Klomifen sitrata rezistan olan polikistik over sendromlu olgularda kronik düşük doz gonadotropin ve konvansiyonel doz gonadotropin tedavi protokollerinin karşılaştırılması
Öz
Abstract
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
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 64% versus 84% 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 24%). 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
Özet
Klomifen sitrata rezistan
olan polikistik over sendromlu olgularda
kronik düşük doz gonadotropin ve konvansiyonel doz gonadotropin tedavi
protokollerinin karşılaştırılması
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 Grup2 'de anlamlı olarak uzun bulundu
(p=0.02). Gruplar, ovulatuar siklus açısından değerlendirildiğinde düşük doz
kullanılan grupta ovulatuar siklus oranı %64 iken konvansiyonel grupta %84 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 %24) 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
Anahtar Kelimeler
Kaynakça
- 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
- Ajmal N, Khan ZS, Shaikh R. Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article. European Journal of Obstetrics & Gynecology and Reproductive Biology: X 2019; 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
- 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
- Tsilchorozidou T, Overton C, Conway GS. The pathophysiology of polycystic ovary syndrome. Clin Endocrinol 2004;60(1):1-17
- 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
- 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
- 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
- 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)
- Brown JB. Pituitary control of ovarian function concepts derived from gonadotropin therapy.Aust NZJ Obstet Gynecol 1978; 18:47
- Petersen KB, Pedersen NG, Pedersen AT , Lauritsen MP , Freiesleben NC. Mono-ovulation in women with polycystic ovary syndrome: a clinical review onovulation induction. Reproductive BioMedicine Online 2016; 32, 563–583
- 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
- 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
- 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
- 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
- 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. Fertility Sterility 2006; 85, 1766–1773
- 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
- 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
- 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
- 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
- Regan L, Owen EJ, Jacobs HS. Hypersecretion of luteinizing hormone, infertility and miscarriage. Lancet 1990; 336:1141-4
- 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
- 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
- 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
- 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