Post on 12-Apr-2017
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OBESE ADOLESCENT ANDFERTILITY IMPLICATIONS
DR PRANAY PHUKAN MD FICOGASSOCIATE PROFESSOR
DEPARTMENT OF OBSTETRICS AND GYNAECOLOGYASSAM MEDICAL COLLEGE
OBESITY
A new world wide health problem The greatest epidemic ever experienced by humans Resulting from
increasing population increasing lifespanUrbanizationPlentiful foodPhysical inactivity
Rate of obesity has doubled over the past decade
Obesity
Fertility implications both genders Pregnancy Complications Metabolic syndrome Malignancy Economic burden
Adolescent obesity is associated with three fold increase in nulliparity and four fold increase in nulligravidity
People of such constitution cannot beProlific. .fatness and flabbiness are to blame
The womb is unable to receive the semen And they menstruate infrequently and little
Hippocrates (Lloyd et al 1978)
Focus
Pathophysiology of obesity and infertility
Influence of obesity on PCOS Benefits of weight loss on reproduction
Measuring Obesity (BMI)
Some Asian populations have a genetically higher percent body fat than Caucasians resulting in greater risk of complications at a lower BMI of 23 to 25
(ASRM 2015)
Overweight 25 -29.9 increased disease riskClass I obesity 30 – 34,9 high disease riskClass II Obesity 35 – 39.9 very high disease riskClass III obesity > 40 extremely high disease risk
Genetic factor Heritability (40 to 70 % ) Genes for Leptin Suppressor of Cytokine signalling 3 Genes for glucose transporter
GeneticBehaviourEnvironment
Causes
Decreased Physical activity
Excess TV; computer, & play station time Children are home alone (dual income parents) Decreased physical activity at school & at home Transportation by car or school bus Neighbourhood safety ? Few public parks, sidewalks, swimming
pools ..etc
An imperfect body reflects an imperfect person
Changing Dietary Habits
Increased intake of caloric sweeteners & edible oil Increased intake of processed foods, refined
carbohydrates & salty high fat snacks Reduced intake of fruits and vegetables Increased global beverage due to: increased accessibility, lower price, income dynamics and marketing
Development of obesity
From Traditional to Modern Leisure and food
Obesity In Developing Countries
The burden of obesity & its complications is shifting rapidly towards the poor.
Simultaneous malnutrition & overweight exist. Obesity is now 4X more common than
malnutrition in some developing countries. Evidence from Brazil & China points to a clear
shift in obesity and overweight from middle class to the poor.
These observations are replicated across many countries in Asia, Africa & Latin America.
CHILDHOOD OBESITY IS INCREASING EVEN IN THE POOR COUNTRIES.
Lipotoxicity
Ectopic lipid accumulation in non adipose cells When energy intake exceeds the capacity of
normal adipose tissue to safely store fat Excess free fatty acids accumulates in abnormal
locations such as muscle liver etc Oxidative stress develops in these tissues Insulin resistance and inflammation
(ASRM 2015)
Lipotoxicity affects granulosa cells and leads to impaired oocyte maturation and poor oocyte quality
Possible mechanisms (Adipokines abnormalities)
Abnormalities of adipokines cause inflammation and abnormal cell signalling which leads to impaired cellular function and metabolism
Reproductive concerns
Menstrual cycle abnormalities Ovulatory dysfunction Altered ovarian responsiveness Poor Oocyte quality Miscarriage Adverse maternal fetal
environment Male infertility
Obesity’s reproductive targetsCNSOvary ovarian follicles and oocytesThe embryoThe EndometriumSemen
Obesity and the Menstrual Cycle
Affects HPO axis
Amenorrhoea, Anovulation : Adipokines inhibit ovulation Long cycle length (usually defined as >35 days) Even childhood obesity has been shown to be associated
with menstrual difficulties in later life (Lake et al. 1997 ) .
