Impact of FSH Dosage During Ovarian Stimulation for IVF/ICSI in Granulosa Cells

NCT05330130 | Completed Phase 1 DMC

• 1 other identifier: 2107-ABU-010-BL
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

To study the influence of different daily rec-FSH dosages (150 IU versus 300 IU), performed in the same patient in consecutive cycles, on the relation between FSH- and LH-receptors of the granulosa cells of the growing follicle.

Conditions

Ovarian Function Insufficiency; Fertility Issues; Infertility,Female; Infertility

Keywords

Ovarian stimulation; Granulosa cells; Follicle Stimulating Hormone Receptor; Luteinising Hormone Receptor; Elevated progesterone

Outcome Measures

Primary Outcomes (4)

• Number of FSHR- and LHR of the GC, obtained from one follicle on the morning of day 5, before the administration of the first GnRH-antagonist, punctured during the ovarian stimulation cycle

  5 days

• Number of FSHR- and LHR of the GC, obtained from tone follicle of the size of 12 to 14 mm, when at least 2 to 3 follicles have reached a size of 12 to 14 mm, punctured during the ovarian stimulation cycle

  1 day

• Number of FSHR- and LHR of the GC, obtained from two follicles (= pre-ovulatory follicle) on the morning of the day of final oocyte maturation, punctured during the ovarian stimulation cycle

  1 day

• Number of FSHR- and LHR of the GC, obtained from the follicular fluid of follicles aspirated during OPU

  1 day

Secondary Outcomes (32)

• Level of E2 hormone in the blood, the morning of day 5, before the administration of the first GnRH-antagonist

  5 days

• Level of P4 hormone in the blood, the morning of day 5, before the administration of the first GnRH-antagonist

  5 days

• Level of FSH hormone in the blood, the morning of day 5, before the administration of the first GnRH-antagonist

  5 days

• Level of LH hormone in the blood, the morning of day 5, before the administration of the first GnRH-antagonist

  5 days

• Level of E2 hormone in the blood, when there are at least 2 to 3 follicles with a size of 12 to 14 mm

  1 day

Study Arms (2)

Daily 150 IU recFSH

ACTIVE COMPARATOR

Follitropin beta injection 150 IU daily

Drug: Follitropin beta injection 150 IU

Daily 300 IU recFSH

ACTIVE COMPARATOR

Follitropin beta injection 300 IU daily

Drug: Follitropin beta injection 300 IU

Interventions

Follitropin beta injection 150 IU DRUG

Participants commence ovarian stimulation on day 2 or 3 of their menstrual cycle with a daily dosage of 150 IU rec-FSH. The dosage will remain constant throughout the course of the stimulation. From the morning of the 5th stimulation day, GnRH-antagonist will be administered daily to prevent LH-rise. As soon as ≥ 3 follicle of a size of 17mm are seen, 0.3 mg GnRH-Agonist will be administered for final oocyte maturation. During ovarian stimulation, follicle puncture procedures with the aspiration of follicular fluid will be performed at the following time: * one follicle on the morning of day 5, before the administration of the first GnRH-antagonist * one follicle of the size of 12 to 14 mm, when at least 2 to 3 follicles have reached a size of 12 to 14 mm * two follicles (= pre-ovulatory follicle) on the morning of the day of final oocyte maturation. Oocyte retrieval of all other follicles will be carried out 36 hours after injection of the medication for final oocyte maturation.

Also known as: FOLLISTIM AQ

Daily 150 IU recFSH

Follitropin beta injection 300 IU DRUG

Participants commence ovarian stimulation on day 2 or 3 of their menstrual cycle with a daily dosage of 300 IU rec-FSH. The dosage will remain constant throughout the course of the stimulation. From the morning of the 5th stimulation day, GnRH-antagonist will be administered daily to prevent LH-rise. As soon as ≥ 3 follicle of a size of 17mm are seen, 0.3 mg GnRH-Agonist will be administered for final oocyte maturation. During ovarian stimulation, follicle puncture procedures with the aspiration of follicular fluid will be performed at the following time: * one follicle on the morning of day 5, before the administration of the first GnRH-antagonist * one follicle of the size of 12 to 14 mm, when at least 2 to 3 follicles have reached a size of 12 to 14 mm * two follicles (= pre-ovulatory follicle) on the morning of the day of final oocyte maturation. Oocyte retrieval of all other follicles will be carried out 36 hours after injection of the medication for final oocyte maturation.

