Physicians' attitudes towards using elective oocyte cryopreservation to accommodate the demands of their career.

PURPOSE: Among medical professionals, there appears to be a significant lack of knowledge about oocyte cryopreservation. Medical professionals may be potential candidates for elective oocyte cryopreservation due to the demands and commitments of medical training. There is a paucity of data on this topic among medical professionals. The aim of this study was to assess knowledge, understanding, and beliefs towards elective egg freezing among medical professionals to assess whether they are potential candidates for elective egg freezing. METHODS: This is a cross-sectional descriptive study in a university-based training program. All medical students, residents, fellows, and faculty were included. An online survey was emailed to potential participants. It included demographic questions regarding childbearing decision-making factors, fertility knowledge, and attitudes towards using elective oocyte cryopreservation. RESULTS: A total of 1000 emails were sent. Of those, 350 completed surveys were received. On average, 33% of responders provided a correct answer to each fertility knowledge question. The duration of training and the heavy workload with long duty hours were the most common influencing factors when deciding the timing of childbearing. Overall, 65% of the male and female responders were concerned about their future fertility. Among those women who had future fertility concerns, 8% were not aware of egg freezing as a fertility option and wished they had had an opportunity to freeze their eggs at an earlier time. CONCLUSIONS: Physicians' childbearing decisions can be affected by the demands of their careers. Elective oocyte cryopreservation could be considered an option for family planning. Educational sessions and awareness programs are needed to provide information about available fertility preservation options, which can potentially decrease the rate of regret.

Caesarean Delivery Surgical Site Infection: What are Expected Rates and Potentially Modifiable Risk Factors?

OBJECTIVE: This study sought to determine baseline Caesarean delivery (CD) surgical site infection (SSI) rates in various patient subgroups and to identify potentially modifiable and non-modifiable risk factors for SSI. METHODS: This is a secondary analysis of a multicentre CD registry. Women who underwent CD were divided into SSI versus no SSI. SSI was defined as an infection that occurred in the part of the body where the surgery took place, within 30 days of surgery. Clinical characteristics and potential risk factors were compared between groups. RESULTS: Of 57 182 women, 3696 (6.5%) had SSI. SSI rates were higher in primary versus repeat CD (9.7% vs. 4.2%; P <0.001), and in CD after labour vs. no labour (9.5% vs. 3.8%; P <0.001). After adjustment for confounding factors, low transverse CD (adjusted OR [aOR] 0.7 [0.6-0.9]), CD performed between 7 pm and 7 am (aOR 0.9 [0.83-0.98]), primary CD (aOR 0.5 [0.5-0.6]), and intrapartum antibiotics (aOR 0.3 [0.1-0.4]) were associated with a decreased in the rate of SSI. Black race (aOR 1.9 [1.7-2.1]), tobacco use (aOR 1.4 [1.2-1.6]), increasing American Society of Anesthesiologists category (aOR 1.3 [1.1-1.6]), vertical skin incision (aOR 1.2 [1.1-1.3], emergency CD (aOR 1.3 [1.1-1.5]), and postpartum transfusion (aOR 2.7 [2.1-3.6]) were associated with an increase in the rate of SSI. CONCLUSION: This study estimates the CD SSI rates in different subgroups and serves as a baseline for future trials designed to develop preventive guidelines and protocols.

Neonatal outcomes among twins stratified by method of conception: secondary analysis of maternal fetal medicine (MFMU) network database.

PURPOSE: To investigate whether twin pregnancies conceived by different forms of fertility treatments are associated with adverse neonatal outcomes and to examine the difference in maternal and obstetrical characteristics between patients. METHODS: Our study was a retrospective analysis of twin pregnancies conceived by fertility treatments from a prospectively collected database. Treatments were stratified into two groups: group 1 (ART) consisted of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), and group 2 (non-ART) included intrauterine insemination (IUI) and ovulation induction (OI). Composite neonatal morbidity included respiratory distress syndrome, intraventricular hemorrhage, leukomalacia, chronic lung disease, and death prior to discharge. RESULTS: There were 460 neonates in our study; among them, 67% (n = 310) were in group 1, and 33% (n = 150) in group 2. Group 1 patients were more likely to be older (p = 0.004), nulliparous (p = 0.01), delivered twins with lower birth weights (2278 g ± 605 vs. 2427 ± 519, p = 0.009), and had more deliveries < 32 weeks gestation (p = 0.001). In multivariable Poisson regression model, only neonatal intensive care unit admission rate was increased for group 1 twins (aRR = 1.27, 95% CI 1.003-1.60). CONCLUSIONS: After adjusting for confounders, twins conceived via ART compared to non-ART had similar neonatal outcomes. These data can help when counseling this patient population and assist in planning larger prospective cohorts.

