COMMENTARY
Assisted Reproductive Therapy in Women With Higher Body Mass Index Natalie Dayan, MD, MSc,1 Louise Pilote, MD, MPH, PhD,1,2 Lucie Opatrny, MD, MSc,3 Stella S. Daskalopoulou, MD, MSc, PhD1 Division of General Internal Medicine, Department of Medicine, McGill University Health Centre, Montreal QC
1
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal QC
2
Department of Medicine, St. Mary’s Hospital, Montreal QC
3
P
art of the growing demand for assisted reproductive technologies (ART), including in vitro fertilization, intrauterine insemination, and ovulation induction, is related to delayed childbearing and the increasing proportion of obese reproductive-aged women with ovulatory dysfunction.1 ART is associated with adverse health events in singleton pregnancies, including hypertensive disorders of pregnancy, preterm birth, low birth weight, and perinatal mortality.2 It remains uncertain whether access to ART should be universal or based on selection criteria that consider risks to the woman and her offspring. In particular, obese women (BMI > 30 kg/m2) experience more complicated pregnancies.3 Nearly one quarter of the adult Canadian female population is obese,4 and infertility in this subgroup is common.1 We discuss here the medical and economic aspects of balancing the goals of assisting pregnancy and mitigating risk in obese infertile women. In 2010, Quebec became the first Canadian province to fund ART, expanding access to and increasing awareness of infertility treatments to a more ethnically and economically diverse population.5 Simultaneously, mandatory single embryo transfer (SET) was instituted, and this has reduced perinatal risks related to multiple gestation.6 Risk factors for adverse events other than multiple gestation, such as obesity, have not been similarly addressed. In Quebec, no formal provincial BMI restrictions for ART access exist, although individual centres may impose internal restrictions. Key Words: Assisted reproduction, obesity, obstetrical outcomes, pregnancy, health risks, perinatal outcomes Competing Interests: None declared.
Conversely, national recommendations for BMI cut-offs have been proposed in other systems that publicly fund ART, because of concerns about reduced success rates, increased health risks, and higher costs.1,7 The British Fertility Society guideline recommends deferral of ART until a woman achieves a BMI below 35 kg/m2, and in New Zealand, a national restriction for IVF in women with a BMI greater than 32 kg/m2 has been implemented.7 The rationale for such guidelines is that funding of ART may not be offset by costs related to managing downstream events, including failed treatments, obstetrical complications, and the epigenetic consequences of maternal obesity. Given these wide-ranging implications, careful resource allocation to infertility treatment in obese populations should be considered in the broader context of our overburdened health care system. However, imposing BMI cut-offs for access to ART as a strategy to minimize cost and maximize favourable outcomes may be viewed as arbitrary and paternalistic if alternative solutions are not easily accessible. Firstly, the evidence supporting restricted access to ART based on BMI is controversial at best. While obese women are more resistant to gonadotropins,8 data are inconclusive regarding live birth rates in obese ART-treated women.7,9 A recent meta-analysis reported comparable IVF live birth rates across the range of maternal BMI,1 countering previous reports. It has been argued that studies examining these questions have variably adjusted for age and polycystic ovary syndrome, which may contribute to higher miscarriage rates.7 Whether cost per live birth is increased in ART cycles in obese women is also a matter of debate. A comprehensive economic framework
Received on December 20, 2013 Accepted on February 5, 2014
J Obstet Gynaecol Can 2014;36(6):513–514
JUNE JOGC JUIN 2014 l 513
Commentary
has estimated the cost per live birth in obese anovulatory women to be about twice the cost estimated in normalweight anovulatory women,9 while others have demonstrated overlapping confidence intervals related to mean costs at different BMI levels.5 So, at what BMI level is the success rate too low, or treatment too costly? These questions are difficult to answer with current available evidence. Is using BMI cut-offs effective in reducing health risks? Consideration of adverse ART events as well as obesityrelated pregnancy complications is of foremost importance in this discussion. Indeed, the Quebec parliamentary Bill 26 mandates physicians to “protect the health of women who resort to assisted procreation activities that may be medically required and of children born to such activities.” Health risks in pregnancies in obese women include hypertensive disorders of pregnancy, gestational diabetes, Caesarean section, thromboembolism, infection, and