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Preconception risk stratification before fertility care
CONCEPTIONS Preconception risk stratification before fertility care Care for the medically complex woman who desires fertility is an increasingly common event. Deciding when and whether one should proceed to fertility care has implications for the intended parents, the resulting offspring, and the health-care systems that care for these individuals. Significant barriers to assessment and communication with these patients include the patient's desire to conceive despite major medical concerns, the lack of tools to communicate the risks, and the reluctance of health-care providers to limit access to medically assisted pregnancy. To address the communication gap, we have developed the Mayo Clinic Preconception Risk Stratification (MC-PRS) tool to delineate the categories of risk in a simple, transparent way. The model uses a graded, color-coded continuum to provide clarity to patients, providers, and health-care systems, addressing both the modifiable and fixed risk factors and outlining a pathway to risk reduction. As with many such processes, the development of the MC-PRS was spurred by the clinical management of medically complex patients who desired fertility care and the lack of a standard approach to their assessment. Women with major medical comorbidities who seek pregnancy often have already overcome significant adversity. Thus, to attain a desired pregnancy, they may willingly underplay or accept significant maternal risks—including death and fetal and neonatal morbidity and mortality—that would be unacceptable to other women. Additionally, the health-care system financially penalizes patients who require fertility care, even more so those who use egg donors and gestational carriers. There is little in the literature to guide patient selection for fertility treatment in this medically and ethically complex area, which is difficult for both patients and providers. Historically, infertility patients have been healthy women for whom advanced maternal age has been the only significant maternal risk factor. The risks of multifetal gestation and its associated complication of prematurity also have been well documented. A noteworthy example of fertility specialists improving obstetric outcomes would include the limitation of the number of embryos transferred, leading to a reduction in higher order multiple gestations. This single practice change resulted in a significant reduction in neonatal morbidity and mortality. As the obstetric population seeking treatment has been growing significantly older, with increasing obesity and medical comorbidities, these same patients are requesting fertility care, so we must readdress whether our goal of pregnancy or even a live-born infant is sufficient. Moreover, with oocyte and embryo cryopreservation more widely available to women with complex medical conditions, infertility practices without clear guidelines will be forced to evaluate the health and welfare of both mother and baby before proceeding with fertility care. Evaluation before pregnancy would allow providers to modify medical comorbidities for fertility patients and potentially improve maternal and neonatal outcomes. We now have the opportunity to optimize the quality and add high-value care for women who request fertility services. 28
Preconception risk assessment in fertility patients provides an opportunity for optimization of maternal and child health through minimization of the risks associated with fertility procedures, screening for medical disease, optimization of current conditions and medications, assessment of risks and their effect on pregnancy, discussion of genetic risks and testing options, and healthy pregnancy planning related to common issues such as tobacco, diet, stress, and weight management. There are few published reports on fertility care in the medically complicated patient. Retrospective data on diabetic women undergoing fertility treatment compared with spontaneous pregnancy noted 31% with good control in the fertility treatment group compared with 40% in the spontaneous pregnancy group (1). Additionally, there was no increased use of folic acid in the fertility treatment group and a continuation of use of category X medications. These examples highlight the often unrecognized opportunities for preconception optimization of medical conditions and improved patient, provider, and team communication before fertility treatment. The rationale for further preconception care is both improved pregnancy rates through the optimization of medical conditions before fertility treatment and improved maternal and neonatal outcomes. Preconception consultation and medical comorbidity optimization before fertility care require a team approach in which reproductive endocrinologists, obstetricians, maternal fetal medicine