If you find yourself on a mountain or at a lake this summer with those rarest of modern gifts-peace, solitude, and the chance for a few days of uninterrupted reading-I recommend Tom Friedman’s 

 It is vintage Friedman with the meticulously researched reportage expected from a three-time Pulitzer Prize winner. The book addresses three of the weightiest subjects of our time: the simultaneous acceleration of information technology, economic globalization, and climate change. While these three challenges ought to matter to every human on the planet, they have special resonance for ob/gyns because globally their impacts fall disproportionately on women and because women hold a key to the planet’s ability to overcome their collective threat.
	 


	While these three forces seem suddenly upon us, climate change reflects centuries of industrialization. On the other hand, the explosion in computing power and economic globalization have emerged over decades. In fact, most of the critical components of the latter two forces date back to one year – 2007.

 That year the iPhone and Android operating system were introduced, AT&T invested in a massive expansion in software-enabled networks setting the stage for logarithmic increases in wireless traffic, and IBM’s Watson was created giving birth to the dawn of artificial intelligence (AI). Also, in 2007, Kindle was rolled out by Amazon, and Airbnb was conceived. Twitter, LinkedIn and Facebook all started around that year using software developed by a company called Hadoop that generated software algorithms allowing hundreds of thousands of computers to function as one. In biotech, 2007 saw leveraging of this raw computational power to begin to dramatically reduce the cost and unimaginably increase the speed of DNA sequencing. Interestingly, that was also the year that experimental proof of CRISPR was reported.

 Thus, “infotech” and “biotech” are inextricably linked. All these changes accelerated economic globalization disrupting traditional markets in goods and services (including healthcare), labor and capital. 


	Moore’s law states that the speed and capacity of computing doubles every 2 years in parallel to the number of transistors that can be placed on a microchip. To illustrate this geometric expansion, Friedman notes that compared to its first-generation microchip, Intel’s sixth-generation chip has 3,000 times the performance and 90,000 times the energy efficiency at 60,000 times lower cost. The acceleration in information technology has also been made possible by startling advances in collectively developed open-source software (e.g., GitHub) and development of seamlessly interactive application programming interfaces (APIs). These APIs are the programming commands that allow you to save and send files, connect various web applications, buy stuff on-line, make apps, and permit individual computers to be networked – basically they make the Web the Web. Moreover, investments in ultra-fast transmission fiberoptic cabling coupled with introduction of 

 (CDMA) software to exponentially increase wireless capacity have allowed unprecedented and previously unimaginable levels of connectivity. 

The “cloud,” a vast network of computers spread across the globe, now stores, accesses, and shares data and permits software and services to run directly off the Internet, further amplifying acceleration of information technologies. Simultaneously, there have been dramatic improvements in computer sensors from cameras to detectors of motion, water pressure, energy consumption, engine performance, traffic congestion, temperature, global positioning, etc., all of which can broadcast their data, leading to the “Internet of things” and permitting both preventive and prescriptive maintenance (i.e., letting you know when a device will fail). In health care the Internet of things will generate 1 million GB of personal health information for each patient in her lifetime, which is equivalent to about 300 million books.

All these advances have vastly amplified the flow of data while reducing the complexity and cost of accessing it and accelerating the potential power of AI. One consequence for physicians is that a primary care doctor would need 630 hours per month just to keep up with the explosion of new literature.

 However, this accelerated flow of information affects all professions, contributing to the pervasive burnout being experienced across society.


	Friedman’s second great acceleration is globalization of the economy. Access to abundant and nearly free flows of information has led to many disruptive business innovations from Amazon, Lyft and Uber to Airbnb, all of which have displaced workers and whole industries across the planet. I recently received a harangue from a taxi driver in Nashville about the evils of Uber and what it had done to his income. While I sympathized with his plight, I realized he might as well be howling at the moon. Self-service whether it’s to create legal contracts, complete tax returns, book hotel and airline flights, or conduct real estate transactions has disrupted all those industries. Your iPhone is quickly replacing credit cards, and blockchain-derived currencies like Bitcoin may soon replace cash. Physicians will not be immune from this revolution. Wait till telehealth and facilitated self-service Internet-based medicine drive the provision of health care to the lowest bidder and soon we may be howling at the moon as well.

Access to abundant and free information also allows innovative start-ups to blossom from anywhere in the world where someone has sufficient training, a computer, and access to the Internet.

 Friedman notes that Massive Open Online Courses (MOOCs) are allowing poor students in rural India take some of the most advanced IT courses offered by top US colleges. Even manufacturers now crowdsource across the globe to optimize designs for new products. All this is fueling acceleration of the globalized economy. And restricting immigration will not limit the spread of innovative business disruption delivered via a new app developed by a creator in Turkey or Turkmenistan. Friedman points out that in 2014, $30 trillion in goods, services, and capital-equal to nearly 40% of the planet’s gross domestic product-crossed national borders, a 6-fold increase from 1990. And that does not begin to measure the impact of the free flow of information around the world. Tariffs may raise costs but are unlikely to stop that flow! 


	Freidman’s third great acceleration is climate change. The atmosphere now has 400 parts per million (ppm) of carbon dioxide, which is 50 ppm above the limit needed to prevent catastrophic global warming. Biodiversity is diminishing as deforestation has reduced the earth’s original forests to 62% while most climate scientists believe we cannot afford to dip below 75%. Pesticides and fertilizers are creating toxic algae blooms while ocean acidification is destroying our coral reefs and native fish populations. Desertification is a major threat to sub-Saharan Africa and drought is leading to crop failure in Central America. Climate change is also harming global health by driving alterations in vector ecology including expansion of pathogens such as malaria and Lyme disease, and arboviruses such as chikungunya, dengue, Zika, and West Nile. Additional adverse health effects accrue related reductions in drinking water quality, air pollution, and heat-related illnesses. 

