Yüksek bazal LH seviyeleri daha iyi yardımcı üreme siklus sonuçları ile ilişkilidir

Yıl 2020, , 152 - 156, 01.02.2020

Vehbi Yavuz Tokgöz , Ahmet Basar Tekin

https://doi.org/10.28982/josam.666963

Öz

Amaç: Gonadotropin stimülasyonuna over yanıtını değerlendirmek için birçok parametre bulunmaktadır. Basal LH seviyeleri FSH seviyelerine ek olarak over yanıtında önerilmektedir. Bu çalışma ile GnRH-antagonist IVF (in-vitro fertilizasyon) siklusu uygulanan hastalarda bazal LH seviyelerinin siklus ve gebelik sonuçları ile ilişkisini değerlendirmek amaçlanmıştır.
Yöntemler: Retrospektif kohort çalışmaya FSH değeri 10 IU/L’den daha düşük olan 317 siklus dahil edilmiştir. Bazal hormonal bulgular (FSH, LH, estradiol) ovaryan stimülasyon başlamadan önce kaydedildi. Hastalara GnRH-antagonist protokol ve rekombinant FSH tedavisi uygulandı. Hastalar; LH değeri için belirlenmiş olan eşik değerlere göre kategorize edilmişlerdir (Grup 1: LH <4,1 IU/L ve Grup 2: LH 4,1). Elde edilen toplam oosit sayısı, matür oosit sayısı, implantasyon oranı, klinik gebelik ve devam eden gebelik oranı çalışma grupları arasında analiz edilerek karşılaştırıldı.
Bulgular: Grup 2 hastalarda, Grup 1 ile karşılaştırıldığında daha fazla oosit sayısı ve matür oosit sayısı tespit edilmiştir (P=0,006 ve P=0,03). İstatistiksel olarak anlamlı olmasa dahi, yüksek LH seviyelerinde daha yüksek gebelik oranları lehine bir eğilim saptandı. Klinik gebelik ve devam eden gebelik oranları Grup 1’de daha düşüktü ancak bu farklılık istatistiksel olarak anlamlı değildi (Klinik ve devam eden gebelik için sırasıyla %38,3’e karşı %48,5, P=0,162 ve %29,4’e karşı %34,0, P=0,535). Bazal LH seviyeleri oosit sayısı ile pozitif olarak korele olarak saptandı ve düşük FSH seviyeleri ile kombinasyonu da daha fazla oosit sayısı ve pik östrojen düzeyleri ile ilişkili bulundu.
Sonuç: Artmış bazal LH seviyeleri toplam elde edilen oosit sayısı gibi siklus sonuçları üzerinde faydalı etki sağlayabilir. Bununla birlikte klinik gebelik oranları LH seviyesi eşik değerinin altında ve üstünde olanlar arasında benzer olarak tespit edildi.

Anahtar Kelimeler

Luteinize edici hormon, IVF (in-vitro fertilizasyon), İnfertilite, Oosit sayısı, Gebelik oranı

High basal LH levels are associated with improved cycle outcomes of assisted reproduction

Öz

Aim: Several parameters are used to observe the ovarian responsiveness to gonadotropin stimulation. Basal LH levels have been suggested on ovarian response as well as basal FSH levels. This study was aimed to evaluate the correlation of basal LH levels with cycle and pregnancy outcomes in patients who underwent GnRH-antagonist IVF (in-vitro fertilization) cycles.

Methods: This retrospective cohort study recruited a total of 317 cycles with values of FSH <10 IU/L. Basal hormonal parameters (FSH, LH, estradiol) were recorded prior to ovarian stimulation. Patients were treated with GnRH antagonist protocols and stimulated with recombinant FSH. The patients were categorized according to designated threshold levels for LH values (Group 1: LH <4.1 IU/L and Group 2: LH 4.1). The number of total retrieved oocytes and mature oocytes, implantation rate, clinical pregnancy rate and ongoing pregnancy rate were analyzed between study groups. 

Results: Group 2 had a higher number of retrieved oocytes and mature oocytes compared to Group 1 (P=0.006 and P=0.03, respectively). Although not statistically significant, there was a trend towards higher rates of pregnancy on high LH levels. Clinical and ongoing pregnancy rates were insignificantly lower in Group 1 (38.3% vs. 48.5%, P=0.162 and 29.4% vs. 34.0%, P=0.535; respectively). The basal LH levels positively correlated with the number of oocytes, and the combination with low FSH levels was also found to be associated with higher number of retrieved oocytes and peak estradiol levels. 