Also known as: FOLLISTIM AQ

Daily 300 IU recFSH

Eligibility Criteria

• Age: 18 Years - 38 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Desire to perform oocyte freezing for social fertility preservation, age 18 - 38 years
• BMI of 18-32 kg/m2
• Regular menstrual cycles with a length of 24-35 days
• Anti-Muellerian-Hormone levels between 1.3 - 6.25 ng/ml (Ferraretti and Gianaroli, 2014; Calzada et al., 2019)

You may not qualify if:

• Occurrence of ovarian hyperstimulation syndrome (OHSS)
• Occurrence of poor ovarian response (AFC \< 5 and AMH \< 0,5ng/ml) in previous ovarian stimulation treatment (20)
• Polycystic ovary syndrome (PCOS) (21)

Sponsors & Collaborators

• ART Fertility Clinics LLC: lead
• Organon and Co: collaborator

Study Sites (1)

ART Fertility Clinics LLC

Abu Dhabi, 60202, United Arab Emirates

Location

Related Publications (19)

• Baker VL, Brown MB, Luke B, Smith GW, Ireland JJ. Gonadotropin dose is negatively correlated with live birth rate: analysis of more than 650,000 assisted reproductive technology cycles. Fertil Steril. 2015 Nov;104(5):1145-52.e1-5. doi: 10.1016/j.fertnstert.2015.07.1151. Epub 2015 Aug 18.

  PMID: 26297646 BACKGROUND

• Bosch E, Valencia I, Escudero E, Crespo J, Simon C, Remohi J, Pellicer A. Premature luteinization during gonadotropin-releasing hormone antagonist cycles and its relationship with in vitro fertilization outcome. Fertil Steril. 2003 Dec;80(6):1444-9. doi: 10.1016/j.fertnstert.2003.07.002.

  PMID: 14667881 BACKGROUND

• Calzada M, Lopez N, Noguera JA, Mendiola J, Hernandez AI, Corbalan S, Sanchez M, Torres AM. AMH in combination with SHBG for the diagnosis of polycystic ovary syndrome. J Obstet Gynaecol. 2019 Nov;39(8):1130-1136. doi: 10.1080/01443615.2019.1587604. Epub 2019 Jun 17.

  PMID: 31208261 BACKGROUND

• Erickson GF, Wang C, Hsueh AJ. FSH induction of functional LH receptors in granulosa cells cultured in a chemically defined medium. Nature. 1979 May 24;279(5711):336-8. doi: 10.1038/279336a0. No abstract available.

  PMID: 221826 BACKGROUND

• Fauser BC. Towards the global coverage of a unified registry of IVF outcomes. Reprod Biomed Online. 2019 Feb;38(2):133-137. doi: 10.1016/j.rbmo.2018.12.001. Epub 2018 Dec 14. No abstract available.

  PMID: 30593441 BACKGROUND

• Ferraretti AP, Gianaroli L. The Bologna criteria for the definition of poor ovarian responders: is there a need for revision? Hum Reprod. 2014 Sep;29(9):1842-5. doi: 10.1093/humrep/deu139. Epub 2014 Jul 9.

  PMID: 25008235 BACKGROUND

• Filicori M, Cognigni GE, Gamberini E, Parmegiani L, Troilo E, Roset B. Efficacy of low-dose human chorionic gonadotropin alone to complete controlled ovarian stimulation. Fertil Steril. 2005 Aug;84(2):394-401. doi: 10.1016/j.fertnstert.2005.02.036.

  PMID: 16084880 BACKGROUND

• Huang B, Ren X, Wu L, Zhu L, Xu B, Li Y, Ai J, Jin L. Elevated Progesterone Levels on the Day of Oocyte Maturation May Affect Top Quality Embryo IVF Cycles. PLoS One. 2016 Jan 8;11(1):e0145895. doi: 10.1371/journal.pone.0145895. eCollection 2016.

  PMID: 26745711 BACKGROUND

• Jeppesen JV, Kristensen SG, Nielsen ME, Humaidan P, Dal Canto M, Fadini R, Schmidt KT, Ernst E, Yding Andersen C. LH-receptor gene expression in human granulosa and cumulus cells from antral and preovulatory follicles. J Clin Endocrinol Metab. 2012 Aug;97(8):E1524-31. doi: 10.1210/jc.2012-1427. Epub 2012 Jun 1.