Friedman also notes, ironically, that improved global health measures have reduced infant mortality, fueling population increases in impoverished lands already unable to fully feed, educate or employ their current populations. Overpopulation leads to over-farming, deforestation, and a growing scarcity of fresh water, which in turn worsen climate change. For example, Niger’s population in 1950 was 2.5 million, in 2016 it was 19 million, and by 2050 it is predicted to be 72 million, while the planet will have 9.7 billion inhabitants. 

Why adapting to change is so difficult for humans


	Since 2007, the pace of change in information technologies, economic globalization and climate change have all accelerated beyond Homo Sapiens’ ability to adjust their educational structures, economies, energy consumption, government regulations, and social safety nets to accommodate to them. Friedman argues that while technology platforms turn over every 5 to 7 years, it takes 10 to 15 years for humans to adapt to these new technologies. And this maladaptation is far greater in under-resourced countries that are also the most adversely impacted by climate change, leading to further impoverishment, famines, and mass migrations of primarily young men northward into Europe and North America.

 Thus, in these under-resourced areas it is women who are left behind on failing farms, often with no education and with elderly relatives and many young mouths to feed. Increasingly, though, women and children are contributing to the refugee crisis, exacerbating the adverse public health consequences of associated violence, accidents, inadequate nutrition, and lack of medical care. 


	So how do Americans and the citizens of industrialized nations cope with the disruptive impact of information technologies and a globalized economy? For example, how do ob/gyns and other physicians adjust to an era when medical knowledge doubles every 73 days such that between the start of medical school and the end of residency training, students will experienced three doublings of medical knowledge?7 The strategy is the same for physicians and plumbers. To remain viable in this new workplace, everyone must embrace lifelong learning by transforming AI into IA – which includes intelligent assistance and intelligent assistants.  

Friedman suggests that intelligent assistance is a way for government, employers, and, I would add, universities and academic health centers to provide powerful online learning tools to facilitate lifelong learning. New companies are already filling this niche (e.g., Udacity, edX, Coursera, Khan Academy) and LinkedIn has assembled a large repertoire of mini-courses to assist lifelong learning. Universities are offering MOOCs while medical schools and hospitals are expanding their professional development programs and simulation centers. For our part, 

 monitors current women’s health reports and pushes out summaries in our weekly e-newsletter while assembling various resource centers containing curated reviews. 

Intelligent assistants consist of the AI interface between humans and the tools they need to complete a job. (Think of a Da Vinci robot blocking you from ligating a ureter). In medicine, intelligent assistants could also consist of an electronic health record with AI-stoked decision support providing just-in-time and point-of-care access to relevant data needed to precisely choose the correct diagnostic test or prescribe the optimal personalized medication. It could also include AI-empowered search engines that not only search what you query but know what you don’t know and should be searching.

 Of course, when search engines decide what you should know, should do and should think, we will have even bigger problems! 

But what about the vast majority of the globe’s population who do not live in industrialized nations or worse, reside in failed states like Syria where chaos holds sway? It has been estimated that 4.5 billion people are either urban or rural poor. As noted, these parts of the globe are most affected by climate change and overpopulation, which is promoting collapse of their agriculture. They also have substandard educational systems, limited web access, and inchoate manufacturing sectors. This leaves millions of disaffected young men (and some young women) prone to join drug gangs, guerrilla groups or jihadists. While addressing climate change should be the planet’s top priority, Friedman suggests that in the short run we should focus on three simple remedies. The first is planting trees across sub-Saharan Africa to slow desertification (“the Great Green Wall”). The second is providing chickens to desperately poor families because chickens require minimal resources to maintain and can serve as both a source of protein-rich nutrition and modest income. But perhaps the best hope for these countries to escape the effects of the three “accelerations” is increased access to high-quality education for women. This will enhance economic development and help break the cycle of violence generated by disaffected young men who fall prey to irrational ideologies. Education should also help increase access to and use of contraception so desperately needed to break the cycle of poverty in under-resourced nations. 


	We live in the age of acceleration. Advances in information technology occur at a pace exceeding the human mind’s ability to adapt. This, in turn, is fueling acceleration of economic globalization and both trends are disrupting traditional employment models. Economic privation and climate change are also accelerating mass refugee migrations from under-resourced countries and failed states to Europe and North America fueling a toxic cycle of extremism, violence, and nativism. But humans created all three of these accelerations and if we embrace empiricism, rationality, and evidenced-based policies while eschewing baseless ideologies, mysticism, and fear, we have the power to mitigate their adverse impacts. In addition to addressing climate change by thoughtfully but expeditiously transitioning to renewable energy sources and promoting “reforestation”, we need to address accelerating technological complexity and economic globalization by embracing lifelong learning achieved through converting AI to IA. We must also pursue a global commitment to educating all the world’s women and providing universal access to contraception. 

Articles

We have the power to mitigate the adverse impact of rapid advancement in information technology.

Coping in the age of acceleration

Since the 1960s there has been a worldwide increase in primary cesarean deliveries from 5% to 32%.

 North America has the second highest rate of cesareans in the world, which has resulted in high rates of repeat cesarean deliveries and worsening maternal morbidity including surgically-related infections, bowel and bladder injury, transfusions, hysterectomy, abnormal placentation, and cesarean scar pregnancy (CSP).

 While CSP is a rare outcome of pregnancies, and the incidence is not well known, there have been estimates based on different populations of 1:1800-1:2216.

 CSP has been associated with a history of prior cesarean that causes dehiscence of a portion of the uterine wall.

CSP is considered an ectopic pregnancy and can carry very serious consequences, including hemorrhage, abnormal placentation, and uterine rupture.

 Due to the rarity of the condition and the possible serious consequences it requires specialized care to manage appropriately. The number of prior cesarean deliveries does not seem to correlate with risk of CSP and a meta-analysis found that 52% of such pregnancies were in women with one prior cesarean.

