Elevated Early Follicular Phase Estradiol Does Not Predict Unsuccessful Pregnancy in Infertile Women with Polycystic Ovarian Syndrome (PCOS)

Abstract

Background and Significance: Early follicular phase (d2,3) gonadotropin (FSH) and/or estradiol concentrations are commonly used, in conjunction with age and antral follicle count, to counsel women regarding their chances of successful pregnancy. Although elevated FSH has long been accepted as having prognostic value, elevated d2,3 estradiol has become more recently recognized as having good predictive value in prediction of a negative outcome of either stimulation or pregnancy, although precise threshold values remain unclear. However, elevated d2,3 estradiol is not uncommonly seen in young PCOS patients with apparently good ovarian reserve.Objective: This pilot study investigated whether elevated estradiol precluded successful pregnancy and whether the percentage of elevated d2,3 estradiol in PCOS patients with successful pregnancies differed from patients having other infertility diagnoses.Materials and Methods: All consecutive patients seen in a tertiary care infertility clinic and who delivered successfully in a 6-year period (2002-2007) were studied. Diagnoses included: PCOS, male factor infertility, anatomic factor, endocrine factor (primary or secondary hypergonadotropic hypogonadism, hyperprolactinemia, CAH), diminished ovarian reserve (DOR) (elevated D2,3 FSH or AMA), and unexplained infertility. Excluded were patients with recurrent pregnancy loss and pregnancy loss prior to 12 weeks. Therapies included: IVF with/without donor oocytes, intrauterine insemination alone or with oral ovulation induction (OI) or gonadotropins (FSH/HMG), oral OI or FSH/HMG alone, combination OI+HMG/FSH cycles or treatment independent pregnancy. All pregnancy outcomes were ascertained. Chi-square statistics were used to compare percentages between groups.Results: Pregnancy was attained in 442 patients: DOR = 123, PCOS = 128, male factor = 77, anatomic factor = 19, other endocrine = 46, unexplained = 49. Elevated estradiol was seen only in the DOR (4.9%) and PCOS (2.3%) groups; 0% in all other diagnosis groups combined (P<0.001). Some patients having elevated estradiol in the DOR group used donor egg IVF to attain pregnancy.Conclusion: Elevated d2,3 estradiol was seen only in DOR and PCOS delivered patients. These data suggest that for PCOS patients, this laboratory result lacks the negative association for pregnancy prognosis. Disruption of hypothalamic-pituitary-ovarian feedback mechanisms associated with PCOS may account for the poor prognostic performance of d2,3 estradiol in this patient group. Background and Significance: Early follicular phase (d2,3) gonadotropin (FSH) and/or estradiol concentrations are commonly used, in conjunction with age and antral follicle count, to counsel women regarding their chances of successful pregnancy. Although elevated FSH has long been accepted as having prognostic value, elevated d2,3 estradiol has become more recently recognized as having good predictive value in prediction of a negative outcome of either stimulation or pregnancy, although precise threshold values remain unclear. However, elevated d2,3 estradiol is not uncommonly seen in young PCOS patients with apparently good ovarian reserve. Objective: This pilot study investigated whether elevated estradiol precluded successful pregnancy and whether the percentage of elevated d2,3 estradiol in PCOS patients with successful pregnancies differed from patients having other infertility diagnoses. Materials and Methods: All consecutive patients seen in a tertiary care infertility clinic and who delivered successfully in a 6-year period (2002-2007) were studied. Diagnoses included: PCOS, male factor infertility, anatomic factor, endocrine factor (primary or secondary hypergonadotropic hypogonadism, hyperprolactinemia, CAH), diminished ovarian reserve (DOR) (elevated D2,3 FSH or AMA), and unexplained infertility. Excluded were patients with recurrent pregnancy loss and pregnancy loss prior to 12 weeks. Therapies included: IVF with/without donor oocytes, intrauterine insemination alone or with oral ovulation induction (OI) or gonadotropins (FSH/HMG), oral OI or FSH/HMG alone, combination OI+HMG/FSH cycles or treatment independent pregnancy. All pregnancy outcomes were ascertained. Chi-square statistics were used to compare percentages between groups. Results: Pregnancy was attained in 442 patients: DOR = 123, PCOS = 128, male factor = 77, anatomic factor = 19, other endocrine = 46, unexplained = 49. Elevated estradiol was seen only in the DOR (4.9%) and PCOS (2.3%) groups; 0% in all other diagnosis groups combined (P<0.001). Some patients having elevated estradiol in the DOR group used donor egg IVF to attain pregnancy. Conclusion: Elevated d2,3 estradiol was seen only in DOR and PCOS delivered patients. These data suggest that for PCOS patients, this laboratory result lacks the negative association for pregnancy prognosis. Disruption of hypothalamic-pituitary-ovarian feedback mechanisms associated with PCOS may account for the poor prognostic performance of d2,3 estradiol in this patient group.