infertility and pcos presentation

Title of seminar

here

Infertility in Women with

PCOS

Haley Thomas B.S.Appalachian State University

February 29, 2016

Seminar Question:

Is there a MNT protocol to decrease inflammation and enhance fertility in women with PCOS?

Following this presentation the listeners will be able to:• Understand the relationship between PCOS and

female infertility• Have an understanding of the metabolic variables of

PCOS • Discuss the effects weight management has on

fertility • Be able to recognize MNT approaches to support

women with PCOS

What is female infertility?

The World Health Organization (WHO) defines infertility as:

“a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse.”

http://www.who.int/reproductivehealth/topics/infertility/definitions/en/



What is PCOS?• Polycystic Ovary Syndrome• Most common endocrine disorder in women

(6-20%)

http://www.ae-society.org/polycystic_ovaries

PCOS Diagnostic Criterias

Rotterdam criteria:

• Women with 2 of following criteria:• Oligovulation• Anovulation• Excess androgen

activity• Polycystic ovaries

Jayasena CN, Franks S; 2014

What are the challenges for women with PCOS?– Cysts located on ovaries– Hormone imbalance• Androgen excess

– Hirsutism, Acne– Insulin resistance• T2DM

– Lipid abnormalities• CV dysfunction

– Weight gain– Impaired levels of

ghrelin & leptin– Fertility problems– Menstrual dysfunction• Oligo-ovulation/

anovulation

Liepa, G. U et al. 2008

Effects of Hormonal Imbalances in PCOS

Jayasena CN, Franks S; 2014

Connection between infertility and PCOS

Argawal A et al. 2012

Inflammation vs. Infertility?

InflammationHyperinsulinemiaLipid abnormalitiesObesity

InfertilityIncreased androgen

Increased LH and FSHDisrupted ovulation

AmenorrheaOligomenorrhea

Insulin resistance

Role of diet in the treatment of polycystic ovary syndrome

Study 1

Douglas CC, Gower BA, Darnell BE, Ovalle F, Oster RA, Azziz R. Fertility & Sterility. 2006;85(3):679-688.

Study Objective“The primary purpose of this study was to determine whether eucaloric diets enriched in MUFA or reduced in carbohydrate, relative to a “standard” ADA diet, could improve the androgen profile and/or insulin sensitivity in women with PCOS.”

Hypothesized that a decrease insulin concentrations would, in turn, decrease androgen concentrations

Douglas CC et al. 2006

Author’s thought process• The decrease in insulin concentrations

following the Low CHO and high MUFA diets would allow for: 1. Increase in the production of SHBG2. Decrease in free testosterone3. Decrease in insulin-stimulated androgen

synthesis4. Improvement in lipid profiles

Population• 11 subjects with PCOS

5 African Americans 1 Asian4 Caucasians 1 of Caribbean decent


Inclusion• Nondiabetic subjects with PCOS• National Institutes of Child Health

and Human Development PCOS diagnosis criteria

• Ages 19-42 years• BMI: 24-37 kg/m2

Exclusion• Postmenopausal• History of eating disorder• Currently on modified diet• Participating in extreme exercise• Planned to move from area within 6

month• On hormonal or insulin-sensitizing

therapy for at least 2mo

ConsentUniversity of Alabama at Birmingham (UAB) Institutional Review Board approved this study for Human Use

All subjects gave written informed consent


Study Design• Crossover• 16 day diet intervention– Each subjects adhering to 3 different diets for 16

days• “we based our diets on dietary treatments

previously shown to be successful in improving the glucose, insulin, and lipid profiles in select T2DM populations.”


Diet Approach – Why?

STD diet

56% CHO, 16% Pro, 31% Fat

Modeled after 1986 American Diabetes Association (ADA)

guidelines for T2DM

Low CHO diet43% CHO

15% Pro, 45% Fat

Based on the reported changes in lipid and

glucose profiles in a 14-day low CHO and 15-day high CHO diet in subjects with

T2DM

High MUFA diet17% MUFA

55% CHO, 15% Pro, 33% Fat

Based on reported improvements in the

insulin and lipid profile of T2DM population following

high MUFA diet


What did these diets look like in the study?

