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Published in: Trials 1/2018

Open Access 01-12-2018 | Study protocol

A randomized controlled trial comparing lifestyle intervention to letrozole for ovulation in women with polycystic ovary syndrome: a study protocol

Authors: Dylan A. Cutler, Alana K. Shaw, Sheila M. Pride, Mohamed A. Bedaiwy, Anthony P. Cheung

Published in: Trials | Issue 1/2018

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Abstract

Background

Polycystic ovary syndrome (PCOS) affects between 8 and 18% of women and is the leading cause of female anovulatory infertility. Unfortunately, common treatments for women trying to conceive can be ineffective as well as disruptive or harmful to patients’ quality of life. Despite evidence that women with PCOS have expressed the need for alternative fertility treatments, lifestyle interventions incorporating a nutritional plan with supplementation, increased physical activity, and techniques for stress management have not been combined as a program and studied in this population. Literature suggests that each of these individual components can positively influence reproductive hormones and metabolic health.

Methods/design

This is a randomized controlled trial which will include 240 women diagnosed with PCOS, according to the Rotterdam criteria, who are trying to conceive. Participants will be randomized to either a comprehensive lifestyle intervention program or prescribed an oral fertility medication, letrozole. These two groups will be further randomized to consume either myo-inositol or a placebo. Participants will be between the ages of 18 and 37 years. Exclusion criteria include women who have already begun fertility treatment, who are currently using myo-inositol or have taken it within the past 3 months, or who are being treated for, or have a history of, an eating disorder. The primary outcome will be the ovulation rate, the secondary outcome will be conception. Other outcomes include miscarriage rates, validated rating measures of overall quality of life (including social, relational, mind/body and emotional sub-categories) and mental health scores (depression, anxiety, and stress).

Discussion

This trial will determine the effectiveness of a structured lifestyle-based comprehensive intervention program for women with PCOS experiencing infertility. In addition, it will determine whether supplementing with myo-inositol provides any further benefit. The objective of this study is to assess a possible non-pharmacological solution to ovulatory dysfunction in these patients and perhaps improve other associated features of PCOS.

