Step Down FSH Approach and Late Follicular Phase in Progesterone Level

NCT03356964 | Completed Early Phase 1

• 1 other identifier: 1612-ABU-084-HF
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 1

Brief Summary

Step-down approach and late follicular phase progesterone level

Conditions

Progesterone Resistance

Keywords

endometrial receptivity progesterone elevation

Outcome Measures

Primary Outcomes (1)

• Impact of dose reduction in recFSH for IVF on the progesterone level.

  Whether higher progesterone levels on the day of trigger will lead to rapid rise of progesterone after ovulation induction compared to lower progesterone levels.

  1year and 6 months

Study Arms (2)

Control group

ACTIVE COMPARATOR

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).

Drug: follicle stimulating hormone

Study group

EXPERIMENTAL

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).

Drug: follicle stimulating hormone

Interventions

follicle stimulating hormone 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

Also known as: Gonal-F

Control group; Study group

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Female population who will undergo IVF treatment
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• ART Fertility Clinics LLC: lead
• Merck Serono International SA: collaborator

Study Sites (1)

IVI Middle East Fertilty Clinic

Abu Dhabi, United Arab Emirates

Location

Related Publications (15)

• 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.

  PMID: 12137857 BACKGROUND

• 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.

  PMID: 21505041 BACKGROUND

• 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.

  PMID: 12151429 BACKGROUND

• 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.

  PMID: 7926111 BACKGROUND

• 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.

  PMID: 24083873 BACKGROUND

• 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.

  PMID: 22425288 BACKGROUND

• 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.

  PMID: 24077980 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

• 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.

  PMID: 1900481 BACKGROUND

• 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.

  PMID: 19296941 BACKGROUND

• 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.

  PMID: 8822420 BACKGROUND

• 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.

  PMID: 17405832 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

• 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.

  PMID: 21665546 BACKGROUND

• 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.

  PMID: 33927696 DERIVED

MeSH Terms

Conditions

Progesterone Resistance

Interventions

Follicle Stimulating Hormone; follitropin alfa

Intervention Hierarchy (Ancestors)

Gonadotropins, Pituitary; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Human Fatemi

  ART Fertility Clinics LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Doctor

Study Record Dates

• First Submitted: November 14, 2017
• First Posted: November 29, 2017
• Study Start: November 23, 2017
• Primary Completion: February 12, 2020
• Study Completion: August 31, 2020
• Last Updated: September 9, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

AE (1)