ALTERNATE DAY TRIPTORELIN:ALTERNATE DAY TRIPTORELIN:A COST EFFECTIVE METHODA COST EFFECTIVE METHODFOR CONTROLLED OVARIAN FOR CONTROLLED OVARIAN

HYPERSTIMULATIONHYPERSTIMULATION

EE.. Karatekeli, Karatekeli, HH.. ÖÖzörnek,zörnek, E. Ergin, B. Ongun E. Ergin, B. Ongun

EUROFERTIL REPRODUCTIVE HEALTH CENTEREUROFERTIL REPRODUCTIVE HEALTH CENTER

ISTANBUL/TURKEYISTANBUL/TURKEY

THE SUPPRESSION OF PITUITARY THE SUPPRESSION OF PITUITARY GONADOTRPHIN SECRETION USING GONADOTRPHIN SECRETION USING GnRH GnRH

AGONIST HAS SOME BENEFITS:AGONIST HAS SOME BENEFITS:

Prevention of premature luteinizing Prevention of premature luteinizing hormone surge and luteinization,resulting hormone surge and luteinization,resulting a lower cancellation ratea lower cancellation rate..

Synchronization of the follicular cohort with Synchronization of the follicular cohort with greater homogenity and improvement of greater homogenity and improvement of follicular response to ovarian stimulationfollicular response to ovarian stimulation..

BENEFITS OF GnRHBENEFITS OF GnRHa a USEUSE

Improved numbers of harvested oocytes Improved numbers of harvested oocytes and total embryos obtainedand total embryos obtained..

Improved implantation rateImproved implantation rate..

DISADVANTAGES OF GnRHDISADVANTAGES OF GnRHaa USEUSE

Slower ovarian response to gonadotrophinsSlower ovarian response to gonadotrophins,, iincreased total gonadotropin dose per ncreased total gonadotropin dose per treatment cycle and consequently higher treatment cycle and consequently higher costscosts..Disturbance to subsequent menstrual cycles Disturbance to subsequent menstrual cycles due to prolonged pituitary suppression after due to prolonged pituitary suppression after desensitization desensitization is is achievedachieved..Oocyte quality?Oocyte quality?Embryo quality?Embryo quality?

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

Dose reduction may be the key point in Dose reduction may be the key point in optimizing optimizing the overall IVF parametersthe overall IVF parameters..

But minimal But minimal effective doses of GnRHa effective doses of GnRHa havehave not been determined not been determined CLEARLY CLEARLY yet.yet.

Several authors have suggested that Several authors have suggested that PARTPARTIIALAL pituitary desensitization in pituitary desensitization in

assisted reproduction procedure might be assisted reproduction procedure might be sufficsufficiientent..

(Balasch et al(Balasch et al.,., 1992; Simon et al 1992; Simon et al.,.,1994)1994)

It has been proven that with a suppressed It has been proven that with a suppressed pituitary glandpituitary gland,, the dose needed to maintain the dose needed to maintain suppression suppression is is GRADUALGRADUALLLY DECREASEDY DECREASED with the length of treatmentwith the length of treatment..

(Sandow and Donnez(Sandow and Donnez,,1990)1990)

It has been demoIt has been demonnstrated that lowering strated that lowering dose of triptorelin at the start of the dose of triptorelin at the start of the stimulation from 0.5 mg to 0.1 mg per daystimulation from 0.5 mg to 0.1 mg per day is as eis as effective as continuingffective as continuing with 0.5 mgwith 0.5 mg..

(Simon et al.,1994)(Simon et al.,1994)

The previous studies suggested thatThe previous studies suggested that

tthe use of 50he use of 50 µgµg//day triptorelin created day triptorelin created

aa state of desensitization comparable with state of desensitization comparable with

use of 100use of 100 µgµg..

(Janssens et al(Janssens et al.,., 1998 1998 ; ; Dal Prato et alDal Prato et al.,., 2001) 2001)

Even Even 1515 µg triptorelin per day was µg triptorelin per day was sufficient to prevent a premature LH surgesufficient to prevent a premature LH surge..

((JanssensJanssens et al.,2000) et al.,2000)

Pituitary suppression was maintained after Pituitary suppression was maintained after early discontinuation of GnRHa in long early discontinuation of GnRHa in long protocols.protocols.

((PPantos et alantos et al.,., 1994 1994; B; Beckers et aleckers et al.,., 2000) 2000)

Profound LH suppression was seen after Profound LH suppression was seen after

stopping the GnRHstopping the GnRHaa after one week after one week useuse..

((Sungurtekin et alSungurtekin et al.,.,19951995 ; ; Cedrin-Durnerin et alCedrin-Durnerin et al.,.,1996)1996)

Profound LH suppression induces Profound LH suppression induces

deleterious follicular environmentdeleterious follicular environment..

