Current scientific and practical luteal phase support strategies

Kogan I.Iu.; Gerkulov D.A.

doi:https://doi.org/10.17116/repro201622320-27

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Abstract:

The luteal phases of all stimulated IVF cycles are abnormal. Luteal phase support (mainly progesterone administration) is a common practice in infertility treatment to improve the implantation rate, clinical pregnancy rate, and delivery rate. However, new practical strategies aimed to improve protocol safety and commercial conflicts of interests between pharmacological companies necessitate to take desicion about methods of luteal phase support.

Keywords:

IVF

luteal phase support

progesterone

oestradiol

early pregnancy

individualized treatment

Authors:

Kogan I.Iu.

FGBU "NII akusherstva i ginekologii im. D.O. Otta" SZO RAMN, Sankt-Peterburg

Gerkulov D.A.

ФГБНУ «НИИ акушерства и гинекологии им. Д.О. Отта», Санкт-Петербург, Россия, 199034

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References:

Bulletti C, deZiegler D. Uterine contractility and embryoimplantation. Curr Opin Obstet Gynecol. 2005;17(3):265-276.
Hoff JD, Quigley ME, Yen SS. Hormonal dynamics at midcycle: a reevaluation. J Clin Endocrinol Metab. 1983;57:792-796.
Mais V, Yen SS. Prolactin-releasing action of gonadotropin-releasing hormone in hypogonadal women. J Clin Endocrinol Metab. 1986;62(6):1089-1092.
Casper RF, Yen SS. Induction of luteolysis in the human with a long-acting analog of luteinizing hormone-releasing factor. Science. 1979;205:408-410.
Sugino N, Kashida S, Takiguchi S, Karube A, Kato HJ. Expression of vascular endothelial growth factor and its receptors in the human corpus luteum during the menstrual cycle and in early pregnancy. Clin Endocrinol Metab. 2000;85(10):3919-3924.
Wang TH, Horng SG, Chang CL, Wu HM, Tsai YJ, Wang HS, Soong YK. Human chorionic gonadotropin-induced ovarian hyperstimulation syndrome is associated with up-regulation of vascular endothelial growth factor. J Clin Endocrinol Metab. 2002;87:3300-3308.
Licht P, Russu V, Wildt L. On the role of human chorionic gonadotropin (hCG) in the embryo-endometrial microenvironment: implications for differentiation and implantation. Semin Reprod Med. 2001;19:37-47.
Rao CV. Multiple novel roles of luteinizing hormone. Fertil Steril. 2001;76:1097-1100.
Tesarik J, Hazout A, Mendoza C. Luteinizing hormone affects uterine receptivity independently of ovarian function. Reprod Biomed Online. 2003;7:59-64.
Oktay K, Türkçüoğlu I, Rodriguez-Wallberg KA GnRH agonist trigger for women with breast cancer undergoing fertility preservation by aromatase inhibitor/FSH stimulation. Reprod Biomed Online. 2010 Jun;20(6):783-788. doi: 10.1016/j.rbmo.2010.03.004
Gonen Y, Balakier H, PowellW, Casper RF. Use of gonadotropin-releasing hormone agonist to trigger follicular maturation for in vitro fertilization. J Clin Endocrinol Metab. 1990;71:918-922.
Itskovitz J, Boldes R, Levron J, Erlik Y, Kahana L, Brandes JM. Induction of preovulatory luteinizing hormone surge and prevention of ovarian hyperstimulation syndrome by gonadotropin-releasing hormone agonist. Fertil Steril. 1991;56:213-220.
Tavaniotou A, Smitz J, Bourgain C, Devroey P. Ann Ovulation induction disrupts luteal phase function. N Y Acad Sci. 2001 Sep;943:55-63.
Fauser BC, Devroey P.Trends Reproductive biology and IVF: ovarian stimulation and luteal phase consequences. Endocrinol Metab. 2003;14(5):236-242.
Tavaniotou A, Devroey P. Reprod Luteal hormonal profile of oocyte donors stimulated with a GnRH antagonist compared with natural cycles. Biomed Online. 2006;13(3):326-330.
Fatemi HM. The luteal phase after 3 decades of IVF: what do we know? Reprod Biomed Online. 2009;19(Suppl 4):4331.
Duffy DM, Stewart DR, Stouffer RL. Titrating luteinizing hormone replacement to sustain the structure and function of the corpus luteum after gonadotropinreleasing hormone antagonist treatment in rhesus monkeys. J Clin Endocrinol Metab. 1999;84:342-349.
