Gonadotrophins in PCOS Thessaloniki, ESHRE/ASRM, 2008

Prof Aboubakr Elnashar Benha university Hospital, Egypt

Aboubakr Elnashar

Aim of ovulation induction in PCOS

Singleton live birth.

limited number of developing follicles.

{In PCOS: excessive multiple follicle development} (Brown, 1978; Baird, 1987).

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Protocols

I. Step-up:

1. Conventional=Standard

2. Low dose

3. Chronic low dose

II. Step-down

III. Step-up, step-down

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I. Step up

Principle:

Stepwise increase in FSH {determine the FSH

threshold for follicular development}

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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)

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Starting dose : 150 IU/d

2 FSH/hMG/day

Day 3Day 3 Day 7Day 75 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

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.

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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

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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.

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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

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).

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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.

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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).

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III. Sequential step-up& step-down

Reduces risk of over-response (Hugues et al., 1996,

2006).

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Low dose Step-up Step-down

one FSH/day

Day 3

step-up till 14 mm foll.

step-down

hCG Aboubakr Elnashar

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)

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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)

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II. E2 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)

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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).

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Low dose Conventional

≤6% 36% Multiple pregnancy

≤1% 6% OHSS

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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

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

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Thanks elnashar53@hotmail.com Aboubakr Elnashar