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

NCT ID: NCT05330130

Last Updated: 2025-01-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

6 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-07-05

Study Completion Date

2024-06-30

Brief Summary

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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.

Detailed Description

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This is a prospective cross-over study. Investigators want to study the effect of different dosages of recombinant FSH in the same patient on the expression of the FSH- and LH-receptors in the granulosa cells and on the endocrine milieu in the blood and the follicular fluid. An improved understanding of the mechanism leading to progesterone elevation might initiate a change in the ovarian stimulation approach, thereby not only preventing progesterone elevation and its negative consequences on ART (Assisted Reproductive Technology) outcome, but also improving individualization of the ovarian stimulation treatment according to the patients' characteristics.

Conditions

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Ovarian Function Insufficiency Fertility Issues Infertility,Female Infertility

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Daily 150 IU recFSH

Follitropin beta injection 150 IU daily

Group Type ACTIVE_COMPARATOR

Follitropin beta injection 150 IU

Intervention Type 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.

Daily 300 IU recFSH

Follitropin beta injection 300 IU daily

Group Type ACTIVE_COMPARATOR

Follitropin beta injection 300 IU

Intervention Type 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.

Interventions

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Follitropin beta injection 150 IU

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.

Intervention Type DRUG

Follitropin beta injection 300 IU

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.

Intervention Type DRUG

Other Intervention Names

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FOLLISTIM AQ FOLLISTIM AQ

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

* 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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

38 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Organon and Co

INDUSTRY

Sponsor Role collaborator

ART Fertility Clinics LLC

OTHER

Sponsor Role lead

Responsible Party

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Barbara Lawrenz

Scientific Director

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Barbara Lawrenz, PhD

Role: PRINCIPAL_INVESTIGATOR

ART Fertility Clinics LLC

Locations

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ART Fertility Clinics LLC

Abu Dhabi, , United Arab Emirates

Site Status

Countries

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United Arab Emirates

References

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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.

Reference Type BACKGROUND
PMID: 26297646 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14667881 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31208261 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 221826 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30593441 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25008235 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16084880 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26745711 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22659248 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27619773 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28162937 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29653703 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29317175 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16434510 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28472321 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28158500 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21558332 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23827986 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10362823 (View on PubMed)

Related Links

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http://link.springer.com/10.1007/978-1-4684-7103-8_16

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

Other Identifiers

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2107-ABU-010-BL

Identifier Type: -

Identifier Source: org_study_id

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