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Kontrollü Overyan Stimülasyon Protokollerinde rLH Tedaviye Eklenmeli mi?

Year 2021, Volume: 18 Issue: 2, 199 - 203, 27.08.2021
https://doi.org/10.35440/hutfd.949385

Abstract

ÖZ

Amaç: Kontrollü overyan hiper stimülasyon (KOH), in vitro fertilizasyon (IVF) tedavilerinin
temeli durumundadır. Folükül stimüle edici hormon (FSH), antral folliküllerin büyümesinin
temel düzenleyicisi iken, lüteinleştirici hormon (LH) da steroidogenezin desteklenmesinde
etkindir. LH overyan stimülasyonda etkili olmasına rağmen, literatürde KOH’ a LH takviyesi
eklenmesi hakkında net bir görüş birliği bulunmamaktadır. Bizde çalışmamızda kendi
kliniğimizdeki olgularda;İn vitro fertilizasyon/intrasitoplazmik sperm enjeksiyonu (IVF/ICSI)
uygulanan kadınlarda ,over stimülasyonu için, rekombinant luteinize edici hormonun (rLH) ve
rekombinant folikül uyarıcı hormon (rFSH) ile tek başına rFSH kullanımının etkinliğini ve
güvenliğini retrospektif olarak karşılaştırmayı amaçladık.

Materyal Metod: Çalışmamıza Sakarya Üniversitesi Eğitim ve Araştırma Hastanesi Tüp
Bebek Merkezinde 2019-2020 yılları arasında tedavi gören 89 infertil çift dahil edildi. IVF
tedavisine alınan normal over fonksiyonuna sahip hastaların verileri incelendi. KOH için;
yalnızca, rFSH(Gonal-F ) kullanan ve rFSH (Gonal-F ) ve r-LH (Luveris ) ‘ı birlikte

kullanılan hastaların sonuçları retrospektif olarak karşılaştırıldı. Ayrıca 35 yaş üstü ve 35 yaş
altı hasta grupları için rFSH, rFSH+rLH stimülasyon sonuçları alt grup olarak değerlendirildi.
Çalışmamızda toplam oosit sayısı, toplam metafaz II(MII) sayıları ve gebelik oranları da
karşılaştırıldı.

Bulgular: Çalışmaya dahil olan seksen dokuz hastanın, 40’ ı rFSH (Grup 1) ve 49 da rFSH +
rLH (Grup 2) grubundaydı. Tüm yaş grupları içinde değerlendirildiğinde, gruplar arasında total
gonadotropin miktarı ve stimülasyon gün sayısı dışında istatistiksel fark görülen başka bir
parametre izlenmedi.35 yaş üstü ve 35 yaş altı hastalar ayrı ayrı değerlendirildiğinde; oosit
sayısı,toplam MII oositler, Grade I embriyo sayısı ve gebelik oranları bakımından, her iki grup
arasında istatistiksel olarak anlamlı farklılık izlenmedi.

Sonuç: 35 yaş ve üstü over reservi normal hasta grubunda r-LH ilave edilen ve edilmeyen
stimülasyon protokolleri arasında, sonuçlar r-LH grubunda daha olumlu görülse de, istatistiksel
olarak anlamlı fark görülmedi. Çalışmamızda, IVF_ICSI uygulamalarında kullanılan KOH
protokollerine, r-LH ilavesinin tüm yaş gruplarında tedavi başarısı üzerinde etkinliğinin
bulunmadığı görüldü. Bununla birlikte, hasta sayısının daha fazla olduğu çalışmaların
yapılması gerektiğini kanaatindeyiz.

