Step Down FSH Approach and Late Follicular Phase in Progesterone Level

NCT ID: NCT03356964

Last Updated: 2020-09-09

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

EARLY_PHASE1

Total Enrollment

127 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-23

Study Completion Date

2020-08-31

Brief Summary

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Step-down approach and late follicular phase progesterone level

Detailed Description

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The study will be performed using the stimulation medication Gonal-F which is a recombinant FSH-preparation. Due to application as pen-device, it allows reduction of the stimulation dosage in steps of 12.5IU.

It is important to evaluate the dynamics of progesterone-rise after final oocyte maturation, as this dynamic might also have an influence on the receptivity of the endometrium.

Conditions

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Progesterone Resistance

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Control group

Follicle stimulating Hormone will be applied, starting from day 3 of the cycle, the dosage will be choosen between Gonal F 150 - 225 IU, according to the ovarian reserve parameters (13). The stimulation dosage will remain unchanged until the criteria for final oocyte maturation are met (≥ 3 follicles of ≥ 17 mm).

Group Type ACTIVE_COMPARATOR

follicle stimulating hormone

Intervention Type DRUG

Follicle stimulating hormone( will be chosen according to ovarian reserve parameters in the study group the dosage will be reduced in the control group it will remain unchanged

Study group

Follicle stimulating Hormone will be applied, starting from day 3 of the cycle, the dosage will be choosen between Gonal F 150 - 225 IU, according to the ovarian reserve parameters (LaMarca et al.). As soon as ≥ 3 follicle of a size of 14mm are seen, the stimulation dosage will be reduced daily by 12.5 IU recFSH until the criteria for final oocyte maturation are met (≥ 3 follicles of ≥ 17 mm).

Group Type EXPERIMENTAL

follicle stimulating hormone

Intervention Type DRUG

Follicle stimulating hormone( will be chosen according to ovarian reserve parameters in the study group the dosage will be reduced in the control group it will remain unchanged

Interventions

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follicle stimulating hormone

Follicle stimulating hormone( will be chosen according to ovarian reserve parameters in the study group the dosage will be reduced in the control group it will remain unchanged

Intervention Type DRUG

Other Intervention Names

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Gonal-F

Eligibility Criteria

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Inclusion Criteria

* Primary / secondary infertility with the indication for IVF/ICSI
* Patients age 18 - 40 years
* 60 kg up to and including 90 kg
* BMI of 18-32 kg/m2
* Menstrual cycle length of 24-35 days

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this study:


* presence or history of an endocrine abnormality
* abnormal outcome of blood biochemistry or hematology
* relevant ovarian-, tubal- or uterine-pathology that could interfere with the ovarian stimulation treatment
* history of ovarian hyper-response (more than 30 follicles ≥ 11 mm) or ovarian hyper-stimulation syndrome (OHSS), polycystic ovary syndrome (PCOS)
* History of poor ovarian response, according to the Rotterdam-criteria (Ferrarretti et al.)
* ovarian reserve parameter, indicating the risk of poor ovarian response (AFC \< 5 and AMH \< 0,5ng/ml) (14)
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Merck Serono International SA

INDUSTRY

Sponsor Role collaborator

ART Fertility Clinics LLC

OTHER

Sponsor Role lead

Responsible Party

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Prof Dr. Human Fatemi

Professor Doctor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Human Fatemi

Role: PRINCIPAL_INVESTIGATOR

ART Fertility Clinics LLC

Locations

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IVI Middle East Fertilty Clinic

Abu Dhabi, , United Arab Emirates

Site Status

Countries

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United Arab Emirates

References

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Bourgain C, Ubaldi F, Tavaniotou A, Smitz J, Van Steirteghem AC, Devroey P. Endometrial hormone receptors and proliferation index in the periovulatory phase of stimulated embryo transfer cycles in comparison with natural cycles and relation to clinical pregnancy outcome. Fertil Steril. 2002 Aug;78(2):237-44. doi: 10.1016/s0015-0282(02)03228-4.

Reference Type BACKGROUND
PMID: 12137857 (View on PubMed)

Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19.

Reference Type BACKGROUND
PMID: 21505041 (View on PubMed)

Filicori M, Cognigni GE, Pocognoli P, Tabarelli C, Spettoli D, Taraborrelli S, Ciampaglia W. Modulation of folliculogenesis and steroidogenesis in women by graded menotrophin administration. Hum Reprod. 2002 Aug;17(8):2009-15. doi: 10.1093/humrep/17.8.2009.

