature Oocyte Cryopreservation for Fertility Preservation.

In recent decades, advances in cancer treatment have led to a dramatic improvement in long term survival. This has led to an increasing focus on quality of life after surviving cancer treatment, with fertility being an important aspect. Given the known reproductive risks of cancer therapies, there has been a growing interest in the field of fertility preservation (also referred to as oncofertility). Mature oocyte cryopreservation is no longer considered experimental and has become a realistic option for reproductive aged women prior to undergoing cancer treatment. Additionally, as cryopreservation techniques improve, mature oocyte cryopreservation is increasing being marketed to healthy women without cancer wishing to delay child bearing, also termed "social egg freezing". This chapter provides a review of the current technology, use, and outcomes of mature oocyte cryopreservation. It also outlines the ethical debate surrounding social egg freezing and directions for future research in female fertility preservation.

Assisted Reproductive Technologies in Alberta: An Economic Analysis to Inform Policy Decision-Making.

OBJECTIVE: Regulation and public funding of assisted reproductive technologies (ARTs) vary across the Canadian provinces. In Alberta, neither of these exists. We conducted this study to evaluate the cost effectiveness and budget impact of providing ARTs in Alberta under three different policy scenarios (a "restrictive" policy, a policy based on Quebec's model, and a "permissive" policy) in comparison with the status quo. METHODS: To predict the cost effectiveness and budget impact of three policy options for publicly funded ARTs in Alberta, we developed an economic model by combining a state transition Markov model and a decision tree. The primary outcome was cost per healthy singleton. Probabilistic and one-way sensitivity analyses were conducted. RESULTS: The restrictive policy was the most cost effective option for two subgroups of age (< 35 years and 35 to 39 years), while the Quebec policy option was most cost-effective for the ≥ 40 years subgroup. Budget impact analysis extending up to the age of 18 years for the children in the model showed the cost savings of $8.33 million for the restrictive policy for the < 35 years subgroup. For the ≥ 40 years subgroup, the Quebec policy option resulted in total cost savings of $3.75 million. Sensitivity analyses showed that the model results were robust. CONCLUSION: This economic modelling study shows that publicly funded and scientifically regulated ARTs could provide treatment access and save health care expenditures for the province.

Objectif : La réglementation et le financement public des techniques de procréation assistée (TPA) varient d'une province canadienne à l'autre. En Alberta, les TPA ne sont ni réglementées ni financées par les deniers publics. Nous avons mené cette étude dans le but d'évaluer la rentabilité de l'offre de TPA en Alberta et les effets d'une telle mesure sur le budget albertain en fonction de trois scénarios de politique différents (une politique « restrictive ¼, une politique fondée sur le modèle québécois et une politique « permissive ¼), par comparaison avec le statu quo. Méthodes : Pour prédire la rentabilité de ces trois options de politique (prévoyant l'offre de TPA financées par les deniers publics en Alberta) et leurs effets sur le budget provincial, nous avons élaboré un modèle économique en combinant un modèle Markov (transitions d'état) et un arbre décisionnel. Le coût par nouveau-né en santé issu d'une grossesse monofœtale constituait le critère d'évaluation principal. Des analyses simples de la variance en matière de sensibilité et des analyses probabilistes ont été menées. Résultats : La politique « restrictive ¼ a constitué l'option la plus rentable dans deux sous-groupes d'âge (< 35 ans et 35-39 ans), tandis que la politique fondée sur l'approche québécoise a constitué l'option la plus rentable dans le sous-groupe des ≥ 40 ans. L'analyse des effets sur le budget (jusqu'à ce que les enfants générés par le modèle ait atteint l'âge de 18 ans) a indiqué l'obtention d'économies de 8,33 millions de dollars pour ce qui est de la politique « restrictive ¼ dans le sous-groupe des < 35 ans. Dans le sous-groupe des ≥ 40 ans, l'option de la politique fondée sur l'approche québécoise a mené à l'obtention d'économies totales de 3,75 millions de dollars. Les analyses de la sensibilité ont indiqué que les résultats modélisés étaient robustes. Conclusion : Cette étude de modélisation économique indique que l'offre de TPA financées par les deniers publics et faisant l'objet d'une réglementation scientifique pourrait assurer l'accès au traitement et permettre l'obtention d'économies pour la province.

DEFINING ELIGIBILITY CRITERIA FOR FUNDING POLICIES AROUND IN VITRO FERTILIZATION.

OBJECTIVES: This review aims to assess the state of the science around the potential impact of certain patient characteristics on the safety and effectiveness of in vitro fertilization (IVF). METHODS: Following Cochrane Collaboration guidelines and the PRISMA statement, a comprehensive systematic review of reviews and recent primary studies examining the impact of paternal age and maternal age, smoking, and body mass index (BMI) on the safety and effectiveness of IVF was performed. Papers, published between January 2007 and June 2014, were independently reviewed and critically appraised by two researchers using published quality assessment tools for reviews and primary studies. Due to heterogeneity across papers (different study designs and patient selection criteria), a qualitative analysis of extracted information was performed. RESULTS: Seventeen papers (ten systematic reviews and seven primary studies) were included. They comprised evidence from retrospective observational studies in which maternal age, BMI, and smoking status were explored as part of secondary analyses of larger studies. The majority of papers found that the likelihood of achieving a pregnancy was lower among women who were >40 years, had a BMI ≥ 25 and smoked. Advanced maternal age and BMI were also associated with higher rates of preterm birth and low birth weight. CONCLUSIONS: Based on available evidence, it may be appropriate to consider "maternal age" and "morbid obesity" in public funding policies that aim to maximize the effectiveness of IVF. However, given inconsistencies in the effect of smoking across different pregnancy-related outcomes, support for incorporating it into funding conditions appears weak.