Supporting Institution

HERHANGİ BİR DESTEKLEYEN KURUM BULUNMAMAKTADIR

Project Number

-

References

  • 1. Filicori M, Cognigni GE, Taraborrelli S, at.all.. Low-dose human chorionic gonadotropin therapy can improve sensitivity to exogenous follicle-stimulating hormone in patients with secondary amenorrhea. Fertil Steril. 1999;72(6):1118-1120.
  • 2. Mennini FS, Marcellusi A, Viti R, et al. Probabilistic cost-effectiveness analysis of controlled ovarian stimulation with recombinant FSH plus recombinant LH vs. human menopausal gonadotropin for women undergoing IVF. Reprod Biol Endocrinol. 2018;16(1):68.
  • 3. Leão Rde B, Esteves SC. Gonadotropin therapy in assisted reproduction: an evolutionary perspective from biologics to biotech. Clinics (Sao Paulo). 2014;69(4):279-293.
  • 4. Fleming R, Lloyd F, Herbert M, Fenwick J, Griffiths T, Murdoch A. Effects of profound suppression of luteinizing hormone during ovarian stimulation on follicular activity, oocyte and embryo function in cycles stimulated with purified follicle stimulating hormone. Hum Reprod. 1998;13(7):1788-1792.
  • 5. Hillier SG. Gonadotropic control of ovarian follicular growth and development. Mol Cell Endocrinol. 2001;179(1-2):39-46.
  • 6. Zeleznik AJ. Follicle selection in primates: "many are called but few are chosen". Biol Reprod. 2001;65(3):655-659.
  • 7. Shoham Z. The clinical therapeutic window for luteinizing hormone in controlled ovarian stimulation. Fertil Steril. 2002;77(6):1170-1177.
  • 8. Burgués S. The effectiveness and safety of recombinant human LH to support follicular development induced by recombinant human FSH in WHO group I anovulation: evidence from a multicentre study in Spain. Hum Reprod. 2001;16(12):2525-2532.
  • 9. Schoot DC, Coelingh Bennink HJ, Mannaerts BM, Lamberts SW, Bouchard P, Fauser BC. Human recombinant follicle-stimulating hormone induces growth of preovulatory follicles without concomitant increase in androgen and estrogen biosynthesis in a woman with isolated gonadotropin deficiency. J Clin Endocrinol Metab. 1992;74(6):1471-1473.
  • 10. Fábregues F, Creus M, Peñarrubia J, Manau D, Vanrell JA, Balasch J. Effects of recombinant human luteinizing hormone supplementation on ovarian stimulation and the implantation rate in down-regulated women of advanced reproductive age. Fertility and sterility. 2006;85(4):925-931. 11. De Placido G, Mollo A, Alviggi C, et al. Rescue of IVF cycles by HMG in pituitary down-regulated normogonadotrophic young women characterized by a poor initial response to recombinant FSH. Hum Reprod. 2001;16(9):1875-1879.
  • 12. Tarlatzis B, Tavmergen E, Szamatowicz M, et al. The use of recombinant human LH (lutropin alfa) in the late stimulation phase of assisted reproduction cycles: a double-blind, randomized, prospective study. Human Reproduction. 2005;21(1):90-94.
  • 13. Hill MJ, Levens ED, Levy G, et al. 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;97(5):1108-1114.e1101.
  • 14. Marrs R, Meldrum D, Muasher S, Schoolcraft W, Werlin L, Kelly E. Randomized trial to compare the effect of recombinant human FSH (follitropin alfa) with or without recombinant human LH in women undergoing assisted reproduction treatment. Reprod Biomed Online. 2004;8(2):175-182.
  • 15. Vuong TN, Phung HT, Ho MT. Recombinant follicle-stimulating hormone and recombinant luteinizing hormone versus recombinant follicle-stimulating hormone alone during GnRH antagonist ovarian stimulation in patients aged ≥35 years: a randomized controlled trial. Hum Reprod. 2015;30(5):1188-1195.
  • 16. Lehert P, Schertz JC, Ezcurra D. Recombinant human follicle-stimulating hormone produces more oocytes with a lower total dose per cycle in assisted reproductive technologies compared with highly purified human menopausal gonadotrophin: a meta-analysis. Reprod Biol Endocrinol. 2010;8:112.
  • 17. Bosch E, Labarta E, Crespo J, Simón C, Remohí J, Pellicer A. Impact of luteinizing hormone administration on gonadotropin-releasing hormone antagonist cycles: an age-adjusted analysis. Fertil Steril. 2011;95(3):1031-1036.
  • 18. Humaidan P, Bungum M, Bungum L, Yding Andersen C. Effects of recombinant LH supplementation in women undergoing assisted reproduction with GnRH agonist down-regulation and stimulation with recombinant FSH: an opening study. Reprod Biomed Online. 2004;8(6):635-643.
  • 19. Matorras R, Prieto B, Exposito A, et al. Mid-follicular LH supplementation in women aged 35-39 years undergoing ICSI cycles: a randomized controlled study. Reprod Biomed Online. 2009;19(6):879-887.
  • 20. Wong PC, Qiao J, Ho C, et al. Current opinion on use of luteinizing hormone supplementation in assisted reproduction therapy: an Asian perspective. Reprod Biomed Online. 2011;23(1):81-90.