Reference Type BACKGROUND
PMID: 12151429 (View on PubMed)

Givens CR, Schriock ED, Dandekar PV, Martin MC. Elevated serum progesterone levels on the day of human chorionic gonadotropin administration do not predict outcome in assisted reproduction cycles. Fertil Steril. 1994 Nov;62(5):1011-7. doi: 10.1016/s0015-0282(16)57066-6.

Reference Type BACKGROUND
PMID: 7926111 (View on PubMed)

Griesinger G, Mannaerts B, Andersen CY, Witjes H, Kolibianakis EM, Gordon K. Progesterone elevation does not compromise pregnancy rates in high responders: a pooled analysis of in vitro fertilization patients treated with recombinant follicle-stimulating hormone/gonadotropin-releasing hormone antagonist in six trials. Fertil Steril. 2013 Dec;100(6):1622-8.e1-3. doi: 10.1016/j.fertnstert.2013.08.045. Epub 2013 Sep 29.

Reference Type BACKGROUND
PMID: 24083873 (View on PubMed)

Kyrou D, Al-Azemi M, Papanikolaou EG, Donoso P, Tziomalos K, Devroey P, Fatemi HM. The relationship of premature progesterone rise with serum estradiol levels and number of follicles in GnRH antagonist/recombinant FSH-stimulated cycles. Eur J Obstet Gynecol Reprod Biol. 2012 Jun;162(2):165-8. doi: 10.1016/j.ejogrb.2012.02.025. Epub 2012 Mar 17.

Reference Type BACKGROUND
PMID: 22425288 (View on PubMed)

La Marca A, Sunkara SK. Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: from theory to practice. Hum Reprod Update. 2014 Jan-Feb;20(1):124-40. doi: 10.1093/humupd/dmt037. Epub 2013 Sep 29.

Reference Type BACKGROUND
PMID: 24077980 (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)

Schoolcraft W, Sinton E, Schlenker T, Huynh D, Hamilton F, Meldrum DR. Lower pregnancy rate with premature luteinization during pituitary suppression with leuprolide acetate. Fertil Steril. 1991 Mar;55(3):563-6.

Reference Type BACKGROUND
PMID: 1900481 (View on PubMed)

Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Embryo cryopreservation rescues cycles with premature luteinization. Fertil Steril. 2010 Feb;93(2):636-41. doi: 10.1016/j.fertnstert.2009.01.134. Epub 2009 Mar 17.

Reference Type BACKGROUND
PMID: 19296941 (View on PubMed)

Ubaldi F, Smitz J, Wisanto A, Joris H, Schiettecatte J, Derde MP, Borkham E, Van Steirteghem A, Devroey P. Oocyte and embryo quality as well as pregnancy rate in intracytoplasmic sperm injection are not affected by high follicular phase serum progesterone. Hum Reprod. 1995 Dec;10(12):3091-6. doi: 10.1093/oxfordjournals.humrep.a135864.

Reference Type BACKGROUND
PMID: 8822420 (View on PubMed)

Venetis CA, Kolibianakis EM, Papanikolaou E, Bontis J, Devroey P, Tarlatzis BC. Is progesterone elevation on the day of human chorionic gonadotrophin administration associated with the probability of pregnancy in in vitro fertilization? A systematic review and meta-analysis. Hum Reprod Update. 2007 Jul-Aug;13(4):343-55. doi: 10.1093/humupd/dmm007. Epub 2007 Apr 3.

Reference Type BACKGROUND
PMID: 17405832 (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)

Yding Andersen C, Bungum L, Nyboe Andersen A, Humaidan P. Preovulatory progesterone concentration associates significantly to follicle number and LH concentration but not to pregnancy rate. Reprod Biomed Online. 2011 Aug;23(2):187-95. doi: 10.1016/j.rbmo.2011.04.003. Epub 2011 Apr 28.

Reference Type BACKGROUND
PMID: 21665546 (View on PubMed)

Lawrenz B, Coughlan C, Melado L, Digma S, Sibal J, Jean A, Fatemi HM. Step-Down of FSH- Dosage During Ovarian Stimulation - Basic Lessons to Be Learnt From a Randomized Controlled Trial. Front Endocrinol (Lausanne). 2021 Apr 13;12:661707. doi: 10.3389/fendo.2021.661707. eCollection 2021.

Reference Type DERIVED
PMID: 33927696 (View on PubMed)

Other Identifiers

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1612-ABU-084-HF

Identifier Type: -

Identifier Source: org_study_id

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