The Obesity-Fertility Protocol: a randomized controlled trial assessing clinical outcomes and costs of a transferable interdisciplinary lifestyle intervention, before and during pregnancy, in obese infertile women

Karine Duval, Marie-France Langlois, Belina Carranza-Mamane, Marie-Hélène Pesant, Marie-France Hivert, Thomas G Poder, Hélène B Lavoie, Youssef Ainmelk, Denise St-Cyr Tribble, Sheila Laredo, Ellen Greenblatt, Margaret Sagle, Guy Waddell, Serge Belisle, Daniel Riverin, Farrah Jean-Denis, Matea Belan, Jean-Patrice Baillargeon, Karine Duval, Marie-France Langlois, Belina Carranza-Mamane, Marie-Hélène Pesant, Marie-France Hivert, Thomas G Poder, Hélène B Lavoie, Youssef Ainmelk, Denise St-Cyr Tribble, Sheila Laredo, Ellen Greenblatt, Margaret Sagle, Guy Waddell, Serge Belisle, Daniel Riverin, Farrah Jean-Denis, Matea Belan, Jean-Patrice Baillargeon

Abstract

Background: Obesity in infertile women increases the costs of fertility treatments, reduces their effectiveness and increases significantly the risks of many complications of pregnancy and for the newborn. Studies suggest that even a modest loss of 5-10 % of body weight can restore ovulation. However, there are gaps in knowledge regarding the benefits and cost-effectiveness of a lifestyle modification program targeting obese infertile women and integrated into the fertility clinics. This study will evaluate clinical outcomes and costs of a transferable interdisciplinary lifestyle intervention, before and during pregnancy, in obese infertile women. We hypothesize that the intervention will: 1) improve fertility, efficacy of fertility treatments, and health of mothers and their children; and 2) reduce the cost per live birth, including costs of fertility treatments and pregnancy outcomes.

Methods/design: Obese infertile women (age: 18-40 years; BMI ≥30 kg/m(2) or ≥27 kg/m(2) with polycystic ovary syndrome) will be randomised to either a lifestyle intervention followed by standard fertility treatments after 6 months if no conception has been achieved (intervention group) or standard fertility treatments only (control group). The intervention and/or follow-up will last for a maximum of 18 months or up to the end of pregnancy. Evaluation visits will be planned every 6 months where different outcome measures will be assessed. The primary outcome will be live-birth rates at 18 months. The secondary outcomes will be sub-divided into four categories: lifestyle and anthropometric, fertility, pregnancy complications, and neonatal outcomes. Outcomes and costs will be also compared to similar women seen in three fertility clinics across Canada. Qualitative data will also be collected from both professionals and obese infertile women.

Discussion: This study will generate new knowledge about the implementation, impacts and costs of a lifestyle management program in obese infertile women. This information will be relevant for decision-makers and health care professionals, and should be generalizable to North American fertility clinics.

Trial registration: ClinicalTrials.gov NCT01483612. Registered 25 November 2011.

Keywords: Fertility; Intervention; Lifestyle; Obesity; Polycystic ovary syndrome; Pregnancy; Randomized controlled trial; Weight loss; Women.

Figures

Fig. 1
Fig. 1
Summary of design and data collection of the Obesity-Fertility protocol