Should rLH Be Added to the Treatment in Controlled Ovarian Stimulation Protocols?

Year 2021, Volume: 18 Issue: 2, 199 - 203, 27.08.2021
https://doi.org/10.35440/hutfd.949385

Abstract

ABSTRACT

Background: Controlled ovarian hyperstimulation (KOH) is the basis of in vitro fertilization
(IVF) treatments. At the same time, follicle-stimulating hormone (FSH) is the primary regulator
of the growth of antral follicles. Luteinizing hormone (LH) is also effective in supporting
steroidogenesis. Although LH is effective in ovarian stimulation, there is no clear consensus in
the literature about adding LH supplementation to KOH. In our study, We aimed to compare to
retrospectively analyzed the efficacy and safety of using recombinant luteinizing hormone
(rLH) and recombinant follicle-stimulating hormone (rFSH) and rFSH alone for ovarian
stimulation in women undergoing in vitro fertilization/intracytoplasmic sperm injection
(IVF/ICSI) in cases in our clinic.

Materials and Methods: 89 infertile couples treated at Sakarya University Training and
Research Hospital IVF Center between 2019-2020 included in our study. The data of patients
with a normal ovarian function who treated with IVF were analyzed. For KOH, the results of
patients who used rFSH (Gonal-F) alone and rFSH (Gonal-F) and r-LH (Luveris ) together were
compared retrospectively. In addition, rFSH, rFSH+rLH stimulation results were evaluated as
a subgroup for the patient groups over 35 years old and under 35 years old. Our study also
compared the total number of oocytes, total metaphase II (MII) numbers, and pregnancy rates.
Results: Of the 89 patients included in the study, 40 were in the rFSH group (Group 1), and 49
were in the rFSH + rLH (Group 2) group. No statistical difference was observed between the
groups except the total gonadotropin amount and stimulation days When evaluated within all
age groups. When the patients over 35 years old and under 35 years old assessed separately;
There was no statistically significant difference between the two groups in terms of oocytes
count, total MII oocytes, Grade I embryo count and clinical pregnancy rates.

Conclusions: Although the results were more positive in the r-LH group, we could not detect
a statistically significant difference between the stimulation protocols with and without r-LH in
the 35-40 age range, a regular patient population with ovarian reserve. As in our study, we were
adding r-LH to the controlled ovarian stimulation protocols used in IVF_ICSI applications does
not seem to affect treatment success in women of all age groups. However, we believe that
studies with a more significant number of patients should be conducted.

