Advertisement

Progestins versus GnRH analogues for pituitary suppression during ovarian stimulation for assisted reproductive technology: a systematic review and meta-analysis

Published:February 05, 2020DOI:https://doi.org/10.1016/j.rbmo.2020.01.027

      Abstract

      This systematic review and meta-analysis of comparative studies investigated whether progestins are as effective as gonadotrophin releasing hormone (GnRH) analogues for pituitary suppression in assisted reproduction. The primary outcome was live birth rate per woman. Secondary outcomes were live birth or ongoing pregnancy per woman and per embryo transfer, ongoing pregnancy, clinical pregnancy, numbers of oocytes and metaphase-two oocytes, duration of stimulation and gonadotrophin consumption. Adverse events included miscarriage, ectopic pregnancy and multiple pregnancy rates. The GRADE system was used to assess the quality of evidence. Seven studies involving a total of 2047 women were included. Three studies compared a progestin with a GnRH antagonist and four studies compared a progestin with a GnRH agonist. Most studies are non-randomized and report outcomes per embryo transfer, rather than per woman. Although progestins were similar to GnRH antagonists in effectiveness and safety parameters, they were associated with significantly higher live birth or ongoing pregnancy per embryo transfer compared with the short GnRH agonist protocol (RR 1.49, 95% CI 1.16 to 1.91). Progestin primed stimulation lasted significantly longer (mean difference 0.61 days, 95% CI 0.33 to 0.89) and required significantly more gonadotrophins (mean difference 433.2 IU, 95% CI 311.11 to 555.19) than the short GnRH agonist protocol, but the differences were clinically negligible. Safety parameters were similar between progestins and GnRH agonists. In conclusion, progestins can effectively prevent premature ovulation in assisted reproductive technology cycles. If larger and well-designed studies confirm these findings, progestins may be an effective and low-cost alternative to GnRH analogues when a fresh embryo transfer is not planned owing to a medical indication.

      KEYWORDS

      To read this article in full you will need to make a payment

      References

        • Al-Inany H.G.
        • Youssef M.A.
        • Ayeleke R.O.
        • Brown J.
        • Lam W.S.
        • Broekmans F.J.
        Gonadotrophin-releasing hormone antagonists for assisted reproductive technology.
        Cochrane Database Syst. Rev. 2016; 4CD001750
        • Ata B.
        • Seli E.
        A universal freeze all strategy: why it is not warranted.
        Curr. Opin. Obstet. Gynecol. 2017; 29: 136-145
        • Begueria R.
        • Garcia D.
        • Vassena R.
        • Rodriguez A.
        Medroxyprogesterone acetate versus ganirelix in oocyte donation: a randomized controlled trial.
        Hum. Reprod. 2019; 34: 872-880
        • Evans M.B.
        • Parikh T.
        • DeCherney A.H.
        • Csokmay J.M.
        • Healy M.W.
        • Hill M.J.
        Evaluation of the cost-effectiveness of ovulation suppression with progestins compared with GnRH analogs in assisted reproduction cycles.
        Reprod. Biomed. Online. 2019; 38: 691-698
        • Iwami N.
        • Kawamata M.
        • Ozawa N.
        • Yamamoto T.
        • Watanabe E.
        • Moriwaka O.
        • Kamiya H.
        New trial of progestin-primed ovarian stimulation using dydrogesterone versus a typical GnRH antagonist regimen in assisted reproductive technology.
        Arch. Gynecol. Obstet. 2018; 298: 663-671
        • 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 (e63): 62-70
        • 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;
        • Ubaldi F.M.
        • Capalbo A.
        • Vaiarelli A.
        • Cimadomo D.
        • Colamaria S.
        • Alviggi C.
        • Trabucco E.
        • Venturella R.
        • Vajta G.
        • Rienzi L.
        Follicular versus luteal phase ovarian stimulation during the same menstrual cycle (DuoStim) in a reduced ovarian reserve population results in a similar euploid blastocyst formation rate: new insight in ovarian reserve exploitation.
        Fertil. Steril. 2016; 105 (e1481): 1488-1495
        • Vaiarelli A.
        • Cimadomo D.
        • Trabucco E.
        • Vallefuoco R.
        • Buffo L.
        • Dusi L.
        • Fiorini F.
        • Barnocchi N.
        • Bulletti F.M.
        • Rienzi L.
        • Ubaldi F.M.
        Double Stimulation in the Same Ovarian Cycle (DuoStim) to Maximize the Number of Oocytes Retrieved From Poor Prognosis Patients: A Multicenter Experience and SWOT Analysis.
        Front Endocrinol (Lausanne). 2018; 9: 317
        • Venetis C.A.
        • Kolibianakis E.M.
        • Bosdou J.K.
        • Tarlatzis B.C.
        Progesterone elevation and probability of pregnancy after IVF: a systematic review and meta-analysis of over 60 000 cycles.
        Hum. Reprod. Update. 2013; 19: 433-457
        • Wang Y.
        • Chen Q.J.
        • Wang N.L.
        • Chen H.
        • Lyu Q.F.
        • Kuang Y.P.
        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. 2016; 95
        • Yildiz S.
        • Turkgeldi E.
        • Angun B.
        • Eraslan A.
        • Urman B.
        • Ata B.
        Comparison of a novel flexible progestin primed ovarian stimulation protocol and the flexible gonadotropin-releasing hormone antagonist protocol for assisted reproductive technology.
        Fertil. Steril. 2019; 112: 677-683
        • Zhu X.
        • Ye H.
        • Fu Y.
        The Utrogestan and hMG protocol in patients with polycystic ovarian syndrome undergoing controlled ovarian hyperstimulation during IVF/ICSI treatments.
        Medicine (Baltimore). 2016; 95: e4193
        • Zhu X.
        • Ye H.
        • Fu Y.
        Comparison of neonatal outcomes following progesterone use during ovarian stimulation with frozen-thawed embryo transfer.
        Sci. Rep. 2017; 7: 7835
        • 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: e909

      Biography

      Baris Ata graduated from the Istanbul School of Medicine. He completed a Reproductive Endocrinology and Infertility fellowship at McGill University, Canada. He holds a master's degree in Clinical Trials from the London School of Hygiene and Tropical Medicine. He has authored over 100 publications on endometriosis, female infertility and assisted reproduction.
      Key message
      Progestins effectively inhibit premature ovulation. On the basis of low-quality evidence, progestins are as effective as gonadotrophin releasing hormone analogues. Randomized trials presenting intention to treat analysis are needed. Flexible progestin primed stimulation protocols deserve further study.