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Archives of Gynecology and Obstetrics

, Volume 299, Issue 4, pp 1201–1212 | Cite as

Different progestin-primed ovarian stimulation protocols in infertile women undergoing in vitro fertilization/intracytoplasmic sperm injection: an analysis of 1188 cycles

  • Ying-chun Guo
  • Pan-yu Chen
  • Ting-ting Li
  • Lei Jia
  • Peng Sun
  • Wan-shan Zhu
  • Cun-can Deng
  • Cong FangEmail author
  • Xiao-yan Liang
Gynecologic Endocrinology and Reproductive Medicine
  • 114 Downloads

Abstract

Purpose

To evaluate the efficacy in suppressing the premature LH surge, embryo quality and pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) protocols using medroxyprogesterone acetate versus utrogestan in women of all ages undergoing in vitro fertilization or intracytoplasmic sperm injection.

Methods

1188 patients were enrolled in the retrospective study, of which 1002 patients were treated with medroxyprogesterone acetate (M group) and recombinant follicle-stimulating hormone (r-FSH)simultaneously from day 3 of the cycle until trigger day, while 186 patients were treated with utrogestan (U group) and r-FSH instead. Viable embryos were cryopreserved for later transfer in both groups. Differences in baseline characteristics, ovarian stimulation characteristics, endocrinological characteristics, embryo development and clinical outcome between two groups were assessed. Statistical analyses were performed stratified by age and number of oocytes retrieved.

Results

No significant differences were observed in the baseline characteristics, ovarian stimulation characteristics and clinical outcome of patients between groups. However, blastulation rate in the U group was significantly higher than that in the M group (49.4% vs. 32.9%, P < 0.001). During ovarian stimulation, LH levels remained steady in both groups. Higher percentage of premature LH surge was found in the U group (2.4% vs. 10.2%, P < 0.001), especially for patients aged more than 35 years or who had three oocytes or less retrieved.

Conclusions

Both the administration of medroxyprogesterone acetate and utrogestan in PPOS were sufficient to prevent an untimely LH rise, while for patients with poor ovarian response or aged above 35 years, MPA may result in a more satisfactory LH level. PPOS protocol using medroxyprogesterone acetate or utrogestan was comparable in terms of oocytes and pregnancy outcome, whereas the administration of utrogestan may result in an improved blastulation than medroxyprogesterone acetate, which needs further exploration.

Keywords

Progestin-primed ovarian stimulation (PPOS) Medroxyprogesterone acetate (MPA) Utrogestan Embryo quality Luteinizing hormone surge 

Notes

Author contribution

YG: project development, data collection, data analysis, manuscript writing. PC: project development, data analysis, manuscript writing. TL: project development, data analysis, manuscript writing. LJ: project development, data analysis, manuscript writing. PS: project development, data analysis, manuscript writing. WZ: data collection, data analysis. CD:data collection, data analysis. CF: project development, manuscript writing tutor. XL: project development.

Funding

This study was supported by the National Natural Science Foundation of China (Grant number 81871214) and National Key R&D Program of China (Grant number 2017YFC1001603).

Compliance with ethical standards

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Ethical approval

This study was approved by the Institutional Reviewer Board of Sixth Affiliated Hospital of Sun Yat-sen University.

Research involving human participants and/or animals

For this type of study formal consent is not required. This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Because of the retrospective nature of the study the requirement of informed patient consent was waived.

