Correlation of Endometrial Glycodelin Expression and Pregnancy Outcome in Cases with Polycystic Ovary Syndrome Treated with Clomiphene Citrate Plus Metformin: A Controlled Study

Abstract

Objective. The purpose of this study was to evaluate the relationship between clomiphene citrate (CC) plus metformin treatment and endometrial glycodelin expression and to then correlate this relationship with pregnancy outcomes. Material and Methods. A total of 30 patients diagnosed with polycystic ovary syndrome (PCOS) according to the Rotterdam criteria constituted our study group. All had been admitted to the gynecology outpatient clinic between June 1, 2011, and January 1, 2012, for infertility treatment. Our control group consisted of 20 patients admitted for routine Pap smear control. They had no history of infertility and were not using contraceptives and they were actively attempting pregnancy. Midluteal progesterone measurement and pipelle endometrial biopsies were performed with both groups. For PCOS patients, metformin treatment was initiated right after the biopsy and CC was added in the second menstrual cycle. Pipelle endometrial biopsies were repeated. Histological dating and immunohistochemistry for glycodelin were performed by a single pathologist who was blinded to the patients' clinical data. Result(s). The posttreatment ovulation rate in the study group was 93.3%. No pregnancies were achieved in either group when glycodelin expression was not present, even in the presence of ovulation. When glycodelin expression was high in PCOS group, the pregnancy rate was 60% and all pregnancies ended in live births. In weak expression group, however, three out of four pregnancies ended as early pregnancy losses. Conclusion(s). Endometrial glycodelin expression is an important predictor of pregnancy outcomes in both PCOS and fertile groups.

Chronic Low Grade Inflammation in Pathogenesis of PCOS

“…The decrease of glycodelin in the endometrium and in the serum is associated with increased rate of miscarriage. In PCOS women hyperinsulinemic state decreases the concentrations of circulating glycodelin [ 49 ]. Moreover, hyperinsulinemia may decrease expression of IGF binding protein-1, which is important in adhesion processes of feto-maternal interaction.…”

Estimation of Serum Glycodelin A, Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-3 at 4th Week Gestational Age as Predictors for Early Pregnancy Loss in Pregnant Women With Polycystic Ovary Syndrome.

“…Tapia-Pizarro et al (39) found immunostaining for GdA was significantly decreased in endometrial samples from women experienced repeatedly implantation failure. Also, Uysal et al (40) reported that when GdA expression was high in PCOS group, the pregnancy rate was 60% and all pregnancies ended in live births, while in weak expression group, EPL rate was 75% and concluded that endometrial GdA expression is an important predictor of pregnancy outcomes in both PCOS and fertile groups. Lee et al (41) attributed such role of GdA to the findings that GdA interacts by its unique carbohydrate side chains with the cell surface of various cell types in the human fetomaternal interface and modulates their functions and differentiation to permit successful pregnancy, and documented that abnormal GdA levels in the endometrium, uterine flushings, and/or maternal serum correlate with unexplained infertility, early and recurrent pregnancy loss.…”

Pharmacokinetic, pharmacodynamic, and clinical aspects of ovulation induction agents: A review of the literature

“…Adding metformin to treatment cycle protocols for increasing pregnancy rates among patients with PCOS is a matter of debate. In a systematic review, Palomba et al ( 11 ) concluded that infertile patients with PCOS treated with gonadotrophins for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles, implantation rates seemed improved but pregnancy or live birth rates did not increase by using metformin despite lower rates of ovarian hyperstimulation syndrome (OHSS) and miscarriage ( 11 , 12 ). Specific phenotypes and features of patients with PCOS who will benefit from metformin should be defined before liberally advising metformin to all patients with PCOS.…”