University Medical Centre Department for Reproductive

Medicine Ljubljanska 5

SI-2000 MariborSlovenia

Accredited by EBCOG/ESHRE

ivf.mb@ukc-mb.si

www.ivf-mb.net

IVF Maribor, Lacerta D54°18’59.66’’

8.-11.September 2011, Brijuni

Influence of oocyte number on IVF/ICSI resultsInfluence of oocyte number on IVF/ICSI results

Department of Reproductive Medicine and Gynecologic EndocrinologyUniversity Clinical Centre Maribor

Maribor, Slovenia

Veljko Vlaisavljević

E: ivf-mb@ukc-mb.si

Non stimulated cycle (“natural” cycle) Minimal stimulation Oocyte cryopreservation Single embryo transfer Blastocyst transfer

Today our choice of ovarian stimulation regimen is often made using experience-based medicine

The choice of starting dose takes into account patient characteristics but is used empirically

Decision for cultivation for blastocyst stage takes into account patients age, number of oocytes, embryo quality and its number

From cookery to science Cochrane data (2009)Cochrane data (2009)

Primary outcome ( live births per couple)

Secondary outcome ( clinical pregnancy rate, multiple pregnancy rate, high order MPR, cryopreservation, failure to have any ET per couple )

Outcomes not appropriate for statistical analysis ( live births per OPU and ET, CPR/OPU&ET, implantation rate

The Cochrane Library 2009

The Cochrane Metanalysis 2009 : Live birth rate

Aim: To evaluate the efficacy of using blastocyst stage embryo transfer in routine practice

Design: Retrospective analysis in 7059 IVF/ICSI cycles

SBT: Extended embryo culture through embrionic genome activation to select those embryos with higher implantation rate

Strategy for patients selection for blastocyst culture:

NUMBER OF FLLICLES OR OOCYTES

Good responders on Good responders on COH during the COH during the stimulation stimulation

Patients with 5 oocytes Patients with 5 oocytes and more after OPUand more after OPU

Strategy for patients selection for blastocyst culture:

FERTILIZATION

Patients with more than 4 fertilized oocytes

Patients with more than three embryos on day 3 .

Duration of cultivation ( Day 3 or Day 5) and rate of cancelled embryo transfers on 4009 IVF/ICSI cycles (<10 oocytes)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1 2 3 4 5 6 7 8 9 10

D5

D3

Cancelled ET

Number of aspirated oocytes

Cancelled embryo transfers

0

5

10

15

20

25

30

35

40

Number of aspirated oocytes

Can

celle

d e

mbry

o tr

ansf

ers

(%)

Day 3 ET Day 5 BT

204

11.7 %

Nonstimulated cycles (#391)

12.2 %

187

Delivery rate per cycle

ET on day 2 (204)

ET on day 5 (187)

p- value

Oocyte recovery rate 79.4(162/204) 82.3 (154/187) NS

Fertilization rate 73.8 (113/153) 77.7 (115/148) NS

ET rate per aspiration 51.5 (105/204) 29.4 (55/187) <0.05

Pregnancy rate per ET 23.8 (25/105) 40.0 (22/55) <0.05

PR calculated /day 2 ET 23.8 (25/105) 22.2 (22/99) NS

PR/ aspirated oocyte 15.4 (25/162) 14.3 (22/154) NS

No ET ET

36.1%

6.9%

Delivery rate/cycle = 4.3%

Poor responders(one oocyte)

N=252

160

Delivery rate /ET

Embryo transfer rate on D3 and D5 in patients younger than 40

0

20

40

60

80

100

1 2 3 4 5Number of oocytes retrieved

Em

bryo

tra

nsfe

r ra

te

D3 D5

Delivery rate per embryo transfer on D2 and D5 in 2002 IVF/ICSI cycles)

-10

10

30

50

1 2 3 4 5

Number of oocytes retrieved

Del

iver

y ra

te /

em

bryo

tra

nsfe

r

D3 D5

Delivery rate per cycle

Embryo transferEmbryo transfer rate per cycle was higher when rate per cycle was higher when day 2 embryos were transferredday 2 embryos were transferred

Expected Expected pregnancy ratepregnancy rate in poor responders in poor responders calculated per embryo(s) available on day 2 calculated per embryo(s) available on day 2 waswas not affected by oocyte culture to the blastocyst not affected by oocyte culture to the blastocyst stage. stage.

2 2 3 4 4

320

25.8

74 (D5)

17.3

336

Low responders(2-4 oocytes)

Oocyte number afer OPU (#1276)

3

14 (D5)

Delivery rate per ET

8 (D5) 367

28.6 18.5 37.8 12.6

# oocytes

ET (no ET 12.3%)

10.4% 15.7% 20.2%Delivery/cycle

No BC for transfer eSBT SBT DBT TBT

48.0

125(3.8%)

19.4

957

Normal responders(>4 oocytes/OPU)

# 3131

eDBT

1135

Delivery rate

659 355

55.0 35.5 26.4

224 (6.7%)

Delivery rate per cycle after blastocyst transfers

0

10

20

30

40

50

60

22 24 26 28 30 32 34 36 38 40 42 44

Age (years)

Del

iver

y ra

te

Double blastocyst transfer

Vlaisavljevic et al. RBM Online 2008

Should the practice of double blastocyst transferbe abandoned?

Vlaisavljevic et al., RBM Online, 2008;16:671.

Delivery rate per transfer

Twins rate

Number of embryos transferred in reimbursed cycles (IVF, Raport to Ministy of Health for 2009 Centre Maribor)

TET

DET

SET

48.5%

Number of embryos transferred in cross border patients ( IVF Centre Maribor, Raport for 2009)

TET

DET

SET24.9%

Number of embryos required for transfer per baby born

6,6 6,8

2,8

0,00

5,00

10,00

Day 2&3 Natural Blastocyst

4934 443 2639Embryos

Number of blastocysts required for transfer per baby born

2,8

13,2

5,6

0,00

5,00

10,00

Fresh

blastocyst

Slow

f reezing

Vitrifi cation

ConclusionsConclusions

eSBT is standard procedure in our eSBT is standard procedure in our centrecentre

same number of pregnancies with same number of pregnancies with smaller number of fresh transferred smaller number of fresh transferred embryos embryos actual reimbursement systemactual reimbursement system successfull vitrificationsuccessfull vitrification programme programme

Major barriers for eSET seems to be:Major barriers for eSET seems to be:patients’ lack of knowledgepatients’ lack of knowledge

In 2009 4,2 % of all babies born in Slovenia were concieved with MAR

Symposium

Naših prvih 5000 otrokOur first 5000 children

Hotel HabakukMaribor, Slovenija 9.-10. marec 2012

Reproductive Medicine Maribor

Hospital:

Veljko VlaisavljevićVida Gavrić LovrecMilan ReljičVilma KovačLea MlakarPolona Kores TestenKsenija RakićMarko Došen

Nurses:Božena RodešDaniela HanželMarija KristovičJasna MuršičMarija PiperskiLucija Nikolič

ART Laboratory:

Borut KovačičNina HojnikMartin IvecBarbara BreznikPetra RobičMarjan TaborinNaca Herceg

Secretary:Suzana KnupležMarina Kokol