Clinical Study On Letrozole For Induction Of Ovulation In Polycystic Ovary Syndrome(PCOS)

Background and Objective:Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder in young women which manifests itself in a variety of clinical ways. PCOS accounts 5%～10% for women of childbearing age, 30%～60% for women of anovulatory infertility, even highly 75%.PCOS is one of the main reasons which cause menstrual disorders, hyperandrogenism and persistent anovulation. The exact pathogenesis of PCOS is not clear so far, maybe the result of the interaction of genetics and environment. Clomiphene-citrate (CC) often acts as a first-line treatment for ovulation induction in anovulatory patients. CC has the lifting effect of estrogen on the hypothalamic/pituitary feedback inhibition through antagonism of the hypothalamic-pituitary estrogen receptor (ER), so that increased secretion of pituitary gonadotropin induces follicle growth and development. However, CC occupies endometrial, cervical tissue on the ER, and plays the role of anti-estrogen, resulting in thin endometrium, reduced volume and viscosity traits of cervical mucus secretion which can effect the tract of sperm and implantation of the fertilized egg. The ovulation rate of conventional CC program can be as high as 75%～80%, but after the use of six cycles the cumulative pregnancy rate is as low as 30%～40%. Clomiphene resistance, which refers to persistence of anovulation after standard CC therapy, occurs in 20%～25% of patients. For patients with CC resistance, the current second-line drugs used to treat are HMG or r-FSH. However, PCOS patients are highly sensitive to HMG or r-FSH, so HMG or r-FSH therapy easily leads to multiple follicle development, and increases the occurence of ovarian hyperstimulation syndrome (OHSS) and the risk of multiple pregnancy. Therefore, looking for a new drug to avoid these deficiencies appears to be particularly urgent. Letrozole is a third-generation, nonsteroidal aromatase inhibitor. It has been postulated that blocking estrogen production by inhibiting aromatization, the conversion of androstenedione and testosterone to estrogen in the ovary would release the hypothalamic/ pituitary axis from estrogenic negative feedback. As a result, follicle-stimulating hormone (FSH) secretion increases, stimulating the development of ovarian follicles. Since LE was firstly used abroad in the cases of ovulation failure with CC and achieved success in 2001, the study at home and abroad over the LE of the efficacy of ovarian hyperstimulation has developed. Aromatase inhibitors have potential as alternatives to, or even replacements for CC. In this study, four kinds of ovulation induction programs on PCOS infertility patients are displayed, and the object is to explore the best option for ovulation induction.Material and methods1. General condition of the patients: A total of 81 infertile women (81 cycles) with PCOS from July 2008 to December 2008, divided into 4 groups, were treated with LE in Reproductive Medicine Center of Provincial Hospital Affiliated to Shandong University. The number of follicles, endometrial thickness for HCG day, dose of HMG used per cycle, ovulation rate per cycle, pregnancy rate per cycle were compared. The 4 groups were spectively 23 cycles of letrozole as a separate 5 days program, 14 cycles of Letrozole as a separate 10-day program, 21 cycles of 5 days Letrozole + HMG program, 23 cycles for 10 days Letrozole + HMG program .2. Statistical method:The statistical analyses were performed using SPSS17.0 software for windows statistical package. Measurement data are expressed x±s. Independent-samples t-test was used when comparing mean. Enumeration data are expressed as a percentage, and chi-square test was used when comparing the percentage. The differences are considered to be statistically significant if P <0.05.Result1 .The number of dominant follicle [ 1.0±0 vs 1.14±0.36], ovulation rate per cycle[91.3% vs 100%], pregnancy rate per cycle [34.78% vs 35.71%] in letrozole as a separate 5 days program were lower than in letrozole as a separate 10 days program (P>0.05)> while the endometrial thickness on the day of HCG administration [(0.88±0.16)vs(0.85±0.17)cm] in letrozole as a separate 5 days program was higher than in letrozole as a separate 10 days program (P>0.05) . During the 5 pregnancies in letrozole as a separate 10 days program, one of them was an ectopic pregnancy (having ectopic pregnancy history on the same side), and one of them was a result of traumatic abortion, and one of them had a surgery due to stopped infertility. The two methods tend to single-follicle development, unique pregnancy and no ovarian hyperstimulation symptoms.2. The number of dominant follicle [3.05±3.49 vs 3.91±4.89], HMG volume [(12.76±5.89) vs (13.13±4.76) IU], ovulation rate per cycle[80.95% vs 91.3%] in 5 days Letrozole + HMG program group were lower than in 10 days Letrozole + HMG program group (P>0.05), while the endometrial thickness on the day of HCG administration [(1.06±0.12)vs(0.97±0.23)cm] and pregnancy rate per cycle [42.85%vs 39.13%]in 5 days Letrozole + HMG program group were higher than in 10 days Letrozole + HMG program group (P>0.05).During the nine pregancies in 10 days Letrozole + HMG program group, one of them had a surgery due to stopped infertility, and one of them was a twin pregnancy. A total of two cycles in 10 days Letrozole + HMG program group had minor symptoms of ovarian hyperstimulation, while in 5 days Letrozole + HMG program group no ovarian hyperstimulation occurred.3.In the 5 days letrozole + HMG group the endometrial thickness on the day of HCG administration and the number of dominant follicle were higher than in letrozole as a separate 10 days program(P<0.05) , and pregnancy rate per cycle was also higher (P>0.05), while ovulation rate per cycle in the 5 days letrozole + HMG group was lower than in letrozole as a separate 10 days program (P>0.05).Conclusion1.LE in patients with polycystic ovary syndrome is effective in ovulation induction, and tends to single-follicle development.2.In letrozole as a separate 10 days program, in 10 days Letrozole + HMG program group, in letrozole as a separate 5 days program and in 5 days Letrozole + HMG program group, there is no statistical significance in pregnancy rate per cycle and ovulation rate per cycle.3.Between in letrozole as a separate 10 days program and in 10 days Letrozole + HMG program group the advantage and defect are still required to prove by more research.