(Coppola et al(Coppola et al.,., 2003) 2003)

AIMAIM

There is still much debate about the There is still much debate about the

optimal GnRHoptimal GnRHaa protocol protocol..

The aim of this study was to compare The aim of this study was to compare continuous with alternate day triptorelin continuous with alternate day triptorelin administration on the IVF resultadministration on the IVF results.s.

MATERIALS MATERIALS && METHODS METHODS

INCLUDING CRITERIA:INCLUDING CRITERIA:

NORMAL DAY 3 FSH LEVELS (<10IU/L)NORMAL DAY 3 FSH LEVELS (<10IU/L)UNDER 36 OF AGEUNDER 36 OF AGEFIRST IVF CYCLEFIRST IVF CYCLENO PREVIOUS OVARIAN SURGERYNO PREVIOUS OVARIAN SURGERYNO HISTORY OF ENDOMETRIOSISNO HISTORY OF ENDOMETRIOSIS

AND POLYCYSTIC OVARIAN DISEASEAND POLYCYSTIC OVARIAN DISEASE

MATERIALS MATERIALS && METHODS METHODS

All patients received a daily sc.All patients received a daily sc. injection of injection of 100100 µg triptorelin for 7 days starting from µg triptorelin for 7 days starting from day 21 of the pretreatment cycleday 21 of the pretreatment cycle..

After After aa 7 7-- day period patients were day period patients were randomized in two groups: randomized in two groups:

GROUP A (Everyday protocol, 30 patients)GROUP A (Everyday protocol, 30 patients)

GROUP B (Alternate day protocol, GROUP B (Alternate day protocol, 30 30 patients)patients)

MATERIALS MATERIALS && METHODS METHODS

MATERIALS MATERIALS && METHODS METHODS

Group A patients received daily 100Group A patients received daily 100 µg µg triptorelin until the day of the HCGtriptorelin until the day of the HCG..

Group B patients received every other day Group B patients received every other day 100100 µg triptorelin until the day of the HCGµg triptorelin until the day of the HCG..

Group A (n=30)Group A (n=30) Group B (n=30)Group B (n=30)

AgeAge 28.7 28.7 ± 4.0± 4.0 27.8 27.8 ± 4.7± 4.7

Totally used Totally used gonadotrophingonadotrophin

(Ampoules)(Ampoules)

30 30 ±12.7±12.7 32.2 32.2 ±15.4±15.4

Stimulation Stimulation (Days)(Days) 11.3 11.3 ± 2.1± 2.1 11.711.7±2.6±2.6

Mature oocytesMature oocytes 12.3 12.3 ± 4.8± 4.8 11.411.4± 5.2± 5.2

RESULTSRESULTS

RESULTSRESULTS

GROUP A (n=30) GROUP B (n=30)

Number of Number of eembryos mbryos ttransferredransferred

3.8 3.8 ± 0.9± 0.9 3.73.7±0.7±0.7

Clinical pregnancy rateClinical pregnancy rate (%) (%)

43.343.3 50.050.0

Totally used agonist doseTotally used agonist dose (Amp)(Amp)

23.2 23.2 ±3.7±3.7 13.4 13.4 ± 2.2*± 2.2*

P<0.05 Mean±SDP<0.05 Mean±SD

RESULTSRESULTS

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

RESULTSRESULTS

Although it seemsAlthough it seems to a logical approach, to a logical approach, nono significant difference with respect to the significant difference with respect to the main outcome measuresmain outcome measures (mature oocytes, (mature oocytes, fertilifertilizzation rate and clinical pregnancy rates) ation rate and clinical pregnancy rates) was found in our study. was found in our study.

The duration of the stimulation phase and The duration of the stimulation phase and consequently the number of consequently the number of gonadotropin ampoules were also the same.gonadotropin ampoules were also the same.

RESULTSRESULTS

ONLY ONLY TOTALTOTALLLY USED GnRH AGONY USED GnRH AGONIIST ST DOSEDOSE WAS STAT WAS STATIISTSTIICALCALLLY DY DIIFFERENT FFERENT BETWEEN TWO GROUPSBETWEEN TWO GROUPS..

CONCLUSION:CONCLUSION:

ALTERNATE DAY TRIPTORELIN USE:ALTERNATE DAY TRIPTORELIN USE:

PREVENTS LH SURGEPREVENTS LH SURGE

COST EFFECTIVECOST EFFECTIVE

COMFORTABLE FOR PATIENTSCOMFORTABLE FOR PATIENTS

HAS COMPARABLE IVF RESULTS AS HAS COMPARABLE IVF RESULTS AS

CONTINOUS ADMINISTRATIONCONTINOUS ADMINISTRATION