Eucaloric diets1. STD: 56% CHO, 16% Pro, 31% Fat

2. Low CHO: 43% CHO, 15% Pro, 45% Fat

3. High MUFA: 17% MUFA, 55% CHO, 15% Pro, 33% Fat


Methods

Differences:• Carbohydrate intake• Total fat intake• MUFA• PUFA

Methods- Diet Manipulation1. Low CHO: 43% CHO, 15% Pro, 45% Fat

– Decreased CHO, increased fat (PUFA)• Reducing the amount of bread, rice, and noodles • Providing reduced-carbohydrate bread in place of regular bread• Higher PUFA-rich snacks such as sunflower seeds

2. High MUFA: 17% MUFA, 55% CHO, 15% Pro, 33% Fat– Provided olive oil containers

• Add oil to entrees and salads

Methods- Baseline Assessments•Prior to study: Medical hx form and brief physical exam, including hirsutism scoring

•Consume 250g CHO/day for 3 days– Prior baseline testing

• Metabolic testing– At baseline and last day of each diet intervention

• Metabolic tests– After a evening meal and a 10–12 hour fast– Intravenous glucose tolerance test

• UAB General Clinical Research Center (GCRC)

Assigned Diet(16 days)

Wash Out Period(3 wk)


Wash Out Period(3 wk)


Regimen 1: Low CHO MUFA STD

Regimen 2: Low CHO STD MUFA

Regimen 3: MUFA Low CHO STD

Baseline Testing Testing Testing Testing

Methods- Assessment• Diet compliance monitored through:

1.Frequent weighing• 2-3 times/weeks

2.24-hour urine collection by GCRC Metabolic Kitchen staff• Assess sodium before overnight GCRC admission• Primarily psychological reminder to adhere to intervention

protocol

• Contact RD if any subject gained or lost in excess of 2.2kg


Critique of StudyStrengths• Diverse population• Eucaloric diet – to see

effects not associated with weight loss

• Tightly controlled

Limitations• Intervention not

appropriate for Cross-over RCT study

• Not randomized – high bias risk

• Small sample size• Short diet intervention

period (16 days)• No monitoring during wash-

out periodDouglas CC et al. 2006

Effects of DASH diet on lipid profiles and biomarkers of oxidative stress in overweight and obese women with polycystic ovary syndrome: A

randomized trial

Study 2

Asemi Z, Saminmi M, Tabassi Z, Shakeri H, Sabihi S, Esmaillzadeh A. Nutrition. 2006;30 1287-1293.

Study Objective

“to investigate the effects of the DASH eating plan on lipid profiles and biomarkers of oxidative stress in overweight and obese women with PCOS.”

Asemi Z et al. 2006

Population• 54 women diagnosed with PCOS

– 12 dropped out

Asemi Z et al. 2006

Inclusion• Ages: 18-40 years• PCOS defined by Rotterdam criteria• BMI ≥ 25 kg/m2

• Menstral irregularity and/or modified Ferriman-Gallwey (mF-G) score of 8

Exclusion• BMI < 25 kg/m2

• Presence of neoplastic, hepatic, renal, CV, or malabsorptive disorders

• Current or previous (w/in 6mo) use of hormal, antidiabetic, or antiobesity medication

• Planning to follow specific diet or physical activity plan

ConsentApproved by the ethical committee of Kashan University of Medical Sciences

Written consent obtained from all participants

Study Design• Two-arm parallel, randomized clinical trial (RCT)

• Stratified according to BMI and age – Both: (>30 and <30 kg/m2)

• Randomly assigned to consume:– Control or the DASH diet for 8 weeks

• Do not alter routine, receive lipid lowering medications, or medications that could affect their reproductive physiology

