Protocol of the Fit-For-Fertility study: a multicentre randomised controlled trial assessing a lifestyle programme targeting women with obesity and infertility

Matea Belan, Myriam Gélinas, Belina Carranza-Mamane, Marie-France Langlois, Anne-Sophie Morisset, Stephanie-May Ruchat, Kim Lavoie, Kristi Adamo, Thomas Poder, Frances Gallagher, Marie-Hélène Pesant, Farrah Jean-Denis, Jean-Patrice Baillargeon, Fit-For-Fertility Study Group, R Bouzayen, N Chaillet, W Fraser, F Gallagher, A Godbout, E Greenblatt, C Kamga-Ngande, Kong Weilin, S Laredo, M Sagle, B Taylor, Matea Belan, Myriam Gélinas, Belina Carranza-Mamane, Marie-France Langlois, Anne-Sophie Morisset, Stephanie-May Ruchat, Kim Lavoie, Kristi Adamo, Thomas Poder, Frances Gallagher, Marie-Hélène Pesant, Farrah Jean-Denis, Jean-Patrice Baillargeon, Fit-For-Fertility Study Group, R Bouzayen, N Chaillet, W Fraser, F Gallagher, A Godbout, E Greenblatt, C Kamga-Ngande, Kong Weilin, S Laredo, M Sagle, B Taylor

Abstract

Introduction: Women with obesity are at a higher risk of infertility as well as gestational and neonatal complications. Lifestyle changes are universally recommended for women with obesity seeking fertility treatments, but such intervention has only been assessed in very few robust studies. This study's objectives are therefore to assess the clinical outcomes and cost-effectiveness of an interdisciplinary lifestyle intervention (the Fit-For-Fertility Programme; FFFP) targeting women with obesity and subfertility in a diverse population.

Methods and analysis: This pragmatic multicentre randomised controlled trial (RCT) will include 616 women with obesity (body mass index ≥30 kg/m2 or ≥27 kg/m2 with polycystic ovary syndrome or at-risk ethnicities) who are evaluated at a Canadian fertility clinic for subfertility. Women will be randomised either to (1) the FFFP (experimental arm) alone for 6 months, and then in combination with usual care for infertility if not pregnant; or (2) directly to usual fertility care (control arm). Women in the intervention group benefit from the programme up to 18 months or, if pregnant, up to 24 months or the end of the pregnancy (whichever comes first). Women from both groups are evaluated every 6 months for a maximum of 18 months. The primary outcome is live birth rate at 24 months. Secondary outcomes include fertility, pregnancy and neonatal outcomes; lifestyle and anthropometric measures; and cost-effectiveness. Qualitative data collected from focus groups of participants and professionals will also be analysed.

Ethics and dissemination: This research study has been approved by the Research Ethics Board (REB) of Centre intégré universtaire de santé et des services sociaux de l'Estrie-CHUS (research coordinating centre) on 10 December 2018 and has been or will be approved successively by each participating centres' REB. This pragmatic RCT will inform decision-makers on improving care trajectories and policies regarding fertility treatments for women with obesity and subfertility.

Trial registration number: NCT03908099.

Protocol version: 1.1, 13 April 2019.

Keywords: Diabetes & endocrinology; Health economics; Protocols & guidelines; Reproductive medicine; Subfertility.

Conflict of interest statement

Competing interests: Ferring has provided an unrestricted grant for the trial, without influencing the design or conduct of the trial, or the analysis or dissemination of the study’s results.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Fit-For-Fertility’s study flowchart. CHUM, Centre hospitalier universitaire de Montréal; CHUQ, Centre hospitalier universitaire de Québec; CHUS, Centre hospitalier universitaire de Sherbrooke.

