The role of elagolix in the suppression of ovulation in donor oocyte cycles.

A total of 150 donors were included in this study: 75 donors were included in the prospective group receiving elagolix, and 75 donors were included from a retrospective chart review from the year prior and received ganirelix during their cycles. Patient demographics between groups were similar; there were no statistically significant differences in age or BMI between groups, with the mean age being approximately 26 years old and the mean BMI being 23 in each group. There was also no significant difference in starting AMH levels between the control group and the elagolix group, with AMH 6.2 and 5.3 ng/mL, respectively ( P =.30) ( Table 1 ). Table 1 Summary of treatment outcome. Elagolix group Elagolix Ganirelix P Value Mean age, y 25.7 26.02 0.39 Mean body mass index, kg/m 2 23.49 23.67 0.7 Mean AMH (ng/mL) 5.71 6.2 0.3 Avg. cumulative gonadotripin dose 2855 2741 0.35 Days of stimulation 10.49 10.06 0.07 D of antagonist 4.2 3.4 0.12 Avg. peak estradiol (pg/mL) 3959 3764 0.59 Avg. peak progesterone (ng/mL) 1.9 2.3 0.17 Avg. peak luteinizing hormone (mIU/mL) 0.94 1.3 0.69 Avg. oocytes 30.31 30.55 0.97 Avg. mature oocytes 24.73 25.42 0.71 AMH = antimüllerian hormone; Avg = Average. Summary of treatment outcome. AMH = antimüllerian hormone; Avg = Average. The primary outcome, premature ovulation, was not different between the groups because there were no instances of premature ovulation in either group. Secondary outcomes: the average number of total oocytes was similar between the control and elagolix groups (30.55 vs. 30.31, P =.97, respectively). The average number of mature oocytes was similar as well between the control and study groups (25.42 vs. 24.73, P =.71). There was no significant difference in maximum E 2 level or gonadotropins consumed between groups ( P =.59 and P =.35, respectively). Additional cycle characteristics measured were also similar between groups, including total cycle length, days of stimulation required, and days of suppression required. Serum analysis of LH concentrations was similar between groups, with peak LH concentrations of 0.94 mIU/mL in the elagolix group and 1.3 mIU/mL in the ganirelix group ( P =.69). The average peak P4 concentrations were 2.3 ng/mL in the control group and 1.9 ng/mL in the elagolix group ( Table 1 ). There were no recorded adverse events in either group during the study period. The resultant mature oocytes were used in both fresh oocyte donation and cryopreservation for future use. A total of 580 oocytes from the elagolix group and 737 from the control group underwent fresh fertilization with intracytoplasmic sperm injection, resulting in a fertilization rate of 84.6% in the ganirelix group and 79.7% in the elagolix group. The resultant blastocyst development rate was 57.3% in the ganirelix group and 62.9% in the elagolix group. Embryology outcomes were assessed as outlined in Table 2 . Table 2 Embryology summary. Fresh oocytes Elagolix Ganirelix P Value Total mature inseminated 580 737 Fertilization rate 79.7 84.6% 0.20 Blastocyst development rate 62.9% 57.3% 0.35 Embryology summary. On average, the elagolix group used 4.3 less injections per cycle than the control group using ganirelix. The average cost per cycle was $289.19 lower in the elagolix group.