Conclusions: Elevated basal LH levels provide a beneficial effect on cycle outcome such as number of retrieved oocytes. However, clinical pregnancy rates were found to be similar between below and above the threshold of LH levels.

Anahtar Kelimeler

Luteinizing hormone, IVF (in-vitro fertilization), Infertility, Oocyte number, Pregnancy rate

Kaynakça

• 1. Ho JY, Guu HF, Yi YC, Chen MJ, Ho ES. The serum follicle-stimulating hormone-to-luteinizing hormone ratio at the start of stimulation with gonadotropins after pituitary down-regulation is inversely correlated with a mature oocyte yield and can predict "low responders". Fertil Steril. 2005;83(4):883-8.
• 2. Scott RT, Toner JP, Muasher SJ, Oehninger S, Robinson S, Rosenwaks Z. Follicle-stimulating hormone levels on cycle day 3 are predictive of in vitro fertilization outcome. Fertil Steril. 1989;51(4):651-4.
• 3. Toner JP, Philput CB, Jones GS, Muasher SJ. Basal follicle-stimulating hormone level is a better predictor of in vitro fertilization performance than age. Fertil Steril. 1991;55(4):784-91.
• 4. van Rooij IA, Broekmans FJ, te Velde ER, Fauser BC, Bancsi LF, de Jong FH, et al. Serum anti-Mullerian hormone levels: a novel measure of ovarian reserve. Hum Reprod. 2002;17(12):3065-71.
• 5. Seifer DB, MacLaughlin DT, Christian BP, Feng B, Shelden RM. Early follicular serum mullerian-inhibiting substance levels are associated with ovarian response during assisted reproductive technology cycles. Fertil Steril. 2002;77(3):468-71.
• 6. Toporcerova S, Adam J, Toporcer T, Hredzak R, Ostro A. [Basal concentrations of FSH (follicle stimulating hormone) as a predictor of succes of IVF-ICSI cycle]. Ceska Gynekol. 2006;71(6):474-9.
• 7. Muasher SJ, Oehninger S, Simonetti S, Matta J, Ellis LM, Liu HC, et al. The value of basal and/or stimulated serum gonadotropin levels in prediction of stimulation response and in vitro fertilization outcome. Fertil Steril. 1988;50(2):298-307.
• 8. Fertility: Assessment and Treatment for People with Fertility Problems. National Institute for Health and Clinical Excellence: Guidance. London (UK)2004.
• 9. Taymor ML. The regulation of follicle growth: some clinical implications in reproductive endocrinology. Fertil Steril. 1996;65(2):235-47.
• 10. Noci I, Biagiotti R, Maggi M, Ricci F, Cinotti A, Scarselli G. Low day 3 luteinizing hormone values are predictive of reduced response to ovarian stimulation. Hum Reprod. 1998;13(3):531-4.
• 11. Mukherjee T, Copperman AB, Lapinski R, Sandler B, Bustillo M, Grunfeld L. An elevated day three follicle-stimulating hormone:luteinizing hormone ratio (FSH:LH) in the presence of a normal day 3 FSH predicts a poor response to controlled ovarian hyperstimulation. Fertil Steril. 1996;65(3):588-93.
• 12. Barroso G, Oehninger S, Monzo A, Kolm P, Gibbons WE, Muasher SJ. High FSH:LH ratio and low LH levels in basal cycle day 3: impact on follicular development and IVF outcome. J Assist Reprod Genet. 2001;18(9):499-505.
• 13. Weghofer A, Schnepf S, Barad D, Gleicher N. The impact of luteinizing hormone in assisted reproduction: a review. Curr Opin Obstet Gynecol. 2007;19(3):253-7.
• 14. Liu KE, Greenblatt EM. Elevated day 3 follicle-stimulating hormone/luteinizing hormone ratio >or= 2 is associated with higher rates of cancellation in in vitro fertilization-embryo transfer cycles. Fertil Steril. 2008;90(2):297-301.
• 15. Alpha Scientists in Reproductive M, Embryology ESIGo. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011;26(6):1270-83.
• 16. Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril. 2000;73(6):1155-8.
