KLOMİFEN SİTRATA REZİSTAN OLAN POLİKİSTİK OVER SENDROMLU OLGULARDA KRONİK DÜŞÜK DOZ GONADOTROPİN VE KONVANSİYONEL DOZ GONADOTROPİN TEDAVİ PROTOKOLLERİNİN KARŞILAŞTIRILMASI Comparison of Chronic Low Dose Gonadotropin and Conventional Dose Gonadotropin Treatment Protocols in Patients Who Had Clomiphene Citrate-Resistant Anovulation Associated With Polycystic Ovarian Syndrome
Abstract
ÖZET
Amaç: Anovulatuar polikistik over sendromlu hastalarda kronik düşük doz ve konvansiyonel doz tedavi rejimlerinin
etkinliklerinin karşılaştırılması
Gereç ve yöntemler: Klomifen sitrata rezistan anovulatuar PCOS tanısı almış olan 50 olgu çalışmaya dahil
edildi. Olguların 25 tanesine konvansiyonel stepwise protokol uygulandı ve (Grup 1) olarak adlandırıldı. Diğer
25 olgudan oluşan gruba (Grup 2)’ da kronik düşük doz FSH protokol uygulandı. Hastalar seri ultrasonografi
ve serum estradiol sevilerine bakılarak monitörize edildi. Folliküler gelişim paterni, toplam kullanılan
FSH dozu, serum estradiol konsantrasyonu, siklus fekunditesi, multiple gebelik oranları ve ovarian hiperstimulasyon
sendromu açısından iki grup karşılaştırıldı.
Bulgular: Her iki grup yaş, infertilite süresi, vücut kitle indeksi ve endokrin parametreler açısından benzer
olarak bulundu. Stimulasyon süresi Grup 2 'de anlamlı olarak uzun bulundu (p=0.02). Gruplar, ovulatuar
siklus açısından değerlendirildiğinde düşük doz kullanılan grupta ovulatuar siklus oranı %68 iken konvansiyonel
grupta %76 olarak bulundu. Gebelik oranları açısından değerlendirildiğinde düşük doz grupta gebelik
oranı %24 iken konvansiyonel grupta %20 olarak bulundu. Düşük doz kullanılan grupta ovulatuar siklus başına
gebelik oranı konvansiyonel gruptan daha yüksek (%37 vs %26) idi. Monofolliküler gelişim düşük doz
kullanılan grupta %60, konvansiyonel grupta ise %48 olarak bulundu. Düşük doz kullanılan grupta gerek
OHSS (p < 0.04) gerekse estradiol (p < 0.008) konsantrasyonları anlamlı olarak düşük bulundu. Her iki grupta
da çoğul gebelik izlenmedi.
Sonuç: Kronik düşük doz FSH rejimi ; multifolliküler gelişim ve OHSS riskini azaltarak, ovulasyon indüksiyonunun
güvenliğini artırmakta ve bunun yanında tatmin edici gebelik sonuçları elde edilmesini sağlayabilmektedir.
Anahtar sözcükler: İnfertilite; Ovulasyon indüksiyonu; Polikistik over sendromu
ABSTRACT
Objective: To compare efficiency of conventional and chronic low-dose regimens for treatment of
anovulation associated with polycystic ovary syndrome (PCOS).
Materials and methods: Fifty women, who had clomiphene citrate-resistant anovulation associated with
PCOS, participated in the study. The first 25 patients were treated with urinary FSH using a conventional
stepwise protocol (Group 1), while the second group had a regimen of chronic low dose FSH (Group 2).
Patterns of follicular development, amount of FSH required, serum estradiol concentrations, cycle fecundity,
rates of multiple pregnancy and OHSS were compared.
Results: The two groups were similar in terms of duration of infertility, age, body mass index and endocrine
parameters. The duration of treatment was significantly higher (p = 0.02) in Group 2 . The percentage
of ovulatory cycles occurring in low dose and conventional regimens was 68% versus 76% respectively.
Pregnancy rate was 20% in conventional stepwise protocol group and 24% in chronic low dose group.
The patients in Group 2 had a higher pregnancy rate per ovulatory cycle (37% versus 26%). Monofollicular
development was noted in 60% of the Group 2 patients (48% in Group 1, p = 0.03). Treatment with the
low-dose protocol resulted in significant reduction in OHSS (p < 0.04) and serum oestradiol concentrations
(p < 0.008). No multiple pregnancies occurred in either group.
