Assessing and Addressing Cardiovascular and Obstetric Risks in Patients Undergoing Assisted Reproductive Technology: A Scientific Statement From the American Heart Association.

The following section will focus on counseling before and management during ART. Counseling for individuals with CVD before and management during pregnancy has been discussed previously. 38 Data on outcomes after ART for specific cardiac diseases are limited to small single-center studies, limiting the ability to draw generalizable conclusions and highlighting the need for more data in this field. ART increases the risk for thromboembolism above the baseline risk for pregnancy, and the risk of VTE is higher for patients with a history of VTE. For all women with previous VTE or thrombophilia, clinicians should discuss the elevated risk of VTE with ART. 14 , 48 Clinicians should approach ART with a goal of using protocols with a lower risk for thrombosis and consider initiating prophylactic anticoagulation in women who develop OHSS to prevent VTE. 49 Among those patients in whom thromboprophylaxis is indicated at the start of pregnancy as outlined in recent guidelines, 49 thromboprophylaxis should be initiated at the start of ovarian gonadotropin stimulation, and discussions should occur in concert with the REI specialist on when to hold anticoagulation for oocyte retrieval ( Table 2 ). 49 In small retrospective studies of individuals with CVD undergoing ART, few had ischemic heart disease, limiting the ability to draw meaningful conclusions. 50 – 52 For women with ischemic heart disease in whom thrombosis from thrombophilias (such as Factor V Leiden mutation or protein C and S deficiency causing myocardial infarction with nonobstructive coronaries) was the cause of ischemia, counseling before ART should include discussions on risk for thromboembolism. For those on antiplatelet therapy, clinicians should discuss the elevated risk of bleeding with some ART procedures. Given the elevated risk of bleeding with TVOR, the timing of TVOR and decisions on when to continue or hold antiplatelet therapy should be made in concert with the patient’s REI clinician to balance risks of bleeding with those of thrombotic complications ( Tables 2 and 3 ). No specific data on ART outcomes among women with history of stroke are available. Risk reduction strategies should focus on reducing the risk of hypertension and thrombosis during ART and pregnancy ( Table 2 ). Considerations regarding antiplatelet therapy are similar to those in ischemic heart disease. Hormones, both endogenous and exogenous, have been implicated in the pathophysiology of spontaneous coronary artery dissection (SCAD), although their exact role in SCAD pathophysiology is unclear. Available data on ART use in individuals with CVD do not include individuals with a history of SCAD. 50 – 52 Data on SCAD after fertility therapy 53 or hormones used in fertility therapy 54 are limited to case reports or single-center studies. 55 In a single-center study of patients with SCAD, individuals with pregnancy-associated SCAD had similar rates of ART use compared with patients whose SCAD was not associated with pregnancy (9% pregnancy-associated SCAD versus 4% nonpregnancy-associated SCAD). 55 Because of concerns regarding the role of sex hormones in the pathophysiology of SCAD, exogenous exposure to systemically absorbed estrogen or progesterone is generally avoided in patients with a history of SCAD. 56 In patients with a history of SCAD, there are potential risks to hormonal stimulation protocols used in ART. 57 Although the data on rates of recurrent SCAD during pregnancy are limited, individuals with a history of SCAD are generally counseled against future pregnancies. 58 Thus, given the potential risk with ART and pregnancy, patients with a history of SCAD should be counseled on all possible family-building options, including use of donor oocytes and a gestational carrier. 57 Counseling should include avoiding unplanned pregnancies, and those with a history of SCAD who become pregnant should be managed by a multidisciplinary team. 57 Known complications of ART, such as OHSS with its accompanying fluid shifts and thromboembolic events, bleeding complications, and adverse reactions to anesthesia, may be poorly tolerated in individuals with cardiomyopathy, especially those with substantial ventricular dysfunction. 48 Multifetal gestations are associated with increased hemodynamic stress during pregnancy that could worsen preexisting ventricular dysfunction or lead to cardiac complications such as heart failure. 38 , 50 A single-center retrospective case-control study included 20 patients with CVD undergoing ART, 4 of whom had cardiomyopathy: 3 with congenital cardiomyopathy and 1 with acquired cardiomyopathy. There were no cardiovascular complications among these individuals. 51 A retrospective case review of 34 patients with CVD receiving ART included 1 patient with restrictive cardiomyopathy, who delivered at 36 weeks of gestation because of symptomatic heart failure. 