Uterine Fibroids and Hypertensive Disorders in Pregnancy: A Systematic Review and Meta-Analysis.

Capsule: In this study the presence of uterine fibroids was significantly associated with an increased risk of development of hypertensive disorders of pregnancy even when accounting for age and BMI in meta-regression. This finding has potential implications for risk stratification and monitoring for hypertension during pregnancy in this population. Objective: To examine the association between uterine fibroids and the development of hypertensive disorders in pregnancy. Data sources: Cochrane, Embase, PubMed, MEDLINE, Scopus, and Web of Science databases were searched from inception through April 2023. Study Selection and Synthesis: Cohort, case-control, or case series studies including uterine fibroid status and hypertensive disorders of pregnancy status were included. The comparison group was pregnant women without uterine fibroids. Inverse-variance weighted random effects models were used to pool RR and OR estimates separately. Age and BMI were explored as potential sources of heterogeneity using inverse-variance weighted meta-regression. Main Outcomes: Hypertensive disorders of pregnancy (HDP) defined as gestational hypertension, pre-eclampsia, eclampsia, superimposed preeclampsia, or hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Results: A total of 17 studies were included (Total N=1,374,395 participants, N=64,968 with uterine fibroids). Thirteen studies were retrospective cohorts and four were case-control studies. Women with uterine fibroids had a significantly higher risk of hypertensive disorders in pregnancy compared to women without uterine fibroids with RR 1.74 (95% CI 1.33-2.27, p<0.01), and OR 2.87 (95% CI 1.38-5.97, p<0.01), in cohort studies and case-control studies, respectively. In meta-regression analyses, age did not significantly change the positive association between uterine fibroids and hypertensive disorders in pregnancy. Conclusion: Uterine fibroids were associated with an increased risk of hypertensive disorders of pregnancy when all available literature was synthesized, including when shared risk factors are examined in meta-regression analyses. Relevance: If confirmed in future studies, investigations into the mechanisms of this association are needed as this finding potentially has implications for risk stratification and monitoring for hypertensive disorders of pregnancy in this population. Trial Registration: PROSPERO, ID # 331528.

Elective egg freezing: what is the vision of women around the globe?

AIM: The interest in oocyte cryopreservation (OC) for nonmedically indicated reasons is increasing. Knowing women's beliefs and knowledge from various geographic regions could help providers to understand the similarities and differences that could facilitate proper counseling. MATERIALS & METHODS: Articles about social egg freezing published over the past 18 years were extracted from the literature. RESULTS: We demonstrated that there are common rationales toward OC among women in the USA and other countries. The ultimate goal was to prolong fertility. The most commonly reported reasons were aging, lack of partner, career and financial status. CONCLUSION: The beliefs and rationales toward elective OC among women in the USA and other countries are consistent.

Management and reproductive counseling in cervical, caesarean scar and interstitial ectopic pregnancies over 11 years: identifying the need for a modern management algorithm.

