1) A 25-year-old woman with PCOS and infertility underwent a long protocol with the GnRH agonist triptorelin. Surprisingly during monitoring, she had high estrogen levels and follicles ranging 14-23mm, nearly causing OHSS. 2) HCG was administered and OPU retrieved 19 oocytes, with 11 embryos developed. Four were transferred with five cryopreserved. A chemical pregnancy occurred but ended in bleeding. 3) Rare cases of ovarian hyperstimulation have been induced by GnRH agonists alone through direct ovarian effects. The report recommends HCG triggering in such cases of cyst growth during GnRH agonist cycles to enable oocyte maturation and IVF treatment.

2. M.WALAA EL DEEBM.WALAA EL DEEB
HESHAM ELINANYHESHAM ELINANY
HOSSAM GODAHOSSAM GODA
HAMED YOUSSEFHAMED YOUSSEF
SHERIF SAMI SAIDSHERIF SAMI SAID
GHADA HARFUSHGHADA HARFUSH

4. Gonadotrophin-relesingGonadotrophin-relesing
hormone (GnRH) agonist,hormone (GnRH) agonist,
triptorelin acetate suppressestriptorelin acetate suppresses
the GnRH-induced release ofthe GnRH-induced release of
Luteinizing hormone (LH) andLuteinizing hormone (LH) and
thereby preventsthereby prevents
spontaneous LH surgesspontaneous LH surges
during IVF cycles.during IVF cycles.

5. However, TheHowever, The
pharmacodynamics ofpharmacodynamics of
gonadortopin-releasing hormonegonadortopin-releasing hormone
(GnRH) agonists includes an(GnRH) agonists includes an
initial ‘flare-up’ of the pituitary-initial ‘flare-up’ of the pituitary-
gonadal axis, followed bygonadal axis, followed by
reduced luteinizing hormonereduced luteinizing hormone
(LH) secretion.(LH) secretion.

6. Since GnRH receptors and theirSince GnRH receptors and their
gene expression have been detectedgene expression have been detected
in human ovary, the question isin human ovary, the question is
whether GnRH agonist can exert thiswhether GnRH agonist can exert this
flare up effect on the ovary it self.flare up effect on the ovary it self.
Ovarian hyper stimulation induced byOvarian hyper stimulation induced by
GnRH agonist alone is a rare eventGnRH agonist alone is a rare event
and in this report we describe suchand in this report we describe such
case.case.

7.  A 25 years old Egyptian womenA 25 years old Egyptian women
present to us with primarypresent to us with primary
infertility for 3 years.infertility for 3 years.
 She had episodes of secondaryShe had episodes of secondary
amenorrhea.amenorrhea.
 After infertility routine work up, aAfter infertility routine work up, a
diagnosis of PCO was reached.diagnosis of PCO was reached.
 She underwent four trials ofShe underwent four trials of
ovulation with C.C, but pregnancyovulation with C.C, but pregnancy

8.  She had also a failed trials withShe had also a failed trials with
I.U.II.U.I
 Couple asked to do I.C.S.I asCouple asked to do I.C.S.I as
husband was traveling to Gulf area.husband was traveling to Gulf area.
 A midluteal long protocol wasA midluteal long protocol was
decided for her.decided for her.
 Menses started on 10/7/06 andMenses started on 10/7/06 and
triptorelin (Decapeptyl 0.1 ferring,triptorelin (Decapeptyl 0.1 ferring,
Germany) was administratedGermany) was administrated
29/7/0629/7/06

9. Patient was evaluated for pituitaryPatient was evaluated for pituitary
down regulation on 8/8/06, butdown regulation on 8/8/06, but
surprisingly E2 was 3420 ng/ml andsurprisingly E2 was 3420 ng/ml and
her (US) shows high number ofher (US) shows high number of
follicles ranging between 14-23 mmfollicles ranging between 14-23 mm
and very close to OHSS.and very close to OHSS.

10.  -On the same day :-On the same day :
 S. Progesterone :5.41 ng/mlS. Progesterone :5.41 ng/ml
 S. LH : 9.54 mIu/mlS. LH : 9.54 mIu/ml
 B. HCG : 0.387B. HCG : 0.387
mIu/mlmIu/ml
 HCG 10,000 units wasHCG 10,000 units was
administratedadministrated
(Choriomon IBSA)(Choriomon IBSA)

11.  On 10/8/2006 OPU was done atOn 10/8/2006 OPU was done at
I.F.C center Alexandria, retrievingI.F.C center Alexandria, retrieving
19 oocytes: 15 oocytes were MII19 oocytes: 15 oocytes were MII
and were injected, and 11 embryosand were injected, and 11 embryos
were developed.were developed.
 Four embryos were transferred onFour embryos were transferred on
DAY 2 (4A,4A,4A,3A) and fiveDAY 2 (4A,4A,4A,3A) and five
embryos were cryopreserved forembryos were cryopreserved for
future use (5A, 4A, 4B, 3A, 2A).future use (5A, 4A, 4B, 3A, 2A).

