Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05330130
Other study ID # 2107-ABU-010-BL
Secondary ID
Status Recruiting
Phase Phase 1
First received
Last updated
Start date July 5, 2023
Est. completion date January 30, 2024

Study information

Verified date July 2023
Source ART Fertility Clinics LLC
Contact Barbara Lawrenz, PhD
Phone 026528000
Email barbara.lawrenz@artfertilityclinics.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

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.


Recruitment information / eligibility

Status Recruiting
Enrollment 10
Est. completion date January 30, 2024
Est. primary completion date December 30, 2023
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Female
Age group 18 Years to 38 Years
Eligibility 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)

Study Design


Intervention

Drug:
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.
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.

Locations

Country Name City State
United Arab Emirates ART Fertility Clinics LLC Abu Dhabi

Sponsors (2)

Lead Sponsor Collaborator
ART Fertility Clinics LLC Organon and Co

Country where clinical trial is conducted

United Arab Emirates, 

References & 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 19 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary 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
Primary 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
Primary Number of FSHR- and LHR of the GC, obtained from the follicular fluid of follicles aspirated during OPU 1 day
Secondary Level of E2 hormone in the blood, the morning of day 5, before the administration of the first GnRH-antagonist 5 days
Secondary Level of P4 hormone in the blood, the morning of day 5, before the administration of the first GnRH-antagonist 5 days
Secondary Level of FSH hormone in the blood, the morning of day 5, before the administration of the first GnRH-antagonist 5 days
Secondary Level of LH hormone in the blood, the morning of day 5, before the administration of the first GnRH-antagonist 5 days
Secondary 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
Secondary Level of P4 hormone in the blood, when there are at least 2 to 3 follicles with a size of 12 to 14 mm 1 day
Secondary Level of FSH hormone in the blood, when there are at least 2 to 3 follicles with a size of 12 to 14 mm 1 day
Secondary Level of LH hormone in the blood, when there are at least 2 to 3 follicles with a size of 12 to 14 mm 1 day
Secondary Level of E2 hormone in the blood, on the morning of the day of final oocyte maturation 1 day
Secondary Level of P4 hormone in the blood, on the morning of the day of final oocyte maturation 1 day
Secondary Level of FSH hormone in the blood, on the morning of the day of final oocyte maturation 1 day
Secondary Level of LH hormone in the blood, on the morning of the day of final oocyte maturation 1 day
Secondary Level of E2 hormone in the blood, on the day of OPU 1 day
Secondary Level of P4 hormone in the blood, on the day of OPU 1 day
Secondary Level of FSH hormone in the blood, on the day of OPU 1 day
Secondary Level of LH hormone in the blood, on the day of OPU 1 day
Secondary Level of E2 hormone in the follicular fluid of one follicle on the morning of day 5, before the administration of the first GnRH-antagonist 5 days
Secondary Level of P4 hormone in the follicular fluid of one follicle on the morning of day 5, before the administration of the first GnRH-antagonist 5 days
Secondary Level of FSH hormone in the follicular fluid of one follicle on the morning of day 5, before the administration of the first GnRH-antagonist 5 days
Secondary Level of LH hormone in the follicular fluid of one follicle on the morning of day 5, before the administration of the first GnRH-antagonist 5 days
Secondary Level of E2 hormone in the follicular fluid of 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 1 day
Secondary Level of P4 hormone in the follicular fluid of 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 1 day
Secondary Level of FSH hormone in the follicular fluid of 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 1 day
Secondary Level of LH hormone in the follicular fluid of 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 1 day
Secondary Level of E2 hormone in the follicular fluid of two follicles (= pre-ovulatory follicle) on the morning of the day of final oocyte maturation 1 day
Secondary Level of P4 hormone in the follicular fluid of two follicles (= pre-ovulatory follicle) on the morning of the day of final oocyte maturation 1 day
Secondary Level of FSH hormone in the follicular fluid of two follicles (= pre-ovulatory follicle) on the morning of the day of final oocyte maturation 1 day
Secondary Level of LH hormone in the follicular fluid of two follicles (= pre-ovulatory follicle) on the morning of the day of final oocyte maturation 1 day
Secondary Level of E2 hormone in the follicular fluid of follicles aspirated during OPU 1 day
Secondary Level of P4 hormone in the follicular fluid of follicles aspirated during OPU 1 day
Secondary Level of FSH hormone in the follicular fluid of follicles aspirated during OPU 1 day
Secondary Level of LH hormone in the follicular fluid of follicles aspirated during OPU 1 day
See also
  Status Clinical Trial Phase
Completed NCT03607409 - Role of Inhibin A as Biomarker for Ovarian Response for IVF Treatment
Recruiting NCT02312076 - GnRHa for Luteal Phase Support in Long GnRHa Protocol Cycles Phase 4
Terminated NCT02161861 - Improvement of IVF Fertilization Rates, by the Cyclic Tripeptide FEE - Prospective Randomized Study N/A
Completed NCT03287479 - Comparison of a Semi-automated Closed Vitrification System (Gavi®) With a Manual Open Vitrification Sytem (Cryotop®) N/A
Terminated NCT03522350 - Randomized Trial Comparing EmbryoScope With EmbryoScope+. N/A
Completed NCT04496284 - Embryo Transfer Outcomes After Vitrification With Slush Nitrogen Compared to Liquid Nitrogen N/A
Completed NCT03623659 - pArtiaL zonA pelluciDa Removal by assisteD hatchINg of Blastocysts N/A
Completed NCT03895099 - New Ovarian Stimulation With Random Start, Use of Progestin Protocol for Oocyte Donors Phase 3
Active, not recruiting NCT04142112 - Randomized, Standard-Controlled, Study to Evaluate the Ohana IVF Sperm Preparation Kit, SPeRtility IVF Next Generation N/A
Completed NCT03152643 - Cumulative Live Birth Rates After Cleavage-stage Versus Blastocyst-stage Embryo Transfer N/A
Recruiting NCT03683771 - Assessment of Endometrial Pattern and Sub-endometrial Vascularity in ICSI Outcome
Recruiting NCT03161119 - Comparing Two Different Embryo Transfer Catheters N/A
Completed NCT04108039 - Micronized Progesterone vs Gonadotropin-releasing Hormone (GnRH) Antagonist in Freeze-all IVF Cycles. N/A
Completed NCT03678571 - Oocyte Vitrification Aided With Latrunculin A N/A
Completed NCT03677492 - Supplementing Intracytoplasmic Sperm Injection Handling Medium With Cytochalasin D ( ICSI-CD) N/A
Completed NCT03678558 - Oocyte Vitrification Aided With Cytochalasin B N/A
Completed NCT03678584 - Supplementing Intracytoplasmic Sperm Injection Handling Medium With Chaetoglobosin A ( ICSI-CA) N/A
Completed NCT03678818 - Supplementing Intracytoplasmic Sperm Injection Handling Medium With Latrunculin A (ICSI-LA) N/A
Completed NCT03678597 - Supplementing Intracytoplasmic Sperm Injection Handling Medium With Latrunculin B ( ICSI-LB) N/A
Completed NCT03678610 - Handling Medium for ICSI With Ionomycin and Latrunculin A N/A