An effective alternative to only gonadotrophin for controlled ovarian stimulation in unexplained infertility patients undergoing intra-uterine insemination: a clinical trial

Abstract

Clomiphene citrate, by stimulating the endogenous gonadotrophin secretion, reduces the dose of exogenous gonadotrophin for controlled ovarian stimulation. However, the benefit of clomiphene citrate may be offset by its oestrogen-receptor depleting effect on target tissues like endometrium. Letrozole, an aromatase inhibitor, stimulates endogenous gonadotrophin secretion (like clomiphene citrate). However, it does not deplete oestrogen receptors and hence does not have adverse effect on endometrium (unlike clomiphene citrate). To evaluate the effectiveness of letrozole + FSH combination versus only FSH for contolled ovarian stimulation in unexplained infertility patients undergoing intra-uterine insemination, a prospective randomised trial was undertaken among 55 patients with unexplained infertility completed all together 118 treatment cycles of controlled ovarian stimulation and intra-uterine insemination. All these patients were regularly ovulatory women and had folliculometry by transvaginal ultrasound scanning (without any medication) with timed intercourse for Initial 2 cycles before going for controlled ovarian stimulation and intra-uterine insemination. Thereafter, 29 patients, of these 55 patients, who were allotted to one group (letrozole + FSH group) started the treatment cycle of controlled ovarian stimulation and intrauterine insemination. For controlled ovarian stimulation, each of these 29 patients received letrozole 2.5 mg from day 3 to day 7. From day 7 onwards, each patient received FSH injection intramuscular (50-150 IU/day) until the leading follicle is > or = 18 mm. Twenty-six patients, of these 55 patients, were allotted to another group (only FSH group). Each of these patients received FSH injection intramuscular (50-225 units/day) from day 3 until the leading follicle is > or = 18 mm. Monitoring of follicular development was done by transvaginal ultrasound scan, first on day 2/3 of each treatment cycle, then on day 7 and thereafter on alternate day or sometimes on successive days till the leading follicle is 18 mm or more. The dose and duration of FSH was adjusted depending on the number and size of growing follicles. Injection hCG 10000 units intramuscular was administered when the leading follicle was 18 mm or more. Intra-uterine insemination was performed 36 hours following hCG administration. Urine for pregnancy test was performed 21 days later if the patient did not have period by then. In each group, the outcome measures noted are mean of total dose of FSH/cycle, total number of mature follicles (> 16 mm) (on the day of hCG administration), endometrial thickness (on the day of hCG administration), and pregnancy rate/cycle. Statistical analysis was carried by using unpaired 't' test on continuous variables whereas Fisher's exact test was used on categorical variables. There was no significant difference in mean of total number of mature follicles (> 16 mm) and endometrial thickness on the day of hCG administration as well as pregnancy rate/cycle between two groups. However, the mean total dose of FSH/cycle and mean total duration of FSH administration/cycle were significantly less in letrozole + FSH group compared with only FSH group.