Obesity, Reproduction and

Polycystic Ovarian
Syndrome (PCOS)
Nabal Jose Bracero, M.D., F.A.C.O.G.
Reproductive Endocrinology and Infertility
Assistant Professor
Department of Obstetrics and Gynecology
University of Puerto Rico School of Medicine
Medical Director
GENES fertility institute

Pre-Q1:
A patient with PCOS should have an endometrial biopsy performed:

a. Yearly even if she is having regular

withdrawal menstrual cycles, either due to
ovulation or hormonal therapy
b. If she is having fewer than 3 cycles a year
c. If she is over 35 years of age with regular
ovulatory cycles
d. If an ultrasound reveals her endometrium to
be 7mm in thickness
e. At least once if she is over 40 years of age
independent of her menstrual cycles

Pre-Q2:
Overweight patients with PCOS should be evaluated for type II
diabetes mellitus typically using:

a.
b.
c.
d.

3-hour glucose tolerance test

Fasting blood sugar
Fasting blood sugar to insulin ratio
2-hour glucose tolerance test using 75
grams of glucose solution
e. 1-hour test using 50 grams of glucose
solution

Obesity/Reproduction/PCOS
Reproduction

PCOS

Obesity

Obesity and Reproduction

Obesity is defined as BMI >30
In the United States, there was a 70%
increase in pre-pregnancy Obesity from
1994 to 2003.
Fastest growing health problem in the U.S.
31% of non-Hispanic white women
38% of Hispanic women
49% of non-Hispanic black women

Associated with significant medical problems

and adverse reproductive outcomes

Adverse Impact of Obesity on

Health

Type II Diabetes
Hypertension
Coronary Heart disease
Dyslipidemia
Sleep apnea
Increase in
uterine/ovarian/colon/breast ca
ADDRESS HIGH BMI AS ANOTHER
ABNORMAL VITAL SIGN

Menstrual Disturbances
Increasing BMI and truncal obesity
correlates with menstrual irregularities
Close to 50% of obese women have
menstrual cycle disturbances
Obesity, menstrual disorders, and
increased waist-to-hip ratio are the most
common features of PCOS
However, not all women with PCOS are
obese and not all obese women have PCOS.

Infertility
May be primarily related to ovulatory
dysfunction as opposed to pure high BMI
RR for anovulatory infertility is 1.3 for
BMI 24-31 and 2.7 for BMI >31.
Ovulatory function improves after weight
loss.
Conversely, fecundity down by 4% for
each BMI unit above a BMI of 29 in
ovulatory obese women

Response to Fertility Treatment

Increased length of ovarian
stimulation for ovulation induction
Lower oocyte yield in IVF
Higher cancellation rates for poor
response
Largest study (n=3600) showed
lower pregnancy rates for obese
women (OR 0.5-0.73)
Effects pronounced in IVF scenario

Adverse Obstetrical
Outcomes
Compared to normal-weight women, obese
women have a 2-fold increase risk of
abortion
Birth defects associated with BMI >30
Ventral wall defects OR=3.3
Neural tube defects OR=2.7
Cardiac defects OR= 2.0
Multiple anomalies OR=2.0

Beyond birth defects: Fetal origins of adult

disease hypothesis

Adverse Obstetrical Outcomes

Associated with Obesity
OR
4.8

Preeclampsia
Gestational
4.0
diabetes
Large-forgestational-age
3.8
infant
Early neonatal
3.4
death
Hypertension
3.2
Shoulder dystocia 3.1
Meconium
2.9
aspiration
Antenatal stillbirth 2.8
Fertil
Steril 90,delivery
S21-S29 2008
Cesarean
2.7

95% CI
4.045.74
3.15.2
3.54.16
2.075.63
2.64.0
1.865.31
1.65.07
1.944.02
2.492.90

Pathophysiology:
Obesity and Reproduction
Endocrine changes caused by abdominal
obesity (>80cm) result in menstrual cycle
changes:
Higher insulin levels
Most pronounced in women with PCOS independent
of obesity

Lower SHBG
Higher Ovarian Androgen levels (Testosterone)
Decreased Leptin levels
Higher Ghrelin levels

Dont forget the other half!

Obese men have a 3-fold risk of
abnormal semen analysis compared
to normal weight men.
High ratio of adipocyte peripheral
conversion of androgen to estrogen
suppresses gonadotropins and
testosterone
Higher body mass increases
testicular temperature and influence
sperm parameters

Treatment
Dietary and lifestyle changes:
First line of treatment.
Structured weight loss programs, caloric
restrictions by reducing 500-1000
kcal/day (more important than dietary
composition)= 1-2 lbs of wt loss/week
A minimum of 30 minutes of moderately
intense exercise, 3 x/week

Treatment
Medical Treatment
For BMI > 30 or if BMI >27 with
additional morbidity (HTN, DM,
dyslipidemia)
Anti-absorptive agents (Orlistat),
appetite suppressants (sibutramine),
and insulin sensitizing agents
(Metformin 1500-2000mg/d)
Bariatric surgery for patients with BMI
>40 or >35 with co-morbidities.