  PMID: 22659248 BACKGROUND

• Lawrenz B, Beligotti F, Engelmann N, Gates D, Fatemi HM. Impact of gonadotropin type on progesterone elevation during ovarian stimulation in GnRH antagonist cycles. Hum Reprod. 2016 Nov;31(11):2554-2560. doi: 10.1093/humrep/dew213. Epub 2016 Sep 12.

  PMID: 27619773 BACKGROUND

• Lawrenz B, Fatemi HM. Effect of progesterone elevation in follicular phase of IVF-cycles on the endometrial receptivity. Reprod Biomed Online. 2017 Apr;34(4):422-428. doi: 10.1016/j.rbmo.2017.01.011. Epub 2017 Jan 24.

  PMID: 28162937 BACKGROUND

• Lawrenz B, Labarta E, Fatemi H, Bosch E. Premature progesterone elevation: targets and rescue strategies. Fertil Steril. 2018 Apr;109(4):577-582. doi: 10.1016/j.fertnstert.2018.02.128.

  PMID: 29653703 BACKGROUND

• Lawrenz B, Melado L, Fatemi H. Premature progesterone rise in ART-cycles. Reprod Biol. 2018 Mar;18(1):1-4. doi: 10.1016/j.repbio.2018.01.001. Epub 2018 Jan 6.

  PMID: 29317175 BACKGROUND

• Macklon NS, Stouffer RL, Giudice LC, Fauser BC. The science behind 25 years of ovarian stimulation for in vitro fertilization. Endocr Rev. 2006 Apr;27(2):170-207. doi: 10.1210/er.2005-0015. Epub 2006 Jan 24.

  PMID: 16434510 BACKGROUND

• Munch EM, Sparks AE, Zimmerman MB, Van Voorhis BJ, Duran EH. High FSH dosing is associated with reduced live birth rate in fresh but not subsequent frozen embryo transfers. Hum Reprod. 2017 Jul 1;32(7):1402-1409. doi: 10.1093/humrep/dex094.

  PMID: 28472321 BACKGROUND

• Oktem O, Akin N, Bildik G, Yakin K, Alper E, Balaban B, Urman B. FSH Stimulation promotes progesterone synthesis and output from human granulosa cells without luteinization. Hum Reprod. 2017 Mar 1;32(3):643-652. doi: 10.1093/humrep/dex010.

  PMID: 28158500 BACKGROUND

• Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod. 2011 Jul;26(7):1768-74. doi: 10.1093/humrep/der106. Epub 2011 May 10.

  PMID: 21558332 BACKGROUND

• Venetis CA, Kolibianakis EM, Bosdou JK, Tarlatzis BC. Progesterone elevation and probability of pregnancy after IVF: a systematic review and meta-analysis of over 60 000 cycles. Hum Reprod Update. 2013 Sep-Oct;19(5):433-57. doi: 10.1093/humupd/dmt014. Epub 2013 Jul 4.

  PMID: 23827986 BACKGROUND

• Wilcox AJ, Baird DD, Weinberg CR. Time of implantation of the conceptus and loss of pregnancy. N Engl J Med. 1999 Jun 10;340(23):1796-9. doi: 10.1056/NEJM199906103402304.

  PMID: 10362823 BACKGROUND

Related Links

• Segaloff DL, Richards JS, Ascoli M, Wang H. Regulation of the LH/CG Receptor by Gonadotropins. In Hunzicker-Dunn M, Schwartz NB, editors. Follicle Stimul Horm \[Internet\] 1992;, p. 199-205. Springer New York: New York, NY

MeSH Terms

Conditions

Infertility; Infertility, Female

Interventions

follitropin beta; Glycoprotein Hormones, alpha Subunit

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications

Intervention Hierarchy (Ancestors)

Chorionic Gonadotropin; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Luteinizing Hormone; Pituitary Hormones, Anterior; Pituitary Hormones; Thyrotropin; Placental Hormones; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Barbara Lawrenz, PhD

  ART Fertility Clinics LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Scientific Director

Study Record Dates

• First Submitted: March 31, 2022
• First Posted: April 15, 2022
• Study Start: July 5, 2023
• Primary Completion: March 30, 2024
• Study Completion: June 30, 2024
• Last Updated: January 9, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

AE (1)