References

    1. Practice Committee of the American Society of Reproductive Medicine Optimal evaluation of the infertile female. Fertil Steril. 2004;82(Suppl 1):S169–S172.
    1. Brassard M, AinMelk Y, Baillargeon JP. Basic infertility including polycystic ovary syndrome. Med Clin North Am. 2008;92(5):1163–1192. doi: 10.1016/j.mcna.2008.04.008.
    1. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab. 2006;91(11):4237–4245. doi: 10.1210/jc.2006-0178.
    1. Carmina E, Azziz R. Diagnosis, phenotype, and prevalence of polycystic ovary syndrome. Fertil Steril. 2006;86(Suppl 1):S7–8. doi: 10.1016/j.fertnstert.2006.03.012.
    1. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89(6):2745–2749. doi: 10.1210/jc.2003-032046.
    1. Baptiste CG, Battista MC, Trottier A, Baillargeon JP. Insulin and hyperandrogenism in women with polycystic ovary syndrome. J Steroid Biochem Mol Biol. 2010;122(1–3):42–52. doi: 10.1016/j.jsbmb.2009.12.010.
    1. Massicotte MH, Langlois F, Baillargeon JP. Current procedures for managing polycystic ovary syndrome. Expert Review of Obstetrics & Gynecology. 2010;5(1):77–91. doi: 10.1586/eog.09.74.
    1. Baillargeon JP, Nestler JE. Commentary: polycystic ovary syndrome: a syndrome of ovarian hypersensitivity to insulin? J Clin Endocrinol Metab. 2006;91(1):22–24. doi: 10.1210/jc.2005-1804.
    1. Gambineri A, Pelusi C, Vicennati V, Pagotto U, Pasquali R. Obesity and the polycystic ovary syndrome. Int J Obes Relat Metab Disord. 2002;26(7):883–896. doi: 10.1038/sj.ijo.0801994.
    1. Yildiz BO, Knochenhauer ES, Azziz R. Impact of obesity on the risk for polycystic ovary syndrome. J Clin Endocrinol Metab. 2008;93(1):162–168. doi: 10.1210/jc.2007-1834.
    1. Bolumar F, Olsen J, Rebagliato M, Saez-Lloret I, Bisanti L. Body mass index and delayed conception: a European Multicenter Study on Infertility and Subfecundity. Am J Epidemiol. 2000;151(11):1072–1079. doi: 10.1093/oxfordjournals.aje.a010150.
    1. Gesink Law DC, Maclehose RF, Longnecker MP. Obesity and time to pregnancy. Hum Reprod. 2007;22(2):414–420. doi: 10.1093/humrep/del400.
    1. Jensen TK, Scheike T, Keiding N, Schaumburg I, Grandjean P. Fecundability in relation to body mass and menstrual cycle patterns. Epidemiology. 1999;10(4):422–428. doi: 10.1097/00001648-199907000-00014.
    1. Statistique Canada. Enquête sur la santé dans les collectivités canadiennes (ESCC) 2004–2008; tableau CANSIM 105–0507. 2014.
    1. Bhattacharya S, Porter M, Amalraj E, Templeton A, Hamilton M, Lee AJ, et al. The epidemiology of infertility in the North East of Scotland. Hum Reprod. 2009;24(12):3096–3107. doi: 10.1093/humrep/dep287.
    1. Galtier-Dereure F, Pujol P, Dewailly D, Bringer J. Choice of stimulation in polycystic ovarian syndrome: the influence of obesity. Hum Reprod. 1997;12(Suppl 1):88–96. doi: 10.1093/humrep/12.suppl_1.88.
    1. Lobo RA, Gysler M, March CM, Goebelsmann U, Mishell DR., Jr Clinical and laboratory predictors of clomiphene response. Fertil Steril. 1982;37(2):168–174.
    1. Zaadstra BM, Seidell JC, Van Noord PA, te Velde ER, Habbema JD, Vrieswijk B, et al. Fat and female fecundity: prospective study of effect of body fat distribution on conception rates. BMJ. 1993;306(6876):484–487. doi: 10.1136/bmj.306.6876.484.
    1. Pasquali R, Pelusi C, Genghini S, Cacciari M, Gambineri A. Obesity and reproductive disorders in women. Hum Reprod Update. 2003;9(4):359–372. doi: 10.1093/humupd/dmg024.
    1. Fedorcsak 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):2523–2528. doi: 10.1093/humrep/deh485.
    1. Wang JX, Davies M, Norman RJ. Body mass and probability of pregnancy during assisted reproduction treatment: retrospective study. BMJ. 2000;321(7272):1320–1321. doi: 10.1136/bmj.321.7272.1320.
