Clomiphene resistance treated by Combined CC & Letrozole in the same cycle, in fact on same days.

PCO who are resistant to CC or Letrozole before we switch on to Gonadotrophin & IUI we can offer a fair trail of Combined  CC & Letrozole in the same cycle ,in fact on same days: In CC & later  Letrozole resistant PCO women if HSG & seminal results  are normal then one can try combined CC & letrozole as stated  below backed by r-FSH & IUI

 

 :  Detailed schedule “: A dose of 5 mg Letrozole every night and 100 mg clomiphene every day after lunch was prescribed for 5 days. In Patients with oligomenorrhea the medication (letrozole and clomiphene) started after induction of bleeding with progesterone, and for those patients with regular cycles the medications (letrozole and clomiphene) were started from day 2 or 3 of cycle. To evaluate the growth of follicles, vaginal ultrasound was performed on day 11 of the cycle, and Gonal-f (rFSH, Puregon, NV Organon, OSS, the Netherland) was prescribed to complete follicle growth.

 When not to initiate Ov induction, in general?? It is important to note that prior to administration of drugs on day 2 or 3, vaginal ultrasound should be performed, and in the event of follicles larger than 2 cm, CC & letrozole therapy was not started.

Trigger when ?? After at least one follicle reached 18 mm, the patients were given 5,000 units of human chorionic gonadotropin, and underwent intrauterine insemination 36–38 hours later. The number of Gonal-f doses used, number of mature follicles, endometrial thickness on the day of human chorionic gonadotropin administration, occurrence of pregnancy, multiple pregnancies, and miscarriages were recorded and evaluated for up to 20 weeks of gestation. Success rate were acceptable and in many cases gonadotrophin only  cycle can be avoided.

 

 Considering the extent of adverse effects associated with gonadotropins and surgery, we decided to use a combination of letrozole and clomiphene in our patients, who were resistant to letrozole and clomiphene used alone. It is noteworthy that we did not find any other similar paper with which to compare our results.

The results of our study show that in PCOS patients resistant to clomiphene and letrozole alone, a combination of the two drugs resulted in formation of dominant follicles in 82.9% of cases and pregnancy in 42% of cases. The risk of ovarian hyperstimulation syndrome is very low with this method, and multiple pregnancies occur less frequently than in patients treated with gonadotropins. Moreover, this strategy does not have the cost and adverse effects of surgery, such as adhesions and premature ovarian failure.

The frequency of miscarraige in our study was 23.8%. Speroff and Fritz reported that the frequency of miscarraige following gonadotropins in their clomiphene-resistant patients was 20%–25%, which is more than that in the general population (15%). They also explained that the reason for this was the older age and number of obese subjects in their study population.9 Abu Hashim et al reported that 15%–40% of their PCOS patients were resistant to clomipheneLetrozole causes ovulation in 54.6%–84.4% of clomiphene-resistant patients. In our study, a combination of letrozole and clomiphene resulted in ovulation in 82.9% of cases, and pregnancy occurred in 42% after three cycles of combination therapy.

According to the results of this study, it can be advised that, in PCOS patients resistant to clomiphene and letrozole alone, a combination of the two drugs can be tried prior to treatments having more severe adverse effects, or surgery. More studies need to be initiated, to have a better understanding on the effectiveness of the combination of drugs on a larger population of patients. The combination may also be used as first-line therapy to induce ovulation in severe cases of PCOS in order to save time and expense.