 This review examines the literature on CSP regarding pathophysiology, signs and symptoms, ultrasound diagnosis, management options, and future fertility for women with the condition.


	To better understand CSP, an appreciation of placental development is important. As a brief overview, at the time of implantation, the blastocyst results in modification of endometrial stromal cells, which enhances the decidualization reaction. The decidua, in turn, is able to regulate endometrial receptivity to modulate architectural changes that facilitate immune and vascular cell function to further trophoblastic invasion.

 Trophoblasts continue to invade until meeting the decidua basalis in which a zone of fibrinoid degeneration is created, described as the Rohr stria and Nitabuch layer.

In case you missed it: Advantages and methods of microbial seeding following cesarean birth examined

Prior uterine scar tissue from a cesarean often results in absence of the decidua basalis or partial disruption with a faulty layer of fibrinoid degeneration.

 In the setting of CSP, the pregnancy is not surrounded by or implanting into the decidualized endometrium, but rather, embeds in fibrous scar tissue and myometrium.

 The pregnancy is abnormal from the moment of implantation and management requires careful consideration.

Most patients with CSP are asymptomatic. Symptoms can, however, include light vaginal bleeding that is either painless or associated with mild to moderate abdominal pain.

 There are no signs or symptoms that are pathognomonic for CSP.

Diagnosis is performed using transvaginal ultrasound (TVUS). Transabdominal ultrasound has been used to diagnose CSP but TVUS continues to be the imaging modality of choice. 
	 

Figure 1 shows four ultrasonographic findings that have been described as diagnostic of CSP:

1. Empty uterine cavity with bright hyperechoic endometrial stripe

3. Intrauterine mass in the anterior part of the uterine isthmus

4. Absence of the myometrium, absent or thin between the bladder and gestational sac, measuring less than 5 mm

Using 3D sonography of the lower uterine segment may help to clarify this pathological entity (Figures 2 and 3). Magnetic resonance imaging (MRI) may be an option for diagnosis and evaluation, but the literature appears to demonstrate that overall, TVUS with color Doppler is superior and that MRI should be reserved for inconclusive or difficult-to-diagnose cases.

 Once a diagnosis is made, management should be multidisciplinary, and management options should be reviewed with the patient.

Because CSP is rare, management has largely been described in the literature in case reports and small cases series, as summarized here. We will outline different treatment options that have been most frequently chosen including what we do in our institution. 

Have you read: Evidence-based cesarean delivery guidelines

There are multiple considerations for management of CSP.  Goals of care are to treat the CSP with complete resolution and to ensure the mother’s safety. Keys to optimizing clinical outcomes include identification and termination of an early gestation and a multidisciplinary approach to management.


	Methotrexate (MTX) is standard treatment for many types of ectopic pregnancy and has also been used to treat CSP effectively. Patients who are pain-free, hemodynamically stable, and have an unruptured CSP < 8 weeks’ gestation are candidates for MTX.

 This type of medicine stops cells from dividing. It can be used as a way (other than surgery) to treat a pregnancy that’s implanted outside the uterus (ectopic pregnancy). The drug can be given via intra-sac or local injection, as systemic therapy, or in a combination of systemic therapy and intra-sac injection.

Local injection appears to work well but additional surgical treatment or systemic medical management often is required (Table 1). Administration of a single injection of MTX, potassium chloride (KCL), hyperosmolar glucose, or crystalline trichosanthin under TVUS or transabdominal ultrasound guidance has been used.

Systemic MTX is commonly used for tubal or cervical ectopic pregnancies. Reassuring results have been reported with systemic regimens, with and without intra-sac medication injections, for CSP. Both single-dose and multidose protocols have been used.

 The standard single-dose regimen for MTX is 50 mg/m

 whereas the multidose protocol includes four doses of MTX 1 mg/kg given on Days 1, 3, 5, and 7 with alternating days of folinic acid
	0.1 mg/kg.

 Patients with ectopic pregnancies and HCG levels < 5000 mIU/mL appear to respond best to systemic MTX.

In many case series, a combination of systemic therapy and intra-sac injections have been used as first-line management of CSP. In these regimens, the intra-sac injections have been done primarily with KCL or methotrexate at the doses shown in Table 1.


	We strongly caution against performing uterine curettage as first-line treatment for CSP. The pregnancy is often not in the uterine cavity so the products of conception may not be accessible, resulting in failure of the procedure. In addition, risk of uterine rupture and hemorrhage associated with the procedure is increased because of the thinness of the myometrial layer.

 Uterine curettage, however, can be considered after successful medical management, which is usually performed when Doppler ultrasound does not demonstrate active blood flow around the gestational sac.

Hysteroscopy (HSC) can also be used to guide uterine curettage. Some providers have evaluated CSP with HSC and coagulated vasculature noted around the CSP.

 In a case series by Pan et al, HSC was used in conjunction with laparoscopy.

 If anterior myometrial thickness was < 3 mm on ultrasound, laparoscopy was performed prior to HSC to dissect bladder peritoneum from the lower uterine segment to attempt to remove the bladder from the site of surgical management and decrease risk of injury. In this case series, 44 patients were successfully treated with removal of products of conception.

Have you read: Redefining postpartum care


	Uterine artery embolization (UAE) has been chosen by providers as a first-line approach in managing CSP to theoretically decrease risk of hemorrhage before ultimate management with surgery.

 In the event that UAE is considered for treatment of a CSP, consideration should be given to a patient’s plans for future fertility because information is limited on fertility after the procedure.


	In a small case series, a double uterine balloon was presented as a minimally invasive option for managing CSP.

 This technique is novel and appears to have very high success rates overall. Briefly, a double balloon catheter was placed into the uterus under ultrasound guidance. Each balloon was inflated, with the lower uterine segment balloon placed to compress the CSP.  The patient was then appropriately monitored and returned over the next few days for reevaluation with ultrasound. Once embryonic cardiac activity had ceased, the catheter was removed. With this procedure, treatment of CSP was successful and neither medication or dilation and curettage was needed in the published case series.


