Progestin-Primed Ovarian Stimulation is a Non-inferior Alternative to the GnRH Antagonist Protocol in Patients Undergoing Assisted Reproductive Techniques: a Retrospective Study

Overview

Journal JBRA Assist Reprod

Specialty Reproductive Medicine

Date 2021 Oct 5

PMID 34609115

Citations 1

Authors

Joao Pedro Junqueira Caetano

Luciana Campomizzi Calazans

Leci Veiga Caetano Amorim

Leonardo Matheus Ribeiro Pereira

Erica Becker Sousa Xavier

Ana Luisa Menezes Campos

Bruna Barbosa Coimbra

Ricardo Mello Marinho

Affiliations

Soon will be listed here.

Abstract

Objective: To demonstrate the non-inferiority of Clinical Pregnancy Rates from Progestin-Primed Ovarian Stimulation compared to the GnRH Antagonist Protocol when the freeze-all and blastocyst transfer strategy is applied.

Methods: A retrospective study included all IVF cycles performed at Pró-Criar Reproductive Medicine Center, Belo Horizonte, Minas Gerais, Brazil, between May 2018 and May 2019 using a GnRH antagonist analogue or oral progestins to block the LH peak in IVF/intra-cytoplasmic sperm injection (ICSI) cycles for infertility treatment.

Results: The primary outcome of our study was Clinical Pregnancy Rate at the first ET (Blastocyst), which were 58.4% in the progestin group and 54.9% in the antagonist group (p=0.735), a finding consistent with most studies published to date using different progestins. The mean number of retrieved oocytes was 11 in the antagonist group and 9 oocytes in the progestin group (p=0.009). The fertilization rate was 80% for both groups (p=0.935). The rate of blastocyst formation per cycle was 50% in the antagonist group and 55.6% in the progestin group (p=0.106). The stimulation lasted a mean of 10 days in the two groups (p=0.403) and did not vary with patient age in either group. The gonadotropin dose used was higher in the antagonist group (2025 IU) than in the progestin group (1950 IU) (p=0.057). In addition, the blockade was effective: there was only one case of spontaneous ovulation, which corresponded to less than 1% of the cycles.

Conclusions: Progestin-Primed Ovarian Stimulation is a non-inferior alternative to the GnRH Antagonist Protocol in patients undergoing assisted reproductive techniques. An incidence compatible with the 0.34 to 8% risk described in the literature for failure to control the premature LH surge in antagonist protocol cycles.

Citing Articles

Clomiphene citrate throughout the duration of ovarian stimulation in patients with diminished ovarian reserve: an approach to decrease costs, reduce injection burden, and prevent premature ovulation.

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PMID: 39893355 DOI: 10.1007/s10815-025-03412-w.

Previous Use of Combined Oral Contraception in High Complexity Assisted Reproduction Treatments in Protocol with Oral Progestin - Previous use of COC and ART.

Vidal D, Gentil F, Montagna E, Barbosa C, de Oliveira R JBRA Assist Reprod. 2024; 28(4):639-649.

PMID: 39311653 PMC: 11622397. DOI: 10.5935/1518-0557.20240058.

References

Yu S, Long H, Chang H, Liu Y, Gao H, Zhu J . New application of dydrogesterone as a part of a progestin-primed ovarian stimulation protocol for IVF: a randomized controlled trial including 516 first IVF/ICSI cycles. Hum Reprod. 2018; 33(2):229-237. DOI: 10.1093/humrep/dex367. View

Barnhart K . Introduction: are we ready to eliminate the transfer of fresh embryos in in vitro fertilization?. Fertil Steril. 2014; 102(1):1-2. PMC: 4146486. DOI: 10.1016/j.fertnstert.2014.05.024. View

Begueria R, Garcia D, Vassena R, Rodriguez A . Medroxyprogesterone acetate versus ganirelix in oocyte donation: a randomized controlled trial. Hum Reprod. 2019; 34(5):872-880. DOI: 10.1093/humrep/dez034. View

Shapiro B, Daneshmand S, Garner F, Aguirre M, Hudson C, Thomas S . High ongoing pregnancy rates after deferred transfer through bipronuclear oocyte cryopreservation and post-thaw extended culture. Fertil Steril. 2008; 92(5):1594-9. DOI: 10.1016/j.fertnstert.2008.08.103. View

van Wely M, Westergaard L, Bossuyt P, van der Veen F . Human menopausal gonadotropin versus recombinant follicle stimulation hormone for ovarian stimulation in assisted reproductive cycles. Cochrane Database Syst Rev. 2003; (1):CD003973. DOI: 10.1002/14651858.CD003973. View