Asemi Z et al. 2006

Dietary Approach to Stop Hypertension• Developed to lower blood pressure (BP) without medication• Through research, it has been proven to lower BP, reduce

cholesterol, and improve insulin sensitivity• Designed for everyone

http://dashdiet.org/what_is_the_dash_diet.asp

Diets randomly assigned

Control(n=27)

52% Carbohydrates18% Protein

30% Fat

DASH(n=27)

52% Carbohydrates18% Protein

30% Fat

Rich in fruits, vegetables, whole grains, and low-

fat dairy

Low in saturated fat, cholesterol, refined grains and sweets

Asemi Z et al. 2006

Methods- Diet Manipulation• Both Control and DASH diets calorie-restricted– 350-700 kcal less based on current BMI

• Energy requirements – resting energy expenditure and physical activity– Harris Benedict

Asemi Z et al. 2006

Methods- Baseline Assessment• Trained Midwives• Medical Hx – Focus on PCOS

symptoms• Menstrual irregularities

– Amenorrhea vs. Cycle length/variation b/w cycles

• Clinical hyperandrogeniam• Medication use, hormone

therapy• Hyperandrogenism

– Hirstuism• mF-G scoring

• Hormone Profiles• Metabolic testing• Anthropometrics

Methods- Assessment• Monitored by weekly phone interviews• Double checked with 3-day diet records• Baseline and 8 weeks– Anthropometrics

• Weight– Metabolic testing

• Cholesterol• Triglycerides• Plasma total antioxidant capacity (TAC)• Plasma glutathione (GHS)

Methods- Monitoring• 7-day diet menu • Education with RD– Basics of diet– Exchange list

• 3-day diet records

Asemi Z et al. 2006

Critique of Study

Strengths• Randomized control trial• All study personnel and

participants were blinded to dietary assignment– Exception of RD

Limitations• Relatively short intervention

duration• Not a lot of focus put on

oxidative stress markers

Effect of a low glycemic index compared with a conventional healthy diet on

polycystic ovary syndrome

Study 3

Marsh KA, Steinbeck KS, Atkinson FS, Petocz P, Brand-Miller JC. American Journal of Clinical Nutrition. 2010;92(1):83-92.

Study Objective

“Compare 2 diets of equivalent macronutrient distributions and fiber contents, in which the carbohydrate foods were either low GI or moderate-to-high GI.”

Hypothesis: Independent of weight loss, a low-GI diet would improve underlying insulin resistance in women with PCOS. It will be more effective than conventional low-fat, high-cereal fiber dietary advice for CVD and DM2 risk factors.

Marsh KA et al. 2010

Population• 96 overweight and obese premenopausal women with PCOS• Recruited participants between 2004 and 2007


Inclusion• Age: 18-40 years• PCOS defined by Rotterdam criteria• BMI ≤ 25 kg/m2 without recent wt. loss• Not pregnant, breastfeeding, or plans

to become pregnant

Exclusion• Presence of DM or other endocrine

disorders• Oral contraceptive use• Antidepressants• Lipid-lowering medication use• Current treatment of eating disorder

or depression

ConsentStudy was approved by the Human Research Ethics Committee of the University of Sydney and the Royal Prince Alfred Hospital Ethics Review Committee

Subjects gave written informed consent


Study Design• Participants stratified according to weight and

Metformin use– BMI <30 and ≥30 kg/m2

• Consecutively assigned in alternate order to consume either:Libitum Low-GI diet

orMacronutrient-matched conventional health diet

• 12 months or until 7% weight loss was achievedMarsh KA et al. 2010

Glycemic Index• A measurement of how a specific carbohydrate food raises

blood glucose• Foods ranked• High GI raises blood glucose morethan a medium or low ranked item• Fat and fiber are contributors tolowering GI rankings of items

http://www.glycemicindex.com/about.php

Study Design• Education throughout study– RD saw participants during follow-ups– Guide to portion sizes – lead to gradual weight loss– Electronic newsletter (importance of study, nutrition and

exercise articles, motivational tips, recipes)• Menu and shopping lists provided• Follow-ups– Weekly for first 4-6 visits then every 2-4 weeks