References

    1. Bushnik T, Cook JL, Yuzpe AA, et al. . Estimating the prevalence of infertility in Canada. Hum Reprod 2012;27:738–46. 10.1093/humrep/der465
    1. Zegers-Hochschild F, Adamson GD, Dyer S, et al. . The International glossary on infertility and fertility care, 2017. Hum Reprod 2017;32:1786–801. 10.1093/humrep/dex234
    1. Brandes M, Hamilton CJCM, de Bruin JP, et al. . The relative contribution of IVF to the total ongoing pregnancy rate in a subfertile cohort. Hum Reprod 2010;25:118–26. 10.1093/humrep/dep341
    1. Rebar RW. What are the risks of the assisted reproductive technologies (art) and how can they be minimized? Reprod Med Biol 2013;12:151–8. 10.1007/s12522-013-0156-y
    1. DeAngelis AM, Martini AE, Owen CM. Assisted reproductive technology and epigenetics. Semin Reprod Med 2018;36:221–32. 10.1055/s-0038-1675780
    1. Wharton S, Lau DCW, Vallis M, et al. . Obesity in adults: a clinical practice guideline. CMAJ 2020;192:E875–91. 10.1503/cmaj.191707
    1. Legro RS, Dodson WC, Kunselman AR, et al. . Benefit of delayed fertility therapy with preconception weight loss over immediate therapy in obese women with PCOS. J Clin Endocrinol Metab 2016;101:2658–66. 10.1210/jc.2016-1659
    1. World Health Organization . Obesity: preventing and managing the global epidemic. Available:
    1. NCD Risk Factor Collaboration (NCD-RisC) . Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet 2017;390:2627–42. 10.1016/S0140-6736(17)32129-3
    1. Statistics Canada . Table 13-10-0794-01 - Measured adult body mass index (BMI) (World Health Organization classification), by age group and sex, Canada and provinces, Canadian Community Health Survey - Nutrition, 2015.
    1. Chu SY, Kim SY, Bish CL. Prepregnancy obesity prevalence in the United States, 2004-2005. Matern Child Health J 2009;13:614–20. 10.1007/s10995-008-0388-3
    1. Ramlau-Hansen CH, Thulstrup AM, Nohr EA, et al. . Subfecundity in overweight and obese couples. Hum Reprod 2007;22:1634–7. 10.1093/humrep/dem035
    1. Brassard M, AinMelk Y, Baillargeon J-P. Basic infertility including polycystic ovary syndrome. Med Clin North Am 2008;92:1163–92. 10.1016/j.mcna.2008.04.008
    1. van der Steeg JW, Steures P, Eijkemans MJC, et al. . Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women. Hum Reprod 2008;23:324–8. 10.1093/humrep/dem371
    1. Imani B, Eijkemans MJ, te Velde ER, et al. . Predictors of chances to conceive in ovulatory patients during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. J Clin Endocrinol Metab 1999;84:1617–22. 10.1210/jc.84.5.1617
    1. Mulders AGMGJ, Laven JSE, Eijkemans MJC, et al. . Patient predictors for outcome of gonadotrophin ovulation induction in women with normogonadotrophic anovulatory infertility: a meta-analysis. Hum Reprod Update 2003;9:429–49. 10.1093/humupd/dmg035
    1. Dodson WC, Kunselman AR, Legro RS. Association of obesity with treatment outcomes in ovulatory infertile women undergoing superovulation and intrauterine insemination. Fertil Steril 2006;86:642–6. 10.1016/j.fertnstert.2006.01.040
    1. Maheshwari A, Stofberg L, Bhattacharya S. Effect of overweight and obesity on assisted reproductive technology--a systematic review. Hum Reprod Update 2007;13:433–44. 10.1093/humupd/dmm017
    1. Orvieto R, Meltcer S, Nahum R, et al. . The influence of body mass index on in vitro fertilization outcome. Int J Gynaecol Obstet 2009;104:53–5. 10.1016/j.ijgo.2008.08.012
    1. Hamilton-Fairley D, Kiddy D, Watson H, et al. . Association of moderate obesity with a poor pregnancy outcome in women with polycystic ovary syndrome treated with low dose gonadotrophin. Br J Obstet Gynaecol 1992;99:128–31. 10.1111/j.1471-0528.1992.tb14470.x
    1. Wang JX, Davies MJ, Norman RJ. Obesity increases the risk of spontaneous abortion during infertility treatment. Obes Res 2002;10:551–4. 10.1038/oby.2002.74
    1. Weiss JL, Malone FD, Emig D, et al. . Obesity, obstetric complications and cesarean delivery rate--a population-based screening study. Am J Obstet Gynecol 2004;190:1091–7. 10.1016/j.ajog.2003.09.058
    1. Cedergren MI. Maternal morbid obesity and the risk of adverse pregnancy outcome. Obstet Gynecol 2004;103:219–24. 10.1097/01.AOG.0000107291.46159.00
    1. Fleming TP, Watkins AJ, Velazquez MA, et al. . Origins of lifetime health around the time of conception: causes and consequences. Lancet 2018;391:1842–52. 10.1016/S0140-6736(18)30312-X
    1. Ward ZJ, Long MW, Resch SC, et al. . Simulation of growth trajectories of childhood obesity into adulthood. N Engl J Med 2017;377:2145–53. 10.1056/NEJMoa1703860
