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DR PRANAY PHUKAN MD FICOG
DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY
ASSAM MEDICAL COLLEGE
A new world wide health problem
The greatest epidemic ever experienced by humans
Rate of obesity has doubled over the past decade
Fertility implications both genders
Adolescent obesity is associated with three fold increase in nulliparity
and four fold increase in nulligravidity
People of such constitution cannot be
Prolific. .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)
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
Overweight 25 -29.9 increased disease risk
Class I obesity 30 – 34,9high disease risk
Class II Obesity 35 – 39.9very high disease risk
Class III obesity > 40 extremely high disease risk
Heritability (40 to 70 % )
Genes for Leptin
Suppressor of Cytokine signalling 3
Genes for glucose transporter
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:
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
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.
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
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
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
Increased risk of miscarriage
Impaired folliculogenesis and poor oocyte quality
Endometrial receptivity is impaired
Higher prevalence of PCOS among overweight and obese
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
Comparative reduction in sexual frequency
Due to decreased dopamine activity and increased
serotonoin levels in the brain secondary to overeating
Obesity: more sexual dysfunction
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
Increasesed scrotal temperature
Poor semen quality
Less sexual intercourse
Altered Sperm function
Increased sperm DNA damage
Decreased sperm mitochondrial activity
Induces seminal oxidative stress
Impairs blastocyst development
Suppression of SHBG
Increased androgen bioavailability
Reduced gonadotropin secretions
Decreased total and bioavailable testosterone
Diminishes LH pulse amplitude
Decreased Leydig cell testosterone secretion
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
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.
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
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
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.
• 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
• Weight loss in these women improves their reproductive outcomes; however, in order for this to
be effective it has to be gradual and sustained