Reduced Energy (no specifications)

Low-fatLow sat. fat

Moderate-high fiber

Low GI Diet Conventional Healthy Diet

5 Food Groups1. Grain (cereal)2. Vegetables and

legumes/beans3. Fruit4. Milk, yogurt, cheese and/or

alternatives (mostly red. Fat)5. Lean meats and poultry, fish,

eggs, tofu, nuts, seeds, and legumes/bean

Small Amounts:- Cooking oil, canola spray, and

margarineOnly Sometimes, use small amounts- Soft drinks, wines, chocolates, sausage, cupcakes, creams, potato chips

Diet Manipulation• Participants told that the study was comparing two

different healthy, low-fat diets– Only variance in types of carbohydrate recommended– “Glycemic index” or “GI” verbiage was not used

• Low GI breads and cereals

Methods- Assessments• Asked to keep menstrual diary and to recall

menstrual cycles 6mo prior study• Baseline and study completion

– 2 hour glucose tolerance test• Insulin sensitivity

– PCOS questionnaire – assess changes in quality of life• 26 questions with 7-point rating scale, 5 domains

1. Emotions2. Body hair3. Weight4. Infertility5. Menstrual Problems


Methods- Diet Monitoring• 1 week food diary (x3)– At baseline– 2-4 weeks after dietary intervention– At study completion

• Dietary recall of past 2-4 weeks checked by nutritionist “at each visit”– Diet information entered into customized database

software


Assessment- Administered QuestionnaireCronin L et al, 1998

Cronin L et al, 1998

Methods- Assessment• Anthropometrics– Weight

• Metabolic– Cholesterol– Triglycerides– C-reactive protein (CRP)

• Hormone profiles

– Testosterone– Sex hormone-binding

globulin (SHBG)– LH– Follicle-stimulating

hormone (FSH)

Affect on Menstrual Cycle


Critique of StudyStrengths• Both groups treated equally

(i.e. exercise)• Diet composition examined

independently of weight loss

• Consultations with RD• Detailed food instruction,

meal plans, and education

Limitations• Adequate randomization

was not used• Diets were assigned “ad

libitum”• High drop out rate• Some women taking

Metformin• Duration varied for each

participant

Serum antimüllerian hormone in response to dietary management and/or

physical exercise in overweight/obese women with polycystic ovary syndrome:

secondary analysis of a randomized controlled trial

Study 4

Nybacka A, Carlstom K, Fabri F, Hellstrom PM, Hirschberg A. Fertility and Sterility. 2013; 100(4) 15-282.

What is Antimüllerian hormone? • Antimüllerian hormone (AMH)

– Important factor in folliculogenesis – Correlates with the number of antral follicles

• Produced only in small ovarian follicles = determining amount of growing follicles = Reliable marker of ovarian reserve

• Ovarian Reserve– Remaining egg supply– Antral follicle count – vaginal ultrasound

• Higher chance of pregnancy when count is between 22 and 35• Difficult to get accurate test with polycystic ovaries

– AMH blood level

http://www.advancedfertility.com/amh-fertility-test.htm

PCOS:• Many small follicle • High AMH levels

http://www.infertile.com/beating-biological/

Study Objective“investigate effect of the three interventions on serum AMH and its association with reproductive function and endocrine and metabolic variables.”

“hypothesized that lifestyle interventions would lead to a decrease in AMH levels and that normalized levels of AMH after intervention are associated with improved menstrual function and endocrine and metabolic status.”