    1. Dokras A, Baredziak L, Blaine J, Syrop C, VanVoorhis BJ, Sparks A. Obstetric outcomes after in vitro fertilization in obese and morbidly obese women. Obstet Gynecol. 2006;108(1):61–69. doi: 10.1097/01.AOG.0000219768.08249.b6.
    1. Wang JX, Davies MJ, Norman RJ. Obesity increases the risk of spontaneous abortion during infertility treatment. Obes Res. 2002;10(6):551–554. doi: 10.1038/oby.2002.74.
    1. Cedergren MI. Maternal morbid obesity and the risk of adverse pregnancy outcome. Obstet Gynecol. 2004;103(2):219–224. doi: 10.1097/01.AOG.0000107291.46159.00.
    1. Cnattingius S, Bergstrom R, Lipworth L, Kramer MS. Prepregnancy weight and the risk of adverse pregnancy outcomes. N Engl J Med. 1998;338(3):147–152. doi: 10.1056/NEJM199801153380302.
    1. Weiss JL, Malone FD, Emig D, Ball RH, Nyberg DA, Comstock CH, et al. Obesity, obstetric complications and cesarean delivery rate--a population-based screening study. Am J Obstet Gynecol. 2004;190(4):1091–1097. doi: 10.1016/j.ajog.2003.09.058.
    1. Lewis G, editor. Why mothers die 2000–2002. London: Confidential Enquiry into Maternal and Child Health; 2004.
    1. Watkins ML, Rasmussen SA, Honein MA, Botto LD, Moore CA. Maternal obesity and risk for birth defects. Pediatrics. 2003;111(5 Part 2):1152–1158.
    1. Marchi J, Berg M, Dencker A, Olander EK, Begley C. Risks associated with obesity in pregnancy, for the mother and baby: a systematic review of reviews. Obes Rev. 2015;16(8):621–38. doi: 10.1111/obr.12288.
    1. Chu SY, Bachman DJ, Callaghan WM, Whitlock EP, Dietz PM, Berg CJ, et al. Association between obesity during pregnancy and increased use of health care. N Engl J Med. 2008;358(14):1444–1453. doi: 10.1056/NEJMoa0706786.
    1. Galtier-Dereure F, Boegner C, Bringer J. Obesity and pregnancy: complications and cost. Am J Clin Nutr. 2000;71(5 Suppl):1242S–1248S.
    1. 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):246–254. doi: 10.1093/humupd/dmp053.
    1. Huda SS, Brodie LE, Sattar N. Obesity in pregnancy: prevalence and metabolic consequences. Semin Fetal Neonatal Med. 2010;15(2):70–76. doi: 10.1016/j.siny.2009.09.006.
    1. Jarvie E, Hauguel-de-Mouzon S, Nelson SM, Sattar N, Catalano PM, Freeman DJ. Lipotoxicity in obese pregnancy and its potential role in adverse pregnancy outcome and obesity in the offspring. Clin Sci (Lond) 2010;119(3):123–129. doi: 10.1042/CS20090640.
    1. Bouchard L, Thibault S, Guay SP, Santure M, Monpetit A, St-Pierre J, et al. Leptin gene epigenetic adaptation to impaired glucose metabolism during pregnancy. Diabetes Care. 2010;33(11):2436–2441. doi: 10.2337/dc10-1024.
    1. Crosignani PG, Colombo M, Vegetti W, Somigliana E, Gessati A, Ragni G. Overweight and obese anovulatory patients with polycystic ovaries: parallel improvements in anthropometric indices, ovarian physiology and fertility rate induced by diet. Hum Reprod. 2003;18(9):1928–1932. doi: 10.1093/humrep/deg367.
    1. Guzick DS, Wing R, Smith D, Berga SL, Winters SJ. Endocrine consequences of weight loss in obese, hyperandrogenic, anovulatory women. Fertil Steril. 1994;61(4):598–604.
    1. 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):1502–1505. doi: 10.1093/humrep/13.6.1502.
    1. Clark AM, Ledger W, Galletly C, Tomlinson L, Blaney F, Wang X, et al. Weight loss results in significant improvement in pregnancy and ovulation rates in anovulatory obese women. Hum Reprod. 1995;10(10):2705–2712.
    1. Huber-Buchholz MM, Carey DG, Norman RJ. Restoration of reproductive potential by lifestyle modification in obese polycystic ovary syndrome: role of insulin sensitivity and luteinizing hormone. J Clin Endocrinol Metab. 1999;84(4):1470–1474.
    1. Moran LJ, Noakes M, Clifton PM, Tomlinson L, Galletly C, Norman RJ. Dietary composition in restoring reproductive and metabolic physiology in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88(2):812–819. doi: 10.1210/jc.2002-020815.