	Occasionally, patients fail to respond to all the above-mentioned procedures or they have severe abdominal pain (suspicious for uterine rupture) with bleeding. In these cases, hysterectomy should be considered (Figure 4).

Test your knowledge - Quiz: How to perform an evidence-based cesarean

Very little information exists with which to guide patients with CSP about future fertility. In a few case series, patients with CSP have undergone scar resection.

 The procedure has been performed with laparoscopic excision, CO2 laser, or ultrasound knife, with suture reapproximation of the myometrium afterwards in all cases.

Data are limited regarding fertility after these procedures, but all patients who did achieve fecundity appeared to deliver via planned cesarean.

 eight of 18 patients with CSP treated with unclear methods went on to become pregnant again. Two of the eight ended up with a repeat CSP, for an incidence of 25%. The remaining six patients all had cesarean deliveries, four of which were uncomplicated and two emergent. The reasons for the emergent cesareans were placental abruption at 34 weeks’ gestation in one case and nonreassuring fetal status at 41 weeks in the other case. 

Currently there is no evidence to indicate that a pregnancy has an affinity to locate in the cesarean delivery scar. Given the unpredictability of CSP, it is important to offer patients who have received treatment a very early ultrasound in their next pregnancy to ensure there is no recurrence. Outcomes of pregnancies in women previously treated for CSP are unclear. 

The multiple challenges associated with managing a suspected CSP start with identification of the abnormal pregnancy. For best clinical outcomes, once a CSP is diagnosed, the following should be prioritized: (1) facilitating a multidisciplinary discussion to create an individualized treatment plan; (2) early gestational termination; and (3) disrupting trophoblastic invasion prior to surgical management. CSP is a complicated medical condition, but possible adverse outcomes can be avoided with a considerate approach to treatment. 

The authors report no potential conflicts of interest with regard to this article.

Rates of cesarean delivery-United States, 1993. Centers for Disease Control and Prevention. 

Hamilton BE, Martin JA, Osterman MJK, Driscoll AK, Rossen LM. Births: provisional data for 2017. 

ACOG Practice Bulletin No. 205: Vaginal Birth After Cesarean Delivery. 

Boerma T, Ronsmans C, Melesse DY, et al. Global epidemiology of use of and disparities in caesarean sections. Lancet. 2018;392:1341-1348.

Jurkovic D, Hillaby K, Woelfer B, Lawrence A, Salim R, Elson CJ. First trimester diagnosis and management of pregnancies implanted into the lower uterine segment Cesarean section scar. 

Seow KM, Huang LW, Lin YH, Lin MY, Tsai Yl, Hwang JL. Cesarean scar pregnancy: issues in management. 

Rotas M, Haberman S, Levgur M. Cesarean scar ectopic pregnanices: etiology, diagnosis, and management. 

Cunningham F, Leveno KJ, Bloom SL, et al. Placentation, embryogenesis, and fetal development. Ectopic pregnancy. In: Williams Obstetrics. McGraw Hill Education. New York, NY; 2018:80-123.

Roberts DJ, Benirschke K. Normal early development. In: Creasy and Resnik’s Maternal-Fetal Medicine: Principles and Practice. Elsevier. Philadelphia, PA: 2019:39-61

Ash A, Smith A, Maxwell D. Cesarean scar pregnancy. 

Soares MJ, Iqbal K, Kozai K. Hypoxia and placental Development. 

Godin PA, Bassil S, Donnez J. An ectopic pregnancy developing in a previous caesarean section scar. 

Weimin W, Wenqing L. Effect of early pregnancy on a previous lower segment cesarean section scar. 

Roberts H, Kohlenber C, Lanzarone DDU, Murray H. Ectopic pregnancy in lower segment uterine scar. 

Shufaro Y, Nadjari M. Implantation of a gestational sac in a cesarean section scar. 

Pan Y, Liu M. The value of hysteroscopic management of cesarean scar pregnancy: a report of 44 cases. 

Xiao Z, Cheng D, Chen J, Yang J, Xu W, Xie Q. The effects of methotrexate and uterine arterial embolization in patients with cesarean scar pregnancy: A retrospective case-control study. 

Mara, M, Kubinova K, Maskova J, Horak P, Belsan T, Kuzel D. Uterine artery embolization versus laparoscopic uterine artery occlusion: The outcomes of a prospective nonrandomized clinical trial. 

Monteagudo A, Cali G, Rebarbar A, et al. Minimally invasive treatment of cesarean scar and cervical pregnancies using a cervical ripening double balloon catheter: Expanding the clinical series. 

Grechukhina O, Deshmukh U, Fan L, et al. Cesarean scar pregnancy, incidence, and recurrence: Five-year experience at a single tertiary care referral center. 

Api M, Boza A, Gorgen H, Api O. Should Cesarean scar defect be treated laparoscopically? A case report and review of the literature. 

Maymon R, Svirsky R, Smorgick N, et al. Fertility performance and obstetric outcomes among women with previous cesarean scar pregnancy. 

 Cali G, Timor-Tritsch I, Palacios-Jaraquemada J, et al. Outcome of cesarean scar pregnancy managed expectantly: systematic review and meta-analysis. 

CSP is a challenge but management is possible with a multidisciplinary approach.

How to diagnose and treat cesarean scar pregnancy

Major organizations currently recommend screening for endometrial cancer (EC) only for women with an inherited mismatch repair defect, commonly known as 

 (hereditary non-polyposis colorectal cancer) and Lynch syndrome. For women with HNPCC-which typically is identified 

 diagnosis of EC-endometrial biopsy is recommended annually or less frequently, starting at age 35. The precise definition and diagnostic criteria for Lynch and HNPCC syndromes vary. Genetic proof of these inherited disorders is not always available. In these circumstances, clinical criteria such as Amsterdam Criteria or a high index of suspicion should be sufficient to consider EC screening at some arbitrary interval and starting age.