maternal and neonatal mortality.3,10 Obesity also carries with it limitations in monitoring and treatment using current standard methods, notably poor ultrasound quality and higher risk for anaesthetic-related morbidity.10 Moreover, many obesityrelated health consequences have a linear dose–response relationship with increasing BMI. Restricting ART access above an arbitrary BMI cut-off in the absence of any documented threshold effect is thus overly simplistic. Strategies to optimize ART outcomes, minimize costs, and protect maternal and fetal well-being must all be considered within an acceptable ethical framework. Oligo-anovulation in obese women is best managed with weight loss, which, even when modest, improves fertility parameters and subsequent ART outcomes.10 Both comprehensive multidisciplinary weight-loss programs and simpler community-based initiatives are cost-effective.10,11 Armed with this evidence, then, we should expect weight-loss programs for obese women with ovulatory dysfunction to be funded by government along with ART, under the same mandate to treat infertility. The ethical issues surrounding restricted access to optimal infertility treatment may be obviated only if evidence-based lifestyle and medical approaches to infertility are equally accessible for these women. We must also consider that adequate weight loss may not occur quickly for obese women battling against their biological clocks. Furthermore, reduction of obesity-related perinatal risks at the population level will take time. Thus, a focus on clear discussions between patients and ART providers about ART-related risks and pregnancy complications is paramount. In these discussions, documented health risks should be presented in the context of personal values. For instance, individual perinatal outcomes may be weighted differently by patients and physicians, and a cumulative event 514 l JUNE JOGC JUIN 2014
rate may be most informative. Beyond patient education, risk stratification and medical optimization of obesity-related risk factors before ART should be considered, as is currently done for other high-risk groups such as prospective mothers with heart disease. The effectiveness of routine medical optimization before ART has not been systematically evaluated, and current guidelines do not address the need for prenatal medical assessment for all high risk subgroups. Obesity is increasing in prevalence and, with it, female infertility. Careful evaluation of infertility treatment options for obese women and other high-risk women is necessary in the context of widely available ART. At the public health level, funded weight-loss programs may be more ethically acceptable than simply implementing BMI cut-offs. Efforts are needed to identify women at particularly high risk of adverse events, and routine medical optimization before infertility treatment should be considered. However, before a call to action, we need a call to more critical analysis and discussion of the medical, ethical, and economic implications of assisting pregnancy in high-risk women. By offering ART to all, perhaps we are biting off more than we can chew. REFERENCES 1. Koning AM, Mutsaerts MA, Kuchenbecher WK, Broekmans FJ, Land JA, Mol BW, et al. Complications and outcome of assisted reproduction technologies in overweight and obese women. Hum Reprod 2012;27(2):457–67. 2. Jackson RA, Gibson KA, Wu YW, Croughan MS. Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstet Gynecol 2004;103(3):551–63. 3. El Chaar D, Finkelstein SA, Tu X, Fell DB, Gaudet L, Sylvain J, et al. The impact of increasing obesity class on obstetrical outcomes. J Obstet Gynaecol Can 2013;35(3):224–33. 4. Statistics Canada. Adult obesity prevalence in Canada and the United States. 2011. Available at: http://www.statcan.gc.ca/chms. Accessed January 5, 2014. 5. Tulandi T, King L, Zelkowitz P. Public funding and access to in-vitro fertilization. N Engl J Med 2013;368:1948–9. 6. Voelker R. Researchers in Canada call for policy to mandate single-embryo transfer in IVF. JAMA 2011;305(18):1848. 7. Pandey S, Maheshwari A, Bhattacharya S. Should access to fertility treatments be based on maternal body mass index? Hum Reprod 2010;25(4):815–20. 8. Fedorcsák P, Dale PO, Storeng R, Ertzeid G, Bjercke S, Oldereid N, et al. Impact of overweight and underweight on assisted reproduction treatment. Hum Reprod 2004;19(11):2523–8. 9. Koning AM, Kuchenbecker WK, Groen H, Hoek A, Land JA, Khan KS, et al. Economic consequences of overweight and obesity in infertility: a framework for evaluating the costs and outcomes of fertility care. Hum Reprod Update 2010;16(3):246–54. 10. Wilkes S, Murdoch A. Obesity and female fertility: a primary care perspective. J Fam Plann Reprod Health Care 2009;35(3): 181–5. 11. Clark AM, Thornley B, Tomlinson L, Galletley C, Norman RJ. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod 1998;13(6):1502–5.