52 Individuals with cardiomyopathy contemplating ART should be counseled on the known risks of ART and the possibility of greater hemodynamic compromise given their left ventricular systolic dysfunction. In those with left ventricular systolic dysfunction, it is reasonable to avoid multiembryo transfers to minimize the hemodynamic load of pregnancy. Individuals with dilated cardiomyopathy may want to consider genetic testing, pregenetic diagnosis, or both before oocyte fertilization. Management before ART should include counseling on risk for pregnancy, assessment of left ventricular systolic function, and optimization of volume status before any procedures ( Table 2 ). Limited data on ART in heart transplant exists and current recommendations are driven by expert consensus. 59 Patients should be counseled that the safety of ART in the transplant population is not known. A multidisciplinary team including transplant cardiology and reproductive endocrinology should counsel patients on risks of graft dysfunction or rejection, infection, teratogenicity of immunosuppression therapy, maternal life expectancy, and early delivery or miscarriage. 59 – 61 ART and pregnancy should be deferred for at least 1 year after transplant with demonstration of stable graft function on a stable immunosuppression regimen. 59 , 61 , 62 Given the risk of multiple gestation with ART, which may further increase the already elevated risk of preeclampsia in patients who have received a heart transplant, single embryo transfer is recommended. 60 OHSS should be carefully monitored for in patients who have received a heart transplant given the potential for reduced tolerance of hemodynamic shifts and risk of thrombotic events ( Table 2 ). 59 , 61 Rates of rejection during pregnancy and in the postpartum period in individuals with heart transplant range from 7% to 9%. 60 , 63 Thus, individuals should also expect more frequent surveillance of graft function given concern for risk of rejection during pregnancy. 59 , 61 Given the concern for rejection, counseling should include discussion of all family-building options, including use of a gestational carrier. Left ventricular assist devices are considered a contraindication to pregnancy on the basis of expert consensus and thus ART cannot be recommended. 59 Data on ART outcomes in patients with substantial valvular heart disease are limited, with little data on prosthetic valves. 50 – 52 A retrospective case review included 2 patients with mechanical valves: 1 aortic and 1 mitral. The patient with the aortic mechanical valve had major abdominal bleeding requiring blood transfusion 5 days after TVOR when warfarin was restarted. 52 A retrospective single-center study including 5 patients with valvular disease, 1 with a mechanical aortic valve, reported no cardiovascular complications. 51 Counseling should be tailored to the individual patient, with the pathogenesis of valve disease, severity of valve disease, and presence of a prosthetic valve factored into the risk assessment. The decision whether or not to continue warfarin during gamete retrieval must be tailored for each individual patient and made in conjunction with the REI specialist ( Tables 2 and 3 ). With >90% of children born with congenital heart disease surviving to adulthood, the number reaching childbearing age has increased substantially. 7 , 64 , 65 A majority of women with congenital heart disease can become pregnant without difficulty, but a number of conditions can compromise fertility, including Fontan single ventricles and unrepaired cyanotic heart disease. 66 , 67 For individuals with conditions that affect fertility, alternatives such as ART may be sought. Studies dedicated to risk stratification for pregnancy in congenital heart disease have been conducted, 38 , 41 , 43 , 65 , 68 but less is known about the risk of ART in congenital heart disease. Available data derive from small, retrospective studies in patients with CVD, including only a subset of modified Word Health Organization II through IV congenital heart disease, who have undergone ART with varying levels of hormonal stimulation. 50 – 52 In these studies, individuals with congenital heart disease had higher rates of cardiovascular complications, such as heart failure, arrhythmias, and thrombosis, which is similar to what has been observed in pregnancies conceived without ART. 38 , 43 , 50 – 52 One of the early studies was based on older ART approaches associated with higher rates of complications, such as OHSS. 50 Together, these small studies found occurrence of preeclampsia, miscarriage, and fetal prematurity to be higher than in pregnancies with ART in patients without congenital heart disease, with an inconsistent increased risk of OHSS, and no reported maternal deaths. 50 – 52 Individuals with single ventricle anomalies who have undergone Fontan palliation represent a unique subset of patients with congenital heart disease. 69 There is a high incidence of infertility in these patients. 66 , 67 For those who do conceive, evidence is limited and based primarily on retrospective studies, with a majority of patients having single morphologic left ventricles. 