Trial registration

ClinicalTrials.gov, ID: NCT02630485. Registered on 15 December 2015.
Appendix
Available only for authorised users
Literature
1.
Fauser BC, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, et al. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-sponsored 3rd PCOS consensus workshop group. Fertil Steril. 2012;97(1):38 e25.CrossRef
2.
Melo AS, Ferriani RA, Navarro PA. Treatment of infertility in women with polycystic ovary syndrome: approach to clinical practice. Clinics. 2015;70(11):765–9.CrossRef
3.
Sozou PD, Hartshorne GM. Time to pregnancy: a computational method for using the duration of non-conception for predicting conception. PLoS One. 2012;7(10):e46544.CrossRef
4.
Legro RS, Dodson WC, Kris-Etherton PM, Kunselman AR, Stetter CM, Williams NI, et al. Randomized controlled trial of preconception interventions in infertile women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2015;100(11):4048–58.CrossRef
5.
Domar AD, Seibel MM, Benson H. The mind/body program for infertility: a new behavioral treatment approach for women with infertility. Fertil Steril. 1990;53(2):246–9.CrossRef
6.
Li J, Long L, Liu Y, He W, Li M. Effects of a mindfulness-based intervention on fertility quality of life and pregnancy rates among women subjected to first in vitro fertilization treatment. Behav Res Ther. 2016;77:96–104.CrossRef
7.
Gibson-Helm M, Teede H, Dunaif A, Dokras A. Delayed diagnosis and a lack of information associated with dissatisfaction in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2017;102(2):604–12.PubMed
8.
Dokras A, Saini S, Gibson-Helm M, Schulkin J, Cooney L, Teede H. Gaps in knowledge among physicians regarding diagnostic criteria and management of polycystic ovary syndrome. Fertil Steril. 2017;107(6):1386 e1.CrossRef
9.
Kitzinger C, Willmott J. ‘The thief of womanhood’: women’s experience of polycystic ovarian syndrome. Soc Sci Med. 2002;54(3):349–61.CrossRef
10.
Veltman-Verhulst SM, Boivin J, Eijkemans MJ, Fauser BJ. Emotional distress is a common risk in women with polycystic ovary syndrome: a systematic review and meta-analysis of 28 studies. Hum Reprod Update. 2012;18(6):638–51.CrossRef
11.
Sills ES, Perloe M, Tucker MJ, Kaplan CR, Genton MG, Schattman GL. Diagnostic and treatment characteristics of polycystic ovary syndrome: descriptive measurements of patient perception and awareness from 657 confidential self-reports. BMC Womens Health. 2001;1(1):3.CrossRef
12.
Arentz S, Smith CA, Abbott JA, Bensoussan A. A survey of the use of complementary medicine by a self-selected community group of Australian women with polycystic ovary syndrome. BMC Complement Altern Med. 2014;14(1):1.CrossRef
13.
14.
Bergh CM, Moore M, Gundell C. Evidence-based management of infertility in women with polycystic ovary syndrome. J Obstet Gynecol Neonatal Nurs. 2016;45(1):111–22.CrossRef
15.
Marsh KA, Steinbeck KS, Atkinson FS, Petocz P, Brand-Miller JC. Effect of a low glycemic index compared with a conventional healthy diet on polycystic ovary syndrome. Am J Clin Nutr. 2010;92(1):83–92.CrossRef
16.
Harrison CL, Lombard CB, Moran LJ, Teede HJ. Exercise therapy in polycystic ovary syndrome: a systematic review. Hum Reprod Update. 2010;17(2):171–83.CrossRef
17.
Stefanaki C, Bacopoulou F, Livadas S, Kandaraki A, Karachalios A, Chrousos GP, Diamanti-Kandarakis E. Impact of a mindfulness stress management program on stress, anxiety, depression and quality of life in women with polycystic ovary syndrome: a randomized controlled trial. Stress. 2015;18(1):57–66.CrossRef
18.
Cousineau TM, Domar AD. Psychological impact of infertility. Best Pract Res Clin Obstet Gynaecol. 2007;21(2):293–308.CrossRef
19.
20.
Regidor P, Schindler AE. Myo-inositol as a safe and alternative approach in the treatment of infertile PCOS women: a German observational study. Int J Endocrinol. 2016;2016:1–5.CrossRef
21.
Unfer V, Carlomagno G, Papaleo E, Vailati S, Candiani M, Baillargeon J. Hyperinsulinemia alters myo-inositol to d-chiroinositol ratio in the follicular fluid of patients with PCOS. Reprod Sci. 2014;21(7):854–8.CrossRef
22.
Milewska EM, Czyzyk A, Meczekalski B, Genazzani AD. Inositol and human reproduction. from cellular metabolism to clinical use. Gynecol Endocrinol. 2016;32(9):690–5.CrossRef
23.
Chiu TT, Rogers MS, Law EL, Briton-Jones CM, Cheung LP, Haines CJ. Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: Relationship with oocyte quality. Hum Reprod. 2002;17(6):1591–6.CrossRef
24.
Costantino D, Minozzi G, Minozzi E, Guaraldi C. Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: a double-blind trial. Eur Rev Med Pharmacol Sci. 2009;13(2):105–10.PubMed
25.
Pizzo A, Laganã AS, Barbaro L. Comparison between effects of myo-inositol and D-chiro-inositol on ovarian function and metabolic factors in women with PCOS. Gynecol Endocrinol. 2014;30(3):205.CrossRef
26.
Ciotta L, Stracquadanio M, Pagano I, Carbonaro A, Palumbo M, Gulino F. Effects of myo-inositol supplementation on oocyte’s quality in PCOS patients: a double blind trial. Eur Rev Med Pharmacol Sci. 2011;15(5):509–14.PubMed
27.
Boivin J, Takefman J, Braverman A. Development and preliminary validation of the fertility quality of life (FertiQoL) tool. Hum Reprod. 2011;26(8):2084–91.CrossRef
28.
Lovibond SH, Lovibond PF. Manual for the Depression Anxiety Stress Scales. 2nd ed. Sydney: Psychology Foundation; 1995.
29.
Legro RS, Brzyski RG, Diamond MP, Coutifaris C, Schlaff W, Casson P, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014;371(2):119–29.CrossRef
30.
McAlister FA, Straus SE, Sackett DL, Altman DG. Analysis and reporting of factorial trials: a systematic review. JAMA. 2003;289(19):2545–53.CrossRef
31.
Jaki T, Vasileiou D. Factorial versus multi-arm multi-stage designs for clinical trials with multiple treatments. Stat Med. 2017;36:563–80.CrossRef
32.
Raffone E, Rizzo P, Benedetto V. Insulin sensitizer agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women. Gynecol Endocrinol. 2010;26(4):275–80.CrossRef
33.
Yanovski SZ. Dieting and the development of eating disorders in overweight and obese adults. Arch Intern Med. 2000;160(17):2581–9.CrossRef
34.
Himelein MJ, Thatcher SS. Polycystic ovary syndrome and mental health: a review. Obstet Gynecol Surv. 2006;61(11):723–32.CrossRef
35.
Raja-Khan N, Stener-Victorin E, Wu X, Legro RS. The physiological basis of complementary and alternative medicines for polycystic ovary syndrome. Am J Physiol Endocrinol Metab. 2011;301(1):E10.CrossRef
36.
Palomba S, Falbo A, Giallauria F, Russo T, Rocca M, Tolino A, et al. Six weeks of structured exercise training and hypocaloric diet increases the probability of ovulation after clomiphene citrate in overweight and obese patients with polycystic ovary syndrome: a randomized controlled trial. Hum Reprod. 2010;25:2783–91.CrossRef
37.
Zeinalzadeh M, Basirat Z, Esmailpour M. Efficacy of letrozole in ovulation induction compared to that of clomiphene citrate in patients with polycystic ovarian syndrome. J Reprod Med. 2010;55(1–2):36–40.PubMed
38.
Karimzadeh MA, Javedani M. An assessment of lifestyle modification versus medical treatment with clomiphene citrate, metformin, and clomiphene citrate-metformin in patients with polycystic ovary syndrome. Fertil Steril. 2010;94(1):216–20.CrossRef
Metadata
Title
A randomized controlled trial comparing lifestyle intervention to letrozole for ovulation in women with polycystic ovary syndrome: a study protocol
Authors
Dylan A. Cutler
Alana K. Shaw
Sheila M. Pride
Mohamed A. Bedaiwy
Anthony P. Cheung
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Trials / Issue 1/2018
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-018-3009-5

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