Comparison of Dydrogesterone and GnRH Antagonists for Prevention of Premature LH Surge in IVF/ICSI Cycles: A Randomized Controlled Trial
Objective: To compare the effect of dydrogesterone and Gonadotropin releasing hormone (GnRH) antagonists on prevention of premature luteinizing hormone (LH) surge and pregnancy outcomes in infertile women undergoing Invitro fertilization/ Intra cytoplasmic sperm injection (IVF/ICSI).
Materials and methods: In a Randomized controlled trial (RCT), two-hundred eligible women undergoing in vitro fertilization (IVF) /intracytoplasmic sperm injection (ICSI) treatment were randomly assigned into two groups. Human menopausal gonadotropin (HMG) was administered for controlled ovarian stimulation (COS) in both groups. Intervention group (group 1) received 20 mg dydrogesterone from day 2 of menstrual cycle till trigger day and control group (group2) received GnRH antagonist from the day that leading follicle reached 13 mm in diameter till trigger day. Serum levels of LH, estradiol and progesterone were measured on the trigger day. The primary outcome measure was the incidence of a premature LH surge, and the secondary outcomes investigated were the chemical and clinical pregnancy rates in the first FET cycles.
Results: There were no significant differences in patients' age, BMI, AMH levels, previous IVF cycle, and cause of infertility between the two groups. None of the patients in two groups experienced a premature luteinizing hormone surge. The numbers of retrieved oocytes, the MII oocytes and good quality embryos, were significantly higher in the intervention group than antagonist group (p < 0.05). The overall chemical pregnancy rate in intervention group (43/91: 46.2%) and control group (45/91: 49.5%) (p = 0.820) was similar. Meanwhile, the clinical pregnancy rate was similar between groups too.
Conclusion: Regarding the cost, efficacy and easy usage of dydrogestrone, it may be reasonable to use it as an alternative to GnRH antagonist for the prevention of premature LH surge.
2. Pirtea P, de Ziegler D, Poulain M, Ayoubi JM. New Twists in Ovarian Stimulation and Their Practical Implications. Front Med (Lausanne) 2019; 6:197.
3. Ledger WL. Patient scheduling for gonadotrophin-releasing hormone antagonist protocols. Hum Fertil (Camb) 2002; 5: G29-32.
4. Mourad S, Brown J, Farquhar C. Interventions for the prevention of OHSS in ARTcycles: an overview of Cochrane reviews. Cochrane Database Syst Rev 2017; 1: CD012103.
5. 5.Iwami N, Kawamata M, Ozawa N, Yamamoto T, Watanabe E, Moriwaka O, et al. New trial of progestin-primed ovarian stimulation using dydrogesterone versus atypical GnRH antagonist regimen in assisted reproductive technology. Arch Gynecol Obstet 2018; 298: 663-71.
6. Berger BM, Ezcurra D, Alper MM. The Agonist-Antagonist Protocol: a novel protocol for treating the poor responder. Fertil Steril 2004; 82: S126.
7. Humaidan P, Ejdrup Bredkjær H, Bungum L, Bungum M, Grøndahl M, et al. GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study. Hum Reprod 2005; 20: 1213-20.
8. Humaidan P, Bungum L, Bungum M, Andersen CY. Rescue of corpus luteum function with peri-ovulatory HCG supplementation in IVF/ICSI GnRH antagonist cycles in which ovulation was triggered with a GnRH agonist: a pilot study. Reprod Biomed Online 2006; 13: 173-8.
9. Pirard C, Donnez J, Loumaye E. GnRH agonist as luteal phase support in assisted reproduction technique cycles: results of a pilot study. Hum Reprod 2006; 21: 1894-900.
10. 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; 4: CD001750.
11. Reichman DE, Zakarin L, Chao K, Meyer L, Davis OK, Rosenwaks Z. Diminished ovarian reserve is the predominant risk factor for gonadotropin-releasing
hormoneantagonist failure resulting in breakthrough luteinizing hormone surges inin vitro fertilization cycles. Fertil Steril 2014; 102: 99-102.
12. Kahyaoğlu S, Yılmaz B, Işık AZ. Pharmacokinetic, pharmacodynamic, and clinical aspects of ovulation induction agents: A review of the literature. J Turk Ger Gynecol Assoc 2017; 18: 48–55
13. 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: 321-31.
14. Kuang Y, Chen Q, Fu Y, Wang Y, Hong Q, Lyu Q,
et al. 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: 62-70. e3.
15. Zhu X, Ye H, Fu Y. The Utrogestan and hMG protocol in patients with polycysticovarian syndrome undergoing controlled ovarian hyperstimulation during IVF/ICSItreatments. Medicine (Baltimore) 2016;
16. Zhu X, Ye H, Fu Y. Duphaston and human menopausal gonadotropin protocol in normally ovulatory women undergoing controlled ovarian hyperstimulation during in vitro fertilization/intracytoplasmic sperm injection treatments in combination with embryo cryopreservation. Fertil Steril 2017; 108: 505-12. e2.
17. 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: e2939.
18. Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, et al. Classification and pharmacology of progestins. Maturitas 2003;46 Suppl 1: S7-S16.
19. Schindler AE. Progestational effects of dydrogesterone in vitro, in vivo and on the human endometrium. Maturitas 2009; 65 Suppl 1: S3-11.
20. Nadarajah R, Rajesh H, Wong KY, Faisal F, Yu SL. Live birth rates and safety profile using dydrogesterone for luteal phase support in assisted reproductive techniques. Singapore Med J 2017; 58: 294-7.
21. Yu S, Long H, Chang HY, Liu Y, Gao H, Zhu J, et al. 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: 229-37.
22. Meyer L, Murphy LA, Gumer A, Reichman DE,
Rosenwaks Z, Cholst IN. Risk factorsfor a suboptimal response to gonadotropin-releasing hormone agonist trigger during in vitro fertilization cycles. Fertil Steril 2015; 104: 637-42.
23. Kuang Y, Hong Q, Chen Q, Lyu Q, Ai A, Fu Y, et al. Luteal-phase ovarian stimulation is feasible for producing competent oocytes in women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, with optimalpregnancy outcomes in frozen-thawed embryo transfer cycles. Fertil Steril 2014; 101: 105-11.
24. Huang P, Tang M, Qin A. Progestin-primed ovarian stimulation is a feasible method for poor ovarian responders undergoing in IVF/ICSI compared to a GnRH antagonist protocol: A retrospective study. J Gynecol Obstet Hum Reprod 2019; 48: 99-102.
25. Beguería R, García D, Vassena R, Rodríguez A. Medroxyprogesterone acetateversus ganirelix in oocyte donation: a randomized controlled trial. Hum Reprod 2019; 34: 872-80.
26. Dong J, Wang Y, Chai WR, Hong QQ, Wang NL, Sun LH, et al. The pregnancy outcome of progestin-primed ovarian stimulation using 4 versus 10 mg of medroxyprogesterone acetate per day in infertile women undergoing in vitro fertilization: a randomized controlled trial. BJOG 2017; 124: 1048-55.
|Issue||Vol 14, No 1 (March 2020)|
|Controlled Ovarian Stimulation Dydrogesterone Gonadotropin Releasing Hormon Antagonist Premature luteinizing Hormone Surge|
|Rights and permissions|
|This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.|