Assisted Reproductive Therapy in Women With Higher Body Mass Index Natalie Dayan, MD, MSc,1 Louise Pilote, MD, MPH, PhD,1,2 Lucie Opatrny, MD, MSc,3 Stella S. Daskalopoulou, MD, MSc, PhD1 Division of General Internal Medicine, Department of Medicine, McGill University Health Centre, Montreal QC
1
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal QC
2
Department of Medicine, St. Mary’s Hospital, Montreal QC
3
P
art of the growing demand for assisted reproductive technologies (ART), including in vitro fertilization, intrauterine insemination, and ovulation induction, is related to delayed childbearing and the increasing proportion of obese reproductive-aged women with ovulatory dysfunction.1 ART is associated with adverse health events in singleton pregnancies, including hypertensive disorders of pregnancy, preterm birth, low birth weight, and perinatal mortality.2 It remains uncertain whether access to ART should be universal or based on selection criteria that consider risks to the woman and her offspring. In particular, obese women (BMI > 30 kg/m2) experience more complicated pregnancies.3 Nearly one quarter of the adult Canadian female population is obese,4 and infertility in this subgroup is common.1 We discuss here the medical and economic aspects of balancing the goals of assisting pregnancy and mitigating risk in obese infertile women. In 2010, Quebec became the first Canadian province to fund ART, expanding access to and increasing awareness of infertility treatments to a more ethnically and economically diverse population.5 Simultaneously, mandatory single embryo transfer (SET) was instituted, and this has reduced perinatal risks related to multiple gestation.6 Risk factors for adverse events other than multiple gestation, such as obesity, have not been similarly addressed. In Quebec, no formal provincial BMI restrictions for ART access exist, although individual centres may impose internal restrictions. Key Words: Assisted reproduction, obesity, obstetrical outcomes, pregnancy, health risks, perinatal outcomes Competing Interests: None declared.
Conversely, national recommendations for BMI cut-offs have been proposed in other systems that publicly fund ART, because of concerns about reduced success rates, increased health risks, and higher costs.1,7 The British Fertility Society guideline recommends deferral of ART until a woman achieves a BMI below 35 kg/m2, and in New Zealand, a national restriction for IVF in women with a BMI greater than 32 kg/m2 has been implemented.7 The rationale for such guidelines is that funding of ART may not be offset by costs related to managing downstream events, including failed treatments, obstetrical complications, and the epigenetic consequences of maternal obesity. Given these wide-ranging implications, careful resource allocation to infertility treatment in obese populations should be considered in the broader context of our overburdened health care system. However, imposing BMI cut-offs for access to ART as a strategy to minimize cost and maximize favourable outcomes may be viewed as arbitrary and paternalistic if alternative solutions are not easily accessible. Firstly, the evidence supporting restricted access to ART based on BMI is controversial at best. While obese women are more resistant to gonadotropins,8 data are inconclusive regarding live birth rates in obese ART-treated women.7,9 A recent meta-analysis reported comparable IVF live birth rates across the range of maternal BMI,1 countering previous reports. It has been argued that studies examining these questions have variably adjusted for age and polycystic ovary syndrome, which may contribute to higher miscarriage rates.7 Whether cost per live birth is increased in ART cycles in obese women is also a matter of debate. A comprehensive economic framework
Received on December 20, 2013 Accepted on February 5, 2014
J Obstet Gynaecol Can 2014;36(6):513–514
JUNE JOGC JUIN 2014 l 513
Commentary
has estimated the cost per live birth in obese anovulatory women to be about twice the cost estimated in normalweight anovulatory women,9 while others have demonstrated overlapping confidence intervals related to mean costs at different BMI levels.5 So, at what BMI level is the success rate too low, or treatment too costly? These questions are difficult to answer with current available evidence. Is using BMI cut-offs effective in reducing health risks? Consideration of adverse ART events as well as obesityrelated pregnancy complications is of foremost importance in this discussion. Indeed, the Quebec parliamentary Bill 26 mandates physicians to “protect the health of women who resort to assisted procreation activities that may be medically required and of children born to such activities.” Health risks in pregnancies in obese women include hypertensive disorders of pregnancy, gestational diabetes, Caesarean section, thromboembolism, infection, and