Conclusion: The use of chronic low-dose regimen of FSH permitted induction of ovulation safely by
minimizing the risk of multifollicular development and OHSS while maintaining a satisfactory pregnancy.
Key words: Infertility; Ovulation induction; Polycystic ovary syndrome
References
- 1. Carvalho LML, Dos Reis FM, Candido AL, Nunes FFC, Ferreira CN, Gomes KB. Polycystic Ovary Syndrome as a systemic disease with multiple molecular pathways: a narrative review. Endocr Regul. 2018 Oct 1;52(4):208-221 2. Ajmal N, Khan ZS, Shaikh R. Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article. Eur J Obstet Gynecol Reprod Biol X: X 2019; 3 3. Balen A. The pathophysiology of polycystic ovary syndrome: trying to understand PCOS and its endocrinology. Best Pract Res Clin Obstet Gynaecol. 2004;18:685-706. 4. BelenkaiaLV, Lazareva LM, Walker W, Lizneva DV, Suturina LV. Criteria, phenotypes and prevalence of polycystic ovary syndrome. Minerva Ginecol. 2019 Jun;71 (3):211-223 5. Tsilchorozidou T, Overton C, Conway GS. The pathophysiology of polycystic ovary syndrome. Clin Endocrinol. 2004;60(1):1-17. 6. Diamanti-Kandarakis E, Piperi C, Spina J Argyrakopoulou G, Papanastasiou L, Bergiele A, Polycystic ovary syndrome: The influence of environmental and genetic factors. Hormones. 2006;5(1):17-34. 7. Amer SA, Li TC, Metwally M, Emarh M, Ledger WL. Randomized controlled trial comparing laparoscopic ovarian diathermy with clomiphene citrate as a first-line method of ovulation induction in women with polycystic ovary syndrome. Hum Reprod. 2009;24 (1) :219-25. 8. Sachdeva G, Gainder S, Suri V, Sachdeva N, Chopra S. Comparison of Clinical, Metabolic, Hormonal, and Ultrasound Parameters among the Clomiphene Citrate-Resistant and Clomiphene Citrate-Sensitive Polycystic Ovary Syndrome Women. J Hum Reprod Sci. 2019 Jul-Sep;12(3):216-223. 9. Alshahrani S, Aldossari K, Al-Zahrani J, Gabr AH,, Henkel R, Ahmad G. Interpretation of semen analysis using WHO 1999 and WHO 2010 reference values: Abnormal becoming normal. Andrologia. 2018 Mar;50(2) 10. Brown JB. Pituitary control of ovarian function concepts derived from gonadotropin therapy.Aust NZJ Obstet Gynecol. 1978; 18:47 11. Petersen KB, Pedersen NG, Pedersen AT , Lauritsen MP , Freiesleben NC. Mono-ovulation in women with polycystic ovary syndrome: a clinical review onovulation induction. RBM Online. 2016; 32, 563–583 12. VTN Lan, RJ Norman, GH Nhu, PH Tuan, HM Tuong. Ovulation induction using low-dose step-up rFSH in Vietnamese women with polycystic ovary syndrome. RBM Online. 2009 Vol 18. No 4 516-521 13. Sagle MA, Hamilton-Fairley DH, Kiddy D, Franks S.A. Comperative randomized study of low-dose human menopausal gonadotropin and follicle stimulating hormone in women with polycystic ovarian syndrome. Fertil Steril. 1991; 55:56 14. Cantineau AEP, Cohlen BJ, Heineman MJ. Ovarian stimulation protocols (anti-oestrogens, gonadotrophins with and without GnRH agonists/antagonists) for intrauterine insemination (IUI) in women with subfertility. Cochrane Database of Systematic Reviews 2, Art.2007 ; No: CD005356 15. Shoham Z, Patel A, Jacobs HS. Polycystic ovary syndrome : safety and effectiveness of stepwise and low dose administration of purified follicle stimulating hormone. Fertil Steril. 1991; 55: 1051 16. Leader A, Monofollicular Ovulation Induction Study Group. Improved monofollicular ovulation in anovulatory or oligo-ovulatory women after a low-dose step-up protocol with weekly increments of 25 international units of follicle-stimulating hormone. Fertil Steril. 2006; 85, 1766–1773. 17. Matsuzaki T, Iwasa T , Yanagihara R, Komasaka M, Yano K, Mayila Y, et al. Pilot study of the optimal protocol of low dose step-up follicle stimulating hormone therapy for infertile women. Reprod Med Biol. 2018;17:315–324. 18. Alsina JC, Balda JAR, Sarrio AR, Fernández CV, Trigo CI, Parga GJL. Ovulation induction with a starting dose of 50 IU of recombinant follicle stimulating hormone in WHO group II anovulatory women: the IO-50 study, a prospective, observational, multicenter, open trial. BJOG. 2003; 110, 1072–1077 19. Taketani Y, Kelly E, Yoshimura Y, Hoshiai H, Irahara M, Mizunuma H, et al. Recombinant follicle-stimulatinghormone (follitropin alfa) versus purified urinary follicle-stimulating hormone in a low-dose step-up regimen to induce ovulation in Japanese women with anti-estrogen-ineffective oligo-oranovulatory infertility: results of a single-blind Phase III study. Reprod Med Biol. 2010;9:99‐106. 20. Homburg R, Armar AN, Eshel A, Adams J, Jacobs HS. Influence of serum luteinizing hormone concentration on ovulation, conception and early pregnancy loss in polycystic ovary syndrome. Br Med J. 1988;297:1024-6. 21. Regan L, Owen EJ, Jacobs HS. Hypersecretion of luteinizing hormone, infertility and miscarriage. Lancet. 1990; 336:1141-4. 22. Ullah K, Rahman TU, Pan HT, Guo MX, Dong XY, Liu J, et al. Serum estradiol levels in controlled ovarian stimulation directly affect the endometrium. J Mol Endocrinol. 2017 Aug;59(2):105-119 23. Hamilton – Firley DH, Kiddy D,Watson H,Sagle M, Franks S. Low dose gonadotropin for induction of ovulation in 100 women with polycystic ovary syndrome. Hum Reprod. 1991;6:1095 24. Dale PO, Tanbo T,Haug E . Polycystic ovary syndrome : Low dose follicle stimulating hormone administration is a safe stimulation regimen even in previous hyperresponsive patients. Hum Reprod. 1992; 7:1085 25. Roy Homburg, Tally Levy, Zion Ben-Rafael, A comparative prospective study of conventional regimen with chronic low-dose administration of follicle-stimulating hormone for anovulation associated with polycystic ovary syndrome. Fertil Steril. 1995 ;Vol. 63, No.4,
Abstract
References
- 1. Carvalho LML, Dos Reis FM, Candido AL, Nunes FFC, Ferreira CN, Gomes KB. Polycystic Ovary Syndrome as a systemic disease with multiple molecular pathways: a narrative review. Endocr Regul. 2018 Oct 1;52(4):208-221 2. Ajmal N, Khan ZS, Shaikh R. Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article. Eur J Obstet Gynecol Reprod Biol X: X 2019; 3 3. Balen A. The pathophysiology of polycystic ovary syndrome: trying to understand PCOS and its endocrinology. Best Pract Res Clin Obstet Gynaecol. 2004;18:685-706. 4. BelenkaiaLV, Lazareva LM, Walker W, Lizneva DV, Suturina LV. Criteria, phenotypes and prevalence of polycystic ovary syndrome. Minerva Ginecol. 2019 Jun;71 (3):211-223 5. Tsilchorozidou T, Overton C, Conway GS. The pathophysiology of polycystic ovary syndrome. Clin Endocrinol. 2004;60(1):1-17. 6. Diamanti-Kandarakis E, Piperi C, Spina J Argyrakopoulou G, Papanastasiou L, Bergiele A, Polycystic ovary syndrome: The influence of environmental and genetic factors. Hormones. 2006;5(1):17-34. 7. Amer SA, Li TC, Metwally M, Emarh M, Ledger WL. Randomized controlled trial comparing laparoscopic ovarian diathermy with clomiphene citrate as a first-line method of ovulation induction in women with polycystic ovary syndrome. Hum Reprod. 2009;24 (1) :219-25. 8. Sachdeva G, Gainder S, Suri V, Sachdeva N, Chopra S. Comparison of Clinical, Metabolic, Hormonal, and Ultrasound Parameters among the Clomiphene Citrate-Resistant and Clomiphene Citrate-Sensitive Polycystic Ovary Syndrome Women. J Hum Reprod Sci. 2019 Jul-Sep;12(3):216-223. 9. Alshahrani S, Aldossari K, Al-Zahrani J, Gabr AH,, Henkel R, Ahmad G. Interpretation of semen analysis using WHO 1999 and WHO 2010 reference values: Abnormal becoming normal. Andrologia. 2018 Mar;50(2) 10. Brown JB. Pituitary control of ovarian function concepts derived from gonadotropin therapy.Aust NZJ Obstet Gynecol. 1978; 18:47 11. Petersen KB, Pedersen NG, Pedersen AT , Lauritsen MP , Freiesleben NC. Mono-ovulation in women with polycystic ovary syndrome: a clinical review onovulation induction. RBM Online. 2016; 32, 563–583 12. VTN Lan, RJ Norman, GH Nhu, PH Tuan, HM Tuong. Ovulation induction using low-dose step-up rFSH in Vietnamese women with polycystic ovary syndrome. RBM Online. 2009 Vol 18. No 4 516-521 13. Sagle MA, Hamilton-Fairley DH, Kiddy D, Franks S.A. Comperative randomized study of low-dose human menopausal gonadotropin and follicle stimulating hormone in women with polycystic ovarian syndrome. Fertil Steril. 1991; 55:56 14. Cantineau AEP, Cohlen BJ, Heineman MJ. Ovarian stimulation protocols (anti-oestrogens, gonadotrophins with and without GnRH agonists/antagonists) for intrauterine insemination (IUI) in women with subfertility. Cochrane Database of Systematic Reviews 2, Art.2007 ; No: CD005356 15. Shoham Z, Patel A, Jacobs HS. Polycystic ovary syndrome : safety and effectiveness of stepwise and low dose administration of purified follicle stimulating hormone. Fertil Steril. 1991; 55: 1051 16. Leader A, Monofollicular Ovulation Induction Study Group. Improved monofollicular ovulation in anovulatory or oligo-ovulatory women after a low-dose step-up protocol with weekly increments of 25 international units of follicle-stimulating hormone. Fertil Steril. 2006; 85, 1766–1773. 17. Matsuzaki T, Iwasa T , Yanagihara R, Komasaka M, Yano K, Mayila Y, et al. Pilot study of the optimal protocol of low dose step-up follicle stimulating hormone therapy for infertile women. Reprod Med Biol. 2018;17:315–324. 18. Alsina JC, Balda JAR, Sarrio AR, Fernández CV, Trigo CI, Parga GJL. Ovulation induction with a starting dose of 50 IU of recombinant follicle stimulating hormone in WHO group II anovulatory women: the IO-50 study, a prospective, observational, multicenter, open trial. BJOG. 2003; 110, 1072–1077 19. Taketani Y, Kelly E, Yoshimura Y, Hoshiai H, Irahara M, Mizunuma H, et al. Recombinant follicle-stimulatinghormone (follitropin alfa) versus purified urinary follicle-stimulating hormone in a low-dose step-up regimen to induce ovulation in Japanese women with anti-estrogen-ineffective oligo-oranovulatory infertility: results of a single-blind Phase III study. Reprod Med Biol. 2010;9:99‐106. 20. Homburg R, Armar AN, Eshel A, Adams J, Jacobs HS. Influence of serum luteinizing hormone concentration on ovulation, conception and early pregnancy loss in polycystic ovary syndrome. Br Med J. 1988;297:1024-6. 21. Regan L, Owen EJ, Jacobs HS. Hypersecretion of luteinizing hormone, infertility and miscarriage. Lancet. 1990; 336:1141-4. 22. Ullah K, Rahman TU, Pan HT, Guo MX, Dong XY, Liu J, et al. Serum estradiol levels in controlled ovarian stimulation directly affect the endometrium. J Mol Endocrinol. 2017 Aug;59(2):105-119 23. Hamilton – Firley DH, Kiddy D,Watson H,Sagle M, Franks S. Low dose gonadotropin for induction of ovulation in 100 women with polycystic ovary syndrome. Hum Reprod. 1991;6:1095 24. Dale PO, Tanbo T,Haug E . Polycystic ovary syndrome : Low dose follicle stimulating hormone administration is a safe stimulation regimen even in previous hyperresponsive patients. Hum Reprod. 1992; 7:1085 25. Roy Homburg, Tally Levy, Zion Ben-Rafael, A comparative prospective study of conventional regimen with chronic low-dose administration of follicle-stimulating hormone for anovulation associated with polycystic ovary syndrome. Fertil Steril. 1995 ;Vol. 63, No.4,
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Case Report |
| Authors | |
| Publication Date | December 27, 2019 |
| Published in Issue | Year 2019 Volume: 9 Issue: 4 |