Nybacka A et al. 2013

Population• 57 women with PCOS started study

– 43 participants completed interventions

Inclusion• Age 18-40• BMI > 27 kg/m2

• Absence of hormonal treatment for last 3 months

• No pregnancy, lactaion, or change in in weight during past year

Exclusion• Presence of other disease or a

different endocrine disorder; an eating disorder, smoking, or continuous medication

Nybacka et al, 2013

ConsentApproved by the Ethics Committee at Karolinska University Hospital

Written informed consent was obtained from participants

Nybacka et al, 2013

Study Design• Secondary analysis of a randomized controlled

trial– First trial compared the influence of dietary management and/or physical

exercise on ovarian function and metabolic parameters in overweight women with polycystic ovary syndrome

– Second trial was conducted the same way, but looking closer at how AMH is affected

• Study performed between January 2003 and December 2008 at Karolinska University Hospital

Nybacka et al, 2013

Study Design• 57 women were randomized into 3 groups: 1. Diet management 2. Exercise or 3. Both in combination

• Intervention lasted 4 months– Monthly visits

• Follow-up continued past a year post termination of study

• Physical examination– Immediately before study, after 4 month intervention, and

long-term follow-up

Study DesignSubjects Randomized

(n= 57)

Diet Management

Diets designed individually

Exercise

Individualized based on condition and

interest

Goal of moderate level

45-60 minutes2-3 times/week

Both in Combination

Methods- Diet Management• Individualized by dietitian• Daily caloric intake reduced by 600 kcal/day in

comparison to current intake• Macronutrients:– CHO 55-60% Protein 10-15% Fat 25-30%

• Strict meal schedule– 3 main meals with 2-3 snacks

Intervention AssessmentsDietary Exercise Both

- Supervised by RD- Self-report: once every

24hrs for 4 days immediately before and after intervention

- Physical examination

- Supervised by physiotherapist

- Pedometers: during 4 days immediately before and after intervention

- Physical examination

- Not addressed

Nybacka et al, 2013

Comparisons Post Interventions

• Participants with normal AMH levels (5-43 pmol/L) after intervention• Significantly lower:

• LH• Total testosterone• Free testosterone

• Significantly improved menstrual pattern

• However,• Higher fasting insulin

and HOMA index

Nybacka et al, 2013

Critique of Study

Strengths• Randomized study• Diet design by RD

Limitations• Small population• High drop out rate

Anti-Inflammatory Dietary Combo in Overweight and Obese Women with

Polycystic Ovary Syndrome

Study 5

Salama A, Amine E, Salem H, Fattah N. North American Journal of Medicine Sciences. 2015; 7(7): 310-16.

Study ObjectiveHypothesis: consuming a hypocaloric low glycemic load (GL) diet with anti-inflammatory properties (as a combo diet) will:

1. Reduce total and visceral adipose tissue2. Promote weight loss3. Improve reproductive, metabolic, and hormonal profiles

“to investigate the effect of anti-inflammatory dietary combo on metabolic, endocrine, inflammatory, and reproductive profiles in overweight and obese women with PCOS.”

Salama A et al. 2015

Population

• 95 participants recruited• 75 non-pregnant, overweight, and obese adult females with

PCOS – 17 dropped out, 2 participants conceived at weeks 5 and 7

Inclusion

• Age 20-40 years• Diagnosed PCOS according to

Rotterdam criteria• Referred by Obstertrics and

Gynecology dept. of Alexandria University

Exclusion

• DM I or II• Receiving Metformin• Receiving ovulation induction

medications• Following a diet regimen within

the last month


ConsentApproved by the Nutrition Outpatient Clinic of the High Institute of Public Health, Alexandria University ethics committee and University’s research committee

Informed consent was obtained from participants


Study Design

• Quasi-experimental trial• 12 weeks of dietary intervention and physical activity• Nutrition outpatient clinic and local laboratory• Attended clinic every 2 weeks (6 visits total)

– Weight, height, waist circumference, hip circumference– Meal plans

• Physical activity encouraged– Stairs: 30min/day– Sit ups or abdominal crunches: 10min/day X 3