The menstrual disturbances may be further aggravated in the presence of PCOS
Increased risk of miscarriage
Impaired folliculogenesis and poor oocyte quality
Endometrial receptivity is impaired Higher prevalence of PCOS among overweight
and obese women British Fertility Society guidance suggests that
fertility treatment should be deferred until BMI is less than 35 kg/m 2
ART can help to select healthy embryo
Obesity and psychosocial and psychobiological factors
Comparative reduction in sexual frequency
Due to decreased dopamine activity and increased serotonoin levels in the brain secondary to overeating
Obesity: more sexual dysfunction(Brody 2004)
Impact of obesity on ART
Obstetric Complications in Obese Pregnant Women
Early pregnancy Spontaneous abortion Recurrent miscarriage Congenital anomalies Neural tube defects Spina bifida Congenital heart disease Omphalocele Late pregnancy Hypertensive disorder of pregnancy Gestational nonproteinuric hypertension Preeclampsia Gestational diabetes mellitus Preterm birth Intrauterine fetal demise
PeripartumCesarean delivery Decreased VBAC success Operative morbidity Anesthesia complicationsExcessive blood lossPostpartum endometritisWound infection/breakdownPostpartum thrombophlebitis
Fetal/neonatal complications
Fetal macrosomia ( Shoulder dystocia Birth weight < 4000 g Birth weight < 4500 g Childhood obesity
Maternal obesity and health risk of the offspring
‘Developmental over nutrition hypothesis' which proposes that the increased fuel supply to the foetus in maternal obesity or over nutrition leads to permanent changes in offspring metabolism, behaviour and appetite regulation with resultant obesity, metabolic and behavioural problems in adult life
Obesity and Male Reproduction
Obese men (Not all) Impaired erectile function Sleep apnoea Increasesed scrotal temperature Poor semen quality
OligospermiaAsthenospermia
Less sexual intercourse
Mechanism
Altered Sperm function Increased sperm DNA damage Decreased sperm mitochondrial activity Induces seminal oxidative stress Impairs blastocyst development Increases miscarriage Failed ART
Male Obesity
Hyperinsulinemia Suppression of SHBG Increased androgen bioavailability Oestrogen production Reduced gonadotropin secretions
Decreased total and bioavailable testosterone Diminishes LH pulse amplitude Decreased Leydig cell testosterone secretion
Hyperestrogenic Hypogonadotric hypogonadism
Fertility treatment should be deferred until BMI is less than 35 kg/m 2
Current recommendation for lifestyle modification
Weight loss of 7% of body weight Increased physical activity (150 minutes/week) A 500 to 1000 Kcal/day decrease from usual diet 1 to 2 pound weight loss per week Low calorie diet of 1000 to 12000 Kcal/day Achieving total 10 % decrease in total body weight
over 6 months Reductions in weight of 5–10% of initial body weight
may reduce the levels of insulin and androgens
Weight gain recurs when life style modifications are not sustained
Weight loss
Lifestyle modification, dietary restriction, physical activity pharmacotherapy with varied results. Dietary interventions are associated with increasing weight
regain over time, although this can be minimized with continuing care
Only 15% of the subjects can sustain weight loss successfully over time
Rapid weight loss achieved by crash diets or excessive exercise is detrimental to reproductive outcomes during fertility treatments.
Life style modification programs (especially diet programs) have been shown to be associated with poor
levels of compliance
Very low calorie diet resulting in rapid weight loss may have impact on oocyte quality and fertilization rates
Metformin, at a dose of 850 mg twice daily, have not been shown to affect menstrual frequency, body weight or insulin sensitivity, despite a fall in total testosterone and waist circumference.
Orlistat in obese PCOS showing a degree of effectiveness; however, there are no large randomized controlled trials in obese subfertile women.
Not the first line of treatment
The National Institute for Clinical Excellence (NICE) recommends
Lifestyle interventions, which encourage a nutritionally balanced diet with appropriate calorie content and which promote the benefits of regular exercise for individuals with a BMI ≥25,
The drug orlistat for those with a BMI ≥30 and Bariatric surgery for those with a BMI of >50 (National Institute
for Health and Clinical Excellence 2006); There is little evidence that these recommendations are making
an impact on the prevalence of obesity in the population. Thus, it is likely that the ‘challenge’ of obesity will remain for
reproductive biologists for some time to come.
Conclusion
• Obesity in women has impacts on fertility and fertility treatment.
• Increase in BMI reduces the chance of conception in ovulatory women and affects the outcome of ovulation induction treatment.
• Obese women undergoing IVF require higher doses of gonadotrophins, respond poorly to ovarian stimulation and have fewer oocytes harvested.
• Obesity is associated with lower fertilization rates, poor quality embryos and higher miscarriage rates.
• Weight loss in these women improves their reproductive outcomes; however, in order for this to be effective it has to be gradual and sustained
Thank you