STUDY QUESTION: Do management strategies (treatment type and order), including provision of reproductive counseling, differ in patients with non-tubal pregnancies? SUMMARY ANSWER: Medical and surgical treatment strategies varied widely for each type of non-tubal pregnancy and reproductive counseling in this patient population is lacking. WHAT IS KNOWN ALREADY: Owing to the rarity of non-tubal pregnancies, there is no consensus regarding treatment strategies or protocol. Furthermore, there is limited data on how patients with a non-tubal pregnancy are counseled about future fertility. STUDY DESIGN SIZE DURATION: This is a descriptive retrospective study. Data were collected from January 2006 to December 2017. A total of 50 patients were included in the study. PARTICIPANTS/MATERIALS SETTING METHODS: Patients with an ultrasound diagnosis of a non-tubal ectopic pregnancy (e.g. cervical ectopic pregnancy [CEP], Caesarean scar pregnancy [CSP] or interstitial ectopic pregnancy [IEP]) were included. This study was performed at a university-based institution tertiary referral center. Demographic and clinical characteristics, treatment type and order, reproductive counseling and outcomes were collected. Descriptive statistics were used for analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 50 patients identified, 13 were CEP (26%), 8 were CSP (16%) and 29 were IEP (58%). Patients with a CSP had a higher parity (median = 3, P = 0.02) and number of prior Caesarean deliveries (mean = 2.1, P < 0.001). A total of 66% (23/35) of patients expressed a desire for future fertility prior to treatment and only 56% (28/50) of patients received reproductive counseling according to the electronic medical records. Among all non-tubal pregnancies, there were variations in the type and the order of treatments that patients received. LIMITATIONS REASONS FOR CAUTION: This study was performed in a tertiary referral center therefore the management strategy could have been influenced by the prior interventions and patient response. The descriptive retrospective design precluded any assumption of causation. WIDER IMPLICATIONS OF THE FINDINGS: The management for non-tubal pregnancies has wide variations. Reproductive counseling in this patient population is lacking. The findings highlight the need for the development of a treatment algorithm and a reproductive counseling protocol for each non-tubal pregnancy to better standardize treatment strategy. STUDY FUNDING/COMPETING INTERESTS: There was no funding for this study. The authors have no conflict of interest to report.

Composite neonatal and maternal morbidities with small- versus appropriate- for gestational age among uncomplicated obese women undergoing repeat cesarean delivery.

PURPOSE: Our goal was to compare composite neonatal and maternal morbidities (composite neonatal morbidity (CNM), composite maternal morbidity (CMM)) among deliveries with small for age (SGA) versus appropriate for gestational age (AGA; birthweight 10-89%) among obese versus non-obese women undergoing repeat cesarean delivery (CD). STUDY DESIGN: This is a secondary analysis of a prospective observational study. Women who had elective CD ≥37 weeks were studied. We excluded multiple gestations, fetal anomalies, > 1 prior CD, and medical diseases. Patients were divided into BMI ≥30 versus <30 kg/m2. CNM included respiratory distress syndrome, necrotizing enterocolitis, severe intraventricular hemorrhage, seizure, or death; CMM included transfusion, hysterectomy, operative injury, coagulopathy, thromboembolism, pulmonary edema, or death. Multivariate logistic regression was used to control for confounding factors. RESULTS: Of 7561 women, we included 65% were obese and 35% were not. SGA rates differed significantly: 8 versus 12% (p < .001). Overall, CNM was significantly higher in patients with SGA versus AGA (adjusted odds ratio (aOR) 2.04, 95% CI 1.19-3.49). CMM of SGA in obese versus non-obese was statistically different (aOR 0.11, 95% CI 0.02-0.68). Among obese mothers, SGA neonates had significantly higher CNM compared with AGA ones (aOR 2.17, 95% CI 1.03-4.59). CONCLUSIONS: SGA occurred in 8% of low-risk obese women with prior CD. CNM of SGA babies in obese versus non-obese women were similar. Paradoxically, CMM was lower in obese cases, possibly reflecting the caution that obese patients receive preoperatively. Our findings may assist in counseling patients and designing trials.

The impact of time of delivery on gestations complicated by preterm premature rupture of membranes: daytime versus nighttime.

