Top

Reproductive Biology and Endocrinology

Published in:

Open Access 01-12-2018 | Research

An extremely patient-friendly and efficient stimulation protocol for assisted reproductive technology in normal and high responders

Authors: Chen-Yu Huang, Guan-Yeu Chen, Miawh-Lirng Shieh, Hsin-Yang Li

Published in: Reproductive Biology and Endocrinology | Issue 1/2018

Abstract

Background

The use of oral progestin has been shown to effectively prevent luteining hormone (LH) surge during ovarian stimulation with daily human menopausal gonadotropin injections. This study was aimed to investigate the efficacy of long-acting follicle stimulating hormone (long-acting FSH; corifollitropin alfa, Elonva®) use in progestin-primed ovarian stimulation for normal and high responders undergoing IVF/ICSI.

Methods

This is a retrospective and proof-of-concept study. We developed an extremely patient-friendly protocol to be applied to forty-five normal or high responders, in which a single injection of corifollitropin alfa (Elonva®) was administered and medroxyprogesterone acetate (MPA) was taken orally every day from the day after Elonva injection to the day of trigger. Seven days after Elonva injection, folliculometry and hormone tests were performed, followed by short-acting daily FSH/LH injections, if needed, until the day before trigger. Duration of stimulation, number of injections and visits before trigger, incidence of premature LH surge, the number of oocytes retrieved, fertilization rate, cleavage rate, the rate of day 2 good embryos available, and cumulative ongoing pregnancy rate per retrieval were assessed.

Results

The average age of the population was 34.7 years. Duration of stimulation was 9.4 days in average. Before trigger, only 3.6 injection shots and 1.4 visits were needed on average. There was no case of premature LH surge. Number of oocytes retrieved was 13.7, fertilization rate was 79.04%, cleavage rate was 91.11%, and day 2 good embryo rate was 64.34%, in average respectively. There was no case of ovarian hyperstimulation syndrome. The cumulative ongoing pregnancy rate per oocyte retrieval achieved a satisfactory level as 53.1%.

Conclusions

Our protocol consisting of long-acting FSH injection and oral MPA preventing LH surge reduces the number of injections and visits to an extreme and achieves a satisfactory reproductive outcome, and, therefore, is a really patient-friendly and effective approach to ovarian stimulation.

Maheshwari A, Gibreel A, Siristatidis CS, Bhattacharya S. Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction. Cochrane Database Syst Rev. 2011; https://doi.org/10.1002/14651858.CD006919.pub3.

Al-Inany HG, Youssef MA, Ayeleke RO, Brown J, Lam WS, Broekmans FJ. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2016; https://doi.org/10.1002/14651858.CD001750.pub4.

von Wolff M, Thaler CJ, Frambach T, Zeeb C, Lawrenz B, Popovici RM, Strowitzki T. Ovarian stimulation to cryopreserve fertilized oocytes in cancer patients can be started in the luteal phase. Fertil Steril. 2009;92(4):1360–5. https://doi.org/10.1016/j.fertnstert.2008.08.011.CrossRefPubMed

Wang N, Wang Y, Chen Q, Dong J, Tian H, Fu Y, Ai A, Lyu Q, Kuang 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. 2016;84(5):720–8. https://doi.org/10.1111/cen.12983.CrossRef

Boots CE, Meister M, Cooper AR, Hardi A, Jungheim ES. Ovarian stimulation in the luteal phase: systematic review and meta-analysis. J Assist Reprod Genet. 2016;33(8):971–80. https://doi.org/10.1007/s10815-016-0721-5.CrossRefPubMedPubMedCentral

Kuang Y, Chen Q, Hong Q, Lyu Q, Fu Y, Ai A, Shoham Z. Luteal-phase ovarian stimulation case report: three-year follow-up of a twin birth. J IVF Reprod Med Genet. 2013;1:106. https://doi.org/10.4172/2375-4508.1000106.CrossRef

Kuang Y, Hong Q, Chen Q, Lyu Q, Ai A, Fu Y, Shoham Z. Luteal-phase ovarian stimulation is feasible for producing competent oocytes in women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, with optimal pregnancy outcomes in frozen-thawed embryo transfer cycles. Fertil Steril. 2014;101(1):105–11. https://doi.org/10.1016/j.fertnstert.2013.09.007.CrossRefPubMed

Chen H, Wang Y, Lyu Q, Ai A, Fu Y, Tian H, Cai R, Hong Q, Chen Q, Shoham Z, Kuang Y. Comparison of live-birth defects after luteal-phase ovarian stimulation vs. conventional ovarian stimulation for in vitro fertilization and vitrified embryo transfer cycles. Fertil Steril. 2015;103(5):1194–1201.e2. https://doi.org/10.1016/j.fertnstert.2015.02.020.CrossRefPubMed

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;104(1):62–70.e3. https://doi.org/10.1016/j.fertnstert.2015.03.022.CrossRefPubMed

10.

