1. Natural IVF/ET - treatment success Neda Smiljan Severinski Marko Gospić

2. 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

3. Success of assisted reproduction ?

4. How to define or calculate IVF/ET cycle suc c ess ? CLINICAL PREGNANCY RATE (CPR): CLINICAL PREGNANCY 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

5. How to define or calculate IVF/ET 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

6. What is fail ed cycle of assisted reproduction ?  Cycle cancelation before ovum pick up ?  Cycle with bad quality oocytes or without oocytes ?  Oocytes fertilisation fa i lure 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? .....

7. Absent foliculogenesis and oogenesis Patients category ? Patients category ?  Young reproductive age with diminished ovarian reserve or premature ovarian failure  Older reproductive age (> 35 – 40)  Old reproductive age ( > 40 ) Treatment options: Treatment options: Natural cycle IVF/ET Natural cycle IVF/ET  „Patient fr i endly IVF/ET”  Conventi on al ovarian stimulation  Agressive ovarian stimulation – „fight for ev e ry egg”  Adjuvan t drugs – androgens DHEA

8. Cycle without embryo transfer  Bad quality of oocytes, sperm or embryos  Growth retarded embryos  Disturbance in endometrium development  Other complication Treatment options: Treatment options:  DHEA, corticosteroids, LH  Estrogen, progesteron, sildenafil

9. Interpretation of treatment suc c ess?  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 programm e : represent the real succes s of some institutio ns in conventi on al IVF/ET treatment  Who are patients in the center for infertility treatment?

10. Natural fecundability Nulliparous Parous 5 months 2.7 months 50

11. Patients 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

12. 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

13. Age structure Age structure only 36% < 33 year

14. Results of treatment Total Number of cycles181 Number of ET/cycles65 (35,9%) Pregnancy number: /cycle / ET 15 (8,3%) (23,1%) Failed cycles116 (64,1%) -No oocyte -No fertilisation -No developed embryo -Growth retarded embryo -Polyploid y

15. Period of treatment = 8 months = 8 modified natural cycle T reatment months n = 89 n = 1

16. Pregnancy Pregnancy n = 15 /89 couples (16,8%) T reatment months Max 8 Min 1

17. C ompleted cycles (n=65/181 – 35,9% ) T reatment months

18. Pregnancy per cycle, overview Min 4,2% Max 15,4% Month of treatment

19. P regnancy per embryotransfer, overview Min 14,3% Max 40%

20. Failed cycles

21. Cum m ulative results Month of treatment12345678 Cumulative cycles89126147159164 165166 Cumulative pregnacies811121415 Cumulative pregnancies % 8,988,738,168,889,14 9,099,03 Chance for concieving in natural IVF/ET is 8-9% in each month of treatment. After six months of treatment chance to concive would be 54 % !!!!

22. Month of treatment12345678 Theoretical number of women ( n ) 898178777574 Real number of women ( n ) 8945 (-36) 24 (-54) 13 (-63) 7 (-68) 1 (-73) 1 (-73) 1 (-73) Pregnancy per month ( n ) 83121000 Real cummulative pregnancies 811121415 Theoretical cummulative pregnancy ( 9%) 815 (+4) 22 (+10) 29 (+15) 36 (+21) 36 Monthly c um m ulative suc c ess % 8,988,738,168,889,14 9,099,03 Theoretical calculation of success: pregnancy rate

23. Treatment problems 100% 45/89 = 50,6% 24/45 = 53,3% 13/24 = 54,2% 7/13 = 53,8%

24. 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

25. 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