Clinical Experience With Corifollitropin alfa

(1)

Clinical Experience With Corifollitropin alfa

L. Cem Demirel, M.D.

Memorial Ataşehir Hospital IVF Department, İstanbul

(2)

2

Conflict of interest

Our team has no financial interaction with MSD company, nor has received any

support for the medications used by the patients

(3)

Corifollitropin alfa

Corifollitropin alfa rFSH

1 2 3 4 5 6 7 8 9 10

hCG

Direct gonadotropin

suppression LH

Time

≤ 60 kg : 100 µg

> 60 kg : 150 µg

(4)

4

Inclusion criteria

§  First cycle

§  All infertility etiologies excluding PCOS

§  AFC > 5

§  D3 FSH < 10 mIU / mL and E

₂

< 80 pg / mL

§  Ejaculate sperm

§  Age < 42

(5)

Patient and cycle characteristics

Age 33.7 ( range 25-42)

Mean number of oocytes and MII oocytes retrieved / OPU

11,2 and 7,2

Fertilization rate (%) 68

Mean number of embryos transferred / cycle 1.4 embryo / transfer

Pregnancy rate per transfer % 66

Clinical pregnancy rate per transfer % 57 Ongoing pregnancy rate per transfer % 50

(6)

6

D5 of stimulation

Lead follicle ≥ 14 mm +

the rest ≤ 10 mm

Asynchronous follicular growth

Specific problems of antagonist cycles

Definition

(7)

D5 of stimulation

Lead follicle ≥ 14 mm +

the rest ≤ 10 mm

Asynchronous follicular growth

Specific problems of antagonist cycles

Definition

1 in 30 cycles

(8)

8

Day when hCG criteria was met

0 5 10 15 20 25 30 35 40

5 6 7 8 9 10 11 12 13 14 15 16 17 18

Stimulation day

% of patients

Corifollitropin alfa 150 µg rFSH 200 IU/d

1/3 rd of patients had not required additional rFSH

Data on file.

Engage

(9)

1

2

11

12

2

1

0

1 0

2 4 6 8 10 12 14

6 7 8 9 10 11 12 13

number of patients

stimulation period (days)

How long did the stimulation last?

(10)

10

1

2

11

12

2

1

0

1 0

2 4 6 8 10 12 14

6 7 8 9 10 11 12 13

stimulation period (days)

How long did the stimulation last?

% 47 completed the stimulation without any extra dose

% 87 completed the stimulation with a maximum of single dose

(11)

Did the outcome differ in cycles reaching hCG criteria with a single corifollitropin alfa shot (quick responders) ?

71 %

62 %

20 30 40 50 60 70 80 90

quick responders slower responders

%

Pregnancy rate per embryo transfer

(12)

12

Additional dose requirement

In 15 cycles that have not reached the criteria for hCG triggerring within 7 days of corifollitropin alfa injection, the mean additional dose requirement per patient was;

310 IU of gonadotropin per patient

(13)

Peak serum E ₂ levels on the day of hCG

2

5

9

8

1 1 1

3

0 1 2 3 4 5 6 7 8 9 10

pg / mL

(14)

14

Peak serum E ₂ levels on the day of hCG

2

5

9

8

1 1 1

3

0 1 2 3 4 5 6 7 8 9 10

pg / mL

87 % relatively safe zone for OHSS

(15)

Peak serum E ₂ levels on the day of hCG

2

5

9

8

1 1 1

3

0 1 2 3 4 5 6 7 8 9 10

pg / mL

Median P₄on the day of hCG:

0.9 ng / mL

(16)

16

Peak serum E ₂ levels on the day of hCG

2

5

9

8

1 1 1

3

0 1 2 3 4 5 6 7 8 9 10

pg / mL

Median P₄on the day of hCG:

0.9 ng / mL Median P₄on the day of hCG:

0.6 ng / mL

(17)

What about P ₄ elevation in follicular phase?

Serum P

₄

on the day of hCG

Number of cycles

≥ 1.5 ng / mL 0

(18)

18

What about P ₄ elevation in follicular phase?

cases Peak estradiol (pg / mL) Corresponding P₄(ng / mL)

13 5412 1,01

18 3802 0,4

26 4926 0,7

Serum P

₄

on the day of hCG

Number of cycles

≥ 1.5 ng / mL 0

(19)

Unexpected poor response rate

n (%)

number of cycles with

≤3 eggs retrieved

3 / 30 ( %10)

(20)

20

A systematic review and meta-analysis

Mahmoud Youssef, et al. Fertil Steril 2012

(21)

no cancellation in this first series of patients

(22)

22

OHSS

% of patients Corifollitropin

alfa

(n=30) Engage trial Ensure trial

Hafif 3.3 2.9 3.0

Orta 0 2.3 2.2

Şiddetli 0 1.9 1.8

(23)

Day of ET

15 1

14 D5

transfer D2

transfer D3

transfer

Embryo quality

44 56

grade I grade II-IV

(24)

24

(25)

D2 vs D3 start of corifollitropin alfa

D2 D3

Stimulation phase in

days (median)

9 8

Duration of antagonist

use in days (median)

5 4

Number of oocytes

retrieved per OPU (mean)

10 14,4

Number of MII oocytes

per OPU (mean)

6,4 9,6

Pregnancy rate / ET (%)

63 % 75 %

(26)

26

D2 vs D3 start of corifollitropin alfa

D2 D3

days (median)

9 8

5 4

Number of oocytes

10 14,4

per OPU (mean)

6,4 9,6

63 % 75 %

-1

(27)

D2 vs D3 start of corifollitropin alfa

D2 D3

days (median)

9 8

5 4

Number of oocytes

10 14,4

per OPU (mean)

6,4 9,6

63 % 75 %

-1

(28)

28

D2 vs D3 start of corifollitropin alfa

D2 D3

days (median)

9 8

5 4

Number of oocytes

10 14,4

per OPU (mean)

6,4 9,6

63 % 75 %

-1

(29)

D2 vs D3 start of corifollitropin alfa

D2 D3

days (median)

9 8

5 4

Number of oocytes

10 14,4

per OPU (mean)

6,4 9,6

63 % 75 %

-1

(30)

30

D2 vs D3 start of corifollitropin alfa

D2 D3

days (median)

9 8

5 4

Number of oocytes

10 14,4

per OPU (mean)

6,4 9,6

63 % 75 %

-1

+ 4

(31)

D2 vs D3 start of corifollitropin alfa

D2 D3

days (median)

9 8

5 4

Number of oocytes

10 14,4

per OPU (mean)

6,4 9,6

63 % 75 %

-1

+ 4

(32)

32

D2 vs D3 start of corifollitropin alfa

D2 D3

days (median)

9 8

5 4

Number of oocytes

10 14,4

per OPU (mean)

6,4 9,6

63 % 75 %

-1 -1 + 4

+ 3

(33)

D2 vs D3 start of corifollitropin alfa

D2 D3

days (median)

9 8

5 4

Number of oocytes

10 14,4

per OPU (mean)

6,4 9,6

63 % 75 %

-1 -1 + 4

+ 3

(34)

34

D2 vs D3 start of corifollitropin alfa

D2 D3

days (median)

9 8

5 4

Number of oocytes

10 14,4

per OPU (mean)

6,4 9,6

63 % 75 %

-1 -1 + 4

+ 3

+ 12

(35)

Clinical Experience With Corifollitropin alfa