Comparing rLH with hMG in embryo transfers at the stage of blastocyst and pregnancy outcomes in poor responders

Abstract

Abstract Objective: Despite showing the beneficial effects of adding LH activity to FSH, based on the pregnancy rate (PR) in patients in the previous studies, no studies have been done to compare two different gonadotrophin preparations with activity of LH in the same group of poor responders. Metods: The present study was a single-center retrospective one conducted in January 2015 - December 2019 among 30 women under 39 years old who had reduced ovarian reserve and underwent ICSI cycles. The same patient group received rFSH combined with hMG or rLH. The ovarian stimulation cycle began on the second day of the menstrual cycle, and the initial doses of gonadotrophin were 225 IU/day rFSH in addition to 75 IU/day hMG or 75 IU/day rLH. In all cycles , a flexible antagonist protocol was used. Results: Adding rLH significantly increased the mean number of MII oocytes and COC(cumulus oophorus complex) (p < 0.001). There was no significant difference between poor responders treated with rLH or with hMG in terms of blastocyst transfer,implantation rates and clinical pregnancy rates(p>0.05). Conclusion: There should be further studies to confirm the better effect of rLH addition to rFSH than hMG in young poor responders. Interventions for poor responders obviously need large randomized studies which were designed properly, due to the lack of evidence-based treatment to date for this particular patient group.

Keywords

• rLH
• hMG
• poor responeder

References

1. Blumenfeld Z. What is the best regimen for ovarian stimulation of poor responders in ART/IVF.Front Endocrinol(Lausanne)2020.11:192.
2. Bosch E, Labarta E, Crespo J, Simon C,Remohi J,Pellicer A.Impact of luteinizing hormone administration on gonadotropin-releasing hormone antagonist cycles: an age-adjusted analysis. Fertil Steril. 2011.1;95(3):1031-6.
3. Buhler KF, Fischer R. Recombinant human LH supplementation versus supplementation with urinary hCG-based LH activity during controlled ovarian stimulation in the long GnRH-agonist protocol: a matched case-control study. Gynecol Endocrinol. 2012.28(5):345-50.
4. Casarini L, Santi D, Brigante G, Simoni M. Two Hormones for One Receptor: Evolution, Biochemistry, Actions, and Pathophysiology of LH and hCG. Endocr Rev. 2018.1;39(5):549-92.
5. Dahan MH, Agdi M, Shehata F, Son W,Tan S. A comparison of outcomes from in vitro fertilization cycles stimulated with either recombinant luteinizing hormone (LH) or human chorionic gonadotropin acting as an LH analogue delivered as human menopausal gonadotropins, in subjects with good or poor ovarian reserve: a retrospective analysis. Eur J Obstet Gynecol Reprod Biol. 2014 Jan;172:70-3.
6. Drakopoulos P, Vuong TNL, Ho NAV, Vaiarelli A,Ho MT,Blockeel C,et al. Corifollitropin alfa followed by highly purified HMG versus recombinant FSH in young poor ovarian responders: a multicentre randomized controlled clinical trial. Hum Reprod. 2017.1;32(11):2225-33.
7. Ferraretti AP, La Marca A, Fauser BC,Tarlatzis B,Nargund G.Gianoroli L. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011.26(7):1616-24.
8. Ferraretti AP, Gianaroli L, Motrenko T, Feliciani E,Tabanelli C,Magli MC. LH pretreatment as a novel strategy for poor responders. Biomed Res Int. 2014;2014:926172.

9. Hill MJ, Levens ED, Levy G,Ryan M,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 May;97(5):1108-14.
10. Humaidan P, Chin W, Rogoff D,Hoohhe TD,Longobardi S,Hubbard J et al. Efficacy and safety of follitropin alfa/lutropin alfa in ART: a randomized controlled trial in poor ovarian responders. Hum Reprod. 2017.1;32(3):544-55.
11. Kolibianakis EM, Venetis CA, Diedrich K,Tarlatzis BC,Griesinger G. Addition of growth hormone to gonadotrophins in ovarian stimulation of poor responders treated by in-vitro fertilization: a systematic review and meta-analysis. Hum Reprod Update. 2009. 15(6):613-22.
12. Kyrou D, Kolibianakis EM, Venetis CA, Papanicolaou G,Bontis Bontis J,Tarlatzis BC.How to improve the probability of pregnancy in poor responders undergoing in vitro fertilization: a systematic review and meta-analysis. Fertil Steril. 2009.91(3):749-66.
13. Lehert P, Kolibianakis EM, Venetis CA,Schertz J,Saunders H,Arriagada P, et al. Recombinant human follicle-stimulating hormone (r-hFSH) plus recombinant luteinizing hormone versus r-hFSH alone for ovarian stimulation during assisted reproductive technology: systematic review and meta-analysis. Reprod Biol Endocrinol. 2014.20;12:17.
14. Levi Setti PE, Alviggi C, Colombo GL,Pisanelli C,Ripellino C,Longobardi S.,et al. Human recombinant follicle stimulating hormone (rFSH) compared to urinary human menopausal gonadotropin (HMG) for ovarian stimulation in assisted reproduction: a literature review and cost evaluation. J Endocrinol Invest. 2015.38(5):497-503.
15. Mochtar MH, Danhof NA, Ayeleke RO,Veen FV,Welly M.Recombinant luteinizing hormone (rLH) and recombinant follicle stimulating hormone (rFSH) for ovarian stimulation in IVF/ICSI cycles. Cochrane Database Syst Rev. 2017 .24;5(5):CD005070.
16. Oudendijk JF, Yarde F, Eijkemans MJ,Broekmans FJM,Brooer SL. The poor responder in IVF: is the prognosis always poor?: a systematic review. Hum Reprod Update. 2012.18(1):1-11.
17. Polyzos NP, De Vos M, Corona R,Vloeberghs V,Ortega-Hrepich C,Stoop D, et al. Addition of highly purified HMG after corifollitropin alfa in antagonist-treated poor ovarian responders: a pilot study. Hum Reprod. 2013.28(5):1254-60.
18. Revelli A, Chiado A, Guidetti D, et al. Outcome of in vitro fertilization in patients with proven poor ovarian responsiveness after early vs. mid-follicular LH exposure: a prospective, randomized, controlled study. J Assist Reprod Genet. 2012 Sep;29(9):869-75.
19. Revelli A, Pettinau G, Basso G, et al. Controlled Ovarian Stimulation with recombinant-FSH plus recombinant-LH vs. human Menopausal Gonadotropin based on the number of retrieved oocytes: results from a routine clinical practice in a real-life population. Reprod Biol Endocrinol. 2015 Jul 25;13:77.
20. Ruvolo G, Bosco L, Pane A, et al. Lower apoptosis rate in human cumulus cells after administration of recombinant luteinizing hormone to women undergoing ovarian stimulation for in vitro fertilization procedures. Fertil Steril. 2007;87(3):542-6.
21. Tayyar AT, Kahraman S. Comparison between cycles of the same patients when using recombinant luteinizing hormone + recombinant follicle stimulating hormone (rFSH), human menopausal gonadotropin + rFSH and rFSH only. Arch Med Sci. 2019 ;15(3):673-679.
22. Zhang Y, Zhang C, Shu J, et al. Adjuvant treatment strategies in ovarian stimulation for poor responders undergoing IVF: a systematic review and network meta-analysis. Hum Reprod Update. 2020,26(2):247-263.