YOUR FERTILITY PHARMACIST

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Use of a New Oral Drug in Egg Donor Cycles

Your Fertility Pharmacist

This proof-of-concept study compared the tolerance of elagolix to ganirelix in donor oocyte (egg) cycles.

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Use of a New Oral Drug in Egg Donor Cycles Your Fertility Pharmacist

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