Miyake A, Aono T, Kinugasa T. Suppression of serum levels of luteinizing hormone by short- and long-loop negative feedback in ovariectomized women. Journal of Endocrinology .1979;80:353-356.
Smitz J, Erard P, Camus M Pituitary gonadotrophin secretory capacity during the luteal phase in superovulation using GnRH-agonists and HMG in a desensitization or flare-up protocol. Human Reproduction. 1992;7:1225-1229.
Vinogradova L, Mishieva N, Sorvacheva M, Abubakirov A. Vliyanie prezhdevremennoi lyuteinizatsii follikulov na iskhody programm VRT v tsiklakh s antagonistami gonadotropin-rilizing-gormona. Akusherstvo i ginekologiya. 2013;3:21-25. (In Russ.).
Merkulova A, Niauri D, Gzgzyan A, Dzhemlikhanova L, Kogan I, Tkachenko N. Povyshennyi uroven' progesterona v den' vvedeniya triggera ovulyatsii kak prediktor neudachi implantatsii v tsikle EKO. Ginekologiya Endokrinologiya. Doctor.Ru. 2014;8(96):24-30.
Soliman S, Daya S, Collins J, Hughes EG. The role of luteal phase support in infertility treatment: a meta-analysis of randomized trials. Fertil Steril. 1994;61:1068-1076.
Pritts E, Atwood AKю Luteal phase support in infertility treatment: a meta-analysis of the randomized trials. Hum Reprod. 2002;17:2287-2299.
Nosarka S, Kruger T, Siebert I, Grove D. Luteal phase support in in vitro fertilization: metaanalysis of randomized trials. Gynecol Obstet Invest. 2005;60:67-74.
Daya S, Gunby J. Luteal phase support in assisted reproduction cycles. Cochrane. Database Syst Rev. 2004;3:CD004830.
van der Linden M, Buckingham K, Farquhar C, Kremer JA, Metwally M. Luteal phase support for assisted reproduction cycles. Cochrane Database Syst Rev. 2011;5(10):CD009154. doi: 10.1002/14651858.CD009154
van der Linden M1, Buckingham K, Farquhar C, Kremer JA, Metwally M. Luteal phase support for assisted reproduction cycles. Cochrane Database Syst Rev. 2015;7;7:CD009154. doi: 10.1002/14651858.CD009154
Barbosa MW, Silva LR, Navarro PA, Ferriani RA, Nastri CO, Martins WP. Dydrogesterone versus progesterone for luteal-phase support: systematic review and metaanalysis of randomized controlled trials. Ultrasound Obstet Gynecol. 2015;18. doi: 10.1002/uog.15814
Vaisbuch E, Leong M, Shoham Z. Progesterone support in IVF: is evidence-based medicine translated to clinical practice? A worldwide web-based survey. Reprod Biomed Online. 2012;25(2):139-145. doi: 10.1016/j.rbmo.2012.04.005
el-Refaey H, Rajasekar D, Abdalla M, Calder L, Templeton A. Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol. N Engl J Med. 1995;332(15):983-987.
Bulletti C, de Ziegler D, Flamigni C. Targeted drug delivery in gynaecology: the first uterine pass effect. Hum Reprod. 1997;12:1073-1079.
Wildt L, Kissler S, Licht P, Becker W. Sperm transport in the human female genital tract and its modulation by oxytocin as assessed by hysterosalpingoscintigraphy, hysterotonography, electrohysterography and Doppler sonography. Hum Reprod Update. 1998;4:655-666.
Magness RP, Ford SP. Estrone, estradiol-17 beta and progesterone concentrations in uterine lymph and systemic blood throughout the porcine estrous cycle. J Anim Sci. 1983;57:449-455.
Einer-Jensen N, Kotwica J, Krzymowski T. Rapid absorption and local redistribution of progesterone after vaginal application in gilts. Acta Vet Scand. 1993;34:1-7.
Bulletti C, de Ziegler D, Flamigni C, Giacomucci E, Polli V, Bolelli G, Franceschetti F. Targeted drug delivery in gynaecology: the first uterine pass effect. Hum Reprod. 1997;12(5):1073-1079.
Kunz G, Beil D, Deininger H. The dynamics of rapid sperm transport through the female genital tract: evidence from vaginal sonography of uterine peristalsis and hysterosalpingoscintigraphy. Hum Reprod. 1996;11(3):627-632.
Cicinelli E, Cignarelli M, Sabatelli S. Plasma concentrations of progesterone arehigher in the uterine artery than in radial artery after vaginal administration of micronized progesterone in an oil-based solution to postmenopausal women. Fertil Steril. 1998;69:471-473.