maternal and neonatal mortality.3,10 Obesity also carries with it limitations in monitoring and treatment using current standard methods, notably poor ultrasound quality and higher risk for anaesthetic-related morbidity.10 Moreover, many obesityrelated health consequences have a linear dose–response relationship with increasing BMI. Restricting ART access above an arbitrary BMI cut-off in the absence of any documented threshold effect is thus overly simplistic. Strategies to optimize ART outcomes, minimize costs, and protect maternal and fetal well-being must all be considered within an acceptable ethical framework. Oligo-anovulation in obese women is best managed with weight loss, which, even when modest, improves fertility parameters and subsequent ART outcomes.10 Both comprehensive multidisciplinary weight-loss programs and simpler community-based initiatives are cost-effective.10,11 Armed with this evidence, then, we should expect weight-loss programs for obese women with ovulatory dysfunction to be funded by government along with ART, under the same mandate to treat infertility. The ethical issues surrounding restricted access to optimal infertility treatment may be obviated only if evidence-based lifestyle and medical approaches to infertility are equally accessible for these women. We must also consider that adequate weight loss may not occur quickly for obese women battling against their biological clocks. Furthermore, reduction of obesity-related perinatal risks at the population level will take time. Thus, a focus on clear discussions between patients and ART providers about ART-related risks and pregnancy complications is paramount. In these discussions, documented health risks should be presented in the context of personal values. For instance, individual perinatal outcomes may be weighted differently by patients and physicians, and a cumulative event 514 l JUNE JOGC JUIN 2014
rate may be most informative. Beyond patient education, risk stratification and medical optimization of obesity-related risk factors before ART should be considered, as is currently done for other high-risk groups such as prospective mothers with heart disease. The effectiveness of routine medical optimization before ART has not been systematically evaluated, and current guidelines do not address the need for prenatal medical assessment for all high risk subgroups. Obesity is increasing in prevalence and, with it, female infertility. Careful evaluation of infertility treatment options for obese women and other high-risk women is necessary in the context of widely available ART. At the public health level, funded weight-loss programs may be more ethically acceptable than simply implementing BMI cut-offs. Efforts are needed to identify women at particularly high risk of adverse events, and routine medical optimization before infertility treatment should be considered. However, before a call to action, we need a call to more critical analysis and discussion of the medical, ethical, and economic implications of assisting pregnancy in high-risk women. By offering ART to all, perhaps we are biting off more than we can chew. REFERENCES 1. Koning AM, Mutsaerts MA, Kuchenbecher WK, Broekmans FJ, Land JA, Mol BW, et al. Complications and outcome of assisted reproduction technologies in overweight and obese women. Hum Reprod 2012;27(2):457–67. 2. Jackson RA, Gibson KA, Wu YW, Croughan MS. Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstet Gynecol 2004;103(3):551–63. 3. El Chaar D, Finkelstein SA, Tu X, Fell DB, Gaudet L, Sylvain J, et al. The impact of increasing obesity class on obstetrical outcomes. J Obstet Gynaecol Can 2013;35(3):224–33. 4. Statistics Canada. Adult obesity prevalence in Canada and the United States. 2011. Available at: http://www.statcan.gc.ca/chms. Accessed January 5, 2014. 5. Tulandi T, King L, Zelkowitz P. Public funding and access to in-vitro fertilization. N Engl J Med 2013;368:1948–9. 6. Voelker R. Researchers in Canada call for policy to mandate single-embryo transfer in IVF. JAMA 2011;305(18):1848. 7. Pandey S, Maheshwari A, Bhattacharya S. Should access to fertility treatments be based on maternal body mass index? Hum Reprod 2010;25(4):815–20. 8. Fedorcsák P, Dale PO, Storeng R, Ertzeid G, Bjercke S, Oldereid N, et al. Impact of overweight and underweight on assisted reproduction treatment. Hum Reprod 2004;19(11):2523–8. 9. Koning AM, Kuchenbecker WK, Groen H, Hoek A, Land JA, Khan KS, et al. Economic consequences of overweight and obesity in infertility: a framework for evaluating the costs and outcomes of fertility care. Hum Reprod Update 2010;16(3):246–54. 10. Wilkes S, Murdoch A. Obesity and female fertility: a primary care perspective. J Fam Plann Reprod Health Care 2009;35(3): 181–5. 11. Clark AM, Thornley B, Tomlinson L, Galletley C, Norman RJ. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod 1998;13(6):1502–5.
