Use of a New Oral Drug in Egg Donor Cycles
This proof-of-concept study compared the tolerance of elagolix to ganirelix in donor oocyte (egg) cycles.
Study Background
WHAT
Compared oral elagolix to injectable ganirelix for ovulation suppression during egg donor cycles
WHY
Important to prevent early luteinizing hormone (LH) surge prior to oocyte retrieval
Use of gonadotropin-releasing hormone (GnRH) antagonists often given in ovarian stimulation protocols to inhibit early LH surge / suppress ovulation
Elagolix is newer, works quickly, and is an oral GnRH antagonist that reversibly suppresses LH —> elagolix may be a more patient-friendly alternative to injectable GnRH antagonists
WHERE/WHEN
Coastal Fertility Specialists, Charleston, South Carolina, 2018 - 2019
Prospective elagolix arm, 2019
Retrospective comparative ganirelix arm, 2018
WHO
Inclusion Criteria: passed FDA and ASRM oocyte donor screening
Women ages 21-30 years
Nonsmokers with BMI < 35 kg/m2
AMH > 2 ng/mL and FSH < 10 mIU/mL
No known X-linked disorders or hereditary disorders in close relatives
Passed physical and genetic evaluations
HOW
10-14 days oral contraceptives (OC)
Recombinant FSH (Follistim) started after three-day OC washout; dosed 275-325 IU daily
hCG 20u daily started with 14mm lead follicle + GnRH antagonist (elagolix 200 mg orally HS or ganirelix 250 mcg subQ); GnRH antagonist stopped 24h before trigger with GnRH agonist leuprolide (Lupron) 4 mg subQ
Oocyte retrieval 36h after GnRH agonist trigger
Statistics
Students t-test for two-group comparison
Results
Baseline demographics similar: mean age 26y, mean BMI 23
Efficacy: no premature ovulation noted in either group
Safety: no adverse events recorded in either group
Treatment & embryology outcomes (in fresh oocytes) showed no significant differences
Peak LH concentrations: 0.94 mIU/mL elagolix vs. 1.3 mIU/mL ganirelix
Average mature oocytes collected: 25.4 elagolix vs. 24.7 ganirelix
Total mature oocytes inseminated: 580 elagolix vs. 737 ganirelix
Oocytes fertilized = 80% in elagolix vs. 85% ganirelix
Blastocyst development = 63% elagolix vs. 57% ganirelix
No premature ovulation occurred in either group
Average cost was $289 lower in elagolix vs. ganirelix group
Elagolix group used ~4.3 fewer injections per cycle
Authors’ Thoughts
Elagolix reduced costs and injections per donor cycle
Limitations were analysis of only fresh (not frozen) oocytes + smaller sample size
Randomized-controlled trials (RCTs) needed
This Pharmacist’s Thoughts
Why not compare instead to cetrorelix (Cetrotide), which may be safer and more efficacious than ganirelix?
Direct RCTs needed vs. a 2018-to-2019 comparison
May see outcome differences with larger sample sizes
More infertile women need to try elagolix before concluding safety/efficacy for general indication of ovulation suppression —> oocyte donors can have different health traits vs. populations of women struggling to conceive
Insurance companies will likely require further study to enact coverage for off-label indication
Are lowered costs with elagolix generalizable, or did the investigator-initiated research funding from AbbVie impact savings?
Conclusions
Though further study is unquestionably needed, shortages of alternate GnRH antagonists and the comparative ease of taking a tablet may increase the impetus to try elagolix in donor egg cycles based on current research results.
Resources
Boniface C, Schnorr JN, Gray J, et al. The role of elagolix in the suppression of ovulation in donor oocyte cycles. F S Rep. 2023;4(2):179-182. Published 2023 Mar 25. doi:10.1016/j.xfre.2023.03.006
Check JH, Brasile D, Choe JK, Amui J, Wilson C. The effect of cetrorelix vs. ganirelix on pregnancy outcome using minimal gonadotropin stimulation in women with elevated day 3 serum follicle stimulating hormone levels. Clin Exp Obstet Gynecol. 2009;36(3):148-149.
Fyremadel [package insert]. Parsippany, NJ: Ferring Pharmaceuticals, Inc.; 2022. manufactured by Sun Pharma (India)
Kay, C. Contaminated Drugs, Shredded Papers: US FDA Uncovers Failures in India Pharma Factories. May 31, 2013. Accessed July 11, 2023. https://www.bloomberg.com/news/articles/2023-05-31/us-finds-contaminated-drugs-further-lapses-in-india-pharma-factories-post-covid#xj4y7vzkg
Keenan, J. Sun Pharma pauses US drug exports from India plant after FDA scolding. April 27, 2023. Accessed July 10, 2023. https://www.fiercepharma.com/manufacturing/sun-pharma-hits-pause-mohali-plant-response-fda-letter/
Orilissa [package insert]. North Chicago, IL: Abbvie; 2021.
Zhang J, Zhou X, Chen Y, et al. Effects of cetrorelix versus ganirelix in gonadotropin-releasing hormone antagonist cycles for preventing premature luteinizing hormone surges and on clinical outcomes of IVF-ET cycles. Nan Fang Yi Ke Da Xue Xue Bao. 2019;39(10):1207-1212. doi:10.12122/j.issn.1673-4254.2019.10.12