    1. Geserick M, Vogel M, Gausche R, et al. . Acceleration of BMI in early childhood and risk of sustained obesity. N Engl J Med 2018;379:1303–12. 10.1056/NEJMoa1803527
    1. Battista M-C, Hivert M-F, Duval K, et al. . Intergenerational cycle of obesity and diabetes: how can we reduce the burdens of these conditions on the health of future generations? Exp Diabetes Res 2011;2011:596060–19. 10.1155/2011/596060
    1. Adamo KB, Ferraro ZM, Brett KE. Can we modify the intrauterine environment to halt the intergenerational cycle of obesity?. Int J Environ Res Public Health 2012;9:1263–307. 10.3390/ijerph9041263
    1. Lane M, Zander-Fox DL, Robker RL, et al. . Peri-conception parental obesity, reproductive health, and transgenerational impacts. Trends Endocrinol Metab 2015;26:84–90. 10.1016/j.tem.2014.11.005
    1. Mahutte N, Kamga-Ngande C, Sharma A, et al. . Obesity and reproduction. J Obstet Gynaecol Can 2018;40:950–66. 10.1016/j.jogc.2018.04.030
    1. ESHRE Task Force on Ethics and Law, including, Dondorp W, de Wert G, et al. . Lifestyle-related factors and access to medically assisted reproduction. Hum Reprod 2010;25:578–83. 10.1093/humrep/dep458
    1. American Dietetic Association, American Society of Nutrition, Siega-Riz AM, et al. . Position of the American dietetic association and American Society for nutrition: obesity, reproduction, and pregnancy outcomes. J Am Diet Assoc 2009;109:918–27. 10.1016/j.jada.2009.03.020
    1. Balen AH, Anderson RA. Impact of obesity on female reproductive health: British fertility Society, policy and practice guidelines. Hum Fertil 2007;10:195–206. 10.1080/14647270701731290
    1. Price SA, Sumithran P, Nankervis A, et al. . Preconception management of women with obesity: a systematic review. Obes Rev 2019;20:510–26. 10.1111/obr.12804
    1. Mutsaerts MAQ, van Oers AM, Groen H, et al. . Randomized trial of a lifestyle program in obese infertile women. N Engl J Med 2016;374:1942–53. 10.1056/NEJMoa1505297
    1. van Elten TM, Karsten MDA, Geelen A, et al. . Effects of a preconception lifestyle intervention in obese infertile women on diet and physical activity; a secondary analysis of a randomized controlled trial. PLoS One 2018;13:e0206888. 10.1371/journal.pone.0206888
    1. van Oers AM, Mutsaerts MAQ, Burggraaff JM, et al. . Cost-Effectiveness analysis of lifestyle intervention in obese infertile women. Hum Reprod 2017;32:1418–26. 10.1093/humrep/dex092
    1. Funk KL, LeBlanc ES, Vesco KK, et al. . Women's attitudes towards a pre-conception healthy lifestyle programme. Clin Obes 2015;5:67–71. 10.1111/cob.12088
    1. Loudon K, Treweek S, Sullivan F, et al. . The PRECIS-2 tool: designing trials that are fit for purpose. BMJ 2015;350:h2147. 10.1136/bmj.h2147
    1. WHO Expert Consultation . Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004;363:157–63. 10.1016/S0140-6736(03)15268-3
    1. Bjelland I, Dahl AA, Haug TT, et al. . The validity of the hospital anxiety and depression scale. An updated literature review. J Psychosom Res 2002;52:69–77. 10.1016/s0022-3999(01)00296-3
    1. Stern AF. The hospital anxiety and depression scale. Occup Med 2014;64:393–4. 10.1093/occmed/kqu024
    1. Harris PA, Taylor R, Thielke R, et al. . Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377–81. 10.1016/j.jbi.2008.08.010
    1. DCW L, Douketis JD, Morrison KM. Canadian clinical practice guidelines on the management and prevention of obesity in adults and children. CMAJ 2007;176:S1–13.
    1. Kamga-Ngandé CN, Carpentier AC, Nadeau-Marcotte F, et al. . Effectiveness of a multidisciplinary program for management of obesity: the Unité d'Enseignement, de Traitement et de Recherche sur l'Obésité (UETRO) database study. Metab Syndr Relat Disord 2009;7:297–304. 10.1089/met.2008.0063
    1. Duval K, Langlois M-F, Carranza-Mamane B, et al. . 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. BMC Obes 2015;2:47. 10.1186/s40608-015-0077-x
    1. Doran GT. There’s a S.M.A.R.T. Way to Write Management’s Goals and Objectives. Management Review 1981;70:35–6.
    1. Dragomir AI, Boucher VG, Bacon SL, et al. . An international Delphi consensus study to define motivational communication in the context of developing a training program for physicians. Transl Behav Med 2021;11:642–52. 10.1093/tbm/ibaa015
    1. Falba TA, Sindelar JL. Spousal concordance in health behavior change. Health Serv Res 2008;43:96–116. 10.1111/j.1475-6773.2007.00754.x