Background: Perinatal death, in particular intrapartum stillbirth and short-term neonatal death, as well as neonatal short-term and long-term morbidity have been associated with the time of day that the birth occurs. Indeed, evening and nighttime deliveries were associated with an increased risk of an adverse perinatal outcome when compared to similar daytime deliveries. Impact of shift change, as well as time of day delivery have been extensively studied in the context of maternal and neonatal complications of cesarean delivery, however, no studies were previously performed on timing of delivery and its effect on the outcome of pregnancies complicated by preterm premature rupture of membranes. Objective: Our objective was to compare obstetric, neonatal as well as long-term outcomes between women delivered in the daytime versus nighttime, in singleton gestations whose pregnancies were complicated by preterm premature rupture of membranes. Study design: This was a secondary analysis of a trial of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network "A Randomized Clinical Trial of the Beneficial Effects of Antenatal Magnesium Sulfate for the Prevention of Cerebral Palsy." For this analysis, the time of delivery was divided into the daytime, from 07:01 to 19:00, and the nighttime, from 19:01 to 07:00. Epidemiological, obstetric characteristics as well as neonatal and long-term outcomes were compared between deliveries occurring during the daytime versus the nighttime periods. Inclusion criteria consisted of singleton gestations diagnosed with preterm premature rupture of membranes (PPROM). Multifetal gestations and pregnancies with preterm labor without preterm premature rupture of membranes were excluded. Results: A total of 1752 patients met inclusion criteria, 881 delivering during the daytime, while 871 during the nighttime. There were no differences in demographic maternal variables. There were no differences in the number of patients receiving steroids and the doses of steroids. Antibiotic prophylaxis was also equal in both groups. Postpartum endometritis, chorioamnionitis, and the latency to delivery were also equivalent between both the groups. Cesarean delivery for distress was the only different outcome, more prevalent in daytime deliveries (157 (44.7%) versus 108 (35.9%) of the nighttime ones p = .02). Neonatal adverse outcomes as well as long-term outcomes were similar between the two groups. Conclusions: In the setting of delivery at a tertiary care center, and in the era of universal use of steroids, and latency antibiotics for the management of preterm premature of membranes, there is no marked difference in pregnancy, neonatal as well as long-term outcomes for infants delivered in the daytime versus nighttime.

A Mentorship Program for Academic Obstetrician Gynecologists that Improved Publication and Overall Confidence for Success.

This article aims to evaluate the impact of a mentorship program to enhance the training of clinical and research scientists in obstetrics and gynecology (OBGYN). A departmental course was developed for junior faculty and fellows based on their areas of interest. The research was IRB-approved. The curriculum consisted of monthly interactive workshops for an interdisciplinary group of trainees in OBGYN. Themes included research, education, and leadership in academic OBGYN. There was a strong emphasis on participatory exercises. Examples of curriculum topics included manuscript publication and review, grant writing, working with an IRB, promotion, and time management. Pre- and post-course questionnaires assessed participants' confidence in skills related to the course topics. Generalized linear models were used to assess changes in post-course response, using each question as the dependent variable and an indicator for post-course as the predictor variable. The control group was composed of junior faculty and fellows before the course was initiated. Outcome measures included the number and impact factor of published manuscripts. A Wilcoxon rank-sum test was used to assess outcome measures. Of the 118 attendees, 26 (22.0%) were junior faculty, 35 (29.66%) were clinical fellows, and 28 (23.7%) were research fellows, other research staff, or students. For each 3-year course series, an average of 20 participants completed the post-course surveys, of which 72% were clinical fellows, 22% were assistant professors, and 5% were instructors. The data revealed a statistically significant change in the participant's overall confidence in skills related to research, education, and leadership when comparing the cumulative results from the pre-to-post course surveys (p < 0.001). Specifically, participants noted improved confidence in their skills related to clinical and translation research (p < 0.001) and leadership and academic career advancement (p = 0.001). Additionally, junior faculty and clinical fellows who attended the course had a higher number of publications during the course period compared with controls (p = 0.003 and p = 0.008, respectively). This subspecialty-tailored, departmental training program was effective in increasing junior faculty and clinical fellows' confidence in skills related to career advancement and research and in the number of peer-reviewed publications.

Same-day confirmation of intrauterine pregnancy failure in women with first- and early second-trimester bleeding.

OBJECTIVE: To determine if alpha-fetoprotein (AFP) concentration in vaginal blood, in the setting of dissolved fetal tissue, is significantly higher than its concentration in the maternal serum. DESIGN: A prospective cohort study. SETTING: Medical center. PATIENT(S): Four groups of women were evaluated: 1) with missed/incomplete miscarriage with vaginal bleeding; 2) with threatened miscarriage; 3) with vaginal bleeding during cerclage placement; and 4) undergoing dilation and curettage (D&C). INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): In each patient, AFP concentration in the vaginal blood or in the liquid component of the evacuated products of conception (POC; D&C group) was compared with the AFP concentration in the maternal serum. RESULT(S): The median (range) concentration ratios of AFP in vaginal blood (or POC) to AFP in maternal serum were 24.5 (5.1-8,620) and 957 (4.6-24,216) for the missed/incomplete (n = 30) and the D&C (n = 22) groups, respectively, whereas they were only 1.2 (0.4-13.4) and 1.01 (0.7-1.5) for the threatened miscarriage (n = 15) and cerclage (n = 9) groups, respectively. Receiver operating characteristic (ROC) analysis demonstrated 100% sensitivity and 86.7% specificity for the detection of the passage of fetal tissue (ratio 4.3, area under the ROC curve 0.96). CONCLUSION(S): Higher concentrations of AFP in vaginal blood than in maternal serum may indicate the presence of dissolved fetal tissue (i.e., confirming a failed pregnancy).