    1. Pelletier L, Baillargeon JP. Clinically significant and sustained weight loss is achievable in obese women with polycystic ovary syndrome followed in a regular medical practice. Fertil Steril. 2010;14(7):2665-9.
    1. Practice Committee of American Society for Reproductive Medicine Obesity and reproduction: an educational bulletin. Fertil Steril. 2008;90(5 Suppl):S21–29.
    1. Siega-Riz AM, King JC. Position of the american dietetic association and american society for nutrition: obesity, reproduction, and pregnancy outcomes. J Am Diet Assoc. 2009;109(5):918–927. doi: 10.1016/j.jada.2009.03.020.
    1. Dondorp W, de Wert G, Pennings G, Shenfield F, Devroey P, Tarlatzis B, et al. Lifestyle-related factors and access to medically assisted reproduction. Hum Reprod. 2010;25(3):578–583. doi: 10.1093/humrep/dep458.
    1. Balen AH, Anderson RA. Impact of obesity on female reproductive health: British fertility society, policy and practice guidelines. Hum Fertil (Camb) 2007;10(4):195–206. doi: 10.1080/14647270701731290.
    1. Lau DC, Douketis JD, Morrison KM, Hramiak IM, Sharma AM, Ur E. 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children [summary] CMAJ. 2007;176(8):S1–13. doi: 10.1503/cmaj.061409.
    1. Kamga-Ngande CN, Carpentier AC, Nadeau-Marcotte F, Ardilouze JL, Baillargeon JP, Bellabarba D, et al. Effectiveness of a multidisciplinary program for management of obesity: the Unité d’enseignement, de traitement et de recherche en obésité (UETRO) database study. Metab Syndr Relat Disord. 2009;7(4):297–304. doi: 10.1089/met.2008.0063.
    1. Kamga CN, Carpentier A, Baillargeon JP, Dionne I, Ardilouze JL, Langlois MF. Treatment of the Metabolic Syndrome in an interdisciplinary obesity clinic: a randomized controlled study. North American Association for the Study of Obesity’s 2005 Annual Scientific Meeting. Obes Res. 2005;13(Abstract Suppl):A1–218.
    1. Gagnon C, Brown C, Couture C, Kamga-Ngande CN, Hivert MF, Baillargeon JP, Carpentier AC, Langlois MF. A cost-effective moderate-intensity interdisciplinary weight-management programme for individuals with prediabetes. Diabetes Metab. 2011;37(5):410-8.
    1. Ministère de la santé et des services sociaux du Québec, Diabète Québec. Meal planning for people with diabetes at a glance. Direction des communications du Ministère de la santé et des services sociaux; Montréal: Diabète Québec. 2014.
    1. Armstrong MJ, Mottershead TA, Ronksley PE, Sigal RJ, Campbell TS, Hemmelgarn BR. Motivational interviewing to improve weight loss in overweight and/or obese patients: a systematic review and meta-analysis of randomized controlled trials. Obes Rev. 2011;12(9):709–723.
    1. Rasmussen KM, Yaktine AL. Weight gain during pregnancy: Reexamining the guidelines. Washington: National Academies Press; 2009.
    1. Brazier J, Roberts J, Deverill M. The estimation of a preference-based measure of health from the SF-36. J Health Econ. 2002;21(2):271–292. doi: 10.1016/S0167-6296(01)00130-8.
    1. Baillargeon JP, Carpentier A, Donovan D, Fortin M, Grant A, Simoneau-Roy J, et al. Integrated obesity care management system -implementation and research protocol. BMC Health Serv Res. 2007;7:163. doi: 10.1186/1472-6963-7-163.
    1. Bandura A. Self-efficacy. In: Ramachaudran VS, editor. Encyclopedia of human behavior. Orlando: Academic; 1994.
    1. Baillargeon JP, St-Cyr-Tribble D, Xhignesse M, Grant A, Carpentier A, Donovan D, et al. Obesity preceptorship and virtual community result in changes of primary care practice. 2008 Annual scientific meeting NAASO, Phoenix AZ. Obesity. 2008;16(Suppl):S152.
    1. Baillargeon JP, Xhignesse M, Carpentier A, Donovan D, Grant A, Fortin M, et al. Preceptorship and virtual community improve health care professionals perceptions toward obesity care and reported management of obesity after one year. San Francisco: The Endocrine Society’s 90th Annual meeting; 2008.