This prospective cohort study of oocyte donors was performed at a single fertility clinic (Charleston, SC), between 2018 and 2019 to compare the effects of elagolix vs. ganirelix for ovulation suppression during donor cycles. This study was approved by the Western Institutional Review Board (Western IRB Pr. No.: 20191163, April 11, 2019). Partial funding was provided by AbbVie, Inc. as an educational grant. Written consent was obtained from all participants. Prospective data were collected from a total of 75 donors enrolling in an established donor program who consented to participate in this study and received elagolix during their cycle as ovulation suppression. Retrospective data were collected from 75 donor cycles at the same clinic the year prior (2018), in which donors used ganirelix for suppression during their cycle under the same stimulation protocols. Donors who passed the FDA and American Society for Reproductive Medicine-approved oocyte donor screening were offered participation in the study. Participants were aged 21–30 years, nonsmokers, with a body mass index (BMI) of 2 ng/mL and an FSH of <10 mIU/mL. All participants had a negative drug screen and underwent psychiatric screening. In addition, participants underwent a full history and physical evaluation, and were excluded if they had chronic medical conditions, first-degree relatives with hereditary disorders, or were known carriers of X-linked disorders. Infectious disease testing was required to be negative within 30 days of oocyte retrieval. All donors began their cycles with oral contraceptives for 10–14 days to lead into ovarian stimulation. Three days after discontinuing oral contraceptives, donors began daily injections of recombinant FSH (Follistim; Merck, NJ), with the initial dose ranging from 275–325 IU per day on the basis of age, FSH level, AMH level, and antral follicular count. On day 6 and then at 2–3 days intervals, serum testing of E 2 and ultrasound monitoring were performed to guide recombinant FSH dosing. Once a 14-mm lead follicle was noted on ultrasound, 20 units per day of subcutaneous human chorionic gonadotropin were administered daily along with ovulation suppression; the study group received elagolix (200 mg PO QHS; Orilissa; AbbVie Inc., IL), and the historical control group received ganirelix (250 mcg, SC QHS; Merck, NJ). Elagolix or ganirelix was then discontinued 24 hours before the GnRH agonist trigger. Once follicular maturity was reached on the basis of follicular number, follicular size, and E 2 levels, a GnRH agonist (4 mg SC; Lupron; AbbVie, IL) was then used to induce ovulation. Oocyte retrieval was performed 36 hours after the trigger. The primary outcome of this study, premature ovulation rate, was assessed using elevated P4 levels >3 ng/mL before GnRH agonist trigger and lack of oocytes at retrieval. Secondary outcomes, such as total oocytes and mature oocytes were assessed by embryologists through microscopic assessment of oocytes after granulosa stripping. Secondary laboratory values such as maximum E 2 , LH, and P4 levels were measured using serum analytics. Embryology outcomes, including the fertilization rate and blastocyst development rates, were assessed between the 2 groups. Patient demographics between the 2 groups were compared using a student’s t -test after confirming normality. Continuous quantitative variables were measured using central parameters (range, mean) and compared similarly.

In this prospective cohort study, there were no cases of premature ovulation in the elagolix group using a dose of 200 mg orally every night at bedtime, starting with a 14-mm follicle. Likewise, the use of a GnRH agonist as an ovulatory trigger was successful in all 75 elagolix cycles because mature oocytes were available in all cycles. The use of elagolix resulted in 4.3 less injections per cycle and a cost savings in excess of $250 per cycle although resulting in similar outcomes. On the basis of existing literature and this study, it can be postulated that an oral GnRH antagonist, such as elagolix, has the pharmacokinetic properties to adequately suppress ovulation during the short period necessary for controlled ovarian stimulation. As efforts continue to make ovarian stimulation more patient-friendly and less cost prohibitive, oral GnRH agents follow as the next step in limiting the injection and cost burdens associated with GnRH antagonist protocol donor cycles. To our knowledge, this is the first study using elagolix as an oral GnRH antagonist in donor oocyte stimulation cycles. Similar outcomes for both mature and total oocytes as well as similar cycle characteristics suggest the noninferiority of elagolix for ovulation suppression when compared with traditional injectable GnRH antagonists in donor cycles. Elagolix reduced the number of injections and total cost per cycle, making it an attractive alternative for fertility clinics that may absorb the cost of donor programs. Our study was designed as a proof-of-concept study, and randomized clinical trials would be necessary to provide more robust data to support these findings. Limitations of our study include the relatively small sample size of 75 egg donation cycles in the study group. A second limitation is that the oocytes derived from this study were used fresh, and a portion were cryopreserved. We were able to analyze the embryology results of the fresh oocytes, which demonstrated no difference in outcomes; however, because of the date of publication, not all of the cryopreserved oocytes were analyzed, and therefore, an analysis of their use is not possible.

The novel oral GnRH antagonist elagolix can be successfully used for ovulation suppression in donor cycles triggered by a GnRH agonist with no apparent differences in clinical or embryological outcomes. Elagolix offers a more patient-friendly approach to ovulation suppression and lower per-cycle costs in a donor population.