Dietary Approach• Anti-inflammatory diet – 12 weeks

– Mediterranean, low glycemic load (GL), low in omega-6 fatty acids, rich in omega-3 fatty acids• Legumes, fish, low-fat dairy, limit red meat to once every 2 weeks, 5 cups of

green tea daily– Hypocaloric

• EER– Institute of Medicine Equation then subtracting 500 calories– 25% protein, 25% fat, 50% carbohydrate

– 1-2-3 ratio for macronutrient distribution• 1g Fat : 2g Pro : 3g CHO• Menu plans and shopping lists provided• Diabetic exchange calculation forum


Dietary Approach Cont’d• Small, frequent meals– 5 small meals, 3hrs apart

• Recommended daily herbs and spices:- Ginger - Cumin- Chili peppers - Coriander- Black pepper - Clove- Curcumin - Clove- Bay leaves - Cinnamon- Fennel - Marjoram- Anise - Rosemary- Caraway - Thyme

• 5 cups green tea daily

Methods- Assessment

• Medical, reproductive, and dietary hx taken• Anthropometrics • Fasting blood samples

– At baseline and end of study– Biological markers

• Body fat percent and visceral fat area– At baseline and end of study

• Total Testosterone (TT); Free Testosterone (FT) • Steroid Hormone Binding Globulin (SHBG) • C Reactive Protein (CRP) and Serum Amyloid A (SAA)

Statistical Analysis• Performed using Statistical Package for Social Sciences (SPSS) software

Type of Data Method Used

Normally distributed quantitative data Descriptive Statistics, mean, and SD

Non-normally distributed data Median

Analysis of numeric data One sample Kolmogorov-Smirnov test

Association between two categorical variables

Pearson’s chi-square testMonte Carlo exact testFisher’s exact test

Comparing paired results from pre-intervention-post intervention difference

Mc Nemar chi-square test

Comparison between two proportions Z-test

Comparing two independent quantitative non-normally distributed variables

Mann-Whitney U test

Test hypothesis for two related quantitative variables contain same distribution

Wilcoxon signed-rank test (nonparametric test)


Results• Two participants conceived (after 5 and 7 weeks) and dropped

out• Mean wt. loss of 6.3kg; 7.9%• Statistical significant P value < 0.05

– BMI 7.1% change (P ≤ 0.001)– FBG decreased by 5.15% (P ≤ 0.001)– FI decreased 27.86% (P ≤ 0.001)– Homeostatic model assessment (HOMA) decrease of 27.50% (P ≤ 0.001)– Drop in free androgen index by 31% (P ≤ 0.001)– 65.6% increase in mean SHBG levels (P ≤ 0.001)– Drop in CRP 35% (P ≤ 0.001)– Drop in SAA 38% (P ≤ 0.001)


“Anti-inflammatory nutrition is the understanding how individual nutrients affect the same molecular targets affected by pharmacological drugs.”

Medications Work at the site of molecular inflammation

Diet Reduce dietary factors that activate nuclear factor kappa B to generate silent inflammation


Critique of Study

Strengths• Valid PCOS diagnosis• High compliance rate• Low drop out rate

Limitations• No figures provided• Not randomized

Case StudyA 28 year old female with PCOS has been trying to conceive for 1 ½ years. She has had DM2 for 3 years and is struggling with keeping her blood sugars controlled. She currently has a BMI of 32. The MD has told her she has elevated testosterone levels. She has labeled herself as a “yo-yo dieter.” She states that she has tried everything to lose weight.

Discussion Question 1

After hearing about different dietary approaches in hopes of increasing fertility. What dietary advice would you give this patient?


What dietary recommendations would you make to decrease inflammation in this population?


How many healthcare dollars do you think is spent on IVF treatment? DM management? per year?