The homogeneity of opinions about EC screening, however, may be ending. The Centers for Disease Control and Prevention (

) publicly announced that it is looking into EC screening, an initiative spurred by an unrelated, highly publicized case of morcellation.

 An incidentally discovered sarcoma is being used by at least one legislator to justify a request to the CDC to examine mandating endometrial biopsy before all hysterectomies. Many surgeons already perform biopsies before all hysterectomies and ovarian surgeries in at-risk women. In essence, these practitioners are screening for EC in an at-risk population: women about to undergo pelvic surgery.
	 


	Routine screening for EC was studied during the initial experience with selective estrogen receptor modulators (

 The attention was due to an increase in EC in patients with breast cancer who use SERMS to prevent recurrence. The conclusion of most opinions at that time was that screening was not warranted due to a low incidence and positive predictive value of the then-favored screening modality, ultrasonography. Only ultrasonography was considered because of a perceived increased risk of office endometrial biopsy. Based on these assumptions, screening was not adopted by most practitioners because of the poor specificity of ultrasonography and the low prevalence of EC. In retrospect, that decision still seems appropriate, given the information available at that time.

Data on complications of endometrial biopsy (perforation, bleeding, pain, infection) are derived from reports of a population with a strong indication for sampling (i.e., symptoms and presumed cancer until proven otherwise). In triage of this patient group, sampling attempts persist until successful, thus adding additional risks to the overall goal of sampling the endometrium.

On the other hand, sampling asymptomatic patients, or screening, would exclude women at increased risk of complications from the procedure. In other words, patients at increased risk of complications from a screening biopsy would not be put through additional invasive procedures or attempts. For instance, a woman considered for screening who has cervical stenosis or severe comorbidities would not be subjected to dilatation and curettage in the operating room. Instead such as a patient could be triaged to serial pelvic ultrasonography or other safer office maneuvers, such as cervical “ripening,” before biopsy.

 Thus, risk associated with biopsy for EC screening could be adjusted and lower than previously reported for endometrial sampling for other indications. In general, in-office sampling for screening should have little to no risk, as there are alternatives for difficult patients and procedures.


	Once risk of screening with biopsy is potentially acceptable, then disease prevalence becomes the next important area to consider. Currently some populations are at higher risk than the originally proposed group of patients using SERMs for breast cancer prevention. In those women, prospective cohort data suggest an endometrial cancer incidence of approximately 1/1000 to 1/2000.

 However, more recently reported data on community-based and risk-adjusted population incidence reveal much higher rates. For instance, in communities with high non-communicable disease (NCD) rates, EC incidence has been reported to be as high as 6/1000.

 In other populations, high-risk cohorts can be identified on the basis of risk factors such as age and weight. Using these risk modifiers, a subpopulation at even higher risk can be identified with rates theoretically approaching 1/100 for 50-year-olds with body mass indices (BMI) of 40 or more.

This prevalence approximates and compares favorably to that in patients with symptoms. In those women, who have the traditional indication for endometrial biopsy, the rate of diagnosed cancers is higher, but that should not be the sole criterion for deciding when to biopsy.

 Using the current standard, EC outcome is not optimal because overall survival can be as low as 80% in communities suffering from disparities. In theory, screening could eliminate all EC-related deaths in these and other populations.


	To justify screening, several other conditions must be met, including existence of a premalignant condition, availability of a realistic intervention, and likelihood that patients will adhere to treatment. EC screening is conceivable based on all of these parameters, including existence of a premalignant condition that can be treated to prevent progression to cancer. 

Hyperplasia in its various forms does respond to medical treatments and likely even lifestyle changes, including weight loss. Medical therapies such as a progesterone-delivering intrauterine device can be both effective for premalignant conditions and less morbid than surgical treatment for EC. The increased safety of medical treatment for a premalignant condition versus surgery for frank EC is a given. That benefit may be magnified because premalignant conditions occur years before development of EC and may have an earlier peak occurrence in women who are younger, and presumably healthier, than patients destined to be diagnosed with EC. Certainly for any patient contemplating surgery, whether for EC or a precursor, doing so at the youngest age possible may be an advantage. 

Most promising of all is evidence to suggest that lifestyle changes such as exercise and weight loss and interventions such as metformin that are aimed at underlying causes may have additional health benefits beyond interrupting progression to EC.

 Even if screening only leads to EC diagnosis at an earlier stage, it is theoretically possible that less invasive surgery, such as simple vaginal hysterectomy, can replace more extensive procedures involving lymph node removal and staging. 


	Finally, compared with other cancers for which screening is done, EC is an attractive target. Its incidence and other characteristics are similar to those of breast, prostate, colon, and lung cancer. To be clear, incidence is lower for endometrial than for breast and prostate cancer, but the latter diseases have an indolent counterpart, which EC does not. Given the potential for overtreatment of breast and prostate cancer, controversy exists regarding the risk/benefit equation for their respective screening programs. There is no way to screen for “indolent” EC, so the watchful waiting, active surveillance, and other treatment algorithms evolving for breast and prostate cancer do not exist for EC. Screening and triage for EC is relatively simple compared with the techniques used for colon and lung cancer. Incidence of the latter two diseases is slightly higher than for EC, but the complexity, expense, and risk of work-up for EC makes screening for it potentially comparable.

Other screening programs have been tailored to specific segments of the population, such as smokers and patients with chronic hepatitis, who are at risk of lung and liver cancer, respectively. EC screening could be further refined by known risk factors, such as age and BMI, until a consensus is agreed upon that the adjusted risk warrants screening.  This risk adjustment could be extended nearly universally in communities that share high-risk factors. For instance, in a community with high reported NCD rates, EC was 2.5, 3.5, 8 and 10.7 times more likely to be diagnosed than breast, colon, cervical and ovarian cancers, respectively.

