1. ALTERNATE DAY TRIPTORELIN: A COST EFFECTIVE METHOD FOR CONTROLLED OVARIAN HYPERSTIMULATION E. Karatekeli, H. Özörnek, E. Ergin, B. Ongun EUROFERTIL REPRODUCTIVE HEALTH CENTER ISTANBUL/TURKEY

2. THE SUPPRESSION OF PITUITARY GONADOTRPHIN SECRETION USING GnRH AGONIST HAS SOME BENEFITS: Prevention of premature luteinizing hormone surge and luteinization,resulting a lower cancellation rate. Synchronization of the follicular cohort with greater homogenity and improvement of follicular response to ovarian stimulation.

3. BENEFITS OF GnRHa USE Improved numbers of harvested oocytes and total embryos obtained. Improved implantation rate.

4. DISADVANTAGES OF GnRHa USE Slower ovarian response to gonadotrophins, increased total gonadotropin dose per treatment cycle and consequently higher costs. Disturbance to subsequent menstrual cycles due to prolonged pituitary suppression after desensitization is achieved. Oocyte quality? Embryo quality?

5. The most important clinical application of GnRHa during ovarian stimulation is PREMATURE LH SURGE PREVENTION. The most important clinical application of GnRHa during ovarian stimulation is PREMATURE LH SURGE PREVENTION.

6. Dose reduction may be the key point in optimizing the overall IVF parameters. Dose reduction may be the key point in optimizing the overall IVF parameters. But minimal effective doses of GnRHa have not been determined CLEARLY yet. But minimal effective doses of GnRHa have not been determined CLEARLY yet.

7. Several authors have suggested that Several authors have suggested that PARTIAL pituitary desensitization in assisted reproduction procedure might be sufficient. PARTIAL pituitary desensitization in assisted reproduction procedure might be sufficient. (Balasch et al., 1992; Simon et al.,1994) (Balasch et al., 1992; Simon et al.,1994)

8. It has been proven that with a suppressed pituitary gland, the dose needed to maintain suppression is GRADUALLY DECREASED with the length of treatment. It has been proven that with a suppressed pituitary gland, the dose needed to maintain suppression is GRADUALLY DECREASED with the length of treatment. (Sandow and Donnez,1990) (Sandow and Donnez,1990)

9. It has been demonstrated that lowering dose of triptorelin at the start of the stimulation from 0.5 mg to 0.1 mg per day is as effective as continuing with 0.5 mg. It has been demonstrated that lowering dose of triptorelin at the start of the stimulation from 0.5 mg to 0.1 mg per day is as effective as continuing with 0.5 mg. (Simon et al.,1994) (Simon et al.,1994)

10. The previous studies suggested that the use of 50 µg/day triptorelin created a state of desensitization comparable with use of 100 µg. (Janssens et al., 1998 ; Dal Prato et al., 2001) (Janssens et al., 1998 ; Dal Prato et al., 2001)

11. Even 15 µg triptorelin per day was sufficient to prevent a premature LH surge. Even 15 µg triptorelin per day was sufficient to prevent a premature LH surge. (Janssens et al.,2000) (Janssens et al.,2000)

12. Pituitary suppression was maintained after Pituitary suppression was maintained after early discontinuation of GnRHa in long early discontinuation of GnRHa in long protocols. protocols. (Pantos et al., 1994; Beckers et al., 2000) (Pantos et al., 1994; Beckers et al., 2000)

13. Profound LH suppression was seen after Profound LH suppression was seen after stopping the GnRHa after one week use. stopping the GnRHa after one week use. ( Sungurtekin et al.,1995 ; Cedrin-Durnerin et al.,1996) ( Sungurtekin et al.,1995 ; Cedrin-Durnerin et al.,1996)

14. Profound LH suppression induces Profound LH suppression induces deleterious follicular environment. deleterious follicular environment. (Coppola et al., 2003) (Coppola et al., 2003)

15. AIM There is still much debate about the There is still much debate about the optimal GnRHa protocol. optimal GnRHa protocol. The aim of this study was to compare continuous with alternate day triptorelin administration on the IVF results.

16. MATERIALS & METHODS INCLUDING CRITERIA: INCLUDING CRITERIA: NORMAL DAY 3 FSH LEVELS (<10IU/L) UNDER 36 OF AGE FIRST IVF CYCLE NO PREVIOUS OVARIAN SURGERY NO HISTORY OF ENDOMETRIOSIS AND POLYCYSTIC OVARIAN DISEASE AND POLYCYSTIC OVARIAN DISEASE

17. MATERIALS & METHODS All patients received a daily sc. injection of 100 µg triptorelin for 7 days starting from day 21 of the pretreatment cycle. All patients received a daily sc. injection of 100 µg triptorelin for 7 days starting from day 21 of the pretreatment cycle.

18. After a 7- day period patients were randomized in two groups: After a 7- day period patients were randomized in two groups: GROUP A (Everyday protocol, 30 patients) GROUP B (Alternate day protocol, 30 patients) MATERIALS & METHODS

19. Group A patients received daily 100 µg triptorelin until the day of the HCG. Group A patients received daily 100 µg triptorelin until the day of the HCG. Group B patients received every other day 100 µg triptorelin until the day of the HCG. Group B patients received every other day 100 µg triptorelin until the day of the HCG.

20. Group A (n=30) Group B (n=30) Age 28.7 ± 4.0 28.7 ± 4.0 27.8 ± 4.7 27.8 ± 4.7 Totally used gonadotrophin (Ampoules) (Ampoules) 30 ±12.7 30 ±12.7 32.2 ±15.4 32.2 ±15.4 Stimulation (Days) 11.3 ± 2.1 11.3 ± 2.1 11.7±2.6 Mature oocytes 12.3 ± 4.8 12.3 ± 4.8 11.4± 5.2 RESULTS

21. RESULTS GROUP A (n=30)GROUP B (n=30) Number of embryos transferred 3.8 ± 0.9 3.8 ± 0.9 3.7±0.7 3.7±0.7 Clinical pregnancy rate (%) 43.3 43.3 50.0 50.0 Totally used agonist dose (Amp) 23.2 ±3.7 23.2 ±3.7 13.4 ± 2.2* 13.4 ± 2.2* P<0.05 Mean±SD

22. RESULTS No premature LH surge was seen in both groups. No premature LH surge was seen in both groups.

23. RESULTS Although it seems to a logical approach, no significant difference with respect to the main outcome measures (mature oocytes, fertilization rate and clinical pregnancy rates) was found in our study. Although it seems to a logical approach, no significant difference with respect to the main outcome measures (mature oocytes, fertilization rate and clinical pregnancy rates) was found in our study. The duration of the stimulation phase and consequently the number of gonadotropin ampoules were also the same. The duration of the stimulation phase and consequently the number of gonadotropin ampoules were also the same.

24. RESULTS ONLY TOTALLY USED GnRH AGONIST DOSE WAS STATISTICALLY DIFFERENT BETWEEN TWO GROUPS. ONLY TOTALLY USED GnRH AGONIST DOSE WAS STATISTICALLY DIFFERENT BETWEEN TWO GROUPS.

25. CONCLUSION: ALTERNATE DAY TRIPTORELIN USE: PREVENTS LH SURGE COST EFFECTIVE COMFORTABLE FOR PATIENTS HAS COMPARABLE IVF RESULTS AS CONTINOUS ADMINISTRATION CONTINOUS ADMINISTRATION