since the first report on the use of the combination of gonadotropin - releasing hormone agonists ( gnrha ) and gonadotropins for in vitro fertilization ( ivf ) in 1984 ( 1 ) , gnrha has widely been used in controlled ovarian stimulation cycles for assisted reproduction .
one known complication of pituitary down - regulation using gnrha in ivf treatment cycles is the formation of functional ovarian cysts ( 2 ) .
several case reports have indicated that a very small subgroup of patients may experience ovarian hyperstimulation following the administration of gnrha without gonadotropins ( 3 - 6 ) . however , since very few case reports have been published on this topic , it is unclear what course to follow in subsequent cycles after ovarian hyperstimulation using only gnrha in the first cycle . in the present report , a depot preparation ( 3.75 mg ) of tryptorelin without gonadotropins induced ovarian multifollicular enlargement with high estradiol level , and was followed by human chorionic gonadotropin ( hcg ) administration and oocyte retrieval . in a subsequent cycle of the same patient ,
a low dose of triptorelin ( 0.05 mg ) did not induce ovarian hyperstimulation , and resulted in clinical pregnancy .
our patient was a 33-yr - old nulliparous korean woman undergoing oocyte donation for her sister on march 2010 .
the patient reported irregular menstrual cycles , with only four to six periods each year .
her body mass index was 21.5 kg / m , with a gynecoid fat distribution .
she had mild acne on her face , but no hirsutism , virilization , or acanthosis nigricans .
her exam results for the 53rd day of her cycle were as follows : negative u - hcg , follicle - stimulating hormone ( fsh ) 5.39 iu / l , luteinizing hormone ( lh ) 11.29 iu / l , estradiol 45 pg / ml , progesterone 0.66 ng / ml , and total testosterone 1.09 ng / ml .
transvaginal ultrasound showed that the right ovary measured 3.9  3.5  2.8 cm ( 19 cm ) and the left ovary 3.0  2.8  2.5 ( 10 cm ) .
we scheduled a gnrha long protocol for controlled ovarian stimulation . on the 54th day of the cycle , a depot preparation of triptorelin ( 3.75 mg decapeptyl cr ; ferring , malmo , sweden ) was administered subcutaneously .
an ultrasound revealed multiple follicles ranging from 15 to 28 mm in diameter ( fig .
her exam results were : estradiol 2,560 pg / ml , lh 9.83 iu / l , fsh 2.24 iu / l , and progesterone 4.18 ng / ml .
since serum estradiol concentrations were considered appropriate for the number of follicles present , a decision was made to continue the oocyte donation cycle .
( fsh 5.96 iu / l , lh 10.78 iu / l , estradiol 41 pg / ml , progesterone 0.54 ng / ml ) , a short - acting preparation of triptorelin ( decapeptyl ; ferring ) was administered s.c . at a dose of 0.05 mg per day , which is half of the conventional dosage .
seven and ten days after the initiation of gnrha , an ultrasound revealed no evidence of functional ovarian cyst .
rockland , ma , usa ) was started , which she received daily for 7 days .
the dosage was later increased to 225 iu for an additional 5 days . on day 13 ,
a total of 11 oocytes were retrieved , and three embryos were transferred to the recipient . a single gestational sac and fetal pulse
one possible explanation is the initial flare - up caused by gnrha , which induced the release of gonadotropins from the pituitary thereby stimulating the growth of ovarian follicles .
these follicles acquired fsh - independent growth dynamics , which finally led to mature follicles by relatively abundant lh .
it is accepted that in the late stages of follicle development , granulosa cells become receptive to lh stimulation and lh becomes active ( 7 ) .
in pcos , lh secretion is characterized by greater sensitivity to gnrh , as compared to women without pcos .
these responses to gnrh are more prominent in lean - pcos ( 8) ; for this reason , we speculate that the serum lh concentration remained high for ten days following the initiation of gnrha due to an extremely high initial flare - up . alternatively , previous researchers have suggested a direct effect of gnrha at the ovarian level ( 3 , 5 , 9 ) .
however , during treatment with gnrha , high concentration of gnrha circulate in the central and peripheral tissue .
many studies have investigated the effects of gnrha on ovarian cell proliferation and steroidogenesis . in bussenot
et al . ( 10 ) , 5 different gnrh agonists were compared based on their effect on estradiol secretion in human granulosa lutein cell cultures . the results showed that buserelin and leuprolein significantly enhanced estradiol secretion .
however , triptorelin , which was used in our case , had no effect on estradiol secretion in their study .
recently , azem et al . ( 11 ) reported a live birth following the administration of gnrha without gonadotropins .
they scheduled a conventional flare - up regimen on day 1 of the cycle ( triptorelin 0.1 mg ) and daily injections of gonadotropins from day 3 and on .
contrary to their expectation , they observed that continued gnrha injection without gonadotropins induced follicular development with high estradiol levels until oocyte retrieval .
however , it is unclear what course to follow in subsequent cycles , after ovarian hyperstimulation using only gnrha in the first cycle , as very few case reports have been published on this topic .
weissman et al . ( 3 ) reported two cases of ovarian hyperstimulation following the administration of gnrha without gonadotropins .
they also reported that recurrent ovarian hyperstimulation occurred in subsequent cycles of the same patients . in the present report
the main difference between their cases and ours is the dose of gnrha . while weissman et al .
( 3 ) used a depot preparation of triptorelin ( first cycle ) and short acting preparation 0.1 mg / day in ( subsequent cycle ) , we used triptorelin at 0.05 mg / day .
however , we can not say that the dose of gnrha is only responsible for different results . some differences regarding patient 's characteristics and the timing of initiation of gnrha should be considered . in summary ,
a small subgroup of patients may develop ovarian hyperstimulation following the administration of gnrha without gonadotropins .
 several case reports have indicated that a small subgroup of patients may develop ovarian hyperstimulation following the administration of gonadotropin - releasing hormone agonists ( gnrha ) without gonadotropins . however , since only few such cases have been published , it is unclear what course to follow in subsequent cycles after ovarian hyperstimulation in the first cycle using only gnrha . 
 a 33-yr - old woman was referred to in vitro fertilization for oocyte donation . a depot preparation ( 3.75 mg ) of tryptorelin without gonadotropins induced ovarian multifollicular enlargement with high estradiol level , and was followed by human chorionic gonadotropin administration and oocyte retrieval . in a subsequent cycle of the same patient , 
 a low dose of tryptorelin ( 0.05 mg ) did not induce ovarian hyperstimulation , and resulted in clinical pregnancy . 
 this report shows potential management of ovarian hyperstimulation following the administration of gnrha without gonadotropins . 
INTRODUCTION
CASE DESCRIPTION
DISCUSSION