Assisted reproductive technologies (ARTs): evaluation of evidence to support public policy development.

Over the years, IVF/ICSI protocols have continued to evolve with efforts to improve outcomes. As a result, treatment success may be related to certain procedural factors, including number of embryos transferred and stage at which they are transferred. This review aims to assess the safety and effectiveness of IVF/ICSI in comparison to spontaneous conception and less invasive ARTs and the impact of procedure-related factors on the outcomes of IVF/ICSI in order to support the development of local clinical and policy guidance. Following Cochrane Collaboration guidelines and the PRISMA statement, a comprehensive systematic review of literature examining the impact of procedural characteristics on the safety or effectiveness of IVF/ICSI from 2007 to date was performed. 33 systematic reviews and 3 primary studies evaluating the impact of procedural differences, IVF/ICSI in comparison to less invasive ARTs, and ARTs in comparison to spontaneous conception were found. IVF was shown to offer significant benefits over no treatment and IUI in achieving pregnancy and live birth among couples with endometriosis or unexplained infertility. Frozen and blastocyst-stage embryo transfers were as effective as fresh and cleavage-stage embryo transfers, respectively. In comparison to single embryo transfer, double embryo transfer significantly increased pregnancy, live birth and multiple pregnancy/birth rates. IVF/ICSI was associated with more complications during pregnancy and delivery, and in infants compared to naturally conceived pregnancies, particularly when multiple embryo transfer was used. Frozen embryo transfer had fewer adverse events during pregnancy and delivery than fresh embryo transfer, and was at least as safe in terms of infant outcomes. The potential complications of IVF/ICSI may be minimized through procedural choices, but such choices often impact effectiveness. Thus, in developing clinical and policy guidance around IVF/ICSI, the risk-benefit trade-offs patients and providers are willing to accept must be carefully considered.

Antegrade late diastolic arterial blood flow in the fetus: insight into fetal atrial function.

OBJECTIVE: The purpose of this study was to examine the presence and frequency of antegrade late diastolic arterial blood flow (ALDAF) in the fetus and to determine its contribution to cardiac output. STUDY DESIGN: We evaluated the presence of ALDAF in 457 fetal and 21 postnatal echocardiograms. The timing of ALDAF to the ventricular systolic Doppler recording (ALDAF-V) was compared with the mechanical atrioventricular interval and, in neonates, the electrical PR interval. Velocity time integrals of ALDAF and the ventricular systolic Doppler signals were measured, and the percent contribution of ALDAF was calculated. RESULTS: ALDAF was observed in 365 of 457 studies and included all <11 weeks' gestations. Strong correlation between ALDAF-V, atrioventricular interval, and electrical PR interval suggests that ALDAF coincides with atrial contraction. ALDAF contributed substantially to cardiac output in early gestation with later decline. CONCLUSION: ALDAF results from atrial contraction. Increasing gestational age results in less ALDAF, and reduced ALDAF contribution to cardiac output likely due to improved diastolic function.

Gonadotropin-releasing hormone agonist in laparoscopic myomectomy: systematic review and meta-analysis of randomized controlled trials.

A systematic review and meta-analysis of randomized controlled trials was performed to estimate the effects on surgical outcomes of pretreatment with gonadotropin-releasing hormone (GnRH) agonist before laparoscopic myomectomy. The electronic bibliographic databases MEDLINE, EMBASE, Web of Knowledge, Scopus, and Cochrane Library, and reference lists from relevant articles were searched for English-language publications describing randomized controlled trials of GnRH agonist pretreatment vs placebo or no treatment before laparoscopic myomectomy. Three studies including 168 participants were identified. Pretreatment with GnRH agonist did not reduce operative time; however, intraoperative blood loss was statistically lowered (mean difference, 60 mL; 95% confidence interval [CI], 39-82). Statistical difference was also observed in postoperative hemoglobin concentration (mean difference, 1.15 g/dL; 95% CI, 0.46-1.83]) and red blood cell count (mean difference, 0.65 × 10(6) cells/mL; 95% CI, 0.16-1.14]) but not serum iron concentration. None of the patients in the studies experienced any major intraoperative or postoperative complications, and only 1 patient in each group required blood transfusion. This study does not show a difference in operative time with GnRH agonist pretreatment, which clarifies the previous conflicting reports on the effect of GnRH agonist therapy on the duration of laparoscopic myomectomy. Furthermore, despite previously reported decreased bleeding conferred by the laparoscopic approach compared with laparotomy, this meta-analysis demonstrates a further reduction in intraoperative blood loss with GnRH agonist pretreatment in patients undergoing laparoscopic myomectomy. Additional high-quality studies with appropriate power and follow-up are needed to corroborate these findings and to evaluate the treatment effects on short- and long-term outcomes such as perioperative complications and fertility.