Using Pyruvate Kinase as a Predictor for Patient With Endometrial Cancer Having Complex Hyperplasia With Atypia to Prevent Hysterectomy and Preserve Fertility: Retrospective Immunohistochemical Study.

OBJECTIVES: To explore whether the metabolic switches proceed or succeed the histological changes in precancerous lesions. To validate pyruvate kinase isoform 1 (PKM1) and pyruvate kinase isoform 2 (PKM2) as a histological biomarker to predict the progression of endometrial hyperplasia into invasive cancer status. METHODS: The records of 56 patients with a primary diagnosis of complex hyperplasia with atypia after endometrial biopsy were selected and analyzed retrospectively. A set of 3 consecutive sections at 4-µm thickness were cut and studied with immunohistochemical stains. From each case, 2 to 3 fields with a diagnosis of complex hyperplasia with atypia were selected and compared. A single pathologist blinded to the final diagnosis assigned the scoring. RESULTS: Positive immunostaining for PKM1 was observed in 31.25% (10 out of 32) of initial endometrial biopsy with the diagnosis of complex hyperplasia with atypia and final diagnosis of endometrial cancer, while 91.67% (out of 24) of patients with final diagnosis of negative endometrial cancer had endometrial biopsy with positive PKM1 staining ( P < .001). Positive immunostaining for PKM2 was observed in 100% of patient with endometrial biopsy result of endometrial hyperplasia with atypia (56 of 56). CONCLUSIONS: Lack of staining with PKM1 expression may help to predict the fate of endometrial hyperplasia. The disappearance of this marker is associated with the progression of hyperplasia toward cancer phenotype. Further studies are needed to understand the causes and potential mechanisms for suppressing Pyruvate Kinase Isoform 1 expression in endometrial hyperplasia.

Adverse pregnancy outcomes in deliveries prior to, at and beyond 39 weeks; low- and high-risk women.

BACKGROUND: Hypertensive disorders are associated with maternal and neonatal complications. Though they are more common in women with history of prior preeclampsia, they can occur in uncomplicated pregnancies. OBJECTIVE: To determine the proportion of adverse pregnancy outcomes in deliveries prior to or at ≥39 weeks, in uncomplicated singleton nulliparous women (low-risk), as well as women with history of preeclampsia in a prior gestation (high-risk). STUDY DESIGN: This was a secondary analysis from the multicenter trials of low dose aspirin for preeclampsia prevention in low and high-risk pregnancies. The proportion of adverse pregnancy outcomes including hypertensive disorders in pregnancy, small for gestational age, placental abruption, neonatal intensive critical unit admission, and respiratory distress syndrome were evaluated in the two groups. Adverse pregnancy outcomes were stratified by gestational age at delivery (<39 weeks and ≥39 weeks). Descriptive statistics were performed, and results reported as percentages. RESULTS: Three thousand twenty-one pregnancies were included in the low risk group, and 600 in the high risk one. In the low risk group 362 (12%) had hypertensive disorders, with 58% occurring at ≥39 weeks. In the low risk group, the rate of small for gestational age was of 5.9%, placental abruption 0.4%, neonatal intensive care unit admission 9%, and respiratory distress syndrome 3.5%. Sixty percent of all small for gestational age, 31% of all placenta abruptions, 44% of all neonatal intensive care unit admissions and 33% of respiratory distress syndrome cases, occurred at ≥39 weeks in the low risk group. In contrast in the high risk group, 197 (33%) patients developed a hypertensive disorder, with 35.5% occurring at ≥39 weeks. The overall rate of small for gestational age was 9.2%, abruption 2%, neonatal intensive care unit admission 15.5%, and respiratory distress syndrome 5%. In this group, 24% of all small for gestational age, 8.3% of all placental abruptions, 16% of all neonatal intensive care unit admissions and 3% of respiratory distress syndrome cases, were at ≥39 weeks. CONCLUSIONS: We found that in low-risk women, the majority of hypertensive disorders occur at ≥39 weeks, whereas in women with prior preeclampsia the majority develops at <39 weeks. Moreover, a third of all placental abruption occurred at or beyond 39 weeks in the low risk group. Our findings suggest that in low-risk women, a policy of delivery at 39 weeks may prevent most of the adverse outcome that occurs beyond that gestational age cutoff.