14.  Luteal phase support wasLuteal phase support was
conducted using vaginalconducted using vaginal
progesterone pessariesprogesterone pessaries
(cyclogest 400 twice daily).(cyclogest 400 twice daily).
 No manifestations for severeNo manifestations for severe
OHSS was noticed during theOHSS was noticed during the
next two weeks.next two weeks.

15. Cytological examination of theCytological examination of the
yielded follicular fluid reveals fewyielded follicular fluid reveals few
groups of granulosa cells intermixedgroups of granulosa cells intermixed
with groups of liteinized theca cellswith groups of liteinized theca cells
having abundant pale cytoplasm,having abundant pale cytoplasm,
and surrounded bye amildand surrounded bye amild
inflammatory cellular infiltrateinflammatory cellular infiltrate
mainly composed of lymphocytes &mainly composed of lymphocytes &
polymorphs.polymorphs.

17. On 26/8/06 B-HCG was 22 mIu/ml,On 26/8/06 B-HCG was 22 mIu/ml,
96 hours later it was 34 few days96 hours later it was 34 few days
later, she developed attack oflater, she developed attack of
vaginal bleding and B-HCG wasvaginal bleding and B-HCG was
negative. She is waiting to transfernegative. She is waiting to transfer
her cryoembryos next month.her cryoembryos next month.

19. Over the last two decades, GnRH agonistsOver the last two decades, GnRH agonists
have been use in ovarian stimulationhave been use in ovarian stimulation
protocols in assisted reproductiveprotocols in assisted reproductive
techniques (ART) in combnation withtechniques (ART) in combnation with
gonadotrophins to achieve multifolliculargonadotrophins to achieve multifollicular
development without premature LH surge.development without premature LH surge.
GnRH agonists induce an initial rise ofGnRH agonists induce an initial rise of
gonadotrophins (flare-up) before theygonadotrophins (flare-up) before they
achieve suppression throughachieve suppression through
desensitization (Ortmann et al,2001).desensitization (Ortmann et al,2001).

20. This flare up induces release ofThis flare up induces release of
gonadotophins from the pituitary glandgonadotophins from the pituitary gland
stimulating the growth of follicles. Thusstimulating the growth of follicles. Thus
follicular cyst developes as a response offollicular cyst developes as a response of
this flare up but soon pituitarythis flare up but soon pituitary
desensitization is achieved resulting indesensitization is achieved resulting in
stop of stimulus and impaired ovulation.stop of stimulus and impaired ovulation.
Development of cyst with GnRHa is notDevelopment of cyst with GnRHa is not
uncommon however, the development ofuncommon however, the development of
multiple follicles and their growth is raremultiple follicles and their growth is rare
(Fiszbajn et al,2004)(Fiszbajn et al,2004)

21.  There are very few publications in theThere are very few publications in the
literature describing this rare event, withliterature describing this rare event, with
only two reports mentioning hCGonly two reports mentioning hCG
triggering of ovulation. Fertilization oftriggering of ovulation. Fertilization of
oocytes and transfers of embryos haveoocytes and transfers of embryos have
succeeded in certain cases, but only onesucceeded in certain cases, but only one
pregnancy has been reported that led to apregnancy has been reported that led to a
living birth.living birth.
 It has been suggested that GnRH agonistIt has been suggested that GnRH agonist
directly act on the ovary and contribute todirectly act on the ovary and contribute to
cyst formationcyst formation
(Mehta and Kumar(Mehta and Kumar

22.  Ovarian hyperstimulation following the soleOvarian hyperstimulation following the sole
administration of agonistic analogues ofadministration of agonistic analogues of
gonadortophin releasing hormonegonadortophin releasing hormone
(Weissman et.al Hum. Rep. 1998)(Weissman et.al Hum. Rep. 1998)
 The development of an oocyte-containingThe development of an oocyte-containing
follicle during gonadotrophin-releasingfollicle during gonadotrophin-releasing
hormone agonist administration.hormone agonist administration.
(Almagor et.al Hum. Rep. 2001)(Almagor et.al Hum. Rep. 2001)

23.  Ovarian hyperstimulation-like syndromeOvarian hyperstimulation-like syndrome
after administration of triptorelin to aafter administration of triptorelin to a
woman with endometriosis.woman with endometriosis.
(Inaudi et.al Gynecol Endocrinol 2002)(Inaudi et.al Gynecol Endocrinol 2002)
 Ovarian hyperstimulation induced by aOvarian hyperstimulation induced by a
GnRH agonist about one caseGnRH agonist about one case
(Naifer et.al Gynecol Obstet Fertil 2005)(Naifer et.al Gynecol Obstet Fertil 2005)

25. We recommend that when theWe recommend that when the
growth of cysts after GnRHagrowth of cysts after GnRHa
administration is accompanied byadministration is accompanied by
high concentrations of E2, thehigh concentrations of E2, the
administration of HCG may beadministration of HCG may be
useful to achieve oocyteuseful to achieve oocyte
maturation and advance IVFmaturation and advance IVF
treatmenttreatment