physicians, primary care providers, and surgical, medical, and genetic subspecialists work as a team with the patient. This requires clear communication between the team members and most importantly with the patient. With this in mind, we have created a counseling tool for the patient and her providers that sets specific goals and guidelines for fertility care and for discussing the risks of fertility treatment and pregnancy. This tool also sets parameters before initiation of fertility care and may lead to the recommendation of no fertility treatment due to the increased risks of pregnancy or fertility treatment. Our primary goal is to improve pregnancy outcomes through modifiable risk factor reduction, which is accomplished through team communication and parameter setting before fertility treatment and pregnancy. By taking these steps, we set the expectations for the patient and the team and make the patient an active partner in the goal of a healthy pregnancy and child. The MC-PRS tool includes the following risk factor categories: reproductive endocrinology and infertility procedure risk factors, medical risk factors, obstetric risk factors, fetal and neonatal risk factors, genetic risk factors, preconception evaluation and medications, habit and habitus risk factors, and psychosocial risk factors. This tool could be used with all fertility patients to assess their risks related to age, obesity, lifestyle, and family history, but it is intended specifically for those with medical comorbidities. This model was developed for our center, but the risk factors used here may be modified for application elsewhere. Using our MC-PRS tool, we identify the risk areas and assess whether counseling, testing, treatment, or avoidance of pregnancy are recommended. The basic concepts of the
VOL. 104 NO. 1 / JULY 2015
Fertility and Sterility®
FIGURE 1
Defining features of the MC-PRS tool. Borowski. Conceptions. Fertil Steril 2015.
tool are displayed in Figure 1. On this color-coded continuum, the green portion of the table suggests an optimal current condition with no need for specific intervention before fertility treatment. The yellow portion of the table indicates a potential risk warranting further discussion or evaluation before fertility treatment. The red portion of the table confers either significant risk that should be corrected before fertility treatment or an indication that a gestational carrier or alternative reproductive option should be seriously considered. We have color-coded black those rare red scenarios that are not modifiable, where fertility treatment should never be recommended because of the profound risks. Key components of the tool include an evaluation of maternal, fetal, and neonatal risk factors conferred by maternal medical conditions, assessment of whether the current maternal medical condition is optimized, and finally recommendations for and timing of when fertility services should be initiated. It is important to note that the decision to place a clinical component within the table does not denote equivalent risks within and across a colored category. These color-coded regions can be used to individualize a patient's risk and provide direction and timing of care, elucidate needed consultations, and set clinical targets. This template can become a tool for interactions between patients and providers, clearly marking the objectives and goals before an attempt at pregnancy and making everyone involved an active participant. VOL. 104 NO. 1 / JULY 2015
Case example Here we provide a brief example of how to use the riskstratification tool. Jennifer is a 35-year-old G1P0010 Caucasian female with a body mass index of 31 who desires pregnancy but is anovulatory. She previously underwent a liver transplant 5 years ago for biliary atresia. She has no other medical comorbidities and has normal baseline laboratory test results. She is taking mycophenolate mofetil for immunosuppression, and she is compliant with her immunosuppressive regimen and care. She does not drink alcohol or use tobacco or other substances. She is not taking folic acid or prenatal vitamins at this time. Using our color-coded risk stratification tool, a team of medical professionals can easily assess the risks and communicate the issues of a pregnancy, convey the need for further evaluations before an attempted pregnancy, or determine whether a pregnancy would not be advisable. Figure 2 represents our liver-transplant risk-stratification tool, which can be used to assess Jennifer's candidacy for fertility care as well as outline the recommendations for optimization of her health and medical regimen before any upcoming fertility treatment or pregnancy. As can be seen on the table, Jennifer meets the red criteria because of her medication use 29
CONCEPTIONS
FIGURE 2
Liver transplant preconception risk stratification tool. Borowski. Conceptions. Fertil Steril 2015.