• 17. Kassab A, Sabatini L, Lieberman G, Tozer A, Zosmer A, Davis C, et al. Does measuring early basal serum follicular luteinising [correction of lutinising] hormone assist in predicting in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcome? Reprod Biol Endocrinol. 2007;5:32.
• 18. Prasad S, Gupta T, Divya A. Correlation of the Day 3 FSH/LH Ratio and LH Concentration in Predicting IVF Outcome. J Reprod Infertil. 2013;14(1):23-8.
• 19. Lyu SW, Kim JW, Choi CH, Seok HH, Yoon TK, Kim A. Impact of high basal FSH/LH ratio in women with normal FSH levels on in vitro fertilization outcomes. Gynecol Endocrinol. 2013;29(5):424-9.
• 20. Sun L, Ye J, Wang Y, Chen Q, Cai R, Fu Y, et al. Elevated basal luteinizing hormone does not impair the outcome of human menopausal gonadotropin and medroxyprogesterone acetate treatment cycles. Sci Rep. 2018;8(1):13835.
• 21. Platteau P, Smitz J, Albano C, Sorensen P, Arce JC, Devroey P. Exogenous luteinizing hormone activity may influence the treatment outcome in in vitro fertilization but not in intracytoplasmic sperm injection cycles. Fertil Steril. 2004;81(5):1401-4.
• 22. Gomez-Palomares JL, Acevedo-Martin B, Andres L, Ricciarelli E, Hernandez ER. LH improves early follicular recruitment in women over 38 years old. Reprod Biomed Online. 2005;11(4):409-14.
• 23. Kolibianakis EM, Albano C, Kahn J, Camus M, Tournaye H, Van Steirteghem AC, et al. Exposure to high levels of luteinizing hormone and estradiol in the early follicular phase of gonadotropin-releasing hormone antagonist cycles is associated with a reduced chance of pregnancy. Fertil Steril. 2003;79(4):873-80.
• 24. Tas M, Ozcelik B. Does the combination of myo-inositol improve pregnancy outcomes in obese polycystic ovary syndrome women undergoing ovarian stimulation with clomiphene citrate? J Surg Med. 2019;3(9):4.
• 25. Fleming R, Rehka P, Deshpande N, Jamieson ME, Yates RW, Lyall H. Suppression of LH during ovarian stimulation: effects differ in cycles stimulated with purified urinary FSH and recombinant FSH. Hum Reprod. 2000;15(7):1440-5.
• 26. Noci I, Maggi M, Fuzzi B, Biagiotti R, Ricci F, Marchionni M. Effects of low day 3 luteinizing hormone levels on in vitro fertilization treatment outcome. Gynecol Endocrinol. 2000;14(5):321-6.
• 27. Cabrera RA, Stadtmauer L, Mayer JF, Gibbons WE, Oehninger S. Follicular phase serum levels of luteinizing hormone do not influence delivery rates in in vitro fertilization cycles down-regulated with a gonadotropin-releasing hormone agonist and stimulated with recombinant follicle-stimulating hormone. Fertil Steril. 2005;83(1):42-8.
• 28. Kolibianakis EM, Collins J, Tarlatzis B, Papanikolaou E, Devroey P. Are endogenous LH levels during ovarian stimulation for IVF using GnRH analogues associated with the probability of ongoing pregnancy? A systematic review. Hum Reprod Update. 2006;12(1):3-12.
• 29. Van Wely M, Westergaard LG, Bossuyt PM, Van der Veen F. Human menopausal gonadotropin versus recombinant follicle stimulation hormone for ovarian stimulation in assisted reproductive cycles. Cochrane Database Syst Rev. 2003(1):CD003973.
• 30. Kolibianakis EM, Kalogeropoulou L, Griesinger G, Papanikolaou EG, Papadimas J, Bontis J, et al. Among patients treated with FSH and GnRH analogues for in vitro fertilization, is the addition of recombinant LH associated with the probability of live birth? A systematic review and meta-analysis. Hum Reprod Update. 2007;13(5):445-52.
• 31. Brodin T, Bergh T, Berglund L, Hadziosmanovic N, Holte J. High basal LH levels in combination with low basal FSH levels are associated with high success rates at assisted reproduction. Hum Reprod. 2009;24(11):2755-9.
• 32. Bansal S, Singh N, Gupta P, Malhotra N, Mahendru R. Does basal luteinizing hormone help predict the fate of in vitro fertilization? JBRA Assist Reprod. 2016;20(2):66-71.