Gonadotrophins in PCOS

Gonadotrophins in PCOS

1. Gonadotrophins in PCOS
Thessaloniki, ESHRE/ASRM, 2008
Prof Aboubakr Elnashar
Benha university Hospital, Egypt

Aboubakr Elnashar

2. Aim of ovulation induction in PCOS
Singleton live birth.
limited number of developing follicles.
{In PCOS: excessive multiple follicle development}
(Brown, 1978; Baird, 1987).

Aboubakr Elnashar

3. Protocols
I. Step-up:
1. Conventional=Standard
2. Low dose
3. Chronic low dose
II. Step-down
III. Step-up, step-down

Aboubakr Elnashar

4. I.Step up
Principle:
Stepwise increase in FSH {determine the FSH
threshold for follicular development}
Aboubakr Elnashar

5. Aboubakr Elnashar

6. 1.Conventional:
Starting dose: 150 IU/d:
Duration of starting dose: 5 d
Increased by: 75 IU/3-5 d
Excessive follicle development
Increased OHSS (Thompson and Hansen, 1970; Dor et al., 1980; Wang and Gemzell, 1980).
No longer recommended (Buvat et al., 1989; Brzyski et al., 1995)
Aboubakr Elnashar

7. Starting dose : 150 IU/d 2 FSH/hMG/day
Day 3Day 3 Day 7Day 7
5 days5 days
If
Follicle > 12 mm
E2 > 400U
Continue
2 FSH/d
No response® 3 FSH/day
for 3 more days
Endocrine Rev. 1997; 18: 71
Aboubakr Elnashar

8. 2. low-dose
•Stating dose: 37.5-75 IU/d
(White et al., 1996; Hayden et al., 1999; Balasch et al., 2000; Calaf et al., 2003).
•Duration of starting dose: 5-7 d
-No follicle development: increase the dose
by 100%
-Follicle growth: maintain same dose until
follicular selection is achieved.


Aboubakr Elnashar

9. Starting dose : 37.5-75 IU/d
If
Follicle > 12 mm
E2 > 400US
Continue
1 FSH/d
No response 75-150 FSH/d
for 1 more w (max. 3 amp.)
Endocrine Rev. 1997; 18: 71
37.5-75 FSH/hMG/day
Day 3 Day 7
5 days
Aboubakr Elnashar

10. 3. Chronic low-dose
•Starting dose: 37.5 IU
•Duration of starting dose:14 d
•The weekly dose increment: reduced from
100% to 50% or 37.5 IU
(Seibel et al., 1984; Polson et al., 1987; Sagle et al., 1991; Dale et al., 1993).
:Markedly reduce excessive ov stimulation
Marked dec in OHSS.



Aboubakr Elnashar

11. 0 14 21 28 35
75 iu
112.5 iu
150 iu
187.5 iu
225 iu
Days
7
37.5 iu
½ Amp.
One Amp.
42 49
2 Amp.
3 Amp.
White et al. J Clin Endocrinol Metab 1996;81:3821–4
Aboubakr Elnashar

12. II. Step-down:
Principle:
To achieve the FSH threshold through a
loading dose of FSH with a subsequent
stepwise reduction as soon as follicular
development is observed
(Schoot et al., 1992; van Dessel et al., 1996; Fauser and Van Heusden, 1997).

Aboubakr Elnashar

13. Aboubakr Elnashar

14. Starting dose:150-225 IU/d for 3-4 d
decreased to 75Iu to maintain f develop
Day 3
2 FSH/d 1½ FSH/d 1 FSH/d
3-4 days.
U/S & E2
Foll > 11 mm
2-3 days
U/S
hCG
D7
FSH dose may be high or low:
• Need to dose.

•Need to dose by one ampoule.
Aboubakr Elnashar

15. Step up Vs step down:
-Similar high rates of monofollicular development
(van Santbrink and Fauser, 1997; Balasch et al., 2001).
-Step-up regimen:
safer in terms of monofollicular development
(Christin-Maitre and Hugues, 2003).
monitoring require less experience & skill
(van Santbrink et al., 1995).
Aboubakr Elnashar

16. III. Sequential step-up& step-down
Reduces risk of over-response (Hugues et al., 1996,
2006).
Aboubakr Elnashar

17. Low dose Step-up Step-down
one FSH/day
Day 3
step-up till 14 mm foll.
step-down
hCG
Aboubakr Elnashar

18. Monitoring

I. US
-Baseline:
-Serial
Documentation of all follicles >10 mm {predict
the risk of multiple pregnancies}.
Monofollicular cycle:
Single follicle of 16 mm or higher
Single follicle of 16 mm or higher with no other follicle 12 mm or higher
(Leader , 2006)

Aboubakr Elnashar

19. Cycle cancellation
>3 follicles ≥16 mm
(White et al., 1996; Homburg and Howles, 1999; Calaf et al., 2003a)
>4 follicles ≥ 14 mm (Kamrava et al., 1982; Hugues et al., 2006).
>2 follicles ≥ 14 mm (Farhi et al., 1996)
>3 follicles ≥ 10 mm (Tur et al., 2001; Dickey et al., 2005).
>3 follicles ≥ 14 mm.
>2 follicles ≥16 mm or
>1 follicle ≥16 mm& 2 additional follicles ≥14
mm (ASRM, ESGRE, 2008)


Aboubakr Elnashar

20. II. E
2
levels:
•Used to
cancel cycles (due to over- or under-response)
adjust the dose of Gnt
•Caution when
rapidly rising or
>2500 pg/ml (ASRM, 2006).
<1000 pg/ml (Tur et al., 2001; Dickey et al., 2005)
Aboubakr Elnashar

21. Efficacy

low-dose regimens
Monofollicular ovulation: 70%,
Pregnancy: 20%
(Homburg and Howles, 1999).
Multiple pregnancies: <6%
OHSS: <1%
(Hamilton-Fairley et al., 1991; van Santbrink et al., 1995; White et al., 1996; Balasch et al., 1996).
Conventional dose protocols:
Multiple pregnancies: 36%
Severe OHSS: 4.6%
(Hamilton-Fairley and Franks, 1990).
Aboubakr Elnashar

22. Low dose Conventional
≤6% 36% Multiple pregnancy
≤1% 6% OHSS
Aboubakr Elnashar

23. Conclusion
Low-dose FSH protocols are effective
in achieving ovulation in PCOS
Starting dose: 37.5-50 IU/day.
Starting period: 14 d
FSH dose increment: 50% of the initial or
previous dose
Intense ovarian response monitoring
Strict cycle cancellation criteria

Aboubakr Elnashar

24. •Duration: should not exceed 6
ovulatory cycles.
•Preventing all multiple pregnancies
&OHSS is not possible at this time.


Aboubakr Elnashar

25. Thanks
[email protected] Aboubakr Elnashar