ReferenceAgarwal, A., Aponte-Mellado, A., Premkumar, B. J., Shaman, A., & Gupta, S. (2012). The effects of oxidative stress on female reproduction: a review. Reprod Biol Endocrinol, 10, 49. doi: 10.1186/1477-7827-10-49

Asemi, Z., Samimi, M., Tabassi, Z., Shakeri, H., Sabihi, S. S., & Esmaillzadeh, A. (2014). Effects of DASH diet on lipid profiles and biomarkers of oxidative stress in overweight and obese women with polycystic ovary syndrome: a randomized clinical trial. Nutrition, 30(11-12), 1287-1293. doi: 10.1016/j.nut.2014.03.008 Bergh, C. M., Moore, M., & Gundell, C. (2016). Evidence-Based Management of Infertility in Women With Polycystic Ovary Syndrome. J Obstet Gynecol Neonatal Nurs, 45(1), 111-122. doi: 10.1016/j.jogn.2015.10.001 Cassar, S., Teede, H. J., Moran, L. J., Joham, A. E., Harrison, C. L., Strauss, B. J., & Stepto, N. K. (2014). Polycystic ovary syndrome and anti-Mullerian hormone: role of insulin resistance, androgens, obesity and gonadotrophins. Clin Endocrinol (Oxf), 81(6), 899-906. doi: 10.1111/cen.12557 Chicago, A. F. C. o. (1996). Anti-Mullerian Hormone Testing of Ovarian Reserve. Retrieved 2/1, 2016 Douglas, C. C., Gower, B. A., Darnell, B. E., Ovalle, F., Oster, R. A., & Azziz, R. (2006). Role of diet in the treatment of polycystic ovary syndrome. Fertil Steril, 85(3), 679-688. doi: 10.1016/j.fertnstert.2005.08.045 Gaskins, A. J., Chiu, Y. H., Williams, P. L., Ford, J. B., Toth, T. L., Hauser, R., . . . Team, E. S. (2015). Association between serum folate and vitamin B-12 and outcomes of assisted reproductive technologies. Am J Clin Nutr, 102(4), 943-950. doi: 10.3945/ajcn.115.112185

Jayasena, C. N., & Franks, S. (2014). The management of patients with polycystic ovary syndrome. Nat Rev Endocrinol, 10(10), 624-636. doi: 10.1038/nrendo.2014.102

Liepa, G. U., Sengupta, A., & Karsies, D. (2008). Polycystic ovary syndrome (PCOS) and other androgen excess-related conditions: can changes in dietary intake make a difference? Nutr Clin Pract, 23(1), 63-71. Marsh, K. A., Steinbeck, K. S., Atkinson, F. S., Petocz, P., & Brand-Miller, J. C. (2010). Effect of a low glycemic index compared with a conventional healthy diet on polycystic ovary syndrome. Am J Clin Nutr, 92(1), 83-92. doi: 10.3945/ajcn.2010.29261 Mmbaga, N., & Luk, J. (2012). The impact of preconceptual diet on the outcome of reproductive treatments. Curr Opin Obstet Gynecol, 24(3), 127-131. doi: 10.1097/GCO.0b013e3283530524 Nybacka, A., Carlstrom, K., Fabri, F., Hellstrom, P. M., & Hirschberg, A. L. (2013). Serum antimullerian hormone in response to dietary management and/or physical exercise in overweight/obese women with polycystic ovary syndrome: secondary analysis of a randomized controlled trial. Fertil Steril, 100(4), 1096-1102. doi: 10.1016/j.fertnstert.2013.06.030 Organization, W. H. (2016). Sexual and reproductive health. Retrieved 11/1, 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ Salama, A. A., Amine, E. K., Salem, H. A., & Abd El Fattah, N. K. (2015). Anti-Inflammatory Dietary Combo in Overweight and Obese Women with Polycystic Ovary Syndrome. N Am J Med Sci, 7(7), 310-316. doi: 10.4103/1947-2714.161246 Sydney, T. U. o. (2015, 2/19/2016). About Glycemic Index. from http://www.glycemicindex.com/index.php


http://www.glycemicindex.com/index.php

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