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;94(21):e909. https://doi.org/10.1097/MD.0000000000000909.CrossRef

11.

Fares FA, Suganuma N, Nishimori K, LaPolt PS, Hsueh AJ, Boime I. Design of a long-acting follitropin agonist by fusing the C-terminal sequence of the chorionic gonadotropin beta subunit to the follitropin beta subunit. Proc Natl Acad Sci U S A. 1992;89(10):4304–8.CrossRefPubMedPubMedCentral

12.

Pouwer AW, Farquhar C, Kremer JA. Long-acting FSH versus daily FSH for women undergoing assisted reproduction. Cochrane Database Syst Rev. 2015; https://doi.org/10.1002/14651858.CD009577.pub3.

13.

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):211–20. https://doi.org/10.1093/humupd/dmw047.PubMed

14.

de Greef R, Zandvliet A, de Haan AF, Ijzerman-Boon PC, Marintcheva-Petrova M, Mannaerts BM. Dose selection of corifollitropin alfa by modeling and simulation in controlled ovarian stimulation. Clin Pharmacol Ther. 2010;88(1):79–87. https://doi.org/10.1038/clpt.2010.54.CrossRefPubMed

15.

Veeck LL. An atlas of human gametes and conceptuses. New York: Parthenon; 1998. p. 40–5.

16.

Soules MR, Steiner RA, Clifton DK, Cohen NL, Aksel S, Bremner WJ. Progestin modulation of pulsatile luteinizing hormone secretion in normal women. J Clin Endocrinol Metab. 1984;58(2):378–83. https://doi.org/10.1210/jcem-58-2-378.CrossRefPubMed

17.

Wildt L, Hutchison JS, Marshall G, Pohl CR, Knobil E. On the site of action of progesterone in the blockade of the estradiol-induced gonadotropin discharge in the rhesus monkey. Endocrinology. 1981;109(4):1293–4. https://doi.org/10.1210/endo-109-4-1293.CrossRefPubMed

18.

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;17(3):161–9. https://doi.org/10.1111/j.1365-2826.2005.01287.x.CrossRefPubMed

19.

Blockeel C, Drakopoulos P, Santos-Ribeiro S, Polyzos NP, Tournaye H. A fresh look at the freeze-all protocol: a SWOT analysis. Hum Reprod. 2016;31(3):491–7. https://doi.org/10.1093/humrep/dev339.CrossRefPubMed

20.

Messinis IE, Vanakara P, Zavos A, Verikouki C, Georgoulias P, Dafopoulos K. Failure of the GnRH antagonist ganirelix to block the positive feedback effect of exogenous estrogen in normal women. Fertil Steril. 2010;94(4):1554–6. https://doi.org/10.1016/j.fertnstert.2009.12.055.CrossRefPubMed

21.

Reichman DE, Zakarin L, Chao K, Meyer L, Davis OK, Rosenwarks 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. https://doi.org/10.1016/j.fertnstert.2014.04.010.CrossRefPubMed

22.

Messinis IE, Loutradis D, Domali E, Kotsovassilis CP, Papastergiopoulou L, Kallitsaris A, Drakakis P, Dafopoulos K, Milingos S. Alternate day and daily administration of GnRH antagonist may prevent premature luteinization to a similar extent during FSH treatment. Hum Reprod. 2005;20(11):3192–7. https://doi.org/10.1093/humrep/dei210.CrossRefPubMed

23.

Wang Y, Chen Q, Wang N, Chen H, Lyu Q, Kuang Y. Controlled ovarian stimulation using Medroxyprogesterone acetate and hMG in patients with polycystic ovary syndrome treated for IVF: a double-blind randomized crossover clinical trial. Medicine (Baltimore). 2016;95(9):e2939. https://doi.org/10.1097/MD.0000000000002939.CrossRef

24.

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;124(7):1048–55. https://doi.org/10.1111/1471-0528.14622.CrossRefPubMed

25.

Chen Q, Wang Y, Sun L, Zhang S, Chai W, Hong Q, Long H, Wang L, Lyu Q, Kuang Y. Controlled ovulation of the dominant follicle using progestin in minimal stimulation in poor responders. Reprod Biol Endocrinol. 2017;15(1):71. https://doi.org/10.1186/s12958-017-0291-0.CrossRefPubMedPubMedCentral

26.

Fauser BC, Mannaerts BM, Devroey P, Leader A, Boime I, Baird DT. Advances in recombinant DNA technology: corifollitropin alfa, a hybrid molecule with sustained follicle-stimulating activity and reduced injection frequency. Hum Reprod Update. 2009;15(3):309–21. https://doi.org/10.1093/humupd/dmn065.CrossRefPubMed

27.

