Natural IVFET treatment success Neda Smiljan Severinski Marko

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

Terminology • Natural IVF/ET cycle: cycle – Monitoring of natural cycle - ultrasound – No any medication • Modified natural cycle – Monitoring of natural cycle – Only medication is h. CG injection for final oocyte maturation

Success of assisted reproduction ?

How to define or calculate IVF/ET cycle success ? • 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

How to define or calculate IVF/ET cycle sucess ? • LIVEBIRTH RATE: • In relation to started cycle • In relation to number of oocytes aspirations • In relation to number of embryo transfers

What is failed cycle of assisted reproduction ? v Cycle cancelation before ovum pick up ? v Cycle with bad quality oocytes or without oocytes ? v Oocytes fertilisation failure or irregular fertilisation ? v Cycle without embryo transfer or bad quality embryos ? v Cycle with implantation failure ? v Cycle with positive h. CG, without clinical pregnancy ? v Cycle with vital clinical pregnancy but spontaneus abortion in first trimester? v. . .

Absent foliculogenesis and oogenesis • Patients category ? • Treatment options: v. Young reproductive age • Natural cycle IVF/ET with diminished ovarian reserve or premature ovarian failure v. Older reproductive age (> 35 – 40) v. Old reproductive age ( > 40 ) v„Patient friendly IVF/ET” v. Conventional ovarian stimulation v. Agressive ovarian stimulation – „fight for every egg” v. Adjuvant drugs – androgens DHEA

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

Interpretation of treatment success? v Institutions with excellent succes of treatment : inclusion - exclusion criterias to starting treatment v Some institution have „cut off” values: age, FSH, AMH or AFC v Results of donation treatment programme: represent the real success of some institutions in conventional IVF/ET treatment v. Who are patients in the center for infertility treatment?

Natural fecundability 5 months 50 Nulliparous 2. 7 months Parous

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

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 structure only 36% < 33 year

Results of treatment Total Number of cycles Number of ET/cycles Pregnancy number: /cycle / ET Failed cycles - 181 65 (35, 9%) 15 (8, 3%) (23, 1%) 116 (64, 1%) No oocyte No fertilisation No developed embryo Growth retarded embryo Polyploidy

Period of treatment = 8 months = 8 modified natural cycle n = 89 n=1 Treatment months

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

Completed cycles (n=65/181 – 35, 9%) Treatment months

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

Pregnancy per embryotransfer, overview Max Min 14, 3% 40%

Failed cycles

Cummulative results Month of treatment Cumulative cycles Cumulative pregnacies Cumulative pregnancies % 1 2 3 4 5 6 7 8 89 126 147 159 164 165 166 8 11 12 14 15 15 8, 98 8, 73 8, 16 8, 88 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 concive would be 54 % !!!!

Theoretical calculation of success: pregnancy rate Month of treatment 1 2 3 4 5 6 7 8 Theoretical 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) Pregnancy per month (n) 8 3 1 2 1 0 0 0 Real cummulative pregnancies 8 11 12 14 15 15 Theoretical cummulative pregnancy ( 9%) 8 15 (+4) 22 29 36 (+10) (+15) (+21) 36 36 36 8, 98 8, 73 8, 16 9, 14 9, 09 9, 03 Monthly cummulative success % 8, 88 9, 14

Treatment problems 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