69 – 71 In general, well-selected patients who have undergone Fontan palliation who are followed closely in a center with adult congenital heart disease and maternal–fetal medicine expertise have no reported maternal deaths, but high rates of morbidity are observed, largely due to arrhythmia (8%–11%) and heart failure (4%–14%). 70 , 71 Given the limitations of Fontan circulation, cardiac output may not be augmented to a level necessary to sustain pregnancy. Rate of miscarriage is high (upwards of 50%), with a higher proportion occurring in those with cyanosis. 69 , 70 For pregnancies that are carried to live birth, neonatal complications are common, and include preterm birth, small for gestational age newborns, and intrauterine growth restriction. 70 , 71 The effect of older maternal age and extracardiac complications associated with Fontan circulation, including Fontan-associated liver disease, renal dysfunction, and chronic venous stasis, are not known. Furthermore, long-term effects of pregnancy on Fontan circulation are also not known. 69 ART may be considered but poses some risk, with OHSS being of particular concern given inherent susceptibility of Fontan circulation to thrombosis and volume shifts. 69 Use of techniques to minimize risks of OHSS, 13 assessing for euvolemia before ovarian stimulation, and initiation of thromboprophylaxis if indicated by established guidelines 49 is recommended. One small series including 6 patients who received Fontan palliation suggested that oocyte stimulation and retrieval using prophylactic systemic anticoagulation can be done safely, but acknowledged that more data are needed. 72 Caution must be exercised when applying current, limited data on ART risk in CVD broadly to the congenital heart disease population, particularly those with moderate to high-risk lesions. 50 – 52 Evaluation before ART must be done by an adult congenital heart disease specialist, as advocated for by current guidelines. 73 This provides an opportunity to optimize the patient’s cardiovascular status and ensure it is not of prohibitive risk before ART, allowing for appropriate counseling regarding risks of carrying a pregnancy versus consideration of a gestational carrier. Given the overlap of congenital heart disease with acquired cardiovascular conditions, such as valvular heart disease, ventricular dysfunction or heart failure, and arrhythmia, recommendations regarding pre-ART counseling and risk assessment from these sections may be applicable for the patient with congenital heart disease. For individuals with congenital heart disease classified as intermediate to substantially increased risk of maternal mortality and moderate to severe risk of maternal morbidity (modified Word Health Organization II/III or III), performing ART procedures in a monitored setting with multidisciplinary collaboration should be considered ( Table 2 ). Women with CVD have increased risk of de novo arrhythmia during pregnancy, and pregnancy may aggravate preexisting arrhythmias. 41 , 47 Whether use of ART further increases risk of arrhythmias above this already increased risk is not known. Available data do not include enough patients with a history of arrhythmia before ART to draw any meaningful conclusions. 50 – 52 Patients who develop arrhythmias during pregnancy should be managed according to existing guidelines and expert consensus statements. 38 , 47 Individuals who pursue ART are likely to be older and have higher rates of atherosclerotic CVD (ASCVD) risk factors compared with individuals who do not undergo ART. 3 Before initiating ART, individuals with ASCVD risk factors should undergo medical optimization and receive counseling on medication changes to occur before, and known cardiovascular risks associated with, ART. Oocyte retrieval and pregnancy is rarely contraindicated in individuals with risk factors for, but no manifest, ASCVD. Established guidelines exist on the management of preexisting diabetes and hypertension before and during ART, and have been discussed previously. 74 ART is well tolerated by individuals with type 2 diabetes, although few studies have investigated the effect of ovarian stimulation on glucose control. Medications used for ovarian suppression and stimulation affect cardiovascular hemodynamics, with the former causing a small increase in blood pressure and peripheral vascular resistance and the latter lowering both. 75 These hemodynamic changes during ART are unlikely to be clinically substantial in individuals with hypertension. Preexisting hypertension is a major risk factor for developing preeclampsia during pregnancy. In addition, ART is associated with an elevated risk of hypertensive disorders of pregnancy. 24 – 26 Individuals with preexisting hypertension who pursue ART should be counseled on their elevated risk for preeclampsia and receive close blood pressure monitoring, and may benefit from aspirin therapy as advocated for in current guidelines. 