Combined Letrozole and Clomiphene versus Letrozole with low dose gonadotropin protocol for ovulation induction in infertile clomiphene-resistant women with polycystic ovary syndrome: Comparative study

Objectives: To compare the effect of combined clomiphene citrate (100mg) and Letrozole (5mg) versus Letrozole (5mg) followed by gonadotropin injection for one cycle in CC resistant PCOs patients.
Design: Prospective randomized trial.
Setting: Infertility Outpatient Clinic and Cytogenetic and Endoscopy Unit of Obstetrics and Gynecology Department of Zagazig University Hospitals.
Study group: About 212 PCOs patients with CC resistance (anovulatory response with CC at a dose of 100-150 mg for 3 cycles) were divided into two groups (106 in each group).
Intervention: A studied group was randomly divided into two groups. Group A received combined Letrozole 5mg (2 tablets) in the morning and clomid 100 mg (2 tablets) in the evening from the 3rd day of menses for 5 days, group B received Letrozole 5 mg (2 tablets) from the 3rd day of menses for 5 days followed by human menopausal gonadotropin (hMG) injection every other day from cycle day 7. Moreover, ultrasound folliculometry started on cycle day 10 then the dose was adjusted according to follicular size. Both groups received treatment regimen for only one cycle.
Results: There was higher ovulation rate (85.8%) in letrozole plus hmG group than in the other group receiving letrozole and CC (80.2%), but with no statistical significant difference (P -value =0.65). But, there was statistical significant difference between both groups regarding stimulation characters including total number of mature follicles (≥18 mm) 2.1 ± 1.01 in combined letrozole and CC was greater in group A than in group B (1.66 ± 0.98) with (P - value = 0.009). Stimulation days were longer in group B (18.2 ± 2.5) than in group A (16.2 ± 2.1). Mean total E2 on the day of hCG administration was significantly higher among patients in the clomiphene-letrozole group as compared with that in the other group of letrozole with hmG ( 650 ± 190.3 and 540 ± 180.5, respectively). Also, higher day 21 serum progesterone in group A (11 ± 1.1) than (9.5 ± 0.9) in group B. But, there was no statistical significant difference in mean endometrial thickness in both groups (A and B) (9.6 ± 1.7 versus 9.8 ± 1.5mm, respectively) (P-value = 0.41). The pregnancy rate did not show any statistical significant difference in both groups (P-value = 0.45) ; 32 patients out of 106 (30.1%) in group A compared with 27 patients (25.4%) in group B. Four cases were aborted in group A compared with 3 cases in group B. Four cases had twin pregnancy in group A with only 3 cases in group B. Also, there was no significant difference between both groups regarding ovarian hyperstimulation ; as there were 2 cases with combined clomid and letrozole group and one case only in letrozole plus hmG group.
Conclusion: This study showed that lerozole is an effective medication when combined with CC or sequentially with hmG injection in improving the ovulation and pregnancy rate in CC-resistant PCOs patients with higher results when combined with hmG injection, but did not reach statistical significance.