Co-Administration of Clomiphene Citrate and Letrozole in Mild Ovarian Stimulation Versus Conventional Controlled Ovarian Stimulation Among POSEIDON Group 4 Patients

Abstract

This retrospective study assessed the effect of the co-administration of clomiphene citrate (CC) and letrozole in mild ovarian stimulation, compared to conventional regimens, among Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) Group 4 patients. There were 114 POSEIDON Group 4 patients undergoing in vitro fertilization treatments with 216 stimulation cycles recruited from a Taiwan’s reproductive center during 2016-2020. Main outcomes were the numbers, quality of retrieved oocytes and embryo development. Pregnancy outcomes were assessed after embryo transfers. Per stimulation cycle, patients receiving mild stimulation with a combination of CC and letrozole (study group) versus those with COS (control group) had lower numbers of pre-ovulatory follicles (2.00 ± 1.23 vs. 2.37 ± 1.23, p=0.0066) and oocytes retrieved (1.83 ± 1.17 vs. 2.37 ± 1.23, p=0.0017), and lower follicular output rate (58.6% vs. 68.38%, p=0.0093) and mature oocyte output rate (44.29% vs. 52.88%, p=0.0386) but a higher top-quality metaphase II oocyte ratio (66.7% vs. 54.59%, p=0.0444) and a similar fertilization rate (91.67% vs. 89.04%, p=0.4660). With adjustment for significant between-group baseline differences using multivariable logistic generalized estimating equation model analyses, there was no statistical difference in oocytes retrieved and embryo development between the study and control groups, and insignificant increases in successful pregnancies in the study group were found compared to the control group (i.e., odds ratios [95% CIs]: 1.13 [0.55, 232] and 1.50 [0.65, 3.49] for ongoing pregnancy and live birth, respectively). For POSEIDON Group 4 patients, cotreatment of CC and letrozole in mild stimulation may increase the high-quality oocyte ratio and yield comparable fertilization rate and pregnancy outcomes.

Potential Role of Quercetin in Polycystic Ovary Syndrome and Its Complications: A Review

“…Letrozole inhibits estrogen synthesis, and clomiphene competitively binds estrogen receptors, both of which reduce estrogen levels, increase follicle-stimulating hormone (FSH) release, and promote follicular development. This low estrogen status increases the risk of pregnancy loss or multiple pregnancies [ 6 ]. Secondly, the continuous stimulation of multiple follicles will induce the occurrence of follicular hyperstimulation syndrome.…”

Comparison of ovarian induction outcome in Mongolian women classified by POSEIDON criteria

“…Another retrospective study evaluated pregnancy rates for mild stimulation with the co-administration of CC and letrozole among POSEIDON Group 4 patients receiving IVF treatment. They showed that patients receiving mild stimulation with the co-administration of CC and letrozole (study group) had higher successful pregnancy rate compared to those for patients receiving COS (control group) despite the higher age and lower baseline AMH [30].…”

Reproductive outcomes of dual trigger therapy with GnRH agonist and hCG versus hCG trigger in women with diminished ovarian reserve: a retrospective study

“…Previous studies have shown that both letrozole and clomiphene could increase the release of gonadotropin-releasing hormone (GnRH) by affecting the feedback regulation of GnRH release by estrogen, thereby reducing the use of gonadotropins (Gn) in ART patients [ 4 , 5 ]. Therefore, mild stimulation protocols [ 6 ], including letrozole or clomiphene, are increasingly used in the process of ART because of their good efficacy and relatively low cost.…”

“…Previous studies have suggested that mild stimulation protocols could significantly increase the proportion of high-quality oocytes in patients with DOR [ 5 ]. Researchers are still uncertain whether dual trigger can improve the reproductive outcomes of patients with DOR, especially patients undergoing in vitro fertilization (IVF) treatments via mild stimulation protocols.…”