 All of those other benchmark cancers are either being screened for or are the subjects of intense investigations for improved screening. EC is not currently experiencing the same focus, but the relative incidence of it suggests that it should be. Further, the high mortality associated with some cancers for which effective screening is being sought-such as ovarian and cervical cancer-is the rationale for that screening. In high-risk communities, however, EC, however, may actually be a more common cause of death than those diseases.

In-office versus hospital-based screening


	Screening can take many forms and may need to be community- or hospital-based, depending on the anticipated impact on compliance. Hospital-based screening, however, might be effective, given the association between EC and comorbid conditions and NCDs that lead to frequent hospital visits. For instance, at our safety net hospital, approximately 96% of women with EC had been seen an average of 1.7 years before their diagnosis, suggesting that earlier detection at screening may have been possible.

Many of these patients had prior Pap smears, imaging, and biopsies for other diagnoses, which suggests that a hospital-based screening program would be possible. Women at risk for EC who have intermittent, unpredictable, and uncertain access to healthcare may benefit even more from hospital-based screening for the disease because it may be effective even at long intervals between screening. This is based on the well-established relationship of EC with hyperplasia and the long latency period between EC and its premalignant precursors.


	Relative incidence of EC is higher than that for many cancers for which we already screen, including cervical cancer and other cancers with active screening research programs, such as ovarian cancer. EC does not have the same controversies that exist around prostate and breast cancer screening.  (Screening may do more harm than good in the subsets of patients with those cancers whose disease has a long indolent natural history.) Overall, as risks factors for EC become more prevalent, and the affected population grows older with increasing related comorbidities, the need becomes more urgent for a thorough, rigorous, and scientific approach to determining who, when and how to screen. It will also be important to consider relative costs and benefits associated with these strategies. Changes in the overall health of our society have now made it imperative for all stakeholders to reconsider screening for EC. 

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Elsandabesee D, Greenwood P. The performance of Pipelle endometrial sampling in a dedicated postmenopausal bleeding clinic. J Obstet Gynaecol. 2005;25:32.

GÃ¼ney M, Oral B, Mungan T. Intrauterine lidocaine plus buccal misoprostol in the endometrial biopsy. Int J Gynaecol Obstet. 2007; 97:125.

de Leon MC, Wu HH, Lennon AE, Del Priore G. Novel approach to outpatient endometrial biopsy to detect endometrial cancer. J Reprod Med. 2016 May-Jun;61(5-6):243-248.

Sierecki AR, Gudipudi DK, Montomarano N, Del Priore G. Comparison of endometrial aspiration biopsy techniques: specimen adequacy. J Repro Med. 2008;53(10):760-764.

Timoteo-Liaina I Khozaim K Buenconsejo-Lum LE, Del Priore G. Screening for endometrial cancer should be considered in special population. Available at 

https://www.sgo.org/wp-content/uploads/2017/03/Saturday-March-11-2017-SGO-Annual-Meeting-International-Session-Abstracts.pdf

Scott OW, Tin Tin S, Bigby SM, Elwood JM. Rapid increase in endometrial cancer incidence and ethnic differences in New Zealand. Cancer Causes Control. 2019 Feb;30(2):121-127.

Arthur R, Brasky TM, Crane TE, Felix AS, et al. Associations of a healthy lifestyle index with the risks of endometrial and ovarian cancer among women in the Women’s Health Initiative Study. Am J Epidemiol. 2019 Feb 1;188(2):261-273.

Luo J, Chlebowski RT, Hendryx M, et al. Intentional weight loss and endometrial cancer risk. J Clin Oncol. 2017 Apr 10;35(11):1189-1193.

Del Priore G, MD, Hamed KK, Chen, YJ, Timoteo-Liaina I, Matthews RPW, Buenconsejo-Lum, L. Is screening for uterine cancers an opportunity to reduce cancer’s burden among populations with disparities? Obstet Gynecol. May 2019; 133: 84S

A rigorous assessment of who, when, and how to screen may lead to regular testing in a broader population.

Will screening for endometrial cancer soon be routine?

Sexual violence continues to be a major public health problem affecting millions of adults and children in the United States. Medical consequences of sexual assault include sexually transmitted infections; mental health conditions, including posttraumatic stress disorder; and risk of unintended pregnancy in reproductive-aged survivors of sexual assault. Obstetrician-gynecologists and other women’s health care providers play a key role in the evaluation and management of sexual assault survivors and should screen routinely for a history of sexual assault. When sexual violence is identified, individuals should receive appropriate and timely care. A clinician who examines sexual assault survivors in the acute-care setting has a responsibility to comply with state and local statutory or policy requirements for the use of evidence-gathering kits. This document has been updated to include model screening protocols and questions, relevant guidelines from other medical associations, trauma-informed care, and additional guidance regarding acute evaluation of survivors and evidence-gathering kits.

Why and how to perform trauma-informed care

Violence against women, including intimate partner violence and sexual violence, has been characterized by the World Health Organization (

) as a major public health problem, and a violation of women’s human rights.

 The Committee on Health Care for Underserved Women of the American College of Obstetricians and Gynecologists (

 This document recognizes the frequency of sexual assault as a public health problem, exhorts ob/gyns and other women’s health care clinicians to screen all women for a history of sexual assault, addresses the issues that must be addressed in the acute evaluation of survivors, highlights the short- and long-term health consequences of sexual assault, and emphasizes the need to provide trauma-informed care when assessing the needs of sexual assault survivors.  

Because sexual assault is so common (nearly one in five US women have been victims of a completed or attempted rape during their lifetime), all of us as ob/gyns will see women who have been sexually assaulted, even if this event occurred in the distant past.

 Thus it is imperative that we be familiar with the issues addressed in this Committee Opinion. The acute consequences of sexual assault include acute traumatic injuries that may be severe and life-threatening, as well as pregnancy and sexually transmitted infections.  

