The increasing incidence of obesity if affecting fertiliyu . Can we do something as health care personnel ?

1. OBESE ADOLESCENT
AND
FERTILITY
IMPLICATIONS
DR PRANAY PHUKAN MD FICOG
ASSOCIATE PROFESSOR
DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY
ASSAM MEDICAL COLLEGE

2. OBESITY
 A new world wide health problem
 The greatest epidemic ever experienced by humans
 Resulting from
increasing population
increasing lifespan
Urbanization
Plentiful food
Physical inactivity
 Rate of obesity has doubled over the past decade

3. 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 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)

4. Focus
 Pathophysiology of obesity and infertility
 Influence of obesity on PCOS
 Benefits of weight loss on reproduction

5. 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 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

6. Genetic factor
 Heritability (40 to 70 % )
 Genes for Leptin
 Suppressor of Cytokine signalling 3
 Genes for glucose transporter
Genetic
Behaviour
Environment
Causes

7. 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

8. 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

9. Development of obesity
From Traditional to Modern
Leisure and food

10. 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.

11. CHILDHOOD OBESITY IS INCREASING EVEN IN THE POOR COUNTRIES.

12. 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

13. Possible mechanisms (Adipokines abnormalities)
Abnormalities of adipokines cause inflammation and abnormal cell signalling
which leads to impaired cellular function and metabolism

14. Reproductive concerns
 Menstrual cycle abnormalities
 Ovulatory dysfunction
 Altered ovarian responsiveness
 Poor Oocyte quality
 Miscarriage
 Adverse maternal fetal environment
 Male infertility
Obesity’s reproductive targets
CNS
Ovary ovarian follicles and oocytes
The embryo
The Endometrium
Semen

15. 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

17. 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

18. 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)

20. Impact of obesity on ART

21. 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
Peripartum
Cesarean delivery
Decreased VBAC success
Operative morbidity
Anesthesia complications
Excessive blood loss
Postpartum endometritis
Wound infection/breakdown
Postpartum thrombophlebitis
Fetal/neonatal complications
Fetal macrosomia (
Shoulder dystocia
Birth weight < 4000 g
Birth weight < 4500 g
Childhood obesity

22. 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

23. Obesity and Male Reproduction
Obese men (Not all)
 Impaired erectile function
 Sleep apnoea
 Increasesed scrotal temperature
 Poor semen quality
Oligospermia
Asthenospermia
 Less sexual intercourse

24. Mechanism
Altered Sperm function
 Increased sperm DNA damage
 Decreased sperm mitochondrial activity
 Induces seminal oxidative stress
 Impairs blastocyst development
 Increases miscarriage
 Failed ART

26. 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

27. Fertility treatment should be deferred until BMI is less than 35 kg/m 2

29. 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

30. 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

31.  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.

32. Not the first line
of treatment

34. 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.

35. 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

36. Thank you