45 , 46 , 76 Several small studies have investigated changes in blood lipid levels in response to ovarian stimulation. Triglyceride levels increase in the 2-week period after ovarian stimulation, although changes in total cholesterol and low-density lipoprotein cholesterol vary by treatment protocol and study population. 77 , 78 Levels of lipoprotein(a), a low-density lipoprotein that is an independent risk factor for ASCVD, also increase after ovarian stimulation, and return to baseline in those who do not conceive. 77 , 79 The clinical significance of these changes during ART are not well studied, but the cumulative effects may be greater with multiple attempts, particularly if lipid-lowering medications are interrupted. Familial hypercholesterolemia is an autosomal dominant genetic disorder that affects 1 in 200 individuals, causes substantial elevation in low-density lipoprotein cholesterol levels, and is associated with premature ASCVD. Individuals with familial hypercholesterolemia experience substantial elevations in low-density lipoprotein cholesterol levels during pregnancy, but changes during ART have not been well described. 80 Individuals with familial hypercholesterolemia should undergo multidisciplinary management by a lipidologist or cardiologist and REI specialist before and during ART. Statins may be continued during ART, although the decision to continue statin use through pregnancy should be made between the patient and the physician, factoring in individual risk for ASCVD events. Rates of lipid screening in individuals of reproductive age are suboptimal. Lipid screening before ART or during the first trimester of pregnancy may be an opportunity to identify individuals with severe lipid disorders. 81 Individuals with hypertriglyceridemia, in particular familial hypertriglyceridemia, should have serial lipid panels given risk of elevated triglycerides with ART and pregnancy and be monitored for signs and symptoms of pancreatitis.

ART encompasses in vitro handling of oocytes, embryos, or both. In 2020, >326 000 ART cycles were performed at 449 clinics in the United States reporting data, which yielded 75 023 live births resulting in 79 942 live-born infants. 8 Depending on the cause of infertility, various treatment options are available. 9 Options include ovulation induction or ovarian stimulation, which involve the use of pharmacologic treatments to induce ovulation in the former or induce multiple mature ovarian follicles in the latter. 9 This can then be followed by timed intercourse or intrauterine insemination to achieve fertilization. Various fertility treatment options exist and have been reviewed previously 9 ; we focus on oocyte retrieval and embryo transfer, either to the patient or a gestational carrier, because these entail higher risk and cardiology clinicians are commonly asked to evaluate patients before these specific therapies. Before oocyte retrieval, patients undergo ovarian stimulation with injectable gonadotropins for ≈10 to 14 days ( Figure 1 ). During this time, patients undergo frequent monitoring, including transvaginal ultrasound and serial blood tests to evaluate hormone levels. Once ovarian follicles reach at least 18 mm, an injection is administered to trigger the maturation process; ≈36 hours later, transvaginal oocyte retrieval (TVOR) is performed. TVOR is typically done under conscious sedation in an outpatient setting and lasts ≈20 minutes. Once the oocytes are retrieved, they are cryopreserved or fertilized, using conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), to create embryos. Conventional fertilization in IVF is performed by placing both oocytes and sperm in a dish and allowing the sperm to fertilize the oocyte. During ICSI, 1 sperm is chosen and injected into the cytoplasm of the oocyte. The original indication for ICSI was to overcome male factor infertility and increase the fertilization rate. The resulting embryo can then be transferred into the uterus (of either the patient or a gestational carrier) if pregnancy is desired currently, in a process called fresh embryo transfer, or cryopreserved for future use. Cryopreserved embryos can be thawed and transferred into the uterus (of either the patient or a gestational carrier) in a process known as frozen embryo transfer. Progesterone, with or without estrogen depending on the individual REI center’s protocol, is given before fresh and frozen embryo transfer. In fresh embryo transfer, the presence of circulating estrogen after ovarian stimulation thickens the endometrial lining. Additional estrogen may or may not be given, depending on the center. The patient is then placed on progesterone for 5 days before transfer. For frozen embryo transfer, some centers may use natural cycle frozen embryo transfer, timing embryo transfer to the individual’s own menstrual cycle without using exogenous estrogen. If natural cycle frozen embryo transfer is not used, the patient will typically be placed on estrogen for ≈14 days to stimulate the growth of the endometrial lining. After an acceptable endometrial thickness is reached, progesterone will be given before the embryo is thawed and transferred into the uterus. Estrogen can be given in transdermal, oral, or injectable formulations.