In today’s world, myths about women’s reproductive health abound and are being perpetuated by misinformed politicians and others with a political agenda. It has been inaccurately claimed that “legitimate rapes” (whatever that hot-button term means) don’t result in pregnancies. The statistics from a longitudinal study on the prevalence and incidence of rape found the national rape-related pregnancy rate to be 5.0% per rape among victims of reproductive age, with approximately 32,000 pregnancies yearly in the United States resulting from rape.

 It really should go without saying that we must counter this misinformation at every turn.  

The long-term health consequences of sexual assault can include physical symptoms, decreased social functioning, changes in health perception, and decreased quality of life. Many women with a history of sexual assault may not volunteer this history, but may present with chronic pelvic pain, dysmenorrhea, and sexual dysfunction. The psychological and mental health sequelae of sexual assault can be profound, from an acute disorganization phase to delayed symptoms such as nightmares, flashbacks, phobias, somatic symptoms, and post-traumatic stress disorder (PTSD), characterized by a re-experience of the trauma, avoidance, and hyper-arousal. Women with substance use disorders have very high rates of a history of rape or sexual assault, and thus it is particularly important to screen for this history when we detect substance use disorders, and conversely, when a history of sexual assault is elicited, to screen for substance use disorders that may result as a mechanism for coping with the history of trauma.   

ACOG recommends screening all women for a history of sexual assault by asking direct questions in a nonjudgmental manner, validating the patient, as well as providing appropriate referrals. The Committee Opinion provides examples of appropriate screening questions. When a history of sexual abuse is disclosed, medical procedures including pelvic, rectal, and breast exams, as well as transvaginal ultrasound exams, may be triggering and associated with PTSD. Women with a history of sexual assault are at increased risk for PTSD and depression after childbirth.

Trauma-informed care is essential for all women with a history of sexual assault, but I would suggest that we approach ALL women with these principles, including acknowledging the effects of trauma, recognizing its signs and symptoms, and practicing so as to avoid retraumatizing. To that end, we need to ensure every woman’s physical and emotional safety, assure patients of our trustworthiness, prioritize individual choice and control during examinations, and seek to empower individuals. We should also encourage peer support, including during gynecologic exams. I would suggest that we treat all women in this manner, given that women may not feel comfortable acknowledging a difficult past history of sexual assault. In addition, we must avoid doing exams that themselves can be traumatizing or triggering. Our performance of the gynecologic exam should be predicated on the principles of “catalyzing women’s empowerment,” as described by Wijma and Siwe.

Many hospitals today have implemented programs whereby acute medical exams for sexual assault victims are performed by Sexual Assault Nurse Examiners (

). When I was an intern, many moons ago, I learned how to assess the appropriate medical issues for sexual assault survivors, and to collect forensic evidence using a “rape kit,” which fortunately included a checklist of the appropriate steps and required documentation. The Committee Opinion lists a website that facilitates localization of a specialized sexual assault examiner, because for an assault victim, being examined by such an expert is much preferable to being in the hands of someone who is inexperienced. Today, many fewer residents in ob/gyn do these evaluations, which is likely preferable for individual survivors of sexual assault, but which means that many clinicians today have never done such exams. The ACOG document acknowledges that in some locations or situations, the ob/gyn may remain responsible for the acute exam. A detailed protocol for sexual assault medical forensic examinations is available online from the U.S. Department of Justice’s Office of Violence Against Women at 

https://www.justice.gov/ovw/sexual-assault

. ACOG has other resources on this topic, available at 

. When we do provide acute care for survivors of sexual assault, it is important to provide instructions in writing, and also critically important to arrange for both clinical and psychologic follow-up.  

As ob/gyns, it is our responsibility to screen all patients for physical and sexual violence, and to provide compassionate trauma-informed care for all women. This ACOG Committee Opinion provides basic information that can inform that care. 

The author reports no potential conflicts of interest with regard to this article

World Health Organization. RESPECT women: preventing violence against women. Available at 

https://www.who.int/reproductivehealth/topics/violence/respect-women-framework/en/

Sexual assault. ACOG  Committee Opinion No. 777. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2019;133:e296-302.

Breiding MJ, Smith SG, Basile KC, Walters ML, Chen J, Merrick MT. Prevalence and characteristics of sexual violence, stalking, and intimate partner violence victimization--national intimate partner and sexual violence survey, United States, 2011. MMWR Surveill Summ. 2014;63(8):1-18.

Holmes MM, Resnick HS, Kilpatrick DG, Best CL. Rape-related pregnancy: estimates and descriptive characteristics from a national sample of women. Am J Obstet Gynecol. 1996;175(2):320-324; discussion 324-325.

Soderquist J, Wijma B, Thorbert G, Wijma K. Risk factors in pregnancy for post-traumatic stress and depression after childbirth. BJOG. 2009;116(5):672-680.

Wijma B, Siwe K. Examiner’s unique possibilities to catalyze women’s empowerment during a pelvic examination. Acta Obstet Gynecol Scand. 2004;83(12):1102-1103.

Commentary on ACOG Committee Opinion 777: Sexual Assault, which discusses the role of the ob/gyn in caring for sexual assault survivors and includes information on screening.

ACOG Guidelines at a Glance: Sexual Assault

Up to 20% of all pregnant and postpartum women will suffer from depression during the perinatal period, including the period up to 1 year postpartum. Although perinatal depression is more common than hypertensive disorders in pregnancy (2%-8%) and gestational diabetes (7%), many women with it go untreated for lack of diagnosis and/or intervention.

 There are several reasons that perinatal depression may not be identified and subsequently treated, but the two most common are non-disclosure from patients and inadequate screening of pregnant and postpartum women. Given the far-reaching effects of perinatal depression on mothers and their offspring, appropriate and timely diagnosis and treatment are imperative. 


	A diagnosis of perinatal and/or postpartum depression is made when symptoms of depression last longer than 14 days.