Project Number

-

References

  • 1. Filicori M, Cognigni GE, Taraborrelli S, at.all.. Low-dose human chorionic gonadotropin therapy can improve sensitivity to exogenous follicle-stimulating hormone in patients with secondary amenorrhea. Fertil Steril. 1999;72(6):1118-1120.
  • 2. Mennini FS, Marcellusi A, Viti R, et al. Probabilistic cost-effectiveness analysis of controlled ovarian stimulation with recombinant FSH plus recombinant LH vs. human menopausal gonadotropin for women undergoing IVF. Reprod Biol Endocrinol. 2018;16(1):68.
  • 3. Leão Rde B, Esteves SC. Gonadotropin therapy in assisted reproduction: an evolutionary perspective from biologics to biotech. Clinics (Sao Paulo). 2014;69(4):279-293.
  • 4. Fleming R, Lloyd F, Herbert M, Fenwick J, Griffiths T, Murdoch A. Effects of profound suppression of luteinizing hormone during ovarian stimulation on follicular activity, oocyte and embryo function in cycles stimulated with purified follicle stimulating hormone. Hum Reprod. 1998;13(7):1788-1792.
  • 5. Hillier SG. Gonadotropic control of ovarian follicular growth and development. Mol Cell Endocrinol. 2001;179(1-2):39-46.
  • 6. Zeleznik AJ. Follicle selection in primates: "many are called but few are chosen". Biol Reprod. 2001;65(3):655-659.
  • 7. Shoham Z. The clinical therapeutic window for luteinizing hormone in controlled ovarian stimulation. Fertil Steril. 2002;77(6):1170-1177.
  • 8. Burgués S. The effectiveness and safety of recombinant human LH to support follicular development induced by recombinant human FSH in WHO group I anovulation: evidence from a multicentre study in Spain. Hum Reprod. 2001;16(12):2525-2532.
  • 9. Schoot DC, Coelingh Bennink HJ, Mannaerts BM, Lamberts SW, Bouchard P, Fauser BC. Human recombinant follicle-stimulating hormone induces growth of preovulatory follicles without concomitant increase in androgen and estrogen biosynthesis in a woman with isolated gonadotropin deficiency. J Clin Endocrinol Metab. 1992;74(6):1471-1473.
  • 10. Fábregues F, Creus M, Peñarrubia J, Manau D, Vanrell JA, Balasch J. Effects of recombinant human luteinizing hormone supplementation on ovarian stimulation and the implantation rate in down-regulated women of advanced reproductive age. Fertility and sterility. 2006;85(4):925-931. 11. De Placido G, Mollo A, Alviggi C, et al. Rescue of IVF cycles by HMG in pituitary down-regulated normogonadotrophic young women characterized by a poor initial response to recombinant FSH. Hum Reprod. 2001;16(9):1875-1879.
  • 12. Tarlatzis B, Tavmergen E, Szamatowicz M, et al. The use of recombinant human LH (lutropin alfa) in the late stimulation phase of assisted reproduction cycles: a double-blind, randomized, prospective study. Human Reproduction. 2005;21(1):90-94.
  • 13. Hill MJ, Levens ED, Levy G, et al. 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;97(5):1108-1114.e1101.
  • 14. Marrs R, Meldrum D, Muasher S, Schoolcraft W, Werlin L, Kelly E. Randomized trial to compare the effect of recombinant human FSH (follitropin alfa) with or without recombinant human LH in women undergoing assisted reproduction treatment. Reprod Biomed Online. 2004;8(2):175-182.
  • 15. Vuong TN, Phung HT, Ho MT. Recombinant follicle-stimulating hormone and recombinant luteinizing hormone versus recombinant follicle-stimulating hormone alone during GnRH antagonist ovarian stimulation in patients aged ≥35 years: a randomized controlled trial. Hum Reprod. 2015;30(5):1188-1195.
  • 16. Lehert P, Schertz JC, Ezcurra D. Recombinant human follicle-stimulating hormone produces more oocytes with a lower total dose per cycle in assisted reproductive technologies compared with highly purified human menopausal gonadotrophin: a meta-analysis. Reprod Biol Endocrinol. 2010;8:112.
  • 17. Bosch E, Labarta E, Crespo J, Simón C, Remohí J, Pellicer A. Impact of luteinizing hormone administration on gonadotropin-releasing hormone antagonist cycles: an age-adjusted analysis. Fertil Steril. 2011;95(3):1031-1036.
  • 18. Humaidan P, Bungum M, Bungum L, Yding Andersen C. Effects of recombinant LH supplementation in women undergoing assisted reproduction with GnRH agonist down-regulation and stimulation with recombinant FSH: an opening study. Reprod Biomed Online. 2004;8(6):635-643.
  • 19. Matorras R, Prieto B, Exposito A, et al. Mid-follicular LH supplementation in women aged 35-39 years undergoing ICSI cycles: a randomized controlled study. Reprod Biomed Online. 2009;19(6):879-887.
  • 20. Wong PC, Qiao J, Ho C, et al. Current opinion on use of luteinizing hormone supplementation in assisted reproduction therapy: an Asian perspective. Reprod Biomed Online. 2011;23(1):81-90.
There are 19 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Research Article
Authors

Özcan Budak 0000-0002-2617-3175

Mehmet Sühha Bostancı 0000-0002-4776-6244

Songül Doğanay 0000-0002-1730-1331

Nermin Akdemir 0000-0002-9129-2103

Serhan Cevrioğlu 0000-0002-3810-6519

Project Number -
Publication Date August 27, 2021
Submission Date June 8, 2021
Acceptance Date July 8, 2021
Published in Issue Year 2021 Volume: 18 Issue: 2

Cite

Vancouver Budak Ö, Bostancı MS, Doğanay S, Akdemir N, Cevrioğlu S. Kontrollü Overyan Stimülasyon Protokollerinde rLH Tedaviye Eklenmeli mi?. Harran Üniversitesi Tıp Fakültesi Dergisi. 2021;18(2):199-203.

Harran Üniversitesi Tıp Fakültesi Dergisi  / Journal of Harran University Medical Faculty