Micronized Progesterone vs Gonadotropin-releasing Hormone (GnRH) Antagonist in Freeze-all IVF Cycles.

NCT04108039 | Completed

• 1 other identifier: FSD-PRG-2019-02
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

To examine whether the number of euploid embryos following ovarian stimulation with micronized progesterone is equivalent as compared with the number of embryos after ovarian stimulation with the use of a GnRH antagonist in patients undergoing ovarian stimulation for IVF or intracytoplasmatic sperm injection (ICSI).

Conditions

Infertility; IVF; Preimplantation Diagnosis

Outcome Measures

Primary Outcomes (1)

• Number of euploid embryos as compared between the 2 ovarian stimulation cycles

  Number of euploid embryos between oocytes received from the antagonist GnRh protocol or the micronized progesterone protocol.

  15-45 days following oocyte retrieval procedure

Secondary Outcomes (9)

• Endocrine profile at specific intervals

  Stimulation day 0, day 6, day 8, day of final oocyte maturation and day +1 after oocyte maturation (actual day may vary between 9-15)

• Endocrine profile at specific intervals

  Stimulation day 0, day 6, day 8, day of final oocyte maturation and day +1 after oocyte maturation (actual day may vary between 9-15)

• Endocrine profile at specific intervals

  Stimulation day 0, day 6, day 8, day of final oocyte maturation and day +1 after oocyte maturation (actual day may vary between 9-15)

• Duration of stimulation

  9-20 days from initiation of ovarian stimulation

• Incidence of premature LH rise

  9-20 days from initiation of ovarian stimulation

Study Arms (2)

GnRH antagonist

ACTIVE COMPARATOR

In the antagonist cycle, LH suppression will be accomplished by subcutaneous (SC) injections of 0.25 mg of Cetrorelix or Ganirelix starting in the presence of follicles \>14mm or E2 levels \>400 pg/ml and continuing until ovulation triggering.

Drug: GnRh antagonist

Micronized progesterone

EXPERIMENTAL

In the progesterone cycle, endogenous LH suppression will be accomplished by oral administration of micronized progesterone (200 mg) once a day at bed time, from stimulation day 1 and continuing until ovulation triggering.

Drug: Micronized progesterone

Interventions

GnRh antagonist DRUG

In the antagonist cycle, LH suppression will be accomplished by subcutaneous (SC) injections of 0.25 mg of Cetrorelix or Ganirelix starting in the presence of follicles \>14mm or E2 levels \>400 pg/ml and continuing until ovulation triggering to avoid LH surge in COS

Also known as: Cetrorelix or Ganirelix

GnRH antagonist

Micronized progesterone DRUG

Micronized progesterone protocol to avoid LH surge in COS, from stimulation day 1 and continuing until ovulation triggering.

Also known as: Utrogestan

Micronized progesterone

Eligibility Criteria

• Age: 36 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Infertile patients
• Age 36-40 years old
• BMI 18-30 kg/m2
• Undergoing preimplantation genetic screening cycles
• Planned to undergo at least two treatment cycles, to accumulate embryos to increase the chance of obtaining euploid embryos for transfer
• Willing to participate in the study

You may not qualify if:

• Age\> 41
• Severe male factor requiring TESE (testicular sperm extraction)
• Low ovarian reserve (AMH \< 1.2 ng/ml)
• Administration of any other drug potentially interfering with the treatment.

Sponsors & Collaborators

• Fundacion Dexeus: lead

Study Sites (1)

Institut Universitari Dexeus

Barcelona, Catalonia, 08028, Spain

Location

Related Publications (12)

• Zhang J, Mao X, Wang Y, Chen Q, Lu X, Hong Q, Kuang Y. Neonatal outcomes and congenital malformations in children born after human menopausal gonadotropin and medroxyprogesterone acetate treatment cycles. Arch Gynecol Obstet. 2017 Dec;296(6):1207-1217. doi: 10.1007/s00404-017-4537-z. Epub 2017 Sep 25.

  PMID: 28948397 BACKGROUND

• Zhu X, Ye H, Fu Y. Use of Utrogestan during controlled ovarian hyperstimulation in normally ovulating women undergoing in vitro fertilization or intracytoplasmic sperm injection treatments in combination with a "freeze all" strategy: a randomized controlled dose-finding study of 100 mg versus 200 mg. Fertil Steril. 2017 Feb;107(2):379-386.e4. doi: 10.1016/j.fertnstert.2016.10.030. Epub 2016 Nov 16.

  PMID: 27865446 BACKGROUND

• Zhu X, Zhang X, Fu Y. Utrogestan as an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Medicine (Baltimore). 2015 May;94(21):e909. doi: 10.1097/MD.0000000000000909.