(mycophenolate mofetil). This would lead to our recommending a discussion with her liver transplant physicians about altering her medication to a medication safe in pregnancy, and then waiting for a year of stability before attempting fertility treatment. Additionally, she is not taking folic acid supplementation and has a body mass index of 31, both of which fall under the yellow category; the recommendation for her would be to initiate folic acid at least 3 months before pregnancy and undergo weight loss to achieve a body mass index of <30. The recommendations for the patient are provided under the heading Implications and Consultations. 30
This is a single example of how this tool can be used; medical risk factors can be determined for other conditions as well, including diabetes, hypertension, thrombosis/thrombophilia, maternal cardiac disease, or other common medical conditions. The other columns of the risk stratification tool are applicable to all patients undergoing fertility care; the goal is to optimize the maternal condition before pregnancy to produce a singleton pregnancy with a healthy mother and baby. In our example, Jennifer can undergo some minor changes in her medical care and fall in the green category, with her condition optimized to the best of our ability. At VOL. 104 NO. 1 / JULY 2015
Fertility and Sterility® that point, fertility treatment and pregnancy become acceptable options.
CONCLUSION Why should clinicians use the MC-PRS tool? Use of the MCPRS tool in clinical practice improves communication with the patient and the health-care team and provides guidelines for initiating fertility care. It is a proactive tool to coordinate medical care teams and provide guidelines for treatment before fertility treatment and pregnancy. The modifiable risk factors in the yellow and red categories should be addressed before fertility treatment. Whether an individual clinic performs fertility treatment during a yellow or red scenario depends on the clinic, the patient, and the multidisciplinary team. Fertility treatment and pregnancy would not routinely be recommended for women in the red category, but treatment may be considered in some clinical scenarios if a multidisciplinary care team is involved. For women in the red or black categories, the alternative reproductive options could include donor sperm, donor eggs, gestational carriers, or adoption, and should be discussed as appropriate. The practice of assisted reproductive technology has markedly changed in the last several decades with the use of intracytoplasmic sperm injection, cryopreservation of oocytes and embryos, and improved culture conditions. The resulting success in implantation and pregnancy rates has been remarkable. Currently, when patients are being counseled, the greatest risk they may face is pregnancy, and fertility treatment-related adverse events such as ovarian hyperstimulation, hemorrhage, or infection are not frequent issues. By using a visual system that displays a complete set of information for complex patients, such as the liver-
VOL. 104 NO. 1 / JULY 2015
transplant patient described here, we can identify the areas of concern and provide treatment and evaluation guidelines. We believe these steps will help optimize the safety and outcomes for women with medical comorbidities and their offspring before consideration of pregnancy and fertility treatment. Kristi S. Borowski, M.D.a Brian C. Brost, M.D.a Elizabeth A. Stewart, M.D.b Eileen J. Hay, M.B., Ch.B.c Charles C. Coddington III, M.D.b a Division of Maternal Fetal Medicine, b Division of Reproductive Endocrinology, and c Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota http://dx.doi.org/10.1016/j.fertnstert.2015.03.036 You can discuss this article with its authors and with other ASRM members at http://fertstertforum.com/borowskik-preconception-riskfertility-care/ Use your smartphone to scan this QR code and connect to the discussion forum for this article now.* * Download a free QR code scanner by searching for “QR scanner” in your smartphone’s app store or app marketplace.
REFERENCE 1.
Riskin-Mashiah S, Auslander R. Quality of medical care in diabetic women undergoing fertility treatment. Diabetes Care 2011;34:2164–9.