Kuang Y, Chen Q, Fu Y, Wang Y, Hong Q, Lyu Q . 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; 104(1):62-70.e3. DOI: 10.1016/j.fertnstert.2015.03.022. View

Roque M . Freeze-all policy: is it time for that?. J Assist Reprod Genet. 2014; 32(2):171-6. PMC: 4354191. DOI: 10.1007/s10815-014-0391-0. View

Massin N . New stimulation regimens: endogenous and exogenous progesterone use to block the LH surge during ovarian stimulation for IVF. Hum Reprod Update. 2017; 23(2):211-220. DOI: 10.1093/humupd/dmw047. View

Reichman D, Zakarin L, Chao K, Meyer L, Davis O, Rosenwaks Z . Diminished ovarian reserve is the predominant risk factor for gonadotropin-releasing hormone antagonist failure resulting in breakthrough luteinizing hormone surges in in vitro fertilization cycles. Fertil Steril. 2014; 102(1):99-102. DOI: 10.1016/j.fertnstert.2014.04.010. View

10.

Cobo A, de Los Santos M, Castello D, Gamiz P, Campos P, Remohi J . Outcomes of vitrified early cleavage-stage and blastocyst-stage embryos in a cryopreservation program: evaluation of 3,150 warming cycles. Fertil Steril. 2012; 98(5):1138-46.e1. DOI: 10.1016/j.fertnstert.2012.07.1107. View

11.

Iwami N, Kawamata M, Ozawa N, Yamamoto T, Watanabe E, Moriwaka O . New trial of progestin-primed ovarian stimulation using dydrogesterone versus a typical GnRH antagonist regimen in assisted reproductive technology. Arch Gynecol Obstet. 2018; 298(3):663-671. DOI: 10.1007/s00404-018-4856-8. View

12.

La Marca A, Capuzzo M . Use of progestins to inhibit spontaneous ovulation during ovarian stimulation: the beginning of a new era?. Reprod Biomed Online. 2019; 39(2):321-331. DOI: 10.1016/j.rbmo.2019.03.212. View

13.

De Geyter C . Assisted reproductive technology: Impact on society and need for surveillance. Best Pract Res Clin Endocrinol Metab. 2019; 33(1):3-8. DOI: 10.1016/j.beem.2019.01.004. View

14.

Wang N, Wang Y, Chen Q, Dong J, Tian H, Fu Y . Luteal-phase ovarian stimulation vs conventional ovarian stimulation in patients with normal ovarian reserve treated for IVF: a large retrospective cohort study. Clin Endocrinol (Oxf). 2015; 84(5):720-8. DOI: 10.1111/cen.12983. View

15.

Wong K, Mastenbroek S, Repping S . Cryopreservation of human embryos and its contribution to in vitro fertilization success rates. Fertil Steril. 2014; 102(1):19-26. DOI: 10.1016/j.fertnstert.2014.05.027. View

16.

Inhorn M, Patrizio P . Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2015; 21(4):411-26. DOI: 10.1093/humupd/dmv016. View

17.

Yu C, Dai X, Wang Y, Gao T, Cao F, Xia X . Progestin-primed ovarian stimulation improves the outcomes of IVF/ICSI cycles in infertile women with diminished ovarian reserve. J Chin Med Assoc. 2019; 82(11):845-848. DOI: 10.1097/JCMA.0000000000000177. View

18.

Albertini D . Phasing in and out of the FREEZE-ALL mentality: was Mother Nature right after all?. J Assist Reprod Genet. 2015; 32(2):169-70. PMC: 4354185. DOI: 10.1007/s10815-015-0448-8. View

19.

Wang Y, Kuang Y, Chen Q, Cai R . Gonadotropin-releasing hormone antagonist versus progestin for the prevention of premature luteinising hormone surges in poor responders undergoing in vitro fertilisation treatment: study protocol for a randomised controlled trial. Trials. 2018; 19(1):455. PMC: 6106816. DOI: 10.1186/s13063-018-2850-x. View

20.

Chen Q, Wang Y, Sun L, Zhang S, Chai W, Hong Q . Controlled ovulation of the dominant follicle using progestin in minimal stimulation in poor responders. Reprod Biol Endocrinol. 2017; 15(1):71. PMC: 5583982. DOI: 10.1186/s12958-017-0291-0. View