 Symptoms include changes in sleep and appetite, which may be considered “normal” for pregnancy and thus overlooked by both the patient and the clinician. In addition, patients may report decreased energy, concentration, and interest, as well as feelings of guilt. These symptoms interfere with a woman’s ability to perform normal activities of daily living and cause significant impairment. Patients who describe symptoms of depression should always be screened for thoughts of self-harm/suicide. If thoughts of self-harm are accompanied by a plan, intervention becomes acutely necessary. In addition, women should be screened for signs and symptoms of psychosis as this may be associated with the rare diagnosis of postpartum psychosis, which is considered a psychiatric emergency because it puts women at risk of suicide and infanticide.

Patients who suffer from perinatal depression may have concomitant anxiety disorders, such as generalized anxiety disorder, which affects approximately 10% of pregnant and postpartum women.

 Diagnosis may be delayed or overlooked due to the overlap of anxiety and depression symptoms. Symptoms of generalized anxiety disorder (GAD) include excessive worry, inability to focus/concentrate, irritability, restlessness, fatigue and muscle tension.

 Another associated anxiety disorder seen in perinatal women is obsessive-compulsive disorder (OCD). Perinatal and postpartum OCD is believed to affect approximately 3% of pregnant and postpartum women. Approximately 50% of women with perinatal OCD also have a diagnosis of perinatal depression. Symptoms include obsessions related to fears of harm or death of the infant, contamination fears, and, compulsions such as frequent checking and cleaning behaviors.


	Women are at risk of developing perinatal depression when they have been diagnosed with a depressive disorder previously, have a history of postpartum depression in a prior pregnancy, or have a family member with a diagnosis of depression or anxiety. In addition, women who are young, of lower socioeconomic status, and who have limited resources and limited social support are at higher risk.

 Interestingly, women who have a history of premenstrual dysphoric disorder are also at risk for perinatal depression. Research shows that hormone fluctuations, and not specific levels of estrogen and progesterone, may be related to onset or exacerbation of symptoms.

 In fact, women are at increased risk of depression during specific times in their lives, including onset of menses, pregnancy, and the perimenopausal period, all times in which there is noted fluctuation in hormone levels.


	Screening women for depression during pregnancy and in the postpartum period is recommended.

 Several self-report screening tools have been validated for use in the perinatal period. Two commonly used screening tools for use in pregnant and postpartum women are the PHQ-9 and the Edinburgh Postnatal Depression Scale (EPDS). The EPDS is available in 50 languages including Spanish. The PHQ-9 is available in English and Spanish. Patients who have a positive screening result (a 12 or greater for EPDS, a 10 or greater for PHQ9) should be further evaluated to determine whether they require intervention.

It is important to remember that when a self-report questionnaire is given to a patient for completion, the findings should be reviewed. The screening tools previously mentioned both include a question related to self-harm. Thus, it is imperative that the clinician review the responses before the patient leaves the office. Some patients may not feel comfortable speaking the words “I have thoughts of hurting myself” but they will indicate this feeling by circling a response. 


	Therapy and pharmacologic management are mainstays of treatment for perinatal depression. For patients who have mild-to-moderate symptoms, therapy should be considered first line. Typically interpersonal therapy is preferred for depression, but cognitive behavioral therapy (CBT) is also beneficial and is preferred for coexisting anxiety disorders.

 For moderate-to-severe symptoms, pharmacologic management can be initiated, and selective serotonin reuptake inhibitors (SSRIs) typically are considered first line.

 A combination of therapy and medications is preferable for patients who have moderate to severe symptoms. In patients with severe symptoms or suicidal/homicidal thoughts, hospitalization in a psychiatric facility should be considered.

Initiating psychiatric medications in pregnancy may cause anxiety for both patient and physician, thus it is important to understand the indications, risks, benefits, and alternatives for treatment in pregnancy. First, there are well-
	documented risks to the fetus if a woman with moderate to severe depression in pregnancy is left untreated. These risks include limited prenatal care, preterm labor, low infant birth weight, hypertensive disorders of pregnancy, and risk of exposure to illicit substances and alcohol.

 After delivery, if the mother continues to be moderately to severely depressed or develops postpartum depression, additional risks come into play. Risks to the newborn include attachment disorders between mother and infant, inability of the mother to identify and respond to newborn cues, and poor bonding.

 Later in childhood, affected children are at increased risk of behavioral and psychiatric disorders and their total IQ points may be affected.

 Based on this information, there are adequate data to illustrate the importance of intervention and initiation of treatment of depression in pregnancy.


	When reviewing risks of SSRIs for treatment of perinatal depression, the following perinatal risks should be reviewed with the patient: congenital malformations, persistent pulmonary hypertension of the neonate (PPHN), neonatal adaptation syndrome and cognitive/behavioral issues.

In the general population, 2% to 4% of neonates unexposed to prenatal antidepressants will be born with a congenital malformation versus 3% to 5% with such drug exposure. Thus, exposure to antidepressants does not significantly increase the risk of congenital malformation.

Risk of PPHN has been investigated in several studies. Chambers et al demonstrated the risk of PPHN in the general population, for neonates not exposed to antidepressants in pregnancy to be approximately 1 to 2/1000 and the risk in exposed neonates to be approximately 6 to 12/1000.

Left untreated, depression in the perinatal period can have serious repercussions for both mother and offspring.

Vol 64 No 08

Coping in the age of acceleration

How to diagnose and treat cesarean scar pregnancy

Will screening for endometrial cancer soon be routine?

ACOG Guidelines at a Glance: Sexual Assault

Perinatal depression: What ob/gyns need to know

Non-healing vulvar ulcerations in a 33-year-old woman

If a patient is noncompliant, can the ob/gyn be at fault?

Residents Corner - Hubris

Financial, health implications of 12-month supplies of OCs

WHO issues new Zika updates

CDC releases ‘benchmark’ data on pelvic exams