    1. St-Cyr-Tribble D, Gallagher F, Vanasse A, Doré C, Archambault J, Fortin M. Programme d’intervention fondé sur un modèle de collaboration interprofessionnelle et de promotion de l’autosoin auprès des diabétiques de type 2. Rapport de recherche, FCRSS & Aventis Canada. 2007.
    1. Langlois MF, et al. Integrated obesity care management system: executive summary. 2008.
    1. Kolotkin RL, Head S, Hamilton M, Tse CK. Assessing impact of weight on quality of life. Obes Res. 1995;3(1):49–56. doi: 10.1002/j.1550-8528.1995.tb00120.x.
    1. Levasseur M, Tribble DS, Desrosiers J. Analysis of quality of life concept in the context of older adults with physical disabilities. Can J Occup Ther. 2006;73(3):163–177. doi: 10.2182/cjot.05.0013.
    1. Poirier P, Despres JP. Waist circumference, visceral obesity, and cardiovascular risk. J Cardiopulm Rehabil. 2003;23(3):161–169. doi: 10.1097/00008483-200305000-00001.
    1. Cable A, Nieman DC, Austin M, Hogen E, Utter AC. Validity of leg-to-leg bioelectrical impedance measurement in males. J Sports Med Phys Fitness. 2001;41(3):411–414.
    1. Gagnon C, Menard J, Bourbonnais A, Ardilouze JL, Baillargeon JP, Carpentier AC, et al. Comparison of foot-to-foot and hand-to-foot bioelectrical impedance methods in a population with a wide range of body mass indices. Metab Syndr Relat Disord. 2010;8(5):437–441. doi: 10.1089/met.2010.0013.
    1. Santos-Lozano A, Santin-Medeiros F, Cardon G, Torres-Luque G, Bailon R, Bergmeir C, et al. Actigraph GT3X: validation and determination of physical activity intensity cut points. Int J Sports Med. 2013;34(11):975–982. doi: 10.1055/s-0033-1337945.
    1. Hulens M, Vansant G, Claessens AL, Lysens R, Muls E. Predictors of 6-minute walk test results in lean, obese and morbidly obese women. Scand J Med Sci Sports. 2003;13(2):98–105. doi: 10.1034/j.1600-0838.2003.10273.x.
    1. Hulens M, Vansant G, Lysens R, Claessens AL, Muls E. Exercise capacity in lean versus obese women. Scand J Med Sci Sports. 2001;11(5):305–309. doi: 10.1034/j.1600-0838.2001.110509.x.
    1. Solway S, Brooks D, Lacasse Y, Thomas S. A qualitative systematic overview of the measurement properties of functional walk tests used in the cardiorespiratory domain. Chest. 2001;119(1):256–270. doi: 10.1378/chest.119.1.256.
    1. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002;166(1):111–117. doi: 10.1164/ajrccm.166.1.at1102.
    1. Maniscalco M, Zedda A, Giardiello C, Faraone S, Cerbone MR, Cristiano S, et al. Effect of bariatric surgery on the six-minute walk test in severe uncomplicated obesity. Obes Surg. 2006;16(7):836–841. doi: 10.1381/096089206777822331.
    1. Lemoine S, Rossell N, Drapeau V, Poulain M, Garnier S, Sanguignol F, et al. Effect of weight reduction on quality of life and eating behaviors in obese women. Menopause. 2007;14(3 Pt 1):432–440. doi: 10.1097/gme.0b013e31802e46c2.
    1. Beriault K, Carpentier AC, Gagnon C, Menard J, Baillargeon JP, Ardilouze JL, et al. Reproducibility of the 6-minute walk test in obese adults. Int J Sports Med. 2009;30(10):725–727. doi: 10.1055/s-0029-1231043.
    1. Norcross JC, Prochaska JO. Using the stages of change. Harv Ment Health Lett. 2002;18(11):5–7.
    1. Kong W, Langlois MF, Kamga-Ngande C, Gagnon C, Brown C, Baillargeon JP. Predictors of success to weight-loss intervention program in individuals at high risk for type 2 diabetes. Diabetes Res Clin Pract. 2010;90(2):147–153. doi: 10.1016/j.diabres.2010.06.031.
    1. Boivin J, Takefman J, Braverman A. The fertility quality of life (FertiQoL) tool: development and general psychometric properties. Hum Reprod. 2011;26(8):2084–2091. doi: 10.1093/humrep/der171.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться