Endometriozisli hastalarda ovulasyon indüksiyonu ajanı olarak letrozol ve gonedotropinlerin karşılaştırılması: prospektif randomize çalışma

Abstract

Amaç: Bu çalışmada letrozol ve gonadotropinlerin evre 1-2 endometriozisli infertil hastalarda ovülasyon indüksiyonu üzerine etkilerinin karşılaştırılması amaçlanmıştır.

Gereç ve yöntem: Prospektif randomize olarak dizayn edilen çalışmaya tanısal laparoskopi yapılan ve histolojik olarak tanı konulan evre 1-2 endometriozisli 20 hasta dahil edildi. Zamanlanmış cinsel ilişki ile devam etmeyi planlayan hastalar, en az üç en fazla beş ovulasyon indüksiyonu döngüsü için letrozol (n=10) veya gonadotropinler (n=10) olmak üzere iki tedavi grubuna ardışık olarak randomize edildi.

Bulgular: Ovulasyon, letrozol grubunda %82,2 (37/45 siklus) ve gonadotropin grubunda %86,4 (32/37 siklus) oranlarında gerçekleşti. İki grup arasında ovulasyon oranları istatistiksel olarak benzerdi (p=0,590). hCG uygulamasının yapıldığı gün gonadotropin grubunda toplam folikül sayısı anlamlı olarak yüksekti (2,33±0,71 ve 3,05±0,91, p<0,001). Klinik gebelik oranları hem tamamlanmış siklus başına hem de hasta başına iki grup arasında benzerdi (sırasıyla siklus başına %8,1 ve %9,4  p=0,850 ve hasta başına %30 ve%30, p=1,000).

Sonuç: Letrozol iyi tolere edilebilen bir ovulasyon indüksiyonu ajanıdır.  Evre 1-2 Endometriozisli hastalarda letrozolün ovülasyon indüksiyonu üzerindeki etkileri gonadotropinlerle karşılaştırılabilir bulunmuştur.

Keywords

• etrozol,gonadotropin,endometriozis

Letrozole versus gonadotropins for ovulation induction in patients with endometriosis: a prospective randomized trial

Abstract

Purpose: This study aimed to compare the effects of letrozole and gonadotropins for ovulation induction in infertile patients with stage 1-2 endometriosis.

Materials and methods: Twenty patients who underwent diagnostic laparoscopy and histologically diagnosed stage 1-2 endometriosis were included in this prospective randomized study.   Patients who planned to continue with timed sexual intercourse were randomized into two treatment groups including letrozole (n=10) or gonadotropins (n=10) for minimum three and maximum five treatment cycles.

Results: Ovulation occurred in 37/45 cycles (82.2%) in the letrozole group and 32/37 cycles (86.4%) in the gonadotropin group, without statistically significant difference (p=0.590). Total number of follicles was significantly higher in gonadotropin group on the day of hCG administration (2.33±0.71 vs. 3.05±0.91, p<0.001). Clinical pregnancy rates both per completed cycles and per patients were similar between two groups (8.1% vs. 9.4%, p=0.850 and 30% vs. 30%, p=1.000; respectively).

Conclusions: Letrozole is well tolerated and cost effective ovulation induction agent in patients with endometriosis and effects of letrozole for ovulation induction were comparable to gonadotropins. 

Keywords

• Letrozole,gonadotropin,endometriosis

References

1. [1] Greene AD, Lang SA, Kendziorski JA, Sroga-Rios JM, Herzog TJ, Burns KA. Endometriosis: where are we and where are we going? Reproduction. 2016;152(3):R63-https://dx.doi.org/ 10.1530/REP-16-0052.
2. [2] Kiesel L, Sourouni M. Diagnosis of endometriosis in the 21st century. Climacteric. 2019:1-7.https://dx.doi.org/10.1080/13697137.2019.1578743. [Epub ahead of print]
3. [3] Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstetrics &Gynecology Clinics of North America. 1997; 24: 235–258.
4. [4] Guzick DS. Clinical epidemiology of endometriosis and infertility. Obstetrics and Gynecology Clinics of North America 1989; 16: 43–59.
5. [5] Practice Committee of the American Society for Reproductive Medicine. Endometriosis and infertility: a committee opinion. Fertil Steril. 2012;98(3):591-8.
6. [6] Barbieri RL. Endometriosis 1990. Current treatment approaches. Drugs 1990; 39: 502–511.
7. [7] Fisch P, Casper RF, Brown SE et al. Unexplained infertility: evaluation of treatment with clomiphene citrate and human chorionic gonadotropin. Fertil Steril 1989; 51: 828 –833.
8. [8] Ailawadi RK, Jobanputra S, Kataria M, Gurates B, Bulun SE. Treatment of endometriosis and chronic pelvic pain with letrozole and norethindrone acetate: a pilot study. Fertil Steril. 2004; 8: 290-296.