References

  1. 1.
    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 (2017) 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 124(7):1048–1055CrossRefGoogle Scholar
  2. 2.
    Evans NP, Richter TA, Skinner DC, Robinson JE (2002) Neuroendocrine mechanisms underlying the effects of progesterone on the oestradiol-induced GnRH/LH surge. Reprod Suppl 59:57–66Google Scholar
  3. 3.
    Fang C, Huang R, Li TT, Jia L, Li LL, Liang XY (2013) Day-2 and day-3 sequential transfer improves pregnancy rate in patients with repeated IVF-embryo transfer failure: a retrospective case-control study. Reprod Biomed Online 26(1):30–35CrossRefGoogle Scholar
  4. 4.
    Fang C, Huang R, Wei LN, Jia L (2015) Frozen-thawed day 5 blastocyst transfer is associated with a lower risk of ectopic pregnancy than day 3 transfer and fresh transfer. Fertil Steril 103(3):655–661CrossRefGoogle Scholar
  5. 5.
    Harris TG, Dye S, Robinson JE, Skinner DC, Evans NP (1999) Progesterone can block transmission of the estradiol-induced signal for luteinizing hormone surge generation during a specific period of time immediately after activation of the gonadotropin-releasing hormone surge-generating system. Endocrinology 140(2):827–834CrossRefGoogle Scholar
  6. 6.
    Letterie GS (2000) Inhibition of gonadotropin surge by a brief mid-cycle regimen of ethinyl estradiol and norethindrone: possible role in in vitro fertilization. Gynecol Endocrinol 14(1):1–4CrossRefGoogle Scholar
  7. 7.
    Liu JH, Yen SS (1983) Induction of midcycle gonadotropin surge by ovarian steroids in women: a critical evaluation. J Clin Endocrinol Metab 57(4):797–802CrossRefGoogle Scholar
  8. 8.
    Massin N (2017) New stimulation regimens: endogenous and exogenous progesterone use to block the LH surge during ovarian stimulation for IVF. Hum Reprod Update 23(2):211–220Google Scholar
  9. 9.
    Racowsky C, Combelles CM, Nureddin A, Pan Y, Finn A, Miles L, Gale S, O’Leary T, Jackson KV (2003) Day 3 and day 5 morphological predictors of embryo viability. Reprod Biomed Online 6(3):323–331CrossRefGoogle Scholar
  10. 10.
    Richter TA, Robinson JE, Evans NP (2001) Progesterone treatment that either blocks or augments the estradiol-induced gonadotropin-releasing hormone surge is associated with different patterns of hypothalamic neural activation. Neuroendocrinology 73(6):378–386CrossRefGoogle Scholar
  11. 11.
    Richter TA, Robinson JE, Lozano JM, Evans NP (2005) 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 17(3):161–169CrossRefGoogle Scholar
  12. 12.
    Sakkas D, Gardner DK (2005) Noninvasive methods to assess embryo quality. Curr Opin Obstet Gynecol 17(3):283–288CrossRefGoogle Scholar
  13. 13.
    Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH (2003) Classification and pharmacology of progestins. Maturitas 46(Suppl 1):S7–S16CrossRefGoogle Scholar
  14. 14.
    Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH (2008) Classification and pharmacology of progestins. Maturitas 61(1–2):171–180CrossRefGoogle Scholar
  15. 15.
    Soules MR, Steiner RA, Clifton DK, Cohen NL, Aksel S, Bremner WJ (1984) Progesterone modulation of pulsatile luteinizing hormone secretion in normal women. J Clin Endocrinol Metab 58(2):378–383CrossRefGoogle Scholar
  16. 16.
    Zhu X, Ye H, Fu Y (2016) The Utrogestan and hMG protocol in patients with polycystic ovarian syndrome undergoing controlled ovarian hyperstimulation during IVF/ICSI treatments. Medicine (Baltimore) 95(28):e4193CrossRefGoogle Scholar
  17. 17.
    Zhu X, Ye H, Fu Y (2017) 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 107(2):379–386CrossRefGoogle Scholar
  18. 18.
    Zhu X, Zhang X, Fu Y (2015) Utrogestan as an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Medicine (Baltimore) 94(21):e909CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Reproductive Medicine Research CenterSixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina
  2. 2.Reproductive Medicine Research Center, Family Planning Special Hospital of GuangdongGuangzhouChina

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