P-638

EFFECT OF ORAL GnRH ANTAGONIST RELUGOLIX ON BLOOD HORMONE AND OOCYTE RETRIEVAL- A STUDY OF THE METHOD OF RELUGOLIX ADMINISTRATIONCHINAMI YAMASHITA, MOMOYO SONODASONODA MOMOYO ART CLINICOBJECTIVE

EXAMINATION1

The GnRH antagonist protocol is one of the most selected methods of controlled ovarian
stimulation in assisted reproductive technology. Cetrorelix and Ganirelix are used worldwide
to suppress premature LH surge in GnRH antagonist protocol. In Japan, relugolix has beenreleased as an oral treatment for uterus myoma in March 2019, and expected to prevent
premature LH surge in controlled ovarian stimulation due to its mechanism of action. Thisoral GnRH antagonist greatly reduces patient’s distress economically, physically and mentally,
due to the painless of injection. In the present study, we compared the blood hormone
levels, number of oocytes retrieved, and culture results of cycles of those using relugolix
with those adopting the more conventional method using cetrorelix.

Using the E2 level per oocyte retrieval in group C as a standard, group R was divided into
groups below the standard (group RB) and above the standard (group RA), and blood
hormone levels, number of oocytes retrieved, and culture results were compared.
The E2 level per oocyte retrieval in group C was 257.0pg/ml (75 percentile value).

RESULTS
Table2．Comparison of the patient background, the hormone levels of 2 days before oocyte
retrieval and the number of oocytes retrieved in the group C, RB and RA.

EXAMINATION2
A result of examination1 suggested thepossibility that the P4 level was related todecrease of the number of oocytes retrieved.
Then ROC curve was drawn from the P levelsof the group R, and the cutoff value (0.37）
was calculated. Applying this value to thegroup R, we compared the number ofoocytes retrieved, the E2 level and theculture results of the group below 0.37 andabove 0.37.

SUBJECT
From December 2010 to February 2021, 251 cycles [214 cycles in the cetrorelix (C) groupand 37 cycles in the relugolix (R) group] of ovarian stimulation using GnRH antagonists wereincluded in the study.

RESULTS
Table4．Comparison of the E2 levels and the number of oocytes retrieved in the group
below 0.37 and above 0.37.

METHODS
Ovarian stimulation was started by the third day of the menstrual cycle in all patients. The
dosage of gonadotropins was selected based on the patient’s age and an assessment ofovarian function reserve as estimated by antral follicle count and anti-Mullerian hormone(AMH) levels. When the follicle diameter reached about 14mm, GnRH antagonists wereadministered daily. Final oocyte maturation was triggered with GnRH agonist when thelargest follicle attained diameter of 18mm. Oocyte retrieval was performed undertransvaginal ultrasound guidance 36 hours after GnRH agonist administration. The hormonal
profiles were assessed in every patient on the day of ovarian stimulation initiation and 2days before oocyte retrieval.

Table3．Comparison of the culture results in the group C, RB and RA.

RESULTS
Tabel1. Comparison of the patient background, hormone levels of 2 days before oocyte
retrieval and the number of oocytes retrieved in the group C and R.

There were no significant differences in age, AMH, and total HMG/FSH doses among thegroup C, RB, and RA. The P4 levels of 2 days before oocyte retrieval were significantly lower
in the group RB and RA than in the group C. The number of oocytes retrieved wassignificantly fewer in the group RA than in other groups (Table2). Premature ovulation wasobserved in one case each in the group C and RA. There was no significant difference infertilization rate, cleavage rate, and good blastocyst rate among all groups (Table3).

Table5．Comparison of the culture results in the group below 0.37 and above 0.37.

There were no significant differences in the E2 levels among the both groups. However, thenumber of oocytes retrieved was significantly fewer in the group below 0.37 than in thegroup above 0.37 (Table4). There was no significant difference in culture results among theboth groups.

CONCLUSIONS
It was suggested that the oral GnRH antagonist relugolix used during ovarian stimulation did
not affect embryo developmental potential. On the other hand, it was suggested that thelower P4 level of 2 days before oocyte retrieval in relugolix cycle may result in the fewer
number of oocytes retrieved.

IMPACT STATEMENT
There were no significant differences in age, AMH, and total HMG/FSH doses among theboth groups. The P4 and E2 were significantly lower in the group R than in the group C. The
number of oocytes retrieved was significantly fewer in the group R than in the group C.

It is known that relugolix has a longer blood half-life than that of cetrorelix, therefore wethought that this oral GnRH antagonist is more effective about preventing premature LH
surges than cetrorelix. For patients who do not have the expected number of oocytes
retrieved, changing the method of relugolix administration (every other day administrationor half administration) or changing the trigger may improve the number of oocytes
retrieved.