31
Preconception risk assessment in fertility patients provides an opportunity for optimization of maternal and child health through minimization of the risks associated with fertility procedures, screening for medical disease, optimization of current conditions and medications, assessment of risks and their effect on pregnancy, discussion of genetic risks and testing options, and healthy pregnancy planning related to common issues such as tobacco, diet, stress, and weight management. There are few published reports on fertility care in the medically complicated patient. Retrospective data on diabetic women undergoing fertility treatment compared with spontaneous pregnancy noted 31% with good control in the fertility treatment group compared with 40% in the spontaneous pregnancy group (1). Additionally, there was no increased use of folic acid in the fertility treatment group and a continuation of use of category X medications. These examples highlight the often unrecognized opportunities for preconception optimization of medical conditions and improved patient, provider, and team communication before fertility treatment. The rationale for further preconception care is both improved pregnancy rates through the optimization of medical conditions before fertility treatment and improved maternal and neonatal outcomes. Preconception consultation and medical comorbidity optimization before fertility care require a team approach in which reproductive endocrinologists, obstetricians, maternal fetal medicine physicians, primary care providers, and surgical, medical, and genetic subspecialists work as a team with the patient. This requires clear communication between the team members and most importantly with the patient. With this in mind, we have created a counseling tool for the patient and her providers that sets specific goals and guidelines for fertility care and for discussing the risks of fertility treatment and pregnancy. This tool also sets parameters before initiation of fertility care and may lead to the recommendation of no fertility treatment due to the increased risks of pregnancy or fertility treatment. Our primary goal is to improve pregnancy outcomes through modifiable risk factor reduction, which is accomplished through team communication and parameter setting before fertility treatment and pregnancy. By taking these steps, we set the expectations for the patient and the team and make the patient an active partner in the goal of a healthy pregnancy and child. The MC-PRS tool includes the following risk factor categories: reproductive endocrinology and infertility procedure risk factors, medical risk factors, obstetric risk factors, fetal and neonatal risk factors, genetic risk factors, preconception evaluation and medications, habit and habitus risk factors, and psychosocial risk factors. This tool could be used with all fertility patients to assess their risks related to age, obesity, lifestyle, and family history, but it is intended specifically for those with medical comorbidities. This model was developed for our center, but the risk factors used here may be modified for application elsewhere. Using our MC-PRS tool, we identify the risk areas and assess whether counseling, testing, treatment, or avoidance of pregnancy are recommended. The basic concepts of the
VOL. 104 NO. 1 / JULY 2015
Fertility and Sterility®
FIGURE 1
Defining features of the MC-PRS tool. Borowski. Conceptions. Fertil Steril 2015.
tool are displayed in Figure 1. On this color-coded continuum, the green portion of the table suggests an optimal current condition with no need for specific intervention before fertility treatment. The yellow portion of the table indicates a potential risk warranting further discussion or evaluation before fertility treatment. The red portion of the table confers either significant risk that should be corrected before fertility treatment or an indication that a gestational carrier or alternative reproductive option should be seriously considered. We have color-coded black those rare red scenarios that are not modifiable, where fertility treatment should never be recommended because of the profound risks. Key components of the tool include an evaluation of maternal, fetal, and neonatal risk factors conferred by maternal medical conditions, assessment of whether the current maternal medical condition is optimized, and finally recommendations for and timing of when fertility services should be initiated. It is important to note that the decision to place a clinical component within the table does not denote equivalent risks within and across a colored category. These color-coded regions can be used to individualize a patient's risk and provide direction and timing of care, elucidate needed consultations, and set clinical targets. This template can become a tool for interactions between patients and providers, clearly marking the objectives and goals before an attempt at pregnancy and making everyone involved an active participant. VOL. 104 NO. 1 / JULY 2015
Case example Here we provide a brief example of how to use the riskstratification tool. Jennifer is a 35-year-old G1P0010 Caucasian female with a body mass index of 31 who desires pregnancy but is anovulatory. She previously underwent a liver transplant 5 years ago for biliary atresia. She has no other medical comorbidities and has normal baseline laboratory test results. She is taking mycophenolate mofetil for immunosuppression, and she is compliant with her immunosuppressive regimen and care. She does not drink alcohol or use tobacco or other substances. She is not taking folic acid or prenatal vitamins at this time. Using our color-coded risk stratification tool, a team of medical professionals can easily assess the risks and communicate the issues of a pregnancy, convey the need for further evaluations before an attempted pregnancy, or determine whether a pregnancy would not be advisable. Figure 2 represents our liver-transplant risk-stratification tool, which can be used to assess Jennifer's candidacy for fertility care as well as outline the recommendations for optimization of her health and medical regimen before any upcoming fertility treatment or pregnancy. As can be seen on the table, Jennifer meets the red criteria because of her medication use 29
CONCEPTIONS
FIGURE 2
Liver transplant preconception risk stratification tool. Borowski. Conceptions. Fertil Steril 2015.