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;21:1894-1900.
Tesarik J, Hazout A, Mendoza C. Enhancement of embryo developmental potential by a single administration of GnRH agonist at the time of implantation. Hum Reprod. 2004;19:1176-1180.
Kyrou D, Kolibianakis E, Fatemi H, Tarlatzi T, Devroey P, Tarlatzis B. Increased live birth rates with GnRH agonist addition for luteal support in ICSI/IVF cycles: a systematic review and meta-analysis. Hum Reprod Update. 2011;17:734-740. doi: 10.1093/humupd/dmr029
Babayof R, Margalioth EJ, Huleihel M, Amash A, Zylber-Haran E, Gal M, Brooks B, Mimoni T, Eldar-Geva T. Serum inhibin A, VEGF and TNF alpha levels after triggering oocyte maturation with GnRH agonist compared with HCG in women with polycystic ovaries undergoing IVF treatment: a prospective randomized trial. Hum Reprod. 2006;21:1260-1265.
Engmann L, DiLuigi A, Schmidt D, Nulsen J, Maier D, Benadiva C. The use ofgonadotropin-releasing hormone (GnRH) agonist to induce oocyte maturationaftercotreatment with GnRH antagonist in high-risk patients undergoing invitro fertilization prevents the risk of ovarian hyperstimulation syndrome: aprospective randomized controlled study. Fertil Steril. 2008a;89:84-91.
Humaidan P, Bredkjaer HE, Bungum L, Bungum M, Grondahl ML, Westergaard L, Andersen CY. GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study. Hum Reprod. 2005;20:1213-1220.
Humaidan P, Ejdrup Bredkjaer H, Westergaard LG, Yding Andersen C. 1,500 IUhuman chorionic gonadotropin administered at oocyte retrieval rescues the luteal phase when gonadotropin-releasing hormone agonist is used for ovulation induction: a prospective, randomized, controlled study. Fertil Steril. 2010;93:847-854. doi: 10.1016/j.fertnstert.2008.12.042
Papanikolaou EG, Verpoest W, Fatemi H, Tarlatzis B, Devroey P, Tournaye H. A novel method of luteal supplementation with recombinant LH, when aGnRH-аgonist is used instead of HCG for ovulation triggering. A randomized prospective proof of concept study. Fertil Steril. 2011;3:1174-1177. doi: 10.1016/j.fertnstert.2010.09.023
Miles RA, Paulson RJ, Lobo RA, Press MF, Dahmoush L, Sauer MV. Pharmacokinetics and endometrial tissue levels of progesterone after administration by intramuscular and vaginal routes: a comparative study. Fertil Steril. 1994;62(3):485-490.
Polson DW, Rogers PA, Krapez JA, Leeton JF. Vaginal progesterone as luteal phase support in an IVF/GIFT programme. Eur J Obstet Gynecol Reprod Biol. 1992;46(1):35-38.
Schoolcraft WB, Hesla JS, Gee MJ. Experience with progesterone gel for luteal support in a highly successful IVF programme. Hum Reprod. 2000;15:1284-1288.
Van Steirteghem AC, Smitz J, Camus M, Van Waesberghe L, Deschacht J, Khan I, Staessen C, Wisanto A, Bourgain C, Devroey P. The luteal phase after in vitro fertilization and related procedures. Hum Reprod. 1988;3(2):161-164.
Mochtar MH, Hogerzeil HV, Mol BW. Progesterone alone versus progesterone combined with HCG as luteal support in GnRHa/HMG induced IVF cycles: a randomized clinical trial. Hum Reprod. 1996;11(8):1602-1605.
Nyboe Andersen A, Popovic-Todorovic B, Schmidt KT, Loft A, LindhardA, Hojgaard A, Ziebe S, Hald F, Hauge B, ToftB. Progesterone supplementation during early gestations after IVF or ICSI has no effect on the delivery rates: a randomized controlled trial. Hum Reprod. 2002;17:357-361.
Propst AM, Hill JA, Ginsburg ES, Hurwitz S, Politch J, Yanushpolsky EH. A randomized study comparing Crinone 8% and intramuscular progesterone supplementation in in vitro fertilization-embryo transfer cycles. Fertil Steril. 2001;76:1144-1149.
Paikacheva YM. Profilaktikailechenienevynashivaniyaberemennosti u zhenshchinposle EKO. [dissertation]. SPb. 2000. (In Russ.).
Milovanov AP. Patologiyasistemy mat'-platsenta-plod. M.: Meditsina. 1999. (In Russ.).