Natural IVF/ET - treatment success

Neda Smiljan Severinski

Marko Gospić

Terminology

• Natural IVF/ET cycleNatural IVF/ET cycle:– Monitoring of natural cycle - ultrasound– No any medication

• Modified natural cycle– Monitoring of natural cycle– Only medication is hCG injection for final

oocyte maturation

SuccessSuccess of assisted reproduction ? of assisted reproduction ?

How to define or calculate IVF/ET How to define or calculate IVF/ET cycle succycle succcess ?ess ?

• CLINICAL PREGNANCY CLINICAL PREGNANCY RATE (CPR):RATE (CPR):

(positive heart beat in intrauterine embryo):

• In relation to started cycle• In relation to number of oocyte

aspirations

• In relation to number of embryo transfers

How to define or calculate IVF/ET How to define or calculate IVF/ET cycle sucess ?cycle sucess ?

• LIVEBIRTH RATE:LIVEBIRTH RATE:• In relation to started cycle• In relation to number of

oocytes aspirations• In relation to number of

embryo transfers

What is failWhat is faileded cycle of assisted cycle of assisted reproduction ?reproduction ?

Cycle cancelation before ovum pick up ? Cycle with bad quality oocytes or without oocytes ? Oocytes fertilisation failure or irregular fertilisation ? Cycle without embryo transfer or bad quality embryos ? Cycle with implantation failure ? Cycle with positive hCG, without clinical pregnancy ? Cycle with vital clinical pregnancy but spontaneus

abortion in first trimester? . . . . .

Absent foliculogenesisAbsent foliculogenesis and oogenesis and oogenesis

• Patients category ?Patients category ?Young reproductive age with diminished ovarian reserve or premature ovarian failureOlder reproductive age (> 35 – 40)Old reproductive age ( > 40 )

•Treatment options:Treatment options:• Natural cycle IVF/ETNatural cycle IVF/ET„Patient friendly IVF/ET”Conventional ovarian stimulationAgressive ovarian stimulation – „fight for every egg”Adjuvant drugs – androgens DHEA

Cycle without Cycle without embryo transferembryo transfer

Bad quality of oocytes, sperm or embryosGrowth retarded embryosDisturbance in endometrium development

Other complication

• Treatment options:Treatment options:DHEA, corticosteroids, LH

Estrogen, progesteron, sildenafil

Interpretation of treatment success?

Institutions with excellent succes of treatment : inclusion - exclusion criterias to starting treatment

Some institution have „cut off” values: age, FSH, AMH or AFC

Results of donation treatment programme:represent the real success of some institutions in

conventional IVF/ET treatment

Who are patients in the center for infertility treatment?

Natural fecundabilityNatural fecundability

10

100

0 2 4 6 8 10 12

Months of unprotected intercourse

Per

cent

fai

led

Nulliparous

Parous

5 months

2.7 months

50

Patients and methodsPatients and methods

• Period 1.1.2010 – 31.12.2011 ( two years )

• 89 patients (couples)

• Age: mean = 34,2 (min. = 24, max. = 45)• 181 modified natural IVF/ET cycles• mean = 2,03 cycle/patient

• only one patient had 8 natural IVF/ET cycles

Legal aspects of treatment

• VII/2009 – VII/2012 “Restrictive” law

• Health ensurance guarantee:– No age limitation for treatment– Number of IVF/ET in natural cycle was

unlimited

Age structureAge structureonly 36% < 33 year

ResultsResults of treatment of treatment

Total

Number of cycles 181

Number of ET/cycles 65 (35,9%)

Pregnancy number: /cycle / ET

15(8,3%)

(23,1%)

Failed cycles 116 (64,1%)

- No oocyte- No fertilisation- No developed embryo- Growth retarded embryo- Polyploidy

Period of treatment = 8 months = 8 modified natural cycle

0102030405060708090

100

1. 2. 3. 4. 5. 6. 7. 8.

cycle pregnancy

Treatment months

n = 89

n = 1

Pregnancy Pregnancy n = 15/89 couples (16,8%)

0

5

10

15

20

25

30

35

1. 2. 3. 4. 5. 6. 7. 8.

ET pregnancy

Treatment months

Max 8

Min 1

Completed cycles (n=65/181 – 35,9%)

0102030405060708090

100

1. 2. 3. 4. 5. 6. 7. 8.

cycle ET

35,5%

37,1%

38,4%29,2% 57,1%

Treatment months

Pregnancy per cycle, overview

0

20

40

60

80

100

1. 2. 3. 4. 5. 6. 7. 8.

pregnancy % cycle

Min4,2%

Max15,4%

Month of treatment

Pregnancy per embryotransfer, overview

83 1 2 2 0 0 00

10

20

30

40

50

1. 2. 3. 4. 5. 6. 7. 8.

pregnancy % ET

Min14,3%

Max40%

Failed cycles

0102030405060708090

100

1. 2. 3. 4. 5. 6. 7. 8.

cycle faild

63%

64,4%70,1% 42,8%

61,5%

Cummulative results

Month of treatment 1 2 3 4 5 6 7 8

Cumulative cycles 89 126 147 159 164 164 165 166

Cumulative pregnacies 8 11 12 14 15 15 15 15

Cumulative pregnancies %

8,98 8,73 8,16 8,88 9,14 9,14 9,09 9,03

Chance for concieving in natural IVF/ET is 8-9% in each month of treatment.After six months of treatment chance to concivewould be 54 % !!!!

Month of treatment 1 2 3 4 5 6 7 8Theoretical number of women ( n )

89 81 78 77 75 74 74 74

Real number of women ( n )

89 45

(-36)

24

(-54)

13

(-63)

7

(-68)

1

(-73)

1

(-73)

1

(-73)

Pregnancy per month ( n )

8 3 1 2 1 0 0 0

Real cummulative pregnancies

8 11 12 14 15 15 15 15

Theoretical cummulative pregnancy ( 9%)

8 15

(+4)

22

(+10)

29

(+15)

36

(+21)

36 36 36

Monthly cummulative success %

8,98 8,73 8,16 8,88 9,14 9,14 9,09 9,03

Theoretical calculation of success: pregnancy rate

Treatment problems

Cycle (n = 89)

0

10

20

30

40

50

60

70

80

90

100

1 2 3 4 5 6

Months of treatment

%

100%

45/89 = 50,6%

24/45 = 53,3%

13/24 = 54,2%7/13 = 53,8%

Conclusion

• Monthly cummulative cuccess (PR/cycle) in modified natural cycles was about 9% in each month

• Significant amount of couples cancel their treatment after only three months. Why?

• Continuation and repeating of monthly treatment in modified natural cycle may have positive influence on PR

Legal aspects of treatment

• VII/2012 – today “Liberal” law

• Health ensurance guarantee:– age limitation for treatment – 42 year– Number of IVF/ET in natural cycle is only two

– Chance to concive in modified natural cycle is 18% for each patient