PCOS is a Syndrome

PCOS

PCOS
The most common endocrinopathy in
women (5-10 million women in the U.S.)
The converging point of metabolic
alterations, endocrinopathies, and
reproductive dysfunction.
Approximately 50% of women with
PCOS are clinically obese
Etiology still elusive since described in
1935 (Stein-Leventhal)

Consequences of PCOS

Cosmetic (acne, hirsutism, alopecia)

Unopposed estrogen (uterine ca 2.7-fold)
Infertility (ovulatory factors)
Metabolic Syndrome (MetS); 11x in PCOS
Increase risk of CVD

Abdominal Obesity
Dyslipidemia
BP >140/90
Insulin resistance

PCOS Symptoms

Definition of PCOS
1990 NICHD
Clinical or biochemical hyperandrogenism
Oligo- or anovulation

2003 Rotterdam
Added PCO-US appearance (at least one
ovary >10cm3 or >12 antral follicles)
2 out of the 3 above

In both, must rule out Cushings, CAH

and Androgen producing tumors.

2012 PCOS Consensus

2012 PCOS Consensus

Diagnosis of PCOS
Adolescence
Acne and menstrual irregularities are common
All 3 Rotterdam criteria should be present
Irregular cycles for 2 yrs after menarche

Ethnic considerations
Asian: lower BMI, milder androgenic sx
South Asian: higher T2D, MetS
African American: HTN, CVD
Hispanic: BMI, MetS
Middle Eastern: hirsutism

Evaluation of PCOS

Anovulation evaluation: TSH/Prolactin

Total and free testosterone
DHEAS
17-hydroxy-progesterone (follicular phase)
Fasting glucose or 2hr-75gm-GTT
IGT FG 100-125; IR 2hr GTT 140-199

Fasting lipid panel

Pelvic ultrasound
Vital signs and BMI
Pregnancy test
Endometrial biopsy

Management of PCOS
Cornerstone of treatment for
overweight or obese women with
PCOS, regardless of their desire to
conceive is:
Intensive lifestyle modification
through diet, exercise and weight
loss
5-10% loss of body weight may lead
to resumption of normal ovulation

Weight Loss:
Most Difficult But Most Efficient!

Management of PCOS
Hirsutism/Acne/Alopecia
OCPs still best option (Vaniqa, Laser, Elysis)
No significant value to add an antiandrogen (spironolactone, flutamide, or
finasteride)
While anti-androgens are effective,
insulin sensitizing agents are not
Prolonged >6 mos of treatment required
No treatment for alopecia

Management of PCOS
Menstrual Irregularities/Cancer Risk
Overall OCPs outweigh the risks in most PCOS
patients.
Alternative: cyclic progestin.

No proof one OCP is better than the other

Cycles become more regular later in life; no
increased risk for menopausal women
No agreement on optimal modality or timing of
monitoring for endometrial hyperplasia/cancer
Length of amenorrhea, bleeding pattern, EM
thickness/appearance, age

<3 menses per year may be best

predictor

Management of PCOS
Infertility
Optimize health to reduce GDM, GHTN
Goal is at least a BMI <35
Restore ovulation
Clomiphene citrate still is first line therapy
Consider referral to REI after 3 failed cycles

Metformin DOES NOT improve live-birth

rates or decrease pregnancy complications
pre- or during pregnancy (Level A)
Use of OCPs do not hinder subsequent
fertility

Post-Q1: A patient with PCOS should have an endometrial biopsy

performed:

a. Yearly even if she is having regular

withdrawal menstrual cycles, either due
to ovulation or hormonal therapy
b. If she is having fewer than 3 cycles a year
c. If she is over 35 years of age with regular
ovulatory cycles
d. If an ultrasound reveals her endometrium
to be 7mm in thickness
e. At least once if she is over 40 years of
age independent of her menstrual cycles

Post-Q2: Overweight patients with PCOS should be

evaluated for type II diabetes mellitus typically using:

a.
b.
c.
d.

3-hour glucose tolerance test

Fasting blood sugar
Fasting blood sugar to insulin ratio
2-hour glucose tolerance test using 75
grams of glucose solution
e. 1-hour test using 50 grams of glucose
solution

THANKS !