4. Review of the Guidelines
for anovulatory infertility in
women with PCOS 2018
5. ACOG 2016 LTZ should be considered as 1st line therapy for OI in
patients with PCOS & BMI>30
WHO 2016 CC or LTZ(when available and permissible) should be 1st
line therapy to improve fertility outcome in women with
PCOS & anovulatory infertility
Australian
NHMRC
2015 LTZ under caution can be offered as treatment for OI for
anovulatory PCOS women with no other infertility
factors
AACE/ACE/An
drogen excess
& pcos
2015 Treatment of women with PCOS & Anovulatory infertility
should begin with oral agent such as CC or letrozole
Endocrine
society
2013 CC or letrozole both are 1st line treatment of
anovulatory PCOS
6. Induction of ovulation
• First line therapy
• Improved ovulation and
pregnancy rate
• Especially in CC-resistant
cases
• OI in polycystic ovary
syndrome (PCOS)
• OI in intrauterine
insemination (IUI)
• Ovarian stimulation for
IVF/ICSI.
ACOG COMMITTEE OPINION 2016
7. A number of studies have shown that letrozole
appears to have a role in the treatment of
clomiphene-resistant patients
50 – 80% of clomiphene non responders have been
shown to ovulate after using letrozole
12. Cochrane library : 24th may 2018
• Letrozole compared to
clomiphene citrate
(2954 pts ; 13 studies)
• Letrozole compared to
laparoscopic ovarian
drilling
Live birth rates were
higher with letrozole
Live birth rates are
similar with letrozole
Clomiphene citrate & Metformin appear to be
less effective for live birth rates than Letrozole
13. Indian PCOS women
• High prevalence of insulin resistance and thus
are likely to have high CC resistance
• letrozole has a definitive role for ovulation
induction in such women
karnath, Reprod Biol Endocrinol. 2011; 9: 86
14. DOSAGE – LETROZOLE
Protocol Condition Letrozole Dosage
Normal
protocol
Anovulatory
infertility, PCOS
Day 3 to Day 7
2.5 mg OD
Extended
protocol1
CC-resistance
cases
Day 1 to day 10
2.5 mg OD
Step-up
protocol2
Option 1
Option 2
CC-resistance
cases
Day 3 to day 7
2.5 mg OD (first cycle),
Day 3 – day 7 ; 5 mg OD (second cycle if
not responded to first cycle)
Day 3 – day 7
7.5 mg (third cycle if not responded to
second cycle)
Day 3 – 2.5 OD
Day 4 – 5 mg (2.5 + 2.5 mg)
Day 5 – 7.5 mg (2.5 + 2.5 + 2.5 mg )
Day 6 – 10 mg (2.5+ 2.5+ 2.5 + 2.5 )
DCGI Approved
15. letrozole step up protocol
Novel induction protocol
fert stert sept 2015
letrozole step up
group
HMG group p value
age 26.3 ± 4.4 25.9 ±3.8 0.749
BMI 26.7 ± 1.2 27.3± 1.6 0.092
number of
follicles
1.5±0.7 3.1±1.0 0.001*
endometrial
thickness
9.5±0.7 9.4±0.8 0.472
clinical
pregnancy rate
16% 18% 0.790
cost
185.0±0.0 egyptian
pound
349.8±65.5
egyptian pound
0.001*
Day 2 or 3 - starting dose
2.5 mg increased daily
by 2.5 mg for other 3
days
(a total of 4 days 2.5
mg,5,7.5,10 mg )
Similar pregnancy rate to the standard HMG OI
lower financial cost ; better patient compliance
16. SIDE EFFECTS
Generally well Tolerated
• Hair thinning and rash
• Hot flushes
• Bone, joint & muscle pains
• Headache and nausea
• Sweating and cough
• Constipation
• Trouble breathing
• Trouble sleeping
• Weight gain