Letrozole Highly Selective 3rd Generation, Non-steroidal Aromatase Inhibitor Very Potent Excellent Safety Profile with lower incidences of thromboembolic phenomena & vaginal bleeding

1. Letrozole in PCOS
Dr. Jyoti Agarwal
Dr Sharda Jain
…Caring hearts, healing hands

2. Letrozole
• Highly Selective
• 3rd Generation, Non-steroidal Aromatase Inhibitor
• Very Potent
• Excellent Safety Profile with lower incidences of
thromboembolic phenomena & vaginal bleeding

3. Letrozole Is a Versatile Drug

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

11. Highest
High Quality Evidence
42 RCT’S ( 7935 women )
24th may 2018

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

17. International Guidelines 2018
Recommends
LETRAZOLE :1st line treatment of
anovulatory infertility in women with PCOS
Ensures Higher Success Rate &
Uncompromised Safety

18. FIRST LINE
Letrozole
SECOND LINE
LOD/GONADOTROPINS
THIRD LINE
IVF
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2018 GUIDELINES ON PCOD
INFERTILITY GUIDELINE FOLLOWED WORLD OVER

19. Forget all the reasons why it won’t work &
believe only one reason why it will !!

20. ADDRESS
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