9. [9] Committee Opinion No. 663:Aromatase Inhibitors in Gynecologic Practice. Obstet Gynecol. 2016;127(6):e170-4. https://dx.doi.org/10.1097/AOG.0000000000001484.
10. [10] Requena A, Herrero J, Landeras J et al. Use of letrozole in assisted reproduction: a systematic review and meta-analysis. Human Reproduction 2008; 14: 571–582. https://dx.doi.org/10.1093/humupd/dmn033.
11. [11] Abu Hashim H. Potential role of aromatase inhibitors in the treatment of endometriosis. Int J Womens Health. 2014;6:671-80. https://dx.doi.org/10.2147/IJWH.S34684.
12. [12] Jacobs HS, Agrawal R. Complications of ovarian stimulation. Baillieres Clin Obstet Gynaecol 1998; 12: 565–579.
13. [13] World Health Organization. Laboratory manual of the WHO for the examination of human semen and sperm–cervical mucus interaction. Ann 1st Super Sanita 2001; 37: 1–123.
14. [14] Revised American Society for Reproductive Medicine classification of endometriosis: Fertil Steril 1997; 67: 817-821.
15. [15] Kodaman PH. Current strategies for endometriosis management. Obstet Gynecol Clin North Am. 2015;42(1):87-101. https://dx.doi.org/10.1016/j.ogc.2014.10.005.
16. [16] Quaas AM, Weedin EA, Hansen KR. On-label and off-label drug use in the treatment of endometriosis. Fertil Steril. 2015;103(3):612-25. https://dx.doi.org/10.1016/j.fertnstert.2015.01.006.
17. [17] Practice Committee of the American Society for Reproductive Medicine. Treatment of pelvic pain associated with endometriosis: a committee opinion. Fertil Steril. 2014;101(4):927-35. https://dx.doi.org/10.1016/j.fertnstert.2014.02.012.
18. [18] Dunselman GA, Vermeulen N, Becker C et al. European Society of Human Reproduction and Embryology. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014;29(3):400-12.https://dx.doi.org/10.1093/humrep/det457.
19. [19] Tummon IS, Asher LJ, Martin JS, Tulandi T. Randomized controlled trial of superovulation and insemination for infertility associated with minimal or mild endometriosis. Fertil Steril. 1997; 68: 8-12.
20. [20] Parazzini F. Ablation of lesions or no treatment in minimal-mild endometriosis in infertile women: a randomized trial. Gruppo Italiano per lo Studio dell'Endometriosi. Hum Reprod. 1999 May;14(5):1332-4.
21. [21] Deaton JL, Gibson M, Blackmer KM, Nakajima ST, Badger GJ, Brumsted JR. A randomized, controlled trial of clomiphene citrate and intrauterine insemination in couples with unexplained infertility or surgically corrected endometriosis. Fertil Steril. 1990;54(6):1083-8.
22. [22] Fedele L, Bianchi S, Marchini M, Villa L, Brioschi D, Parazzini F. Superovulation with human menopausal gonadotropins in the treatment of infertility associated with minimal or mild endometriosis: a controlled randomized study. Fertil Steril. 1992;58(1):28-31.
23. [23] Kemmann E, Ghazi D, Corsan G, Bohrer MK. Does ovulation stimulation improve fertility in women with minimal/mild endometriosis after laser laparoscopy? Int J Fertil Menopausal Stud. 1993;38(1):16-21.
24. [24] Werbrouck E, Spiessens C, Meuleman C, D'Hooghe T. No difference in cycle pregnancy rate and in cumulative live-birth rate between women with surgically treated minimal to mild endometriosis and women with unexplained infertility after controlled ovarian hyperstimulation and intrauterine insemination. Fertil Steril. 2006;86(3):566-71.
25. [25] Homburg R. Oral agents for ovulation induction— clomiphene citrate versus aromatase inhibitors. Hum Fertil (Camb) 2008;11:17–22. https://dx.doi.org/10.1080/14647270701689670.
26. [26] Al-Fadhli R, Sylvestre C, Buckett W, Tan SL, Tulandi T. A randomized trial of superovulation with two different doses of letrozole. Fertil Steril 2006; 85: 161–164.
27. [27] Quintero RB, Urban R, Lathi RB, Westphal LM, Dahan MH. A comparison of letrozole to gonadotropins for ovulation induction, in subjects who failed to conceive with clomiphene citrate. Fertility and Sterility 2007; 88: 879-885.
28. [28] Elnashar A, Fouad H, Eldosoky M, Saeid N. Letrozole induction of ovulation in women with clomiphene citrate resistant polycystic ovary syndrome may not depend on the period of infertility, the body mass index, or the luteinizing hormone/follicle- stimulating hormone ratio. Fertil Steril 2006; 85: 511–513.
29. [29] Alborzi S, Hamedi B, Omidvar A, Dehbashi S, Alborzi S, Alborzi M. A comparison of the effect of short-term aromatase inhibitor (letrozole) and GnRH agonist (triptorelin) versus case control on pregnancy rate and symptom and sign recurrence after laparoscopic treatment of endometriosis. Arch Gynecol Obstet. 2011;284(1):105-10. https://dx.doi.org/10.1007/s00404-010-1599-6.
30. [30] Abu Hashim H, El Rakhawy M, Abd Elaal I. Randomized comparison of superovulation with letrozole vs. clomiphene citrate in an IUI program for women with recently surgically treated minimal to mild endometriosis. Acta Obstet Gynecol Scand. 2012;91(3):338-45. https://dx.doi.org/ 10.1111/j.1600-0412.2011.01346.x
31. [31] Biljan MM, Tan SL, Tulandi T. Prospective randomized trial comparing the effects of 2.5 and 5.0 mg of letrozol (LE) on follicular development, endometrial thickness and pregnancy rate in patients undergoing superovulation. Fertil Steril 2002; 78: 55.
32. [32] Badawy A, Mosbah A, Shady M.Anastrozole or letrozole for ovulation induction in clomiphene-resistant women with polycystic ovarian syndrome: a prospective randomized trial.Fertil Steril. 2008 May;89(5):1209-12. https://dx.doi.org/10.1016/j.fertnstert.2007.05.010
33. [33] Mitwally FM, Casper RF. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril 2001; 75: 305–309.
34. [34] Al-Omari WR, Sulaiman W, Al-Hadithi N. Comparison of two aromatase inhibitors in women with clomiphene- resistant polycystic ovary syndrome. Intern J Gynecol Obstet 2004; 85: 289–291. https://dx.doi.org/10.1016/j.ijgo.2003.11.010
35. [35] Mitwally MF, Biljan MM, Casper RF. Pregnancy outcome after the use of an aromatase inhibitor for ovarian stimulation. Am J Obstet Gynecol 2005; 192: 381–386. https://dx.doi.org/10.1016/j.ajog.2004.08.013.