(mycophenolate mofetil). This would lead to our recommending a discussion with her liver transplant physicians about altering her medication to a medication safe in pregnancy, and then waiting for a year of stability before attempting fertility treatment. Additionally, she is not taking folic acid supplementation and has a body mass index of 31, both of which fall under the yellow category; the recommendation for her would be to initiate folic acid at least 3 months before pregnancy and undergo weight loss to achieve a body mass index of <30. The recommendations for the patient are provided under the heading Implications and Consultations. 30
This is a single example of how this tool can be used; medical risk factors can be determined for other conditions as well, including diabetes, hypertension, thrombosis/thrombophilia, maternal cardiac disease, or other common medical conditions. The other columns of the risk stratification tool are applicable to all patients undergoing fertility care; the goal is to optimize the maternal condition before pregnancy to produce a singleton pregnancy with a healthy mother and baby. In our example, Jennifer can undergo some minor changes in her medical care and fall in the green category, with her condition optimized to the best of our ability. At VOL. 104 NO. 1 / JULY 2015
Fertility and Sterility® that point, fertility treatment and pregnancy become acceptable options.
CONCLUSION Why should clinicians use the MC-PRS tool? Use of the MCPRS tool in clinical practice improves communication with the patient and the health-care team and provides guidelines for initiating fertility care. It is a proactive tool to coordinate medical care teams and provide guidelines for treatment before fertility treatment and pregnancy. The modifiable risk factors in the yellow and red categories should be addressed before fertility treatment. Whether an individual clinic performs fertility treatment during a yellow or red scenario depends on the clinic, the patient, and the multidisciplinary team. Fertility treatment and pregnancy would not routinely be recommended for women in the red category, but treatment may be considered in some clinical scenarios if a multidisciplinary care team is involved. For women in the red or black categories, the alternative reproductive options could include donor sperm, donor eggs, gestational carriers, or adoption, and should be discussed as appropriate. The practice of assisted reproductive technology has markedly changed in the last several decades with the use of intracytoplasmic sperm injection, cryopreservation of oocytes and embryos, and improved culture conditions. The resulting success in implantation and pregnancy rates has been remarkable. Currently, when patients are being counseled, the greatest risk they may face is pregnancy, and fertility treatment-related adverse events such as ovarian hyperstimulation, hemorrhage, or infection are not frequent issues. By using a visual system that displays a complete set of information for complex patients, such as the liver-
VOL. 104 NO. 1 / JULY 2015
transplant patient described here, we can identify the areas of concern and provide treatment and evaluation guidelines. We believe these steps will help optimize the safety and outcomes for women with medical comorbidities and their offspring before consideration of pregnancy and fertility treatment. Kristi S. Borowski, M.D.a Brian C. Brost, M.D.a Elizabeth A. Stewart, M.D.b Eileen J. Hay, M.B., Ch.B.c Charles C. Coddington III, M.D.b a Division of Maternal Fetal Medicine, b Division of Reproductive Endocrinology, and c Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota http://dx.doi.org/10.1016/j.fertnstert.2015.03.036 You can discuss this article with its authors and with other ASRM members at http://fertstertforum.com/borowskik-preconception-riskfertility-care/ Use your smartphone to scan this QR code and connect to the discussion forum for this article now.* * Download a free QR code scanner by searching for “QR scanner” in your smartphone’s app store or app marketplace.
REFERENCE 1.
Riskin-Mashiah S, Auslander R. Quality of medical care in diabetic women undergoing fertility treatment. Diabetes Care 2011;34:2164–9.
31