  PMID: 26020402 BACKGROUND

• Lambalk CB, Banga FR, Huirne JA, Toftager M, Pinborg A, Homburg R, van der Veen F, van Wely M. GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type. Hum Reprod Update. 2017 Sep 1;23(5):560-579. doi: 10.1093/humupd/dmx017.

  PMID: 28903472 BACKGROUND

• Verberg MF, Eijkemans MJ, Heijnen EM, Broekmans FJ, de Klerk C, Fauser BC, Macklon NS. Why do couples drop-out from IVF treatment? A prospective cohort study. Hum Reprod. 2008 Sep;23(9):2050-5. doi: 10.1093/humrep/den219. Epub 2008 Jun 10.

  PMID: 18544578 BACKGROUND

• Richter TA, Robinson JE, Lozano JM, Evans NP. Progesterone can block the preovulatory gonadotropin-releasing hormone/luteinising hormone surge in the ewe by a direct inhibitory action on oestradiol-responsive cells within the hypothalamus. J Neuroendocrinol. 2005 Mar;17(3):161-9. doi: 10.1111/j.1365-2826.2005.01287.x.

  PMID: 15796768 BACKGROUND

• Kuang Y, Chen Q, Fu Y, Wang Y, Hong Q, Lyu Q, Ai A, Shoham Z. Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Fertil Steril. 2015 Jul;104(1):62-70.e3. doi: 10.1016/j.fertnstert.2015.03.022. Epub 2015 May 5.

  PMID: 25956370 BACKGROUND

• Griesinger G, Venetis CA, Tarlatzis B, Kolibianakis EM. To pill or not to pill in GnRH-antagonist cycles: the answer is in the data already! Reprod Biomed Online. 2015 Jul;31(1):6-8. doi: 10.1016/j.rbmo.2015.04.001. Epub 2015 Apr 9.

  PMID: 25985996 BACKGROUND

• Devroey P, Polyzos NP, Blockeel C. An OHSS-Free Clinic by segmentation of IVF treatment. Hum Reprod. 2011 Oct;26(10):2593-7. doi: 10.1093/humrep/der251. Epub 2011 Aug 9.

  PMID: 21828116 BACKGROUND

• Cedrin-Durnerin I, Bstandig B, Parneix I, Bied-Damon V, Avril C, Decanter C, Hugues JN. Effects of oral contraceptive, synthetic progestogen or natural estrogen pre-treatments on the hormonal profile and the antral follicle cohort before GnRH antagonist protocol. Hum Reprod. 2007 Jan;22(1):109-16. doi: 10.1093/humrep/del340. Epub 2006 Aug 26.

  PMID: 16936304 BACKGROUND

• Dong J, Wang Y, Chai WR, Hong QQ, Wang NL, Sun LH, Long H, Wang L, Tian H, Lyu QF, Lu XF, Chen QJ, Kuang YP. The pregnancy outcome of progestin-primed ovarian stimulation using 4 versus 10 mg of medroxyprogesterone acetate per day in infertile women undergoing in vitro fertilisation: a randomised controlled trial. BJOG. 2017 Jun;124(7):1048-1055. doi: 10.1111/1471-0528.14622.

  PMID: 28276192 BACKGROUND

• Vidal MDM, Martinez F, Rodriguez I, Polyzos NP. Ovarian response and embryo ploidy following oral micronized progesterone-primed ovarian stimulation versus GnRH antagonist protocol. A prospective study with repeated ovarian stimulation cycles. Hum Reprod. 2024 May 2;39(5):1098-1104. doi: 10.1093/humrep/deae047.

  PMID: 38498835 DERIVED

MeSH Terms

Conditions

Infertility

Interventions

LHRH, Ac-Nal(1)-Cpa(2)-Trp(3)-Arg(6)-Ala(10)-; cetrorelix; ganirelix; Progesterone; Utrogestan

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical and Scientific Director of Dexeus Mujer

Model Details: 44 women undergoing IVF treatments due to infertility, will be asked to participate in a trial in which they will undergo 2 ovarian stimulation protocols with recombinant follicle stimulating hormone (rFSH): the first one using a flexible antagonist protocol to suppress the endogenous LH rise and the second using oral micronized progesterone 200 mg/day from day 1 of stimulation.

Study Record Dates

• First Submitted: September 20, 2019
• First Posted: September 27, 2019
• Study Start: September 25, 2019
• Primary Completion: January 15, 2022
• Study Completion: May 15, 2022
• Last Updated: May 15, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)