Although the use of ART continues to rise, knowledge gaps persist. Data are sparse overall on outcomes after ART in those with CVD. 50 – 52 Data on rates of infertility may not consider ART accessibility to individuals from different racial or ethnic groups or members of the LGBTQIA+ (lesbian, gay, bisexual, transgender, queer/questioning, intersex, asexual, and other gender identities and sexual orientations) community, and much less is known on the effects of ART in these populations. Multicenter, prospective studies and large, multinational databases with the dedicated purpose of assessing the cardiovascular effects of ART, both long and short term, are needed. These studies must focus on both those at risk for, and with a broad range of, CVDs, and explore how the effect of ART varies with socioeconomic status, race and ethnicity, age, and CVD burden.

The use of ART is growing. The cardiovascular clinician must be aware of the known risks of ART in individuals with CVD and be comfortable with counseling patients on those risks. This need will grow as the population of patients with CVD expands to younger individuals and an increasing number of patients with congenital heart disease survive into adulthood. Previous studies have made inroads to identify risks of ART in individuals with CVD and risk for future CVD after ART; more data are needed to guide patients appropriately in shared decision-making surrounding fertility.

Evaluation and management before undergoing ART are detailed in Figure 2 . Most preconception counseling for individuals with CVD is focused on pregnancy and may neglect the possible use of ART. Changes in hemodynamics and coagulation associated with ART, or multiple gestation and OHSS resulting from ART, may be less well tolerated among those with congenital or acquired CVD. There is also variable time to conception with ART. Often the first attempt at any treatment is unsuccessful, with the live birth rate per intended egg retrieval ranging from 50.8% to 3.9% depending on the individual’s age. 40 Thus, some individuals may use ART and exogenous hormones for several years before conceiving. Individuals with CVD interested in ART should be evaluated by a multidisciplinary team, including their cardiologist, obstetrician, and fertility specialist, before initiating therapy. When assessing individuals with CVD before ART, the following should be considered: (1) the risk of pregnancy and whether pregnancy is contraindicated, (2) candidacy for gamete retrieval, (3) the safety of medications used during the ART process in context of the individual’s CVD, (4) the risk of ART procedures, including those performed to work-up infertility, egg retrieval, and possible embryo transfer, (5) potential ART complications (eg, OHSS, bleeding), and (6) the long-term effect of ART on future CVD risk. Candidacy for gamete retrieval should be made separately from that for pregnancy. Individuals with CVD are at increased risk for pregnancy complications based on the type and severity of their disease; therefore, risk for pregnancy should be assessed using established risk scores. 38 , 41 – 43 Modified Word Health Organization class IV CVDs, defined previously, 38 are contraindications to pregnancy. However, contraindication to oocyte retrieval remains unclear. For those with modified Word Health Organization IV CVD, carrying a fetus to delivery is contraindicated, but they may be candidates for gamete retrieval. Patients with these severe CVDs may want to pursue oocyte retrieval before needed surgery or medical treatment, or for a gestational carrier. Undergoing ART with their own oocytes and subsequently using a gestational carrier may be a safe option for conceiving a genetically related child. Clinicians must be aware that there are a wide range of family-building options (including use of donor gametes, use of a gestational carrier, traditional adoption, and embryo donation) that may be explored by their patients. Patients may wish to pursue pregnancy despite risk counseling, but a multidisciplinary team should discuss risks and benefits of all family-building options with the patient and discuss the use of gestational carriers when gamete retrieval is feasible, but pregnancy is contraindicated. When assessing risk for fertility therapy, a multidisciplinary team should determine the individual’s risk for undergoing procedures included in the fertility assessment (ie, hysteroscopy, laparoscopy, or both) and oocyte retrieval (ie, TVOR and embryo transfer). Discussions should include modifications to the ART protocol, such as single embryo transfer, antagonist protocols to reduce the likelihood of OHSS, and using low doses of gonadotropins, to limit the individual’s risk of complications. Patients should be counseled on specific risks associated with their type of CVD and if those risks can be modified ( Table 2 ). Review of the patient’s current medication list and deciding when to hold and subsequently resume specific medications should be made by the cardiologist in concert with the REI specialist on the basis of where the patient is in the ART process ( Table 3 ). 44 Given the importance of adequate pain control, anesthesia should be considered by the multidisciplinary team. In most centers, procedures for fertility therapy are done in an office setting. However, for individuals with CVD, performing these procedures in a hospital setting with adequate cardiovascular and anesthesia support may be preferrable.

