Effects of Letrozole-HMG and Clomiphene-HMG on Incidence of Luteinized Unruptured Follicle Syndrome in Infertile Women Undergoing Induction Ovulation and Intrauterine Insemination: A Randomised Trial

Abstract

Background:Luteinized unruptured follicle (LUF) syndrome is considered a cause of ovulation failure and a subtle cause of infertility. Preovulatory injection of human chorionic gonadotropin (HCG) prevents or treats LUF syndrome, but it has also occurred after the induction of ovulation with clomiphene/HMG and HCG. This study was designed for evaluation and comparison of LUF incidence in eligible infertile women undergoing two stimulation protocols (clomiphene + HMG and letrozole + HMG) in addition to intrauterine insemination (IUI). Some related factors were compared between LUF and non-LUF cycles as secondary outcomes.Methods:The study was designed as a prospective randomized controlled trial. Patients were randomized using a table of random numbers into two equal protocol groups. For group A, (n = 90) clomiphene citrate was administrated orally in doses of 100 mg/day, and group B (n = 90) orally received letrozole 5 mg/day from day 3 to 7 of the menstrual cycle. Then HMG 75IU/day was administered intramuscularly in both groups on day 8 of the menstrual cycle and the dose was adjusted on the basis of ovarian response. The optimum size of preovulatory follicles for the injection of HCG (10,000 IU) was considered 18–23 mm. The number and size of preovulatory follicles were assessed by vaginal ultrasound 12 h before HCG (D0). Endometrial thickness was measured as well. IUI was performed on all patients 38–40 h after HCG. The second ultrasound examination was performed to observe the evidence of oocyte releasing at the time of IUI (D1). If the follicles were unruptured, a third sonography was performed on day 7 after HCG (D7) to observe LUF syndrome.Results:There was a significant difference between clomiphene-HMG and letrozole-HMG in LUF (p = 0.021) and pregnancy (p = 0.041). The complete LUF in letrozole-HMG was lower than the alternative group and the pregnancy rate was higher. The patients in the non-LUF group had higher midluteal progesterone and a thicker endometrium compared to LUF cycles (p = 0.039) and (p < 0.001). The results of our multivariate logistic regression indicate that size 18–19.9 mm leads to the complete LUF less than ≥22 mm [AOR: 0.25, P = 0.005], and in size 20– 21.9 mm as well [AOR: 0.17, P = 0.002].Conclusion:Letrozole, with lower incidences of LUF, is more effective than clomiphene citrate for the induction of ovulation in IUI cycles. In our study, we illustrated that larger follicles of ≥22 mm diameter were associated with higher incidences of LUF. We recommend that further studies investigate and focus on the relationship between follicular size and/or full hormonal profiles and LUF.

Downregulation of LHCGR Attenuates COX-2 Expression and Induces Luteinized Unruptured Follicle Syndrome in Endometriosis

“…It is further confirmed by the results obtained in Lhcgr knockout zebrafish showing increased unruptured follicles after LH surge ( 40 ). Furthermore, the administration of hCG during gonadotrophin ovulation prevents or treats LUFs ( 41 ), while a lower dose of hCG may induce LUFs ( 42 ). It seems that not only an adequate decrease in intrafollicular prostaglandin but decreased LH or LHCGR responsiveness contributes to the occurrence of LUFs as well.…”

Comparing Effectiveness of Letrozole Versus Clomiphene Citrate to Evaluate the Ovulation Induction in patients with POS

“…The frequency of PCOS is determined by the diagnostic criteria used. According to the World Health Organization, it affects Similarly, Azra Azmoodeh and associates demonstrated higher ovulation and pregnancy rates when treated with Letrozole 8 . This study is being conducted to find out if Letrozole is actually superior to Clomiphene Citrate, to propose and help establish local guideline for ovulation induction, in infertile females suffering from PCOS.…”

Mimicking reproductive endocrinology to achieve successful pregnancy in frozen embryo replacement cycle in luteinized unruptured follicle (LUF

“…LUF is observed in 10% of natural menstrual cycles in fertile women, but in stimulated cycles it is higher. 4 The incidence of LUF has been reported to be 25-43% in infertile women 5 . Concerns do exist regarding impact on success of the embryo transfer in a stimulated cycle with LUF.…”