A Comparative Study Of The Effects Of Letrozole Versus Clomiphene Citrate For Ovulation Induction

As the improvement of the artificial assisted technology, the treatment of ovulation induction has become a key and chief role in assisted reproductive techniques. However, Clomiphene Citrate (CC) and Gonadotropins used for inducing ovulation bring about some side effects, including leading to poor cervical mucus , thin endometrium, OHSS, the multiple pregnancy and so on. Recently many investigations were published to discover letrozole, an aromatase inhibitor that has been used widely in the treatment of diseases depended on estrogen, is able to achieve the pleasant results in inducing ovulation for human and animal model as a fertility regulator, and to acquire LE, meanwhile, is associated with less influence on the cervical mucus, the endometrium and higher pregnancy rates than CC for inducing ovulation without a peripheral antiestrogenic effect unlike CC. We carried out a comparative study of the effects and the outcome letrozole versus clomiphene citrate for ovulation induction through both animal experiment and clinical research, in order to prove that LE can be used to induce ovulation and its effect is better than CC, which was based on the clinical use of LE that was a new ovulation induction agent. PartⅠA comparative study of the effects of letrozole versus clomiphene citrate for ovulation induction on endometrial receptivity in mouseObjective: To investigate the effects of letrozole (LE) versus clomiphene citrate (CC) for induction of ovulation on mouse endometrial morphology during preovulatory and on mouse endometrium of endometrial receptivity during implantation. And compared with CC, the superiority of LE for induction of ovulation would be evaluated, which offer theoretical foundation for the clinical use of LE for inducing ovulation.Methods: The 48 mice were divided into three groups of 16 mice each including the LE group, the CC group and the control group. The serum and uterus of mice in preovulatory phase and implantation phase (on the 4.5 day of pregnancy) and Embryos in implantation phase after ovulation were obtained. The thickness of endometrium and the average area, perimeter and maximal diameter of single gland were determined by computerized multi-functional image analyzer. The concentration of serum sex hormone was measured by the method of chemiluminescence. Embryo development were observed by microscope, the detection of pinopode were examined by scanning electron microscopy and the expression of LIF, ER and PR implantation endometrium of mouse, was examined by immunohistochemistry technique.Result: (1) not only the concentration of serum estradiol( E2) but also the endometrial thickness in the LE group were lower than those in both the CC group and the control group in preovulatory phase. (2) With the level of both serum E2 and progesterone (P) in the CC group being higher than those in other two groups, the thickness of endometrium and the average area, perimeter and maximal diameter of single gland in this group were significantly lower those in the control group. However, these in the LE group were similar to those seen in the control group. Meanwhile the endometrial underdevelopment was found in the CC group. (3) With embryo development of the three groups synchronized with pregnancy day, the expression of not only pinopode but also LIF , ER and PR in mice endometrium of the LE group were similar to that seen in the control group. However, their expression in the CC group was significantly lower than the former two groups.Conclusion:, LE has no effect on and expression in the mouse implantation endometrium. Conclusion: Compared with CC for ovulation induction , the impact of the endometrial thickness that using LE for treatment result in is not better than CC , but it has no effectiveness on the change of endometrial morphology and the expression ultrastructure, pinopode formation, and LIF, ER and PR in mouse during implantation phase, and is beneficial to establish endometrial receptivity.PartⅡA comparison of the effects and pregnancy outcome of letrozole versus clomiphene citrate for ovulation induction in women with polycystic ovarian syndrome.Object: To search for a new drug for ovulation induction through a comparison of the effects and pregnancy outcome of letrozole (LE) versus clomiphene citrate (CC) for induction of ovulation. Methods: The patients with polycystic ovarian syndrome(PCOS)undergoing ovarian stimulation were divided into LE group and CC group. All subjects received either LE at a dosage of 5.0mg daily from cycle day 3 to 7 plus HMG injection staring on day 7 or CC (100mg/day) from day 5 to day 9 plus HMG injection on day 6 until the day of HCG. The number of follicle≥14mm and follicle≥16mm, endometrial thickenss and pattern were observed on the day of HCG. Some samples were analyzed including serum E2, testosterone and LH on the day of HCG and E2 and P on day +7 after follicular rupture. Meanwhile, pregnancy rate were recorded as well as the case of miscarriage, ectopic and ovarian hyperstimulation syndrome (OHSS).Result: Despite there being significantly (P﹤0.01) lower E2 level in the letrozole group, no significant differences between two groups were found in terms of endometrial thickenss and endometrial pattern on the day of HCG. However, endometrial thickenss was thinner 7mm in 13 patients from the CC group at the time of HCG administration, without anyone in the LE group. Compared with the CC group, letrozole was associated with a statistically significantly fewer follicles≥14mm and no one patient with OHSS. The pregnancy rate and ongoing pregnancy rate were higher in the LE group, but a marked difference wasn't found between the two groups. Conclusion: Letrozole results in stimulation of ovarian folliculogenesis and the pregnancy rate similar to that seen with CC.