Ovarian stimulation and oocyte retrieval can affect cardiovascular hemodynamics and, in some cases, result in complications that are poorly tolerated in the CVD population. Under normal physiologic conditions, the hypothalamic-pituitary-ovarian feedback mechanism limits follicular recruitment to 1 dominant follicle per menstrual cycle. However, during ART, this protective mechanism is disrupted by use of exogenous gonadotropins that lead to recruitment of numerous follicles. This, along with an induced luteinizing hormone surge, supports continued follicular enlargement with subsequent massive luteinization of granulosa cells driven by human chorionic gonadotropin administration. The resultant corpus luteum produces supraphysiologic amounts of vascular endothelial growth factor, which can cause excessive perifollicular neovascularization and increased vascular permeability. This change in physiology results in leakage of large amounts of fluid from the perifollicular vessels and the surrounding peritoneal vasculature. 10 Ovarian hyperstimulation syndrome (OHSS) is an exaggeration of this process and causes massive fluid shifts from the intravascular to the extravascular space. OHSS can be seen among 0.1% to 6% of ART cases, and severity varies from mild to critical. 11 The risk of OHSS increases with the number of oocytes retrieved, 11 , 12 but when using techniques recommended by established guidelines, 13 the incidence of OHSS is rare. The hallmark of OHSS is intravascular hypovolemia and third spacing with peripheral edema, ascites, hydrothorax, and multiorgan involvement including the heart. These massive fluid shifts may manifest as hypotension, arrhythmias, syncope, or all three. Intravascular volume depletion coupled with supraphysiologic estrogen levels leads to the other morbid sequalae of OHSS: an increased risk of both venous and arterial thromboembolism. Pregnancy increases the risk of venous thromboembolism (VTE), with the highest risk in the first 6 weeks postpartum. The strongest risk factor for VTE during pregnancy is previous VTE, which increases the risk by ≈25-fold. 14 In addition, there is a 2.5- to 3-fold increased risk of VTE in pregnancies conceived through ART, above the baseline risk of pregnancy, and particularly during the first trimester. 15 – 18 This increased risk may be secondary to, or independent of, OHSS. IVF with fresh, but not frozen, embryo transfer was identified as a risk factor for VTE, which may be attributable to the differences in resulting estrogen levels between them. 18 In a recent systematic review, factor V Leiden, G20210A prothrombin gene variant, protein C and S deficiency, and antiphospholipid antibodies were not associated with a higher risk of VTE during ART 18 ; however, data are scant. The increased risk of thromboembolism may have important implications in patients with CVD who are at high risk for thromboembolic complications, including those with atrial fibrillation, previous stroke, or both, Fontan circulation, or mechanical heart valves. Bleeding is another short-term risk of ART, particularly during TVOR, but the overall rate is low (<1%). 19 Proper pain control during ART procedures is also integral. Procedures to work-up or treat infertility (ie, hysteroscopy or laparoscopy) and TVOR require sedation and regional or general anesthesia for adequate pain control. Embryo transfer is less invasive, requiring cervical visualization and subsequent insertion of a small catheter, so may only occasionally require sedation or anesthesia. 20 Clinicians should be aware of a possible vagal response during TVOR or during cervical manipulation at embryo transfer. 20 Many anesthetics and analgesics can have hemodynamic effects based on the dose administered and may affect patients differently depending on their underlying CVD process.

Infertility can have a negative psychological effect and is often associated with feelings of anxiety, depression, and guilt, particularly when coping with being unable to fulfill hopes of parenthood. 82 , 83 Some who have experienced infertility continue to have negative psychological effects even after conceiving and delivering a child. 83 Infertility can also be a considerable stressor on partnership and can negatively affect the partner who is not undergoing ART. 84 Thus, both partners must be supported throughout this process. Because of the stigma associated with infertility, those undergoing ART may not seek support from their usual network of family and friends. Online peer support groups can help by establishing a greater sense of community. 85 Many clinicians have recognized the importance of having embedded mental health services to provide patient-centered care.