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

NCT ID: NCT04108039

Last Updated: 2023-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-25
• Study Completion Date: 2022-05-15

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).

Detailed Description

The pre-ovulatory surges of GnRH and LH are activated by increased concentrations of circulating estradiol, but ovulation is blocked when progesterone concentrations are elevated, due to a central inhibition of the GnRH surge. Although traditionally GnRH has been traditionally considered the drug of choice to control endogenous LH in controlled ovarian stimulation (COS) cycles, recently, micronized progesterone has been shown to be an effective oral alternative for preventing premature LH surges during COS in women undergoing IVF/ICSI treatments, with excellent results, whereas their safety during pregnancy is well-established. This novel protocol, has several advantages (good tolerance, user convenience, and cost reduction), that are very attractive when it comes to establishing a convenient user regimen in combination with a ''freeze all'' strategy. However, the comparative efficacy of this novel protocol with the more universal use of GnRH-antagonist protocol for the treatment of IVF patients in terms of embryo ploidy has never been evaluated up to date. The current study aims, for the first time, 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/ICSI.

If efficacy would prove to be similar, with no impact on the chromosomal constitution of embryos, there will be obvious advantages for the preferential use of micronized progesterone over the antagonist protocol: oral administration is preferred over subcutaneous injection, and total cost of medication would be lower. This would be particularly interesting for the future in all "freeze all" protocols such as women undergoing ovarian stimulation for fertility preservation, preimplantation genetic screening and oocyte donation programs.

Conditions

Infertility; IVF; Preimplantation Diagnosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GnRH antagonist

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.

Group Type: ACTIVE_COMPARATOR

GnRh antagonist

Intervention Type: 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

Micronized progesterone

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.

Group Type: EXPERIMENTAL

Micronized progesterone

Intervention Type: DRUG

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

Interventions

GnRh antagonist

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

Intervention Type: DRUG

Micronized progesterone

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

Intervention Type: DRUG

Other Intervention Names

Cetrorelix or Ganirelix; Utrogestan

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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.

• Minimum Eligible Age: 36 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Fundacion Dexeus

OTHER

Sponsor Role: lead

Responsible Party

Nikolaos Polyzos

Clinical and Scientific Director of Dexeus Mujer

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Institut Universitari Dexeus

Barcelona, Catalonia, Spain

Countries

Spain

References

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.

Reference Type: BACKGROUND

PMID: 28948397 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27865446 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26020402 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28903472 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18544578 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15796768 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25956370 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25985996 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21828116 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16936304 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28276192 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38498835 (View on PubMed)

Other Identifiers

FSD-PRG-2019-02

Identifier Type: -

Identifier Source: org_study_id