Hill MJ, Levens ED, Levy G, Ryan ME, Csokmay JM, DeCherney AH, Whitcomb BW. The use of recombinant luteinizing hormone in patients undergoing assisted reproductive techniques with advanced reproductive age: a systematic review and meta-analysis. Fertil Steril. 2012;97(5):1108–14.e1. https://doi.org/10.1016/j.fertnstert.2012.01.130.CrossRefPubMed

28.

Xiong Y, Bu Z, Dai W, Zhang M, Bao X, Sun Y. Recombinant luteinizing hormone supplementation in women undergoing in vitro fertilization/ intracytoplasmic sperm injection with gonadotropin releasing hormone antagonist protocol: a systematic review and meta-analysis. Reprod Biol Endocrinol. 2014;12:109. https://doi.org/10.1186/1477-7827-12-109.CrossRefPubMedPubMedCentral

29.

Mochtar MH, Danhof NA, Ayeleke RO, Van der Veen F, van Wely M. Recombinant luteinizing hormone (rLH) and recombinant follicle stimulating hormone (rFSH) for ovarian stimulation in IVF/ICSI cycles. Cochrane Database Syst Rev. 2017; https://doi.org/10.1002/14651858.CD005070.pub3.

30.

Buendgen NK, Schultze-Mosgau A, Cordes T, Diedrich K, Griesinger G. Initiation of ovarian stimulation independent of the menstrual cycle: a case-control study. Arch Gynecol Obstet. 2013;288(4):901–4. https://doi.org/10.1007/s00404-013-2794-z.CrossRefPubMed

31.

Martínez F, Clua E, Devesa M, Rodríguez I, Arroyo G, González C, Solé M, Tur R, Coroleu B, Barri PN. Comparison of starting ovarian stimulation on day 2 versus day 15 of the menstrual cycle in the same oocyte donor and pregnancy rates among the corresponding recipients of vitrified oocytes. Fertil Steril. 2014;102(5):1307–11. https://doi.org/10.1016/j.fertnstert.2014.07.741.CrossRefPubMed

32.

Wikström A, Green B, Johansson ED. The plasma concentration of medroxyprogesterone acetate and ovarian function during treatment with medroxyprogesterone acetate in 5 and 10 mg doses. Acta Obstet Gynecol Scand. 1984;63(2):163–8.CrossRefPubMed

33.

Albuquerque LET, Tso LO, Saconato H, Albuquerque MCRM, Macedo CR. Depot versus daily administration of gonadotrophin-releasing hormone agonist protocols for pituitary down regulation in assisted reproduction cycles. Cochrane Database Syst Rev. 2013; https://doi.org/10.1002/14651858.CD002808.pub3.

34.

Duan L, Bao S, Li K, Teng X, Hong L, Zhao X. Comparing the long-acting and short-acting forms of gonadotropin-releasing hormone agonists in the long protocol of IVF/ICSI cycles: a retrospective study. J Obstet Gynaecol Res. 2017;43(6):1037–42. https://doi.org/10.1111/jog.13305.CrossRefPubMed

35.

Wang HL, Lai HH, Chuang TH, Shih YW, Huang SC, Lee MJ, Chen SU. A patient friendly Corifollitropin alfa protocol without routine pituitary suppression in normal responders. PLoS One. 2016;11(4):e0154123. https://doi.org/10.1371/journal.pone.0154123.CrossRefPubMedPubMedCentral

36.

Eibschitz I, Belaish-Allart J, Frydman R. In vitro fertilization management and the results in stimulated cycles with spontaneous luteinizing hormone discharge. Fertil Steril. 1986;45(2):231–6.CrossRefPubMed

Title: An extremely patient-friendly and efficient stimulation protocol for assisted reproductive technology in normal and high responders
Authors: Chen-Yu Huang
Guan-Yeu Chen
Miawh-Lirng Shieh
Hsin-Yang Li
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Reproductive Biology and Endocrinology / Issue 1/2018
Electronic ISSN: 1477-7827
DOI: https://doi.org/10.1186/s12958-018-0335-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

An extremely patient-friendly and efficient stimulation protocol for assisted reproductive technology in normal and high responders

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2018

Lifestyle and fertility: the influence of stress and quality of life on female fertility

Three-dimensional evaluation of murine ovarian follicles using a modified CUBIC tissue clearing method

The enigmatic seminal plasma: a proteomics insight from ejaculation to fertilization

Type 2 diabetes increases oocyte mtDNA mutations which are eliminated in the offspring by bottleneck effect

In vivo antral follicle wall biopsy: a new research technique to study ovarian function at the cellular and molecular levels

Rosiglitazone ameliorates palmitic acid-induced cytotoxicity in TM4 Sertoli cells