    1. van Dijk MR, Koster MPH, Willemsen SP, et al. . Healthy preconception nutrition and lifestyle using personalized mobile health coaching is associated with enhanced pregnancy chance. Reprod Biomed Online 2017;35:453–60. 10.1016/j.rbmo.2017.06.014
    1. Rasmussen KM, Catalano PM, Yaktine AL. New guidelines for weight gain during pregnancy: what obstetrician/gynecologists should know. Curr Opin Obstet Gynecol 2009;21:521–6. 10.1097/GCO.0b013e328332d24e
    1. Gagnon C, Ménard J, Bourbonnais A, 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;8:437–41. 10.1089/met.2010.0013
    1. Patry-Parisien J, Shields M, Bryan S. Comparison of waist circumference using the world Health organization and National Institutes of health protocols. Health Rep 2012;23:53–60.
    1. Labonté M-È, Cyr A, Baril-Gravel L, et al. . Validity and reproducibility of a web-based, self-administered food frequency questionnaire. Eur J Clin Nutr 2012;66:166–73. 10.1038/ejcn.2011.163
    1. Mollayeva T, Thurairajah P, Burton K, et al. . The Pittsburgh sleep quality index as a screening tool for sleep dysfunction in clinical and non-clinical samples: a systematic review and meta-analysis. Sleep Med Rev 2016;25:52–73. 10.1016/j.smrv.2015.01.009
    1. Craig CL, Marshall AL, Sjöström M, et al. . International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 2003;35:1381–95. 10.1249/01.MSS.0000078924.61453.FB
    1. Feehan LM, Geldman J, Sayre EC, et al. . Accuracy of Fitbit devices: systematic review and narrative syntheses of quantitative data. JMIR Mhealth Uhealth 2018;6:e10527. 10.2196/10527
    1. Ekman MJ, Klintenberg M, Björck U, et al. . Six-minute walk test before and after a weight reduction program in obese subjects. Obesity 2013;21:E236–43. 10.1002/oby.20046
    1. Boivin J, Takefman J, Braverman A. The fertility quality of life (FertiQoL) tool: development and general psychometric properties. Fertil Steril 2011;96:409–15. 10.1016/j.fertnstert.2011.02.046
    1. Baillargeon J-P, St-Cyr-Tribble D, Xhignesse M, et al. . Impact of an integrated obesity management system on patient's care - research protocol. BMC Obes 2014;1:19. 10.1186/s40608-014-0019-z
    1. Baillargeon J-P, Carpentier A, Donovan D, et al. . Integrated obesity care management system -implementation and research protocol. BMC Health Serv Res 2007;7:163. 10.1186/1472-6963-7-163
    1. Paterson N, Sharma AM, Maxwell C, et al. . Obesity-Related health status is a better predictor of pregnancy with fertility treatment than body mass index: a prospective study. Clin Obes 2016;6:243–8. 10.1111/cob.12149
    1. Government of Canada . Good clinical practices, 2012. Available: [Accessed 17 Dec2021].
    1. McHugh ML. Interrater reliability: the kappa statistic. Biochem Med 2012;22:276–82.
    1. Mulhern B, Brazier JE. Developing version 2 of the SF-6D: the health state classification system. in the 21st annual conference of the International Society for quality of life research. Qual Life Res 2014;23:49.
    1. Poder TG, Fauteux V, He J. Consistency Between Three Different Ways of Administering the SF-6Dv2. Value Health.
    1. Mulhern BJ, Bansback N, Norman R, et al. . Valuing the SF-6Dv2 classification system in the United Kingdom using a Discrete-choice experiment with duration. Med Care 2020;58:566–73. 10.1097/MLR.0000000000001324
    1. Canadian Agency for Drugs and Technology in Health . Guidelines for the economic evaluation of health technologies: Canada. 4 ed. Ottawa: CADTH, 2017.
    1. Ramsey S, Willke R, Briggs A. Good research practices for cost-effectiveness analysis alongside clinical trials: the ISPOR RCT-CEA Task force report 2005:521–33.
    1. Gagnon C, Brown C, Couture C, et al. . A cost-effective moderate-intensity interdisciplinary weight-management programme for individuals with prediabetes. Diabetes Metab 2011;37:410–8. 10.1016/j.diabet.2011.01.003
    1. Krueger RA, Casey MA. Focus groups: a practical guide for applied research. 5th ed. Thousand Oaks, CA: Sage Publications Inc, 2014.
    1. Morgan DL. Basic and Advanced Focus Groups. Thousand Oaks, CA: Sage Publications Inc, 2018.
    1. Miles MB, Huberman AM JS. Qualitative data analysis. 3rd ed. CA: Sage: Thousand Oaks, 2014.
    1. St-Cyr Tribble D, Gallagher F, Vanasse A. Programme d’intervention fondé sur un modèle de collaboration interprofessionnelle et de promotion de l’autosoin auprès des diabétiques de type 2. FCRSS & Aventis Canada, 2007.

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