Effect of partial compliance on the prevention of recurrent preterm birth in women receiving weekly 17 alpha-hydroxyprogesterone caproate injections.

PURPOSE: To analyze the effect of partial compliance on preterm birth (PTB) prevention among women with previous PTB and receiving 17 alpha-hydroxyprogesterone caproate (17-OHPC). STUDY DESIGN: This is a secondary analysis of a multicenter trial for the prevention of recurrent PTB. Women with prior PTB were randomly assigned between 15 0/7 and 20 3/7 weeks to weekly injections of either 17-OHPC or placebo. Full 100% compliance (group 1) was compared to 40-80% (group 2). Recurrent PTB rates and odds ratios were calculated. Student's t, Chi-square, Wilcoxon Rank-Sum, multivariate logistic regression and Breslow-Day tests were used. RESULTS: Group 1 included 370 women versus 35 in group 2. In each group, the PTB rate was significantly reduced in pregnancies receiving 17-OHPC compared to placebo. The adjusted odds ratio for PTB rate in group 1 was 0.48 (95% CI 0.31-0.75) versus 0.18 (95% CI 0.04-0.92) in group 2. Comparing the homogeneity of both odds ratios, the rates of recurrent PTB prevention in both groups were not statistically different (Breslow-Day test; p= .15). CONCLUSION: A compliance rate of 40-80% did not significantly reduce 17-OHPC's efficacy. If confirmed, our findings could lead to a dramatic decrease in costs related to prevention of recurrent PTB.

Folic acid supplementation: what is new? Fetal, obstetric, long-term benefits and risks.

The association between folic acid supplementation, prior to conception and/or during pregnancy and pregnancy outcomes, has been the subject of numerous studies. The worldwide recommendation of folic acid is at least 0.4 mg daily for all women of reproductive age, and 4-5 mg in high-risk women. In addition, evidence shows that folic acid supplementation could modulate other adverse pregnancy outcomes, specifically, in pregnancies complicated by seizure disorders, preeclampsia, anemia, fetal growth restriction and autism. This review summarizes the available national and international guidelines, concerning the indications and dosage of folic acid supplementation during pregnancy. In addition, it describes the potential preventive benefits of folic acid supplementation on multiple maternal and fetal outcomes, as well as potential risks.

Catastrophic antiphospholipid syndrome in pregnancy, a diagnosis that should not be missed.

Catastrophic antiphospholipid syndrome (CAPS) is an accelerated form of the antiphospholipid antibody syndrome resulting in multi-organ ischemia and failure. It is a rare and life-threatening condition that can be easily mistaken with hemolysis elevated liver enzymes low platelets syndrome, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome. In order to make a diagnosis, it is required to have multi-organ thrombosis over 1 week affecting at least three organs or systems, and to have positive antiphospholipid antibody on two occasions (6 weeks apart), and histopathologic confirmation of small vessel occlusion. However, due to similarities in clinical and laboratory findings between CAPS and some other obstetric complications, potential misdiagnosis or delay in diagnosis are common, increasing the risk of adverse maternal and perinatal outcomes. In this review we summarized information presented in previous studies, focusing on CAPS related to pregnancy. We reviewed diagnostic criteria, differential diagnosis, and common presentation ranging from malaise, abdominal pain, dyspnea, hypertension, to altered mental status and seizures. We also discussed management in pregnancy and included a detailed algorithm with steps to take. Of note, the most